| 1. |
- Arlock, Per, et al.
(författare)
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Excitation and contraction of cardiac muscle and coronary arteries of brain-dead pigs
- 2023
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Ingår i: FASEB BioAdvances. - : Wiley. - 2573-9832. ; 5:2, s. 71-84
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Tidskriftsartikel (refereegranskat)abstract
- Excitability and contraction of cardiac muscle from brain-dead donors critically influence the success of heart transplantation. Membrane physiology, Ca2+-handling, and force production of cardiac muscle and the contractile properties of coronary arteries were studied in hearts of brain-dead pigs. Cardiac muscle and vascular function after 12 h brain death (decapitation between C2 and C3) were compared with properties of fresh tissue. In both isolated cardiomyocytes (whole-cell patch clamp) and trabecular muscle (conventional microelectrodes), action potential duration was shorter in brain dead, compared to controls. Cellular shortening and Ca2+ transients were attenuated in the brain dead, and linked to lower mRNA expression of L-type calcium channels and a slightly lower ICa,L, current, as well as to a lower expression of phospholamban. The current–voltage relationship and the current above the equilibrium potential of the inward K+ (IK1) channel were altered in the brain-dead group, associated with lower mRNA expression of the Kir2.2 channel. Delayed K+ currents were detected (IKr, IKs) and were not different between groups. The transient outward K+ current (Ito) was not observed in the pig heart. Coronary arteries exhibited increased contractility and sensitivity to the thromboxane analogue (U46619), and unaltered endothelial relaxation. In conclusion, brain death involves changes in cardiac cellular excitation which might lower contractility after transplantation. Changes in the inward rectifier K+ channel can be associated with an increased risk for arrhythmia. Increased reactivity of coronary arteries may lead to increased risk of vascular spasm, although endothelial relaxant function was well preserved.
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| 2. |
- Bozovic, Gracijela, et al.
(författare)
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Circulation stabilizing therapy and pulmonary high-resolution computed tomography in a porcine brain-dead model.
- 2016
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 60:1, s. 93-102
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Tidskriftsartikel (refereegranskat)abstract
- Currently 80% of donor lungs are not accepted for transplantation, often due to fluid overload. Our aim was to investigate if forced fluid infusion may be replaced by a new pharmacological therapy to stabilize circulation after brain death in an animal model, and to assess therapy effects on lung function and morphology trough blood gas parameters and state-of-the-art High-resolution CT (HRCT).
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| 3. |
- Budrikis, Algimantas, et al.
(författare)
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Effects of cardioplegic flushing, storage, and reperfusion on coronary circulation in the pig
- 1999
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Ingår i: Annals of Thoracic Surgery. - 1552-6259. ; 67:5, s. 1345-1349
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of the study was to investigate how flush-perfusion of the heart with cold cardioplegic solution, 2 or 12 hours of cold ischemic storage, and 24 hours of reperfusion affect coronary endothelial function and coronary vascular resistance. METHODS: Porcine coronary arterial endothelial and smooth muscle function was studied in organ baths. An adult porcine working heart model was used to investigate coronary vascular resistance after 24 hours of reperfusion. RESULTS: Flushing the heart with 1 L of St. Thomas' cardioplegic solution, using a perfusion pressure of 60 to 65 mm Hg, significantly reduced endothelium-dependent relaxation. Flushing followed by 12 hours of storage gravely impaired endothelium-dependent relaxation, and 24 hours of reperfusion worsened it still more. CONCLUSIONS: Flushing the heart with cold cardioplegic solution impairs endothelium-dependent relaxation, as does prolonged cold ischemic storage. Reperfusion of injured coronary endothelium may injure it still more. A correlation was found (p < 0.001) between high coronary vascular resistance and low endothelium-dependent relaxation.
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| 4. |
- Critchley, William R., et al.
(författare)
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Non-ischemic Heart Preservation via Hypothermic Cardioplegic Perfusion Induces Immunodepletion of Donor Hearts Resulting in Diminished Graft Infiltration Following Transplantation
- 2020
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Many donor organs contain significant leukocyte reservoirs which upon transplantation activate recipient leukocytes to initiate acute rejection. We aimed to assess whether non-ischemic heart preservation via ex vivo perfusion promotes immunodepletion and alters the inflammatory status of the donor organ prior to transplantation. Methods: Isolated porcine hearts underwent ex vivo hypothermic, cardioplegic perfusion for 8 h. Leukocyte populations were quantified in left ventricle samples by flow cytometry. Cell-free DNA, cytokines, and chemokines were quantified in the perfusate. Tissue integrity was profiled by targeted proteomics and a histological assessment was performed. Heterotopic transplants comparing ex vivo hypothermic preservation and static cold storage were utilized to assess graft infiltration as a solid clinical endpoint. Results: Ex vivo perfusion significantly immunodepleted myocardial tissue. The perfusate displayed a selective, pro-inflammatory cytokine/chemokine pattern dominated by IFN-γ. The tissue molecular profile was improved following perfusion by diminished expression of nine pro-apoptotic and six ischemia-associated proteins. Histologically, no evidence of tissue damage was observed and cardiac troponin I was low throughout perfusion. Cell-free DNA was detected, the source of which may be necrotic/apoptotic leukocytes. Post-transplant graft infiltration was markedly reduced in terms of both leucocyte distribution and intensity of foci. Conclusions: These findings demonstrate that ex vivo perfusion significantly reduced donor heart immunogenicity via loss of resident leukocytes. Despite the pro-inflammatory cytokine pattern observed, a pro-survival and reduced ischemia-related profile was observed, indicating an improvement in graft viability by perfusion. Diminished graft infiltration was observed in perfused hearts compared with those preserved by static cold storage following 48 h of transplantation.
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| 5. |
- Liang, YC, et al.
(författare)
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QT dispersion failed to estimate the global dispersion of ventricular repolarization measured using monophasic action potential mapping technique in swine and patients
- 2005
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Ingår i: Journal of Electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 38:1, s. 19-27
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate whether the QT dispersion measured from 12-lead electrocardiogram (ECG) can estimate the global dispersion of ventricular repolarization (DVR) measured using a monophasic action potential (MAP) mapping technique. Monophasic action potentials were recorded from 75 +/- 12 left ventricular sites in 10 pigs and from 48 +/- 16 left or right ventricular sites in 15 patients using the CARTO mapping system. The maximum DVRs in both end-of-repolarization and MAP duration among all the mapped sites were calculated and termed as global DVR for each measurement. QT intervals, QT(peak) and QT(end), were measured from the 12-lead ECG, and QT dispersions; namely the differences between the maximum and the minimum of the QTpeak and QT(end) were calculated. We found that QT dispersions were significantly smaller than (P < .05) and poorly correlated with the global DVRs both in pigs and patients. Bland-Altman agreement analysis demonstrated a marked variation of the differences and an obvious lack of agreement between the results obtained using the ECG and the MAP methods. In our patients, the global DVR increased markedly during ventricular tachycardia as compared with that during sinus rhythm (P < .05), whereas there was no significant difference in QT dispersion between these 2 subgroups. In conclusion, QT dispersion on the surface ECG could not estimate the global DVR measured using the MAP mapping technique. These findings are not consistent with some previously reported observations, suggesting the need for reappraisal of the electrophysiological implications of QT dispersion.
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| 6. |
- Liao, Qiuming
(författare)
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LUCAS - Lund University Cardiopulmonary Assist System
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lund University Cardiopulmonary Assist System (LUCAS) is a mechanical device providing automatic 5 cm deep chest compressions and active decompressions back to normal anatomical position with a frequency of 100 per minute, and a duty cycle of 50%, i.e., LUCAS is constructed to give chest compressions according to the latest international guidelines in cardiopulmonary resuscitation (CPR). The aim of the thesis was to study cardiac arrest using different porcine models of ventricular fibrillation. Four hypotheses were formulated: 1. LUCAS-CPR is superior to manual CPR regarding coronary perfusion pressure (CPP) and return of spontaneous circulation (ROSC). 2. Hypothermic LUCAS-CPR is superior to normothermic LUCAS-CPR in treating prolonged ventricular fibrillation. 3. The rate of ROSC after prolonged ventricular fibrillation will increase if LUCAS-CPR is given before defibrillation, and if defibrillation is given during on-going chest compressions. 4. LUCAS-CPR will cause fewer rib fractures than manual CPR. LUCAS-CPR gave significantly higher rates of ROSC and significantly higher CPP than manual CPR. LUCAS-CPR combined with surface cooling to 34°C was superior to normothermic LUCAS-CPR during 1 hour of CPR for ventricular fibrillation. Defibrillation was more effective to obtain ROSC after prolonged ventricular fibrillation if chest compressions were done before the shock, and if the shock was given during on-going LUCAS-CPR. LUCAS-CPR caused significantly fewer rib fractures during 20 minutes of CPR compared to manual CPR.
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| 7. |
- Liao, Qiuming, et al.
(författare)
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Manual versus mechanical cardiopulmonary resuscitation. An experimental study in pigs
- 2010
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Optimal manual closed chest compressions are difficult to give. A mechanical compression/ decompression device, named LUCAS, is programmed to give compression according to the latest international guidelines (2005) for cardiopulmonary resuscitation (CPR). The aim of the present study was to compare manual CPR with LUCAS-CPR. Methods: 30 kg pigs were anesthetized and intubated. After a base-line period and five minutes of ventricular fibrillation, manual CPR (n = 8) or LUCAS-CPR (n = 8) was started and run for 20 minutes. Professional paramedics gave manual chest compression's alternating in 2-minute periods. Ventilation, one breath for each 10 compressions, was given to all animals. Defibrillation and, if needed, adrenaline were given to obtain a return of spontaneous circulation (ROSC). Results: The mean coronary perfusion pressure was significantly (p < 0.01) higher in the mechanical group, around 20 mmHg, compared to around 5 mmHg in the manual group. In the manual group 54 rib fractures occurred compared to 33 in the LUCAS group (p < 0.01). In the manual group one severe liver injury and one pressure pneumothorax were also seen. All 8 pigs in the mechanical group achieved ROSC, as compared with 3 pigs in the manual group. Conclusions: LUCAS-CPR gave significantly higher coronary perfusion pressure and significantly fewer rib fractures than manual CPR in this porcine model.
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| 8. |
- Lindberg, Lars, et al.
(författare)
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The effects of epinephrine/norepinephrine on end-tidal carbon dioxide concentration, coronary perfusion pressure and pulmonary arterial blood flow during cardiopulmonary resuscitation
- 2000
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Ingår i: Resuscitation. - 1873-1570. ; 43:2, s. 129-140
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Tidskriftsartikel (refereegranskat)abstract
- End-tidal CO2 concentration correlates with pulmonary blood flow during cardiopulmonary resuscitation and has been claimed to be a useful tool to judge the effectiveness of chest compression. A high concentration of end-tidal CO2 has been related to a better outcome. However, most authors have noticed a decrease in end-tidal CO2 concentration after administration of epinephrine, concomitant with an increase in coronary perfusion pressure and an increased incidence of return of spontaneous circulation. This study was performed to evaluate changes in end-tidal CO2 concentration after injection of vasopressors during cardiopulmonary resuscitation and to investigate the time-course of the response and possible explanations for it. After 1 min of electrically induced cardiac arrest and 5 min of chest compressions, 18 pigs were randomly assigned to receive 0.045 mg kg(-1) epinephrine, 0.045 mg kg(-1) norepinephrine or no drug. After another 4 min of chest compressions the pigs were defibrillated. End-tidal CO2, pulmonary blood flow and coronary perfusion pressure decreased immediately after the induction of cardiac arrest, increased slightly during chest compressions and increased initially to supernormal levels after the return of spontaneous circulation. Injection of epinephrine or norepinephrine during chest compressions decreased end-tidal CO2 51 +/- 2%, (mean +/- S.E.M.), and 43 +/- 1%, respectively, and pulmonary blood flow by 134 +/- 13 and 125 +/- 16%, respectively, within 1 min, simultaneously increasing coronary perfusion pressure from 10 +/- 2 to 45 +/- 5 mm Hg and from 11 +/- 1 to 38 +/- 5 mm Hg, respectively. The coronary perfusion pressure slowly fell, but the effects on end-tidal CO2 and pulmonary blood flow were prolonged. In conclusion, vasopressors increased coronary perfusion pressure and the likelihood of a return of spontaneous circulation, but decreased end-tidal CO2 concentration and induced a critical deterioration in cardiac output and thus oxygen delivery in this model of cardiopulmonary resuscitation.
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| 9. |
- Längin, Matthias, et al.
(författare)
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Cold non-ischemic heart preservation with continuous perfusion prevents early graft failure in orthotopic pig-to-baboon xenotransplantation
- 2021
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Ingår i: Xenotransplantation. - : Wiley. - 0908-665X .- 1399-3089. ; 28:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Successful preclinical transplantations of porcine hearts into baboon recipients are required before commencing clinical trials. Despite years of research, over half of the orthotopic cardiac xenografts were lost during the first 48 hours after transplantation, primarily caused by perioperative cardiac xenograft dysfunction (PCXD). To decrease the rate of PCXD, we adopted a preservation technique of cold non-ischemic perfusion for our ongoing pig-to-baboon cardiac xenotransplantation project. Methods: Fourteen orthotopic cardiac xenotransplantation experiments were carried out with genetically modified juvenile pigs (GGTA1- KO/hCD46/hTBM) as donors and captive-bred baboons as recipients. Organ preservation was compared according to the two techniques applied: cold static ischemic cardioplegia (IC; n = 5) and cold non-ischemic continuous perfusion (CP; n = 9) with an oxygenated albumin-containing hyperoncotic cardioplegic solution containing nutrients, erythrocytes and hormones. Prior to surgery, we measured serum levels of preformed anti-non-Gal-antibodies. During surgery, hemodynamic parameters were monitored with transpulmonary thermodilution. Central venous blood gas analyses were taken at regular intervals to estimate oxygen extraction, as well as lactate production. After surgery, we measured troponine T and serum parameters of the recipient’s kidney, liver and coagulation functions. Results: In porcine grafts preserved with IC, we found significantly depressed systolic cardiac function after transplantation which did not recover despite increasing inotropic support. Postoperative oxygen extraction and lactate production were significantly increased. Troponin T, creatinine, aspartate aminotransferase levels were pathologically high, whereas prothrombin ratios were abnormally low. In three of five IC experiments, PCXD developed within 24 hours. By contrast, all nine hearts preserved with CP retained fully preserved systolic function, none showed any signs of PCXD. Oxygen extraction was within normal ranges; serum lactate as well as parameters of organ functions were only mildly elevated. Preformed anti-non-Gal-antibodies were similar in recipients receiving grafts from either IC or CP preservation. Conclusions: While standard ischemic cardioplegia solutions have been used with great success in human allotransplantation over many years, our data indicate that they are insufficient for preservation of porcine hearts transplanted into baboons: Ischemic storage caused severe impairment of cardiac function and decreased tissue oxygen supply, leading to multi-organ failure in more than half of the xenotransplantation experiments. In contrast, cold non-ischemic heart preservation with continuous perfusion reliably prevented early graft failure. Consistent survival in the perioperative phase is a prerequisite for preclinical long-term results after cardiac xenotransplantation.
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| 10. |
- Längin, Matthias, et al.
(författare)
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Consistent success in life-supporting porcine cardiac xenotransplantation
- 2018
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 564:7736, s. 430-433
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Tidskriftsartikel (refereegranskat)abstract
- Heart transplantation is the only cure for patients with terminal cardiac failure, but the supply of allogeneic donor organs falls far short of the clinical need1–3. Xenotransplantation of genetically modified pig hearts has been discussed as a potential alternative4. Genetically multi-modified pig hearts that lack galactose-α1,3-galactose epitopes (α1,3-galactosyltransferase knockout) and express a human membrane cofactor protein (CD46) and human thrombomodulin have survived for up to 945 days after heterotopic abdominal transplantation in baboons5. This model demonstrated long-term acceptance of discordant xenografts with safe immunosuppression but did not predict their life-supporting function. Despite 25 years of extensive research, the maximum survival of a baboon after heart replacement with a porcine xenograft was only 57 days and this was achieved, to our knowledge, only once6. Here we show that α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and thrombomodulin require non-ischaemic preservation with continuous perfusion and control of post-transplantation growth to ensure long-term orthotopic function of the xenograft in baboons, the most stringent preclinical xenotransplantation model. Consistent life-supporting function of xenografted hearts for up to 195 days is a milestone on the way to clinical cardiac xenotransplantation7.
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| 11. |
- Metzsch, Carsten, et al.
(författare)
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Levosimendan cardioprotection in acutely beta-1 adrenergic receptor blocked open chest pigs.
- 2010
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 54, s. 103-110
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Tidskriftsartikel (refereegranskat)abstract
- Background: Levosimendan and volatile anesthetics have myocardial pre-conditioning effects. beta-1 adrenergic receptor antagonists may inhibit the protective effect of volatile anesthetics. No information exists as to whether this also applies to the pre-conditioning effect of levosimendan. We therefore investigated whether levosimendan added to metoprolol would demonstrate a cardioprotective effect. Methods: Three groups of anesthetized open chest pigs underwent 30 min of myocardial ischemia and 90 min of reperfusion by temporary occlusion of the largest side branch from the circumflex artery or the left anterior descending artery. One group (CTRL) served as a control, in another group (BETA), a metoprolol-loading dose was intravenously injected 30 min before ischemia, and in a third group (BETA+L), a levosimendan infusion was added to metoprolol. Myocardial tissue concentrations of glucose, glycerol, and lactate/pyruvate ratio as the primary end-points were investigated with microdialysis in ischemic and non-ischemic tissues. Results: At the end of the ischemic period, statistically significant differences were only found between CTRL and BETA+L in the ischemic myocardium, with a lower lactate/pyruvate ratio, lower glycerol, and higher glucose concentrations in BETA+L as compared with CTRL. There were no differences in non-ischemic myocardium. From 10 to 90 min of reperfusion, no more differences were found between groups. Conclusion: The cardioprotective effect of levosimendan on ischemic metabolism with a reduction in the myocardial lactate/pyruvate ratio, less glycerol accumulation, and better preserved glucose concentration does not seem to be prevented by beta-1 adrenergic receptor antagonism with metoprolol.
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| 12. |
- Metzsch, Carsten, et al.
(författare)
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Levosimendan cardioprotection reduces the metabolic response during temporary regional coronary occlusion in an open chest pig model.
- 2007
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 51, s. 86-93
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inotropic and myocardial anti-ischemic effects have been demonstrated with levosimendan. The comparison of levosimendan started before an ischemia-reperfusion event as compared with levosimendan started during ischemia has not been studied. Methods: In anesthetized pigs, a major branch of the circumflex artery was completely occluded for 30 min and then reperfused. The metabolism in the ischemic myocardium and in non-ischemic control myocardium was studied with microdialysis concomitantly with monitoring of global hemodynamics and coronary artery flow in the chosen artery. In the protection group (PRO, n = 6), a levosimendan infusion was started 30 min before coronary artery occlusion, and in the treatment group (TRE, n = 6), a levosimendan infusion was started 10 min after the coronary artery occlusion with a loading dose of 13.3 mu g/kg followed by an infusion of 0.67 mu g/kg/min. A two-way repeated measures ANOVA completed with Bonferroni's multiple comparison procedure was applied to the data. A P < 0.05 was considered significant. Results: During the ischemic period, the cardiac output and contractility (dp/dt(max)) were higher in the PRO as compared with the TRE and the systemic vascular resistance was lower. The myocardial microdialysate glucose concentration in the ischemic area during ischemia was higher in the PRO as compared with the TRE, and the lactate/pyruvate ratio and the lactate concentration were lower. The differences in the metabolites persisted into the first 10 min of reperfusion. No differences were found for the non-ischemic areas. Conclusions: Levosimendan used throughout myocardial ischemia-reperfusion might have a cardioprotective affect on the response to myocardial ischemia as compared with levosimendan started during the ischemia.
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| 13. |
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| 14. |
- Pigot, Henry, et al.
(författare)
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A novel nonlinear afterload for ex vivo heart evaluation: Porcine experimental results
- 2022
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Ingår i: Artificial Organs. - : Wiley. - 0160-564X .- 1525-1594. ; 46:9, s. 1794-1803
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Tidskriftsartikel (refereegranskat)abstract
- Background: Existing working heart models for ex vivo functional evaluation of donor hearts often use cardiac afterloads made up of discrete resistive and compliant elements. This approach limits the practicality of independently controlling systolic and diastolic aortic pressure to safely test the heart under multiple loading conditions. We present and investigate a novel afterload concept designed to enable such control. Methods: Six ∼70 kg pig hearts were evaluated in vivo, then ex vivo in left-ventricular working mode using the presented afterload. Both in vivo and ex vivo, the hearts were evaluated at two exertion levels: at rest and following a 20 μg adrenaline bolus, while measuring aortic pressure and flow, left ventricular pressure and volume, and left atrial pressure. Results: The afterload gave aortic pressure waveforms that matched the general shape of the in vivo measurements. A wide range of physiological systolic pressures (93 to 160 mm Hg) and diastolic pressures (73 to 113 mm Hg) were generated by the afterload. Conclusions: With the presented afterload concept, multiple physiological loading conditions could be tested ex vivo, and compared with the corresponding in vivo data. An additional control loop from the set pressure limits to the measured systolic and diastolic aortic pressure is proposed to address discrepancies observed between the set limits and the measured pressures.
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| 15. |
- Pigot, Harry, et al.
(författare)
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Identification of cardiac afterload dynamics from data
- 2021
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Ingår i: IFAC-PapersOnLine. - : Elsevier BV. - 2405-8963. ; 54, s. 508-513
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Tidskriftsartikel (refereegranskat)abstract
- The prospect of ex vivo functional evaluation of donor hearts is considered. Particularly, the dynamics of a synthetic cardiac afterload model are compared to those of normal physiology. A method for identification of continuous-time transfer functions from sampled data is developed and verified against results from the literature. The method relies on exact gradients and Hessians obtained through automatic differentiation. This also enables straightforward sensitivity analyses. Such analyses reveal that the 4-element Windkessel model is not practically identifiable from representative data while the 3-element model underfits the data. Pressure–volume (PV) loops are therefore suggested as an alternative for comparing afterload dynamics.
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| 16. |
- Pigot, Henry, et al.
(författare)
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Ventilator for Improved Cardiopulmonary Resuscitation
- 2018
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Konferensbidrag (refereegranskat)abstract
- Sudden cardiac arrest is the second most common cause of death in Sweden, following tumors. Annually, 10 000 people are subject to sudden cardiac arrest outside of hospital in the country.Following sudden cardiac arrest, blood circulation in the body ceases, and the brain is subject to irreversible damage within minutes. The treatment consists mainly of mechanical chest compressions to circulate blood, combined with artificial gas exchange in the lungs to ventilate carbon dioxide and deliver oxygen.It is possible to achieve improved circulation and increased coronary perfusion pressure when the gas flow to the patient's lungs is automatically controlled using the phase of the chest compression cycle. We have developed this idea into a mobile ventilator prototype, specifically intended to be used in cardiopulmonary resuscitation.In this talk, we show how our phase-controlled ventilator compares to continuous insufflation of oxygen when combined with chest compressions to treat sudden cardiac arrest in healthy pigs.The main result is a statistically significant improvement in coronary perfusion pressure, facilitating increased coronary perfusion, which is known to be correlated with the return of spontaneous circulation upon defibrillation and ultimately patient survival.
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| 17. |
- Qin, Guangqi, et al.
(författare)
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Intact endothelial and contractile function of coronary artery after 8 hours of heart preservation
- 2016
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 50:5-6, s. 362-366
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. The aim of the study was to investigate if adequate preservation of coronary artery endothelium-dependent relaxation and contractility may be obtained after 8 hours of non-ischemic heart preservation. Design. Porcine hearts were perfused for 8 hours at 8 °C, either in cycles of 15 minutes perfusion and 60 minutes non-perfusion, or by continuous perfusion. The perfusate consisted of a cardioplegic, hyperoncotic nutrition solution with oxygenated red cells, and the perfusion pressure was 20 mmHg. In organ baths, coronary artery segments from the preserved hearts were studied and compared to fresh controls. Results. Endothelium-dependent relaxation and contractility were fully preserved after both intermittent and continuous perfusion, as compared to fresh controls. No myocardial edema was seen; water content of the myocardium was 79.5 ± 0.2%, 79.0 ± 0.4% and 79.0 ± 0.3% (ns) for fresh controls, intermittently perfused, and continuously perfused hearts, respectively. Conclusion. Intact endothelial and contractile function of coronary artery may be obtained after 8 hours of non-ischemic heart preservation.
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| 18. |
- Soltesz, Kristian, et al.
(författare)
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Closed-loop Prevention of Hypotension in the Heartbeating Brain-dead Porcine Model
- 2017
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Ingår i: IEEE Transactions on Biomedical Engineering. - 1558-2531. ; 64:6, s. 1310-1317
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The purpose of this paper is to demonstrate feasibility of a novel closed-loop controlled therapy for prevention of hypertension in the heartbeating brain-dead porcine model. Methods: Dynamic modeling and system identification were based on in-vivo data. A robust controller design was obtained for the identified models. Disturbance attenuation properties, and reliability of operation of the resulting control system, were evaluated in vivo. Results: The control system responded both predictably and consistently to external disturbances. It was possible to prevent mean arterial pressure to fall below a user-specified reference throughout 24 h of completely autonomous operation.Conclusion: Parameter variability in the identified models confirmed the benefit of closed-loop controlled administration of the proposed therapy. The evaluated robust controller was able to mitigate both process uncertainty and external disturbances. Significance: Prevention of hypertension is critical to the care of heartbeating brain-dead organ donors. Its automation would likely increase the fraction of organs suitable for transplantation from this patient group.
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| 19. |
- Soltesz, Kristian, et al.
(författare)
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Closed-Loop Regulation of Arterial Pressure after Acute Brain Death
- 2018
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Ingår i: Journal of Clinical Monitoring and Computing. - : Springer Science and Business Media LLC. - 1573-2614 .- 1387-1307. ; 32:3, s. 429-437
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this concept study was to investigate the possibility of automatic mean arterial pressure (MAP) regulation in a porcine heart-beating brain death (BD) model. Hemodynamic stability of BD donors is necessary for maintaining acceptable quality of donated organs for transplantation. Manual stabilization is challenging, due to the lack of vasomotor function in BD donors. Closed-loop stabilization therefore has the potential of increasing availability of acceptable donor organs, and serves to indicate feasibility within less demanding patient groups.Method: A dynamic model of nitroglycerine pharmacology, suitable for controller synthesis, was identified from an experiment involving an anesthetized pig, using a gradient-based output error method. The model was used to synthesize a robust PID controller for hypertension prevention, evaluated in a second experiment, on a second, brain dead, pig. Hypotension was simultaneously prevented using closed-loop controlled infusion of noradrenaline, by means of a previously published controller.Results: A linear model of low order, with variable (uncertain) gain, was sufficient to describe the dynamics to be controlled. The robustly tuned PID controller utilized in the second experiment kept the MAP within a user-defined range. The system was able to prevent hypertension, exceeding a reference of 100 mmHg by more than 10 %, during 98 % of a 12 h experiment.Conclusion: This early work demonstrates feasibility of the investigated modelling and control synthesis approach, for the purpose of maintaining normotension in a porcine BD model. There remains a need to characterize individual variability, in order to ensure robust performance over the expected population.
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| 20. |
- Soltesz, Kristian, et al.
(författare)
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Phase-controlled intermittent intratracheal insufflation of oxygen during chest compression-active decompression mCPR improves coronary perfusion pressure over continuous insufflation
- 2019
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Ingår i: Resuscitation. - : Elsevier BV. - 1873-1570 .- 0300-9572. ; 138, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: It has previously been shown that continuous intratracheal insufflation of oxygen (CIO) is superior to intermittent positive pressure ventilation (IPPV) regarding gas exchange and haemodynamics. The purpose of this study was to investigate gas exchanged and haemodynamics with a new technique of phase-controlled intermittent insufflation of oxygen (PIIO) compared to CIO. Method: Twenty (20) pigs were used, stratified into two groups (CIO, PIIO), with 10 animals each. Upon induction of ventricular fibrillation, standard ventilator support was replaced by either of CIO or PIIO ventilation. Chest compressions were delivered by the LUCAS I mCPR device. Following 20 min of CPR in normothermia, defibrillation was attempted. Results: Return of spontaneous circulation (ROSC) occurrence was not significantly higher (P<0.16) in the PIIO (9/10) than in the CIO (6/10) group. During the decompression phase the PIIO group showed significant increases in mean (P<0.01), maximal (P<0.02) and end-decompression (P<0.01) coronary perfusion pressure (CPP), compared to the CIO group. PIIO resulted in increased compression phase aortic pressure (P<0.03). Intratracheal pressure was 5–30 cmH2O within both groups during mCPR, with a significantly lower (P<0.02) mean for the PIIO group. Arterial and venous blood gas analysis showed comparable results between the groups, when taking base line values into account. An exception was that PIIO resulted in significantly higher (P<0.05) oxygen partial pressure during mCPR, and lower (P<0.05) arterial lactate following ROSC. Conclusion: PIIO results in significantly higher CPP and compression phase aortic pressure during mCPR in a porcine population. Further studies are needed to validate these findings in humans.
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| 21. |
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| 22. |
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| 23. |
- Steen, Stig, et al.
(författare)
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First human transplantation of a nonacceptable donor lung after reconditioning ex vivo.
- 2007
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Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 83:6, s. 2191-2195
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. This article describes an ex vivo method to recondition and transplant rejected donor lungs. Description. A 19-year-old man was brain dead after a traffic accident. A roentgenogram showed bilateral lung contusion. He had ongoing intratracheal bleeding. After optimizing ventilator treatment and suctioning the airways, PaO2 was 9 kPa (67.5 mm Hg) on FiO(2) = 0.7. The lungs were rejected by all transplantation centers in the Nordic countries. We harvested the lungs for research. The right lung was severely injured. The left lung was edematous with bleeding spots in the lower lobe, and the mediobasal segment was atelectatic. The left lung was reconditioned ex vivo and kept in topical extracorporeal membrane oxygenation until it was transplanted into a 70-year-old man with chronic obstructive pulmonary disease 17 hours later. Evaluation. The transplanted lung functioned very well, and the patient recovered uneventfully. At 3 months control, a computed tomographic thoracic scan and transbronchial biopsies showed a normal left lung, and the patient was in very good clinical condition, only to succumb to death from unrelated events 11 months after the transplantation. Conclusions. Rejected donor lungs may be successfully transplanted after being reconditioned ex vivo.
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| 24. |
- Steen, Stig, et al.
(författare)
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Pharmacological normalization of circulation after acute brain death.
- 2012
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 56:8, s. 1006-1012
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Circulatory instability is a serious problem after brain death in organ donors. The hypotension is often counteracted with infusion of large amounts of crystalloid solutions, which may impair lung function leading to rejection of the lungs as donor organs. The aim was to show that the circulation can be normalized pharmacologically for 24 h in pigs after total removal of the brain and brainstem by decapitation (between C2 and C3). METHODS: Twenty-four 40-kg pigs (n = 8 × 3) were included: non-decapitated, decapitated, and decapitated with pharmacological treatment. All animals got the same basal fluid supply and ventilation. The pharmacological treatment consisted of the neuronal monoamine reuptake blocker cocaine and low doses of noradrenaline and adrenaline. Desmopressin, triiodothyroxine, thyroxine and cortisol were also given. RESULTS: After decapitation, a catecholamine storm occurred, with an increase of noradrenaline and adrenaline by a factor of 79 and 298, respectively. Thirty minutes later, the pigs were hypotensive. The median time to the aortic pressure that was less than 40 mmHg was 9:09 h (range 5:50 to 22:01). After 6 h, the concentration of thyroid hormones and cortisol was significantly reduced. With pharmacological treatment of decapitated animals, the aortic pressure, renal blood flow, creatinine, urine production, liver function and blood gases did not differ significantly from the non-decapitated control animals. CONCLUSION: Pharmacological substitution of pituitary gland function, blockade of peripheral catecholamine neuronal reuptake and low doses of catecholamines normalize circulation in decapitated pigs throughout a 24-h observation period, whereas untreated decapitated pigs all develop severe circulatory collapse within 12 h.
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| 25. |
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| 26. |
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| 27. |
- Steen, Stig, et al.
(författare)
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Transplantation of lungs from a non-heart-beating donor
- 2001
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Ingår i: The Lancet. - 1474-547X. ; 357:9259, s. 825-829
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In animals, we have previously done successful lung transplantations using organs from non-heart-beating donors. We have also developed an ex-vivo system of assessing the function of such organs before transplantation. The next stage was to try the technique in human beings. Bearing in mind the sensitive ethical issues involved, our first aim was to find out what procedures would be acceptable, and to use the results to guide a clinical lung transplantation from a non-heart-beating donor. METHODS: The ethical acceptability of the study was gauged from the results of a broad information programme directed at the general public in Sweden, and from discussions with professionals including doctors, nurses, hospital chaplains, and judges. The donor was a patient dying of acute myocardial infarction in a cardiac intensive-care unit after failed cardiopulmonary resuscitation. The next of kin gave permission to cool the lungs within the intact body, and intrapleural cooling was started 65 min after death. Blood samples were sent for virological testing and cross matching. The next of kin then had time to be alone with the deceased. After 3 h, the body was transported to the operating theatre and the heart-lung block removed. The lungs were assessed ex vivo, and the body was transported to the pathology department for necropsy. RESULTS: No contraindications to transplantation were found, and the right lung was transplanted successfully into a 54-year-old woman with chronic obstructive pulmonary disease. The donor lung showed excellent function only 5 min after reperfusion and ventilation, and during the first 5 months of follow-up, the function of the transplanted lung has been good. INTERPRETATION: About half the deaths in Sweden are caused by cardiac and cerebrovascular disease. This group could be a potential source of lung donors. When all hospitals and ambulance personnel in Sweden have received training in non-heart-beating lung donation, we hope that there will be enough donor lungs of good quality for all patients needing a lung transplant.
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| 28. |
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| 29. |
- Stone, J P, et al.
(författare)
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Altered Immunogenicity of Donor Lungs via Removal of Passenger Leukocytes Using Ex Vivo Lung Perfusion.
- 2016
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Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135. ; 16:1, s. 33-43
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Tidskriftsartikel (refereegranskat)abstract
- Passenger leukocyte transfer from the donor lung to the recipient is intrinsically involved in acute rejection. Direct presentation of alloantigen expressed on donor leukocytes is recognized by recipient T cells, promoting acute cellular rejection. We utilized ex vivo lung perfusion (EVLP) to study passenger leukocyte migration from donor lungs into the recipient and to evaluate the effects of donor leukocyte depletion prior to transplantation. For this purpose, female pigs received male left lungs either following 3 h of EVLP or retrieved using standard protocols. Recipients were monitored for 24 h and sequential samples were collected. EVLP-reduced donor leukocyte transfer into the recipient and migration to recipient lymph nodes was markedly reduced. Recipient T cell infiltration of the donor lung was significantly diminished via EVLP. Donor leukocyte removal during EVLP reduces direct allorecognition and T cell priming, diminishing recipient T cell infiltration, the hallmark of acute rejection.
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| 30. |
- Wahlquist, Ylva, et al.
(författare)
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Prevention of ischemic myocardial contracture through hemodynamically controlled DCD
- 2021
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Ingår i: Cardiovascular Engineering and Technology. - : Springer Science and Business Media LLC. - 1869-408X .- 1869-4098. ; 12:5, s. 485-493
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Tidskriftsartikel (refereegranskat)abstract
- Purpose—Ischemic myocardial contracture (IMC) or ‘‘stoneheart’’ is a condition with rapid onset following circulatory death. It inhibits transplantability of hearts donated uponcirculatory death (DCD). We investigate the effectiveness of hemodynamic normalization upon withdrawal of life-sustaining therapy (WLST) in a large-animal controlled DCD model, with the hypothesis that reduction in cardiac work delays the onset of IMC. Methods—A large-animal study was conducted comprising of a control group (n = 6) receiving no therapy upon WLST, and a test group (n = 6) subjected to a protocol for fully automated computer-controlled hemodynamic drug administration. Onset of IMC within 1 h following circulatory death defined the primary end-point. Cardiac work estimates based on pressure-volume loop concepts were developed and used to provide insight into the effectiveness of the proposed computer-controlled therapy. Results—No test group individual developed IMC within 1 h, whereas all control group individuals did (4/6 within30 min). Conclusion—Automatic dosing of hemodynamic drugs in the controlled DCD context has the potential to prevent onset of IMC up to 1 h, enabling ethical and medically safe organ procurement. This has the potential to increase the use of DCD heart transplantation, which has been widely recognized as a means of meeting the growing demand for donor hearts.
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| 31. |
- Wierup, P, et al.
(författare)
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Lung edema formation during cold perfusion: Important differences between rat and porcine lung
- 2005
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Ingår i: The Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1557-3117 .- 1053-2498. ; 24:4, s. 379-385
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to investigate the effect of different perfusion pressures on edema formation during cold flush perfusion with the 2 most commonly used preservation solutions in clinical lung transplantation: Euro-Collins and Perfadex solutions. Methods: Isolated rat and porcine lungs were perfused for 3 minutes at 4 degrees C to 8 degrees C at a pressure of either 10, 15 or 20 mm, Hg. Weight gain was recorded continuously. Weight gain per minute was calculated after the first phase of rapid weight gain was completed. Results: In the rat model, perfusion pressure of 10 mm Hg resulted in a macro- and microscopically apparent edema, irrespective of the type of preservation solution. Perfusion pressures of 10, 15 and 20 nun Hg gave weight gains of 100%, 150% and 350%, respectively, after 3 minutes of perfusion. The corresponding weight gain per minute was 18%, 31% and 84% of the initial weight. There were no statistically significant differences in weight gain between the different solutions at equal perfusion pressure. In the porcine model the flow was extremely low at 10 mm Hg and no weight gain was registered, whereas the weight gain per minute at 15 and 20 mm Hg was 1.0% and 2.1% of the initial weight. Conclusions: In porcine lungs, cold perfusion at 20 mm Hg gives minimal edema formation, whereas in rat lungs the edema formation is deleterious, irrespective of the solution used.
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| 32. |
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| 33. |
- Yang, Yang, et al.
(författare)
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Detection of Bronchial Function of NHBD Lung Following One-h Warm Ischemia by Organ Bath Model
- 2009
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Ingår i: Journal of Huazhong University of Science and Technology-Medical Sciences. - : Springer Science and Business Media LLC. - 1993-1352 .- 1672-0733. ; 29:3, s. 340-343
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the feasibility and effects of organ bath to be used for detection of bronchial function of non-heart-beating donor (NHBD) lung after 1-h warm ischemia. Sixteen Swedish pigs were divided into two groups randomly: heart-beating donor (HBD) group and NHBD with 1-h warm ischemia (NHBD-1 h) group. The bronchial rings whose lengths and inner diameters were both 1.5 mm were obtained from isolated left lungs of all the pigs. Acetylcholine, arachidonic acid natrium and papaverine were used to test and compare the contractile and relaxant function of bronchial smooth muscles and epithelium-dependent relaxation (EpiDR) response between HBD and NHBD-1 h groups. The results showed that there was no significant difference in the values of bronchial precontraction between HBD and NHBD-1 h groups (5.18 +/- 0.07 vs 5.10 +/- 0.11 mN, P > 0.05). No significant difference in the values of EpiDR responses between HBD and NHBD-1 h groups (1.26 +/- 0.05 vs 1.23 +/- 0.07 mN, P > 0.05) was observed either. During the process of EpiDR induction, the rings had no spontaneous relaxation in two groups. In addition, papaverine solution completely relaxed the bronchial smooth muscles of all bronchial rings. It was concluded that after warm ischemia for 1 h, the contractile and relaxant abilities of bronchial smooth muscles, and the epithelium-dependent adjustment both kept intact. Organ bath model could be a liable and scientific way to evaluate the bronchial function of NHBD lung.
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| 34. |
- Zhao, Song, et al.
(författare)
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Organ bath in detecting the effect of one-hour warm ischemia on pulmonic arteries and bronchi from non-heart-beating donor lungs
- 2009
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Ingår i: Chinese Medical Journal. - 0366-6999. ; 122:23, s. 2903-2906
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Tidskriftsartikel (refereegranskat)abstract
- Background Non-heart-beating donor lung has been a promising source of lung transplantation. Many studies on non-heart-beating donor lungs are based on animal lung transplantation. In this study, we assessed by organ bath the effect of one-hour warm ischemia on the non-heart-beating donor lung in terms of the integrity of contractile and relaxant functions and tissue structures of pulmonic arteries and bronchi. Methods Sixteen Swedish pigs were randomly classified into two groups: heart-beating donor group and 1-hour warm ischemia non-heart-beating donor group. Pulmonic and bronchial rings were taken from the isolated left lungs of the pigs. The pulmonic rings were stimulated by U-46619 (5.7 mol/L) and acetylcholine (10(-4) mmol/L) to assess the contractile abilities of smooth muscle and the endothelium-dependent relaxation response, respectively. As such, acetylcholine (10(-5) mmol/L) and natrium arachidonic acid (0.01%) were used to detect the contraction of bronchial smooth muscle and epithelium-dependent relaxation response. Meanwhile, the variances of precontraction tension of control groups were recorded to measure whether there was spontaneous relaxation during endothelium/epithelium-dependent relaxation course. Finally, papaverine solution (10(-4) mmol/L) was used to detect the non-endothelium/epithelium-dependent relaxant abilities of pulmonic and bronchial smooth muscles. Results There was no significant difference in the tension values of precontraction of pulmonic rings (P >0.05), endothelium-dependent relaxation (P >0.05), precontraction of bronchial rings (P >0.05) and epithelium-dependent relaxation (P >0.05) between the heart-beating donor group and the 1-hour warm ischemia non-heart-beating donor group. And the pulmonic and bronchial rings of each subgroup B had no spontaneous relaxation. Finally, papaverine solution relaxed the smooth muscle of all the rings completely. Conclusions The results of this experiment suggest that the contractile and relaxant functions and tissue structures of pulmonic arteries and bronchi are not damaged after warm ischemia for 1 hour, and support the further study of ;non-heart-beating donor lung.
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| 35. |
- Zhu, Yaobin, et al.
(författare)
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A novel, minimally invasive rat model of normothermic cardiopulmonary bypass model without blood priming.
- 2014
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Ingår i: Chinese Medical Journal. - 0366-6999. ; 127:8, s. 1541-1544
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Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary bypass (CPB) has been shown to be associated with systemic inflammatory response leading to postoperative organ dysfunction. Elucidating the underlying mechanisms and developing protective strategies for the pathophysiological consequences of CPB have been hampered due to the absence of a satisfactory recovery animal model. The purpose of this study was to establish a novel, minimally invasive rat model of normothermic CPB model without blood priming.
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