| 1. |
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| 2. |
- Bajc, Marika, et al.
(författare)
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Lung ventilation/perfusion SPECT in the artificially embolized pig.
- 2002
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Ingår i: Journal of Nuclear Medicine. - 0161-5505. ; 43:5, s. 640-647
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Tidskriftsartikel (refereegranskat)abstract
- Planar lung scintigraphy is a standard method used for the diagnosis of lung embolism, but it is hampered by the high incidence of nondiagnostic tests. Ventilation/perfusion SPECT may possibly improve this situation. The objective of this study was to compare planar lung scintigraphy with ventilation/perfusion SPECT using pigs with artificially engendered lung emboli labeled with (201)Tl. METHODS: Sixteen anesthetized pigs were each injected with zero to 4 latex emboli. Cylindric emboli were used in the first 7 pigs and flat 3-tailed emboli were used in the remaining 9 pigs. The pigs spontaneously inhaled 30 MBq (99m)Tc-diethylenetriaminepentaacetic acid aerosol for ventilation scintigraphy. Planar scintigraphy and SPECT were performed using a double-head gamma camera in (99m)Tc and (201)Tl windows. Immediately thereafter, 100 MBq (99m)Tc-labeled macroaggregated albumin were injected intravenously followed by SPECT and, finally, planar scintigraphy. The ventilation background was subtracted from the perfusion tomograms for calculation of a normalized ventilation/perfusion (V/P) quotient image set. RESULTS: The cylindric emboli caused artifacts in the ventilation images; therefore, these were excluded from the final analysis. However, for the planar perfusion images of these pigs, sensitivity and specificity were 71% and 91%, respectively, whereas SPECT yielded 100% for both. For the 3-tailed emboli and ventilation/perfusion images, the sensitivity and specificity were 64% and 79%, respectively, for the planar modality, whereas SPECT yielded values of 91% and 87%, respectively. CONCLUSION: V/P SPECT may improve the diagnostic power of lung scintigraphy.
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| 3. |
- Cunha Goncalves, Doris, et al.
(författare)
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Cardiovascular effects of levosimendan in the early stages of endotoxemia.
- 2007
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Ingår i: Shock. - : Ovid Technologies (Wolters Kluwer Health). - 1073-2322 .- 1540-0514. ; 28:1, s. 71-7
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Tidskriftsartikel (refereegranskat)abstract
- Sepsis-associated myocardial depression is associated with calcium desensitization and adrenergic uncoupling. We conducted a prospective randomized investigation on the effects of the calcium sensitizer, levosimendan, on hemodynamics, myocardial blood flow, and myocardial lactate metabolism during porcine endotoxemia. Twelve pigs were studied. Oxygen consumption was measured by indirect calorimetry, and myocardial blood flow was measured by retrograde thermodilution. Pulmonary, arterial, and venous indwelling catheters allowed measurements of cardiac output, vascular pressures, and blood sampling. Fluids were given at an average of 15 mL . kg . h. After baseline measurements (0 min), an infusion of Escherichia coli LPS (2 microg . kg . min) was started in all animals. Beginning at 100 min, six animals received levosimendan (50 microg . kg . h), whereas six control animals received placebo. The study lasted for 300 min. All animals responded to endotoxin with pulmonary hypertension, a transient decrease in cardiac output, tachycardia, and systemic hypotension. Levosimendan infusion decreased systemic vascular resistance (P = 0.001), coronary vascular resistance (P = 0.004), and mean arterial (P < 0.001) and coronary perfusion pressures (P < 0.001), whereas pulmonary hypertension was unaffected. Heart rate progressively increased in both groups and was significantly higher in the levosimendan group (P = 0.048). Myocardial blood flow remained unchanged in both groups; however, 80 min after the start of levosimendan infusion, left ventricular myocardial hypoxia ensued, as evidenced by a negative myocardial lactate gradient (P = 0.01). Two control and five levosimendan animals died before the end of the study. Early administration of levosimendan during porcine endotoxemia increased heart rate, caused arterial vasodilation, and decreased coronary perfusion pressure, resulting in myocardial hypoxia.
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| 4. |
- Cunha-Goncalves, Doris, et al.
(författare)
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Impact of Body Position on Lung Deposition of Nebulized Surfactant in Newborn Piglets on Nasal Continuous Positive Airway Pressure
- 2020
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 117:4, s. 467-473
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The ideal body position during surfactant nebulization is not known. Objective: The aim of this study was to determine whether body positioning during surfactant nebulization influences surfactant distribution and deposition in the lungs. Methods: Twenty-four 12- to 36-h-old full-termpiglets (1.3-2.2 kg) on nasal continuous positive airway pressure (nCPAP) were randomized into four groups: lateral decubitus with right or left side up, prone or supine positions (n = 6 each). All animals received 200 mg kg-1 of poractant alfa mixed with 200 MBq of 99mtechnetium-nanocolloid via a customized eFlow-Neos investigational vibrating-membrane nebulizer. Surfactant deposition (percentage of the administered dose) was measured by gamma scintigraphy. Results: Comparing all groups, the mean total lung surfactant deposition was significantly higher in the prone position (32.4 ± 7.7%, p = 0.03). The deposition in this group was higher in the right lung (21.0 ± 8.6 vs. 11.3 ± 5.7%, p = 0.04). When nebulization was performed in the lateral decubitus, most of the surfactant was found in the dependent lung, regardless of which side the piglet lay on (right side up 15.3 ± 1.0 vs. 3.4 ± 1.0%, p = 0.06, and left side up 11.2 ± 9.8 vs. 1.8 ± 0.7%, p = 0.04). Conclusions: In spontaneously breathing animals on nCPAP, the prone position yielded the highest lung dose. Higher deposition rates in the dependent lung while on lateral decubitus indicates that deposition was also influenced by gravity.
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| 5. |
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| 6. |
- Cunha Goncalves, Doris, et al.
(författare)
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Inotropic support during experimental endotoxemic shock : part II. A comparison of levosimendan with dobutamine
- 2009
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Ingår i: Anesthesia and Analgesia. - : Ovid Technologies (Wolters Kluwer Health). - 0003-2999 .- 1526-7598. ; 109:5, s. 1576-83
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We compared the association of levosimendan or dobutamine with norepinephrine for the maintenance of systemic and hepatosplanchnic perfusion during early endotoxemic shock. METHODS: Twenty anesthetized pigs (26.8 +/- 0.5 kg) were instrumented with flow probes and catheters to monitor systemic and regional perfusion as described in our companion article in this issue of the journal. Two animals were excluded because of surgical complications. Oxygen consumption (VO(2)) was measured by indirect calorimetry. Starting 1 h after instrumentation, an endotoxin infusion (Escherichia coli lipopolysaccharide, 2 microg x kg(-1) x h(-1)) was administered for 300 min. Sixty minutes after the start of endotoxin, the animals were fluid resuscitated (20 mL/kg dextran 70); at 120 min, they were randomized into three groups of six animals each: levosimendan (25-50 microg x kg(-1) x h(-1)), dobutamine (10-20 microg x kg(-1) x min(-1)), and control. In the first two groups, norepinephrine (0.5-2 microg x kg(-1) x min(-1)) was added when mean arterial blood pressure (MAP) or= baseline. The data were divided into two subsets: before (0-120 min, all animals) and after (120-300 min, three groups) randomization, and analyzed by analysis of variance. P < 0.05 was considered significant. RESULTS: At 120 min, cardiac output was 15% higher (P < 0.001), systemic vascular resistance was 30% lower (P < 0.001), and MAP decreased 12.5% (P = 0.004); blood flow in the hepatic artery, superior mesenteric artery, and portal vein had increased by 100% (P = 0.004), 60% (P < 0.001), and 20% (P < 0.001), respectively. Between 120 and 300 min, cardiac output and systemic oxygen delivery decreased 50% in control animals (P < 0.05), remained unchanged in the levosimendan group, and increased 60% with dobutamine (P = 0.05). MAP (P = 0.043) and VO(2) (P = 0.001) decreased 20% in the control group. Portal vein flow decreased in the control (50%) and levosimendan (30%) groups (P < 0.001) and was therefore higher in the dobutamine group (P = 0.003) at 300 min. Hepatic and gut oxygen deliveries decreased in the levosimendan (50%, and 30%, respectively, P < 0.001) and control groups (70% and 45%, respectively, P < 0.05); thus, regional oxygen deliveries were greater in the dobutamine group (P < 0.05). In this group, mixed venous and hepatic vein oxygen saturation were maintained; the latter variable was higher than in the other groups (P < 0.05). Although unchanged with dobutamine, arterial (P = 0.020), portal (P = 0.020), and hepatic vein (P = 0.034) lactate concentrations increased twofold with levosimendan. CONCLUSION: In volume-resuscitated endotoxemic pigs, the association of either levosimendan or dobutamine with norepinephrine preserved systemic blood flow, oxygen delivery, and VO(2). However, only dobutamine-norepinephrine maintained portal blood flow, which was associated with preservation of splanchnic and hepatic oxygen homeostasis and stable lactate concentrations.
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| 7. |
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| 8. |
- Harnek, Jan, et al.
(författare)
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Intimal Hyperplasia in Balloon Dilated Coronary Arteries is Reduced by Local Delivery of the NO Donor, SIN-1 Via a cGMP-Dependent Pathway.
- 2011
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To elucidate the mechanism by which local delivery of 3-morpholino-sydnonimine (SIN-1) affects intimal hyperplasia after percutaneous transluminal coronary angioplasty (PTCA). METHODS: Porcine coronary arteries were treated with PTCA and immediately afterwards locally treated for 5 minutes, with a selective cytosolic guanylate cyclase inhibitor, 1 H-(1,2,4)oxadiazole(4,3-alpha)quinoxaline-1-one (ODQ) + SIN-1 or only SIN-1 using a drug delivery-balloon. Arteries were angiographically depicted, morphologically evaluated and analyzed after one and eight weeks for actin, myosin and intermediate filaments (IF) and nitric oxide synthase (NOS) contents. RESULTS: Luminal diameter after PCI in arteries treated with SIN-1 alone and corrected for age-growth was significantly larger as compared to ODQ + SIN-1 or to controls (p < 0.01). IF/actin ratio after one week in SIN-1 treated segments was not different compared to untreated segments, but was significantly reduced compared to ODQ + SIN-1 treated vessels (p < 0.05). Expression of endothelial NADPH diaphorase activity was significantly lower in untreated segments and in SIN-1 treated segments compared to controls and SIN-1 + ODQ treated arteries (p < 0.01). Restenosis index (p < 0.01) and intimal hyperplasia (p < 0.01) were significantly reduced while the residual lumen was increased (p < 0.01) in SIN-1 segments compared to controls and ODQ + SIN-1 treated vessels. CONCLUSIONS: After PTCA local delivery of high concentrations of the NO donor SIN-1 for 5 minutes inhibited injury induced neointimal hyperplasia. This favorable effect was abolished by inhibition of guanylyl cyclase indicating mediation of a cyclic guanosine 3',5'-monophosphate (cGMP)-dependent pathway. The momentary events at the time of injury play crucial role in the ensuring development of intimal hyperplasia.
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| 9. |
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| 10. |
- Hedin, Ulf, et al.
(författare)
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Resolving the biological paradox of aneurysm formation in children with tuberous sclerosis complex
- 2021
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Ingår i: JVS-Vascular Science. - : Elsevier BV. - 2666-3503. ; 2, s. 72-78
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Tidskriftsartikel (refereegranskat)abstract
- Aortic aneurysms are rare manifestations in children with tuberous sclerosis complex (TSC) with life threating implications. Although an association between TSC, aortic and other aneurysms has been recognized, mechanistic insights explaining the pathophysiology behind aneurysm development and genetic aberrations in TSC have so far been lacking. Here, we summarize existing knowledge on aneurysms in TSC and present a case of a 2-year-old boy with an infrarenal aortic aneurysm, successfully treated with open aortic reconstruction. Histologic examination of the excised aneurysm wall showed distortion of vessel wall structure with loss of elastin and a pathologic accumulation of smooth muscle cells. Until now, these pathologic features have puzzled researchers as proliferating smooth muscle cells would rather be expected to preserve vessel wall integrity. Recent reports exploring the biological consequences of the dysregulated intracellular signaling pathways in patients with TSC provide plausible explanations to this paradox, which may support the development of future therapeutic strategies.
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| 11. |
- Hopper, Rachel K, et al.
(författare)
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International practice heterogeneity in pre-transplant management of pulmonary hypertension related to pediatric left heart disease
- 2023
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Ingår i: Pediatric Transplantation. - : Wiley. - 1399-3046 .- 1397-3142. ; 27:2, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Elevated pulmonary vascular resistance (PVR) in the setting of left heart failure may contribute to poor outcomes after pediatric heart transplant (HTx), but peri-transplant management is variable.METHODS: We sought to characterize international practice by surveying physicians at pediatric HTx centers.RESULTS: We received 49 complete responses from 39 centers in 16 countries. Most respondents are pediatric cardiologists (90%), practice at centers offering heart (86%) and lung (55%) transplant, and perform pre-HTx acute vasoreactivity testing (AVT, 88%) in patients with elevated PVR. Half (51%) reported defining a PVR cutoff for HTx eligibility as ≤6 WU m 2 (56%) post-AVT (84%). The highest post-AVT PVR ever accepted for HTx ranged from 3-14.4 (median 6) WU m 2 . To treat elevated pre-transplant PVR, phosphodiesterase type 5 inhibitors are most common (65%) followed by oxygen (31%), nitric oxide (14%), endothelin receptor antagonists (11%), and prostacyclins (6%). Nearly a third (31%) do not routinely use pulmonary vasodilators without implantation of a left ventricular assist device (LVAD). Case scenarios highlight treatment variability: in a restrictive cardiomyopathy scenario, HTx listing with post-transplant vasodilator therapy was favored, whereas in a Shone's complex patient with fixed PVR, LVAD ± pulmonary vasodilators followed by repeat catheterization was most common. Management of dilated cardiomyopathy with reactive PVR was variable. Most continue vasodilator therapy until HTx (16%), PVR normalizes (16%) or ≤6 months. CONCLUSIONS: Management of elevated PVR in children awaiting HTx is heterogenous. Evidence-based guidelines are needed to allow for longitudinal determination of optimal outcomes and standardized care.
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| 12. |
- Karlsson, Victoria, 1968-
(författare)
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Aspects of neonatal intensive care and anesthesia : Thermal balance and respiratory management
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is based on four articles originating from three studies conducted in the neonatal intensive care unit and the children’s operating deparment at Uppsala University Hospital, Sweden.The overall aim was to obtain new knowledge about thermal balance and care environment in extremely preterm infants during skin-to-skin care (SSC), evaluate different methods of intraoperative monitoring of carbon dioxide (CO2), and to investigate how different levels of inhaled oxygen affect infants’ oxygenation during anesthesia and surgery. Study I investigated infant thermal balance and the physical environment for extremely preterm infants during SSC. Study II formed part of a prospective study to assess the performance of non-invasive transcutaneous and end-tidal technique to continuously monitor CO2 levels in the infants blood during anesthesia. Study III was a prospective randomized trial to investigate oxygenation during induction of anesthesia with room air versus high fraction (80%) of oxygen in healthy newborn infants.The infants maintained normal body temperature during SSC. In comparison to care in an incubator, during SSC ambient humidity was lower and insensible water loss through the skin was higher. Compared to blood gas Pco2, transcutaneous carbon dioxide monitoring yielded a bias of 0.3 ± 0.7 kPa, and end-tidal technique a bias of -1.9 ± 0.9 kPa. After intubation, saturation measured by pulse oximetry was lower (p < .05) in the group breathing room air than in the group with high oxygen (93% ± 6.7 and 99% ± 1.5). None of the infants spent time below the pre-specified safety oxygen saturation targets to mandate supplemental oxygen.This thesis provides new knowledge about early initiation of SSC after birth for extremely preterm infants, the results will be useful to guide safe routines for implementation of early SSC. These results suggest that during anesthesia would transcutaneous monitoring of carbon dioxide be beneficial, end-tidal monitoring correlated poorly to blood gas and induction of general anesthesia in newborn infants can be safely performed without the use of high levels of supplemental oxygen. Taken together, this new knowledge has the potential to improve intraoperative respiratory management.
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| 13. |
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| 14. |
- Linnér, Rikard, et al.
(författare)
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Circulatory recovery is as fast with air ventilation as with 100% oxygen after asphyxia-induced cardiac arrest in piglets.
- 2009
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Ingår i: Pediatric Research. - 1530-0447. ; 66, s. 391-394
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Tidskriftsartikel (refereegranskat)abstract
- We investigated return of spontaneous circulation and of cerebral oxygenation after asphyxia-induced cardiac arrest, using ventilation with air, throughout, or with 100% oxygen for a shorter or longer period. Arterial pressure, heart rate, regional cerebral oxygen saturation (CrSO2) and brain tissue oxygen tension (PbtO2) were measured in one day old piglets that were hypoventilated with air and left in apnea until cardiac arrest. They were randomly assigned to be resuscitated with air (n=13), or with oxygen for 3 (n=12) or 30 min (n = 13) and then with air. Nine, 10, and 10 animals, respectively, needed closed chest cardiac massage. One, none, and 1, respectively, died. Median (quartile range) times from start of ventilation until heart rate reached 150 bpm were 67 (60-76), 88 (76-126), and 68 (56-81) s. They were not significantly different, nor were the arterial pressure responses, times until CrSO2 reached 30%, or times until PbtO2 had increased by 0.1 kPa from its nadir. Peak PbtO2 values during resuscitation were 4.2 (3.3-5.4), 12 (6.4 - 15), and 25 (15 - 36) kPa. Thus, pure oxygen did not accelerate the recovery of circulation or of cerebral oxygenation, while even a brief exposure caused cerebral hyperoxia.
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| 15. |
- Linnér, Rikard, et al.
(författare)
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Early adrenaline administration does not improve circulatory recovery during resuscitation from severe asphyxia in newborn piglets.
- 2012
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Ingår i: Resuscitation. - : Elsevier BV. - 1873-1570 .- 0300-9572. ; 83:10, s. 1298-1303
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Tidskriftsartikel (refereegranskat)abstract
- AIM OF THE STUDY: : To investigate the effects of early intravenous adrenaline administration on circulatory recovery, cerebral reoxygenation, and plasma catecholamine concentrations, after severe asphyxia-induced bradycardia and hypotension. METHODS: One-day old piglets were left in apnoea until heart rate and mean arterial pressure were less than 50min(-1) and 25mmHg, respectively. They randomly received adrenaline, 10 μg kg(-1) (n=16) or placebo (n=15) and were resuscitated with air ventilation and, when needed, closed-chest cardiac massage (CCCM). Eight not asphyxiated animals served as time controls. RESULTS: CCCM was required in 13 piglets given adrenaline and in 13 given placebo. Time to return of spontaneous circulation was: 72 (66-85) s vs. 77 (64-178) s [median (quartile range)] (p=0.35). Time until cerebral regional oxygen saturation (CrS(O2)) had increased to 30% was 86 (79-152) s vs. 126 (88-309) s (p=0.30). The two groups did not differ significantly in CrS(O2), heart rate, arterial pressure, right common carotid artery blood flow, or number of survivors: 13 and 11 animals. Plasma concentration of adrenaline, 2.5min after resuming ventilation, was 498 (268-868) nmol l(-1)vs. 114 (80-306) nmol l(-1) (p=0.01). Corresponding noradrenaline concentrations were 1799 (1058-4182) nmol l(-1)vs. 1385 (696-3118) nmol l(-1) (ns). In the time controls, the concentrations were 0.4 (0.2-0.6) nmol l(-1) of adrenaline and 1.8 (1.3-2.4) nmol l(-1) of noradrenaline. CONCLUSION: The high endogenous catecholamine levels, especially those of noradrenaline, may explain why early administered adrenaline did not significantly improve resuscitation outcome.
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| 16. |
- Linnér, Rikard, et al.
(författare)
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Lung Deposition of Nebulized Surfactant in Newborn Piglets.
- 2015
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 107:4, s. 277-282
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Tidskriftsartikel (refereegranskat)abstract
- It would be advantageous for the treatment of neonatal respiratory distress syndrome if effective amounts of surfactant could be delivered by nebulization.
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| 17. |
- Linner, Rikard, et al.
(författare)
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One oxygen breath shortened the time to return of spontaneous circulation in severely asphyxiated piglets
- 2017
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Ingår i: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253. ; 106:10, s. 1556-1563
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Asphyxiated neonates should be resuscitated with air, but it remains unclear if oxygen supplementation is needed in ineffectively ventilated newborn infants. We studied the return of spontaneous circulation (ROSC) with oxygen or air in an experimental model of inadequate ventilation. Methods: Asphyxia was induced in 16 newborn piglets until their heart rate was <60 bpm or mean arterial pressure (MAP) <30 mmHg. During the first 10 minutes of resuscitation, they received one breath per minute of oxygen (n = 8) or air (n = 8). Tidal volume was 7.5 mL/kg. If MAP was <30 mmHg for 15 seconds, closed-chest cardiac massage (CCCM) was performed for 45 seconds. From 10 minutes onward, all piglets received normal ventilation with air. ROSC was defined as a heart rate >150 bpm, MAP >40 mmHg and no subsequent CCCM. Results: Before resuscitation, the median arterial pH was 6.73. At 10 minutes, no piglets in the oxygen group needed CCCM, while all did in the air group (p < 0.001). The median time to ROSC was 60 seconds with oxygen and 845 seconds with air (p < 0.001). No brain tissue hyperoxia occurred. Conclusion: When ventilation was inadequate, one oxygen breath reduced time to ROSC in piglets with severe metabolic and respiratory acidosis.
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| 18. |
- Liuba, Petru, et al.
(författare)
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Coronary flow and reactivity, but not arrhythmia vulnerability, are affected by cardioplegia during cardiopulmonary bypass in piglets
- 2013
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Ingår i: Journal of Cardiothoracic Surgery. - : Springer Science and Business Media LLC. - 1749-8090. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Surgery under cardiopulmonary bypass (CPB) is still associated with significant cardiovascular morbidity in both pediatric and adult patients but the mechanisms are not fully understood. Abnormalities in coronary flow and function have been suggested to play an important role. Prior studies suggest protective effects on coronary and myocardial function by short intravenous (i.v.) infusion of cyclosporine A before CPB. Methods: Barrier-bred piglets (10-12 kg, n=20) underwent CPB for 45 min, with or without antegrade administration of cardioplegic solution. Prior to CPB, half of the animals in each group received an i.v. infusion of 100 mg/kg cyclosporine A. The left anterior descending coronary flow velocity responses to adenosine, serotonin, and atrial pacing, as well as left ventricular function and postsurgical vulnerability to atrial fibrillation (Afib) were assessed by intracoronary Doppler, epicardial echocardiography, and in vivo electrophysiological study, before and 8 hours after surgery. Plasma C-reactive protein (CRP) and fibrinogen were measured at both time-points. Results: Cyclosporine infusion did not influence any of the studied variables (p>0.4). Coronary peak flow velocity (cPFV) rose significantly after surgery especially in the cardioplegia group (p<0.01 vs. non-cardioplegia group and pre-surgery). cPFV responses to adenosine, but not to serotonin, tended to decrease (p=0.06) after surgery only in cardioplegia group (p=0.06; p=0.8 in non-cardioplegia group vs pre-surgery). Also, cPFV response to atrial pacing was lower in the cardioplegia than in the non-cardioplegia group (p=0.02). Neither vulnerability nor duration of induced Afib after CPB differed between groups (Chi-square p=0.4). Cyclosporine had no significant effect on coronary indexes or arrhythmia vulnerability (p>0.4). There was no difference in systolic myocardial function between groups at any time point. Conclusion: In piglets, CPB with cardioplegia was associated with profound abnormalities in coronary vasomotor tone and receptor-related flow regulation, whereas arrhythmia vulnerability appeared to be comparable with that in non-cardioplegia group. In this study, preconditioning with cyclosporine had no detectable protective effect on coronary circulation or arrhythmia vulnerability after CPB.
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| 19. |
- Nord, Anders, et al.
(författare)
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A novel delivery system for supraglottic atomization allows increased lung deposition rates of pulmonary surfactant in newborn piglets
- 2020
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Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 87:6, s. 1019-1024
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Tidskriftsartikel (refereegranskat)abstract
- Background: Earlier attempts to deliver effective lung doses of surfactant by aerosolization were unsuccessful, mostly because of technical shortcomings. We aimed at quantifying the lung deposition of poractant alfa with a new supraglottic delivery system for surfactant atomization in an experimental neonatal model. Methods: The method involved six sedated 1-day-old piglets lying in the lateral decubitus, spontaneously breathing on nasal-mask continuous positive airway pressure (nCPAP). A pharyngeal cannula housing a multi-channel air-blasting atomization catheter was placed through the mouth with its tip above the glottis entrance. In all, 200 mg kg-1 of a 99mTc-surfactant mixture was atomized through the catheter synchronously with inspiration. Six intubated control piglets received an equal amount of intratracheally instilled 99mTc-surfactant mixture. The percentage of the 99mTc-surfactant mixture deposited in the lungs was estimated by scintigraphy. Results: Median (range) deposition in the lungs was 40% (24-68%) after atomization and 87% (55-95%) after instillation (p < 0.001). Overall, almost 80% of the deposited surfactant was in the dependent lung. Effective atomization time (atomizer on) was 28 (17-52) min, yielding an output rate of 0.1-0.2 mL min-1. Conclusions: Without endotracheal intubation, in spontaneously breathing newborn piglets, this new supraglottic atomizer delivery system attained a median lung deposition of 40% of the nominal dose of surfactant.
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| 20. |
- Nord, Anders, et al.
(författare)
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Lung deposition of nebulized surfactant in newborn piglets : Nasal CPAP vs Nasal IPPV
- 2020
-
Ingår i: Pediatric Pulmonology. - : Wiley. - 8755-6863 .- 1099-0496. ; 55:2, s. 514-520
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Tidskriftsartikel (refereegranskat)abstract
- Background: Nasal continuous positive airway pressure support (nCPAP) is the standard of care for prematurely born infants at risk of neonatal respiratory distress syndrome (nRDS). However, nasal intermittent positive pressure ventilation (NIPPV) may be an alternative to nCPAP in babies requiring surfactant, and in conjunction with surfactant nebulization, it could theoretically reduce the need for invasive mechanical ventilation. We compared lung deposition of nebulized poractant in newborn piglets supported by nCPAP or NIPPV. Methods: Twenty-five sedated newborn piglets (1.2-2.2 kg) received either nCPAP (3 cmH2O, n = 12) or NIPPV (3 cmH2O positive end expiratory pressure+3 cmH2O inspiratory pressure, n = 13) via custom-made nasal prongs (FiO2 0.4, Servo-i ventilator). Piglets received 200 mg kg−1 of technetium-99m-surfactant mixture continuously nebulized with a customized eFlow-Neos investigational vibrating-membrane nebulizer system. Blood gases were taken immediately before, during, and after nebulization. The deposition was estimated by gamma scintigraphy. Results: Mean surfactant deposition in the lungs was 15.9 ± 11.9% [8.3, 23.5] (mean ± SD [95% CI]) in the nCPAP group and 21.6 ± 10% [15.6, 27.6] in the NIPPV group (P =.20). Respiratory rates were similar in both groups. Minute volume was 489 ± 203 [360, 617] in the nCPAP group and 780 ± 239 [636, 924] mL kg−1 min−1 in the NIPPV group (P =.009). Blood gases were comparable in both groups. Conclusion: Irrespective of the noninvasive ventilatory support mode used, relatively high lung deposition rates of surfactant were achieved with nebulization. The amounts of deposited surfactant might suffice to elicit a pulmonary function improvement in the context of nRDS.
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| 21. |
- Nord, Anders, et al.
(författare)
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Lung deposition of surfactant delivered via a dedicated laryngeal mask airway in piglets
- 2021
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Ingår i: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- It is unknown if the lung deposition of surfactant administered via a catheter placed through a laryngeal mask airway (LMA) is equivalent to that obtained by bolus instillation through an endotracheal tube. We compare the lung deposition of surfactant delivered via two types of LMA with the standard technique of endotracheal instillation. 25 newborn piglets on continuous positive airway pressure support (CPAP) were randomized into three groups: 1—LMA-camera (integrated camera and catheter channel; catheter tip below vocal cords), 2—LMA-standard (no camera, no channel; catheter tip above the glottis), 3—InSurE (Intubation, Surfactant administration, Extubation; catheter tip below end of endotracheal tube). All animals received 100 mg·kg−1 of poractant alfa mixed with99mTechnetium-nanocolloid. Surfactant deposition was measured by gamma scintigraphy as a percentage of the administered dose. The median (range) total lung surfactant deposition was 68% (10–85), 41% (5–88), and 88% (67–92) in LMA-camera, LMA-standard, and InSurE, respectively, which was higher (p < 0.05) in the latter. The deposition in the stomach and nasopharynx was higher with the LMA-standard. The surfactant deposition via an LMA was lower than that obtained with InSurE. Although not statistically significant, introducing the catheter below the vocal cords under visual control with an integrated camera improved surfactant LMA delivery by 65%.
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| 22. |
- Perez de Sá, Valéria, et al.
(författare)
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Hemodilution during bone marrow harvesting in children
- 1991
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Ingår i: Anesthesia and Analgesia. - 1526-7598. ; 72:5, s. 645-650
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Tidskriftsartikel (refereegranskat)abstract
- Eight children (1--17 yr) underwent bone marrow harvesting while in cytostatic-induced remission of their disease (leukemia [n = 6], Ewing sarcoma, and non-Hodgkin lymphoma). After the induction of general anesthesia, all patients were loaded with 10 mL/kg of a 6% high-molecular dextran solution (Macrodex — Pharmacia), which resulted in a significant preoperative decrease in hematocrit (Hct) from 32% ± 6% to 28% ± 5% (hypervolemic hemodilution) and also allowed the procedure to be performed without systemic heparinization. The blood aspirated during the harvest (24 ± 6 mL/kg; mean ± SD) was replaced with a solution of 6% dextran and Ringer's acetate solution, and the Hct decreased from 28% ± 5% to a minimum of 18% ± 3%. Immediately after the harvest, 10 mL/kg of homologous packed red blood cells was transfused, increasing Hct to 25% ± 3%. Oxygen saturation in the superior caval vein (Scvo2) decreased from 79% ± 4% before the harvest to 70% ± 3% (P < 0.01) at the end of it, and then increased to 74% ± 3% after the transfusion of homologous packed red blood cells. There was a strong linear correlation between mean values for Hct and Scvo2 during the various stages (r = 0.99). Mean heart rate decreased gradually during the procedure, from 106 ± 10 to 86 ± 7 beatslmin. There was no significant change in arterial pressure, but cardiac output measured by impedance cardiography was about 30% greater during harvesting than during undisturbed anesthesia. Pulse oximetric saturation was 99% or 100% throughout. Caval venous blood lactate and pyruvate concentrations remained within normal limits in all children. Recovery after anesthesia was uneventful, except in one child in whom severe shivering developed. H is concluded that the hemodilution resulted in a statistically but not clinically significant decrease in Scvo2 that was well tolerated by the patients as judged from hemodynamic responses as well as levels of arterial oxygen saturation (Sao2) and blood lactate.
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| 23. |
- Perez de Sá, Valéria, et al.
(författare)
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High brain tissue oxygen tension during ventilation with 100% oxygen after fetal asphyxia in newborn sheep
- 2009
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Ingår i: Pediatric Research. - 0031-3998 .- 1530-0447. ; 65:1, s. 57-61
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Tidskriftsartikel (refereegranskat)abstract
- The optimal inhaled oxygen fraction for newborn resuscitation is still not settled. We hypothesized that short-lasting oxygen ventilation after intrauterine asphyxia would not cause arterial or cerebral hyperoxia, and therefore be innocuous. The umbilical cord of fetal sheep was clamped and 10 min later, after delivery, ventilation with air (n = 7) or with 100% oxygen for 3 (n = 6) or 30 min (n = 5), followed by air, was started. Among the 11 lambs given 100% oxygen, oxygen tension (PO2) was 10.7 (1.8-56) kPa [median (range)] in arterial samples taken after 2.5 min of ventilation. In those ventilated with 100% oxygen for 30 min, brain tissue PO2 (PbtO2) increased from less than 0.1 kPa in each lamb to individual maxima of 56 (30-61) kPa, whereas in those given oxygen for just 3 min, PbtO2 peaked at 4.2 (2.9-46) kPa. The maximal PbtO2 in air-ventilated lambs was 2.9 (0.8-5.4) kPa. Heart rate and blood pressure increased equally fast in the three groups. Thus, prolonged ventilation with 100% oxygen caused an increase in PbtO2 of a magnitude previously only reported under hyperbaric conditions. Reducing the time of 100% oxygen ventilation to 3 min did not consistently avert systemic hyperoxia.
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| 24. |
- Perez de Sá, Valéria, et al.
(författare)
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Mild hypothermia has minimal effects on the tolerance to severe progressive normovolemic anemia in swine
- 2002
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Ingår i: Anesthesiology. - 1528-1175. ; 97:5, s. 1189-1197
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Tidskriftsartikel (refereegranskat)abstract
- Background: The benefits of hypothermia during acute severe anemia are not entirely settled. The authors hypothesized that cooling would improve tolerance to anemia. Methods: Eight normothermic (38.0 +/- 0.5degreesC) and eight hypothermic (32.0 +/- 0.5degreesC) pigs anesthetized with midazolam-fentanyl-vecuronium-isoflurane (0.5% inspired concentration) were subjected to stepwise normovolemic hemodilution (hematocrit, 15%, 10%, 7%, 5%, 3%). Critical hemoglobin concentration (Hgb(CRIT)) and critical oxygen delivery (DO2CRIT), i.e., the hemoglobin concentration (Hgb) and oxygen delivery (DO2) at which oxygen consumption (VO2 independently measured by indirect calorimetry) was no longer sustained, and Hgb at the moment of death, defined prospectively as the point when VO2 decreased below 40 nil/min, were used to assess the tolerance of the two groups to progressive isovolemic anemia. Results: At hematocrits of 15% and 10% (Hgb, 47 and 31 g/l), VO2 was maintained in both groups by an increase (P < 0.001) in cardiac output (CO) and extraction ratio (ER; P < 0.001) with unchanged mean arterial lactate concentration (L-art.). At hematocrit of 7% (Hgb, 22 g/l), all normothermic but no hypothermic animals had DO2-dependent VO2. No normothermic and three hypothermic animals survived to 5% hematocrit (Hgb, 15 g/l), and none survived to 3%. Hgb(CRIT) was 23 +/- 2 g/l and 19 +/- 6 g/l (mean +/- SD) in normothermic and hypothermic animals, respectively (P = 0.053). Hgb at death was 19 +/- 3 g/l versus 14 +/- 4 g/l (P = 0.015), and DO2CRIT was 8.7 +/- 1.7 versus 4.6 +/- 0.8 ml.kg(-1).min(-1) (P < 0.001). Conclusion: During progressive normovolemic hemodilution in pigs, hypothermia did not significantly change Hgb(CRIT), but it decreased the Hgb at death, i.e., short-term survival was prolonged.
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| 25. |
- Perez de Sá, Valéria
(författare)
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Severe Hemodilution - Clinical and Experimental Studies
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In children, it is often desirable to minimize allogenic blood transfusion, and this thesis explores the physiology of an alternative method of managing perioperative blood loss: hemodilution with Ringer´s dextran. Methods Clinical studies: Arterial pressure, superior caval venous oxygen saturation (ScvO2) and blood lactate concentration (L) were studied during bone marrow harvesting (BMH) on 23 occasions in 19 children, 1-17 years of age, with healthy hearts and lungs. Experimental studies - A. Shivering was induced by surface cooling and the hemodynamic and metabolic responses studied in hemodiluted (Hgb = circa 50 g/L), 12-14 weeks old anesthetized pigs and their normoemic controls. B. The tolerance to progressive isovolemic anemia was studied during hypothermia in anesthetized and paralyzed pigs (32 °C) and their normothermic controls (38.5 °C). Main findings Clinical studies: BMH caused a blood loss of 26 (17-42) ml per kg body weight, and decreased the blood hemoglobin concentration (Hgb) to 54 (47- 84) g/L. ScvO2 was 72 (61-88) % in the awake child, and increased to 82 (70 - 94) % after induction of general anesthesia. During hemodilution, it decreased to 76 (60-92) %. The lowest ScvO2: 66 (55-79) % was seen after awakening the child in spite of the fact that Hgb had now increased to 70 (58-95) g/L by transfusion of the child´s own, preoperatively collected, blood. There was an increase in mean heart rate from 89 to 108 bpm during BMH. Mean L increased from 1.0 to 1.5 mmol/L but was never above the normal limit. Experimental studies: A. During shivering, oxygen consumption (VO2) increased by a mean factor of 2.9 in the hemodiluted pigs, and 3.7 in the controls (P< 0.001). Two of the former exhibited signs of myocardial hypoxia. B. Hgb at death was 14 ± 4 g/L in cooled pigs and 19 ± 3 g/L in the controls (P=0.015). Clinical implications -The healthy child tolerates extreme hemodilution (Hgb 50-70 g/L) if suitably anesthetized. The strain on the organism is greater after awakening. -The findings cannot be extrapolated to children with compromised function of the heart or lungs, who the author believes will frequently benefit from a normal-high Hgb. -Extreme hemodilution reduces oxygen delivery to the body and will, hence, decrease the tolerance to challenges with increased oxygen demand such as shivering. -Cooling is modestly protective during severe anemia.
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