| 1. |
- 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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| 2. |
- Sjöberg, Trygve, et al.
(författare)
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Antagonism of thromboxane receptor induced contractions in isolated human groin lymphatics
- 1989
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Ingår i: Lymphology. - 0024-7766. ; 22:3, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- In vitro studies were performed on lymphatics obtained from the groin in 19 patients undergoing vascular surgery. The lymphatics were mounted in tissue baths, and isometric contractions were induced by increasing concentrations of the thromboxane A2 (TXA2) mimetic U-46619. In comparison to K+ (124mM)-induced contraction, which were used as an internal standard, the response to U-46619 had an Emax of 105 +/- 5.9%. The pEC50-value was 8.14 +/- 0.09. The effects of two thromboxane receptor (TP-receptor) antagonists, L-636,499 and BM-13,505, were investigated. Both antagonists caused concentration-dependent right-ward shifts without depression of Emax of the U-46619 concentration-response curves. The slopes of the regression lines in a Schild plot for both antagonists did not differ from one, indicating competitive antagonism. The pA2-value of BM-13,505 (7.89) was 65 times higher than that of L-636,499 (6.08). The results suggest that the receptor involved in the prostanoid contraction in human groin lymphatics is of the TP-subtype.
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| 3. |
- Sjöberg, Trygve, et al.
(författare)
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Comparative effects of the alpha-adrenoceptor agonists noradrenaline, phenylephrine and clonidine in the human saphenous vein in vivo and in vitro
- 1989
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 136:3, s. 463-471
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Tidskriftsartikel (refereegranskat)abstract
- The alpha-adrenoceptor-mediated contractile effects of noradrenaline (alpha 1 + alpha 2), phenylephrine (alpha 1) and clonidine (alpha 2) on human saphenous veins were investigated in vivo and in vitro. By infusion (0.3 ml min-1) of the drugs (increasing concentrations in the infused solution) into distended (40 mmHg) saphenous veins in six healthy subjects, local vasoconstriction was induced, measured by a photo-electric device. The drugs induced dose-dependent contractions in all subjects, and dose-response curves were constructed. These were compared with concentration-response curves based on in-vitro results. Macroscopically normal saphenous veins, taken at saphenousectomies, were used, and the preparations were contracted isometrically in organ baths by the agonists. From the curves obtained in vivo and in vitro, the relative potencies of phenylephrine and clonidine (in relation to noradrenaline) were calculated and compared. The relative potencies of phenylephrine in vivo (76%) and in vitro (82%) did not differ significantly. However, the relative potency of clonidine was significantly (P less than 0.05) lower in vivo (90%) than in vitro (99%). Thus, it is concluded that there are differences between the results obtained in vivo and in vitro, stressing the importance of comparative in vivo-in vitro studies.
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| 4. |
- Sjöberg, Trygve, et al.
(författare)
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Contractile response in isolated human groin lymphatics
- 1987
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Ingår i: Lymphology. - 0024-7766. ; 20:3, s. 152-160
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Tidskriftsartikel (refereegranskat)abstract
- Lymphatics from the human superficial groin removed at operation in 21 patients (one with lymphedema) were examined in vitro. Histochemically no nerves were identified with either specific catecholamine fluorescence or immunoreactivity to tyrosine hydroxylase or dopamine beta-hydroxylase. Ring preparations of the lymphatics were mounted in tissue baths and isometric induced contractions were recorded after administration of K+ (124 mM), acetylcholine, selected amines and prostanoids. Noradrenaline (NA), adrenaline, dopamine, and acetylcholine had no or only weak contractile effects. In some segments, serotonin induced contractions. Prostaglandin E2 showed no contractile effect and prostaglandin F2 alpha induced contraction in most of the tested lymphatics. The prostaglandin-endoperoxide analogue U44069 uniformly elicited marked concentration-dependent contraction. In the lymphatic segment from the patient with lymphedema, a slightly greater contractile response to NA and serotonin was observed. The results overall suggest an absence of sympathetic innervation and contraction-mediating alpha adrenergic receptors in human superficial groin lymphatics, and support that certain prostanoids may be important regulators of human lymphatic contractility.
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| 5. |
- Sjöberg, Trygve, et al.
(författare)
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Contractility of human leg lymphatics during exercise before and after indomethacin
- 1989
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Ingår i: Lymphology. - 0024-7766. ; 22:4, s. 186-193
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Tidskriftsartikel (refereegranskat)abstract
- Subcutaneous lymphatics in the lower leg were catheterized in the retrograde direction in 6 healthy male subjects. The catheter was connected to a pressure transducer, and pressure was measured during three stages of exercise including standing, tip-toeing, and running in place. Before the third stage, indomethacin (50mg) was given i.v. Rhythmic pressure waves were registered in each subject. During the second stage, when the subjects were "warmed up," the frequency (min-1) was 2.4 +/- 0.5 (mean +/- SEM). The corresponding values during tip-toeing and running were 5.8 +/- 0.7 (p less than 0.05) and 5.4 +/- 0.5 (p less than 0.05), respectively. The amplitudes (mean values between 3.2-4.7mmHg while standing) were not consistently altered during tip-toeing or running in any of the three stages. During standing there was a negative correlation between frequency and amplitude. No such correlation was found during tip-toeing or running, or after injection of indomethacin. Indomethacin did not significantly alter any of the measured parameters, but in two subjects the frequencies and amplitudes were decreased (about 50%) during standing, tip-toeing, and running.
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| 6. |
- Wallinder, Andreas, 1977, et al.
(författare)
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Heparin does not improve graft function in uncontrolled non-heart-beating lung donation: an experimental study in pigs
- 2013
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Ingår i: European Journal of Cardio-Thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940 .- 1873-734X. ; 43:2, s. 413-419
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Non-heart-beating donation (NHBD) has the potential to increase the number of patients treated with lung transplantation. Our study investigated, in a simulated clinical situation in the uncontrolled NHBD setting, whether or not heparin administration after death affects the donor lung function. METHODS: Twelve Swedish domestic pigs underwent ventricular fibrillation and were left untouched for 7 min followed by cardiopulmonary resuscitation with mechanical compressions for 20 min. The animals were declared dead after a 'hands-off' period of 10 min and randomized to heparin (300 IU/kg) or placebo given into a central venous catheter. In the animals receiving heparin, 2 more minutes of chest compression followed. Intrapleural cooling was initiated 1 h after death, and prevailed for 2 h. Ex vivo lung perfusion (EVLP) was performed with the Vivoline (R) system. Lung function was evaluated with blood gases at different oxygen levels, pulmonary vascular resistance (PVR), wet/dry weight ratio, macroscopic appearance and histology. RESULTS: During EVLP, there were no significant differences between groups in PaO2 or PVR at any investigated FiO(2) level (1.0, 0.5 or 0.21). At FiO(2) 1.0 the PaO2 in the heparin group was 64 +/- 2 (range 57-73) kPa and in the non-heparin group 63 +/- 4 (range 51-71) kPa. The values for PVR were 592 +/- 90 (range 402-1007) and 647 +/- 97 (range 426-1044), respectively. There was no significant difference between groups in wet/dry ratio or histology. CONCLUSIONS: The use of heparin is of no obvious benefit to the donor lungs in the uncontrolled NHBD situation. The exclusion of heparin will simplify lung donation from NHBDs.
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| 7. |
- Vagianos, C, et al.
(författare)
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Effects of alpha-adrenoceptor active drugs, prostaglandin F2 alpha and vasopressin on cystic and hepatic arteries of pig and man
- 1990
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Ingår i: Pharmacology and Toxicology. - 1600-0773. ; 66:2, s. 77-82
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Tidskriftsartikel (refereegranskat)abstract
- Human and pig cystic and pig hepatic arteries were suspended in tissue baths and the effect of alpha-adrenoceptor selective drugs, prostaglandin F2 alpha (PGF2 alpha) and vasopressin were investigated. Prazosin fulfilled the criteria for competitive antagonism in concentrations 10(-9)-10(-7) M. The pA2-values were 9.53 in human cystic, 9.74 in pig cystic, and 9.57 in pig hepatic artery. Rauwolscine had no significant effect in the different arteries. In human cystic artery noradrenaline had significantly (P less than 0.05) higher Emax and pEC50-values (135% of the preceding K(+)-induced contraction and 6.4, respectively) compared with pig cystic (106% and 5.7, respectively) and pig hepatic artery (116% and 5.9, respectively). Vasopressin had no effect in the cystic arteries, whereas it had a high potency (pEC50 was 8.5) but low intrinsic activity (Emax was 14%) in pig hepatic artery. Prostaglandin F2 alpha had a significantly higher Emax in human than in pig arteries. No differences were found in pEC50-values. This study indicates a similarity in pharmacological characteristics of some vasoactive drugs especially between pig cystic and hepatic arteries. If this is also true in man, the easily obtainable cystic artery can be used for screening the effect of drugs on the hepatic artery.
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| 8. |
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| 9. |
- Budrikis, A, et al.
(författare)
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Function of adult pig hearts after 2 and 12 hours of cold cardioplegic preservation
- 1998
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Ingår i: Annals of Thoracic Surgery. - 1552-6259. ; 66:1, s. 73-78
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Most cardioplegic solutions have been developed using the classic Langendorf heart perfusion model, which only allows a short experimental follow-up. Our aim was to investigate hearts after prolonged storage by using a physiologic model including prolonged perfusion with normal, fresh blood. METHODS: Sixteen hearts from 60-kg pigs were preserved with dextran-enriched (dextran-40, 35 g/L) St. Thomas' solution for 2 or 12 hours after which they were continuously reperfused for 12 hours with normal blood, supplied by a support pig. A flexible balloon, fixed to an artificial valve apparatus connected to a circuit system, was inserted in the left ventricle for obtaining measurements of hemodynamic performance. RESULTS: During the first 3 to 4 hours of reperfusion there was no significant difference in left ventricular developed pressure, cardiac output, minute work output, or oxygen consumption between the two groups. After this time left ventricular developed pressure (p < 0.001), cardiac output (p < 0.01), minute work output (p < 0.01), and oxygen consumption were significantly lower in the 12-hour group. Coronary flow was higher (p < 0.01) and coronary vascular resistance lower (p < 0.01) during the first 5 to 6 hours of reperfusion in the 12-hour group. After 12 hours of reperfusion coronary vascular resistance was significantly higher (p < 0.01) in the 12-hour group. CONCLUSIONS: High-degree and long-lasting coronary hyperemia at the beginning of reperfusion can be a sign of unsatisfactory preservation of the heart. This investigation shows the importance of reperfusion with normal blood and a long follow-up period after postischemic reperfusion when studying the effect of cardioplegic solutions.
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| 10. |
- Ingemansson, Richard, et al.
(författare)
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Addition of calcium to Euro-Collins solution is essential for 24-hour preservation of the vasculature
- 1997
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Ingår i: Annals of Thoracic Surgery. - 1552-6259. ; 63:2, s. 408-413
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genuine Euro-Collins solution is calcium free. The aim of this study was to investigate whether the addition of calcium would improve its capacity to preserve the vasculature. METHODS: The infrarenal aorta of Sprague-Dawley rats was investigated in organ baths: as fresh controls, after 24 hours of cold (4 degrees C) storage in Euro-Collins solution, or in Euro-Collins solution with the addition of calcium in amounts ranging from 0.05 to 1.5 mmol/L. The thromboxane analogue U-46619 was used to investigate contractility. Endothelium-dependent relaxation was tested by cumulative addition of acetylcholine. Papaverine was used to elicit endothelium-independent relaxation. Investigation by transmission electron microscopy was also performed. RESULTS: Storage of rat aorta for 24 hours in genuine Euro-Collins solution almost abolished smooth muscle function, and severe edema was found in the endothelial cells. However, if calcium was added, the rat aorta could be stored for 24 hours without affecting smooth muscle function, and endothelium-dependent relaxation was only slightly reduced. Furthermore, only slight edema could be demonstrated in the endothelial cells. CONCLUSIONS: If calcium is added to Euro-Collins solution in amounts ranging from 0.4 to 1.5 mmol/L, it allows good preservation of rat aorta for 24 hours. Without calcium, this solution destroys both the function and morphology of the vessels.
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