Heart and liver transplantation. Consistent survival after prolonged donor heart preservation.

Twelve dogs underwent orthotopic cardiac transplantation after donor heart preservation for 24 hr in a hypothermic hypertonic intracellular solution. Donors were divided into two groups: continuous oxygenated perfusion and nonperfusion. After 24 hr, transplantation was performed. All six perfused and four nonperfused donors hearts survived a 24-hr postoperative period. Survivors had normal cardiac output, right and left atrial pressures, and aortic pressures. After transplantation, all perfused hearts demonstrated mild left ventricular damage while nonperfused hearts had severe damage. Hypothermic hypertonic intracellular perfusion may allow improved protection for short-term myocardial preservation and survival after extended myocardial preservation.     

Extended hypothermic heart-lung preservation system for cardiopulmonary preservation with retrograde coronary sinus perfusion and lung immersion

One major restriction of clinical heart-lung transplantation has been the inability to provide extended hypothermic organ preservation. We examined whether core-cooling, retrograde heart perfusion and lung immersion could provide adequate cardiopulmonary preservation. Hence, donor dogs were placed on cardiopulmonary bypass, and rapidly cooled to 15 degrees C. Then heterotopic heart unilateral left lung transplantations were performed. In control group I (n = 5), hearts and lungs were harvested following core-cooling and cardioplegic arrest, and transplanted immediately. In experimental group II (n = 5), heart-lung blocks were similarly excised but stored at 4 degrees C for 12 hours and then transplanted. During preservation, the lungs were immersed in the extracellular solution. For the heart, non-recirculating retrograde coronary sinus perfusion was performed with oxygenated intracellular solution containing perfluorochemicals. Myocardial function determined by the ratio of end-systolic pressure to end-systolic dimension in the experimental group was similar to that in controls. Although pulmonary vascular resistance and extravascular lung water of the experimental group was higher than those in control group, arterial oxygenation was similar in both groups. Thus, extended heart-lung preservation with core-cooling, retrograde heart perfusion and lung immersion technique could be achieved for heart-lung transplantation.     

The experimental study on long-term cardiac preservation: the efficacy of low-flow continuous perfusion with fluorocarbon

We compared the effect of simple immersion and continuous perfusion on long-term cardiac preservation, and evaluated the effectiveness of perfusion with oxygenated fluorocarbon solution. The isolated rabbit hearts were preserved for 24 hours at 4 degrees C using the following five preservation techniques: (1) simple immersion with Collins M solution (Group I), (2) perfusion with oxygenated Collins M solution at a flow rate of 10 ml/hr (Group II), (3) perfusion with the same solution as in Group II at a flow rate of 20 ml/hr (Group III), (4) perfusion with oxygenated Collins M solution containing 10% fluorocarbon at a flow rate of 10 ml/hr (Group IV), (5) perfusion with the same solution as in Group IV at a flow rate of 20 ml/hr (Group V). The hearts of Group I showed a significant decrease of myocardial ATP and an increase of myocardial lactate during preservation compared to the hearts of perfusion groups. Assessment of isovolumic left ventricular function following 24-hour preservation using a support animal showed a significant decrease of Max dp/dt and increase of end-diastolic pressure in the hearts of Group I. Perfusion with fluorocarbon (Group IV and V) significantly increased oxygen consumption compared to Group II and III in association with minimum accumulation of myocardial lactate, indicating that aerobic metabolism during preservation is better maintained in the fluorocarbon-perfused hearts. Moreover, CPK release and myocardial water gain during preservation were significantly less, and left ventricular function following preservation was significantly better in these hearts. Increasing the flow rate from 10 ml/hr to 20 ml/hr resulted in sustained increase in perfusion pressure (1.80 +/- 0.53 to 3.70 +/- 0.34 mmHg) and myocardial water content (79.2 +/- 0.4 to 87.2 +/- 0.3%) during preservation in the hearts of Group III, but it did not further improve left ventricular function despite significant enhancement of myocardial oxygen uptake in both Group III and V. These results suggest that hypothermic low-flow continuous perfusion with oxygenated Collins M solution is superior to simple immersion with the same solution for long-term cardiac preservation, and that the addition of fluorocarbon to the perfusate enhances the efficacy of such a perfusion.     

Cardiac Transplantation Following Storage of the Donor Heart by a Portable Hypothermic Perfusion System

Four patients have undergone heterotopic heart transplantation with donor hearts stored by a portable hypothermic perfusion system. Total ischemic periods ranged from 6 hours 55 minutes to 16 hours 50 minutes. One heart, transplanted into a patient who had acutely rejected a previous graft, suffered accelerated, irreversible, acute rejection within five days, associated with strong antibody formation; donor heart function was never good. In the 3 remaining patients, donor heart function was good after initially being poor for a few hours in 2 patients. One patient died of long-term rejection after 6 months and 1 of tuberculous meningitis after 10 months; 1 remains alive at 15 months.Neither preservation of the donor heart for periods in excess of approximately 4 hours nor the use of continuous hypothermic perfusion as a method of preservation appears to have been reported previously in the context of the clinical situation.     

The effect of superoxide dismutase and catalase on the extended preservation of the ex vivo heart for transplantation

The applicability of heart transplantation remains limited in part by the inability to preserve the excised heart for long periods of time. Free radical scavengers have been shown to protect the anoxic myocardium by preventing damage to the cell membrane and may, therefore, be effective in extending successful preservation of donor hearts. We perfused 10 sheep hearts for 8 hours in an ex vivo perfusion system. The effect of superoxide dismutase combined with catalase, 60,000 units/L, was studied in five sheep, and five received placebo. Control determinations and determinations after 8 hours of preservation were obtained with the heart perfused with autologous blood at 37 degrees C at an aortic perfusion pressure of 60 mm Hg and flow of 180 to 200 ml/min. After control readings, the hearts were arrested and perfused with a cold (6 degrees to 8 degrees C) oxygenated buffered crystalloid solution with or without superoxide dismutase and catalase at a perfusion pressure of 30 cm H2O for 8 hours. Left and right ventricular compliance was measured sequentially with separate intraventricular balloons. After 8 hours of ex vivo preservation, hearts receiving superoxide dismutase and catalase had significantly better left and right ventricular performance, higher myocardial oxygen consumption, and lower lactate production than the control group. The hearts preserved with superoxide dismutase and catalase showed significantly better left and right ventricular compliance, much less increase in heart weight, and no change in the diastolic pressures. The results suggest that superoxide dismutase combined with catalase may be effective in extending ex vivo preservation of hearts for cardiac transplantation.     

Sequential hypothermic and normothermic perfusion preservation and transplantation of expanded criteria donor livers

BackgroundThe purpose of this study was to assess the safety and feasibility of sequential hypothermic oxygenated perfusion and normothermic machine perfusion and the potential benefits of graft viability preservation and assessment before liver transplantation.MethodsWith the Food and Drug Administration and institutional review board approval, 17 expanded criteria donor livers underwent sequential hypothermic oxygenated perfusion and normothermic machine perfusion using our institutionally developed perfusion device.ResultsExpanded criteria donor livers were from older donors, donors after cardiac death, with steatosis, hypertransaminasemia, or calcified arteries. Perfusion duration ranged between 1 and 2 hours for the hypothermic oxygenated perfusion phase and between 4 and 9 hours for the normothermic machine perfusion phase. Three livers were judged to be untransplantable during normothermic machine perfusion based on perfusate lactate, bile production, and macro-appearance. One liver was not transplanted because of recipient issue after anesthesia induction and failed reallocation. Thirteen livers were transplanted, including 9 donors after cardiac death livers (donor warm ischemia time 16–25 minutes) and 4 from donors after brain death. All livers had the standardized lactate clearance >60% (perfusate lactate cleared to <4.0 mmol/L) within 3 hours of normothermic machine perfusion. Bile production rate was 0.2 to 10.7 mL/h for donors after brain death livers and 0.3 to 6.1 mL/h for donors after cardiac death livers. After transplantation, 5 cases had early allograft dysfunction (3 donors after cardiac death and 2 donors after brain death livers). No graft failure or patient death has occurred during follow-up time of 6 to 13 months. Two livers developed ischemic cholangiopathy. Compared with our previous normothermic machine perfusion study, the bile duct had fewer inflammatory cells in histology, but the post-transplant outcomes had no difference.ConclusionSequential hypothermic oxygenated perfusion and normothermic machine perfusion preservation is safe and feasible and has the potential benefits of preserving and evaluating expanded criteria donor livers.     

Hypothermic Preservation of the Heart and Lungs with Collins Solution: Effect on Cardiorespiratory Function Following Heart-Lung Allotransplantation in Dogs

The effect of preserving the heart and lungs with hypothermia and Collins solution was studied in 13 mongrel dogs undergoing combined heart-lung transplantation. The five control animals who underwent an immediate transplant following Collins solution perfusion had small increases in extravascular lung water when measured 2.5 hours posttransplant as seen in a previous study. The eight animals who had hypothermic preservation following Collins solution perfusion had significantly higher extravascular lung water than controls (16.3 ± 1.8 ml/kg in preserved animals; 11.2 ± 1.7 ml/kg in controls p < 0.05). The level of lung water reached at 2.5 hours postoperatively was similar to that reached with a previously reported, unacceptable preservation technique. Survival beyond this point was poor due to severe pulmonary edema. We conclude that the use of this solution, given under the experimental conditions which we describe, is not acceptable for hypothermic preservation of the heart and lungs for combined transplantation.     

Preservation techniques for heart transplantation: comparison of hypothermic storage and hypothermic perfusion

Preservation of the donor heart is an important and controversial subject in heart transplantation. This study compares simple hypothermic storage and hypothermic perfusion in a swine model of heart transplantation (n = 14). The donor hearts of group A (n = 7) were placed in simple hypothermic storage for 5 hours. The donor hearts of group B (n = 7) were placed onto a perfusion apparatus for 5 hours, with pressure maintained at 28 cm of H2O and a myocardial temperature of 8 to 10 degrees C. In both groups the hearts were initially protected with isosmolar potassium cardioplegic solution. The perfusate in group B contained moderate sodium, mannitol, glucose, insulin, and oxygen. The ischemic interval within both groups was 6 hours including orthotopic transplantation. Investigation was conducted at three time periods: prepreservation, postpreservation, and immediately after loading. For both groups there was nonsignificant depression of myocardial function (cardiac index, stroke index, stroke work index, ejection fraction, and wall stress) at the postpreservation period. After volume loading, for the hypothermic perfusion group there was significant improvement of myocardial function (cardiac index, p less than 0.01; stroke index, p less than 0.01) with no significant change in heart rate, systemic vascular resistance, and systolic blood pressure. There was also significant improvement in myocardial performance (p less than 0.05) for the hypothermic perfusion group after volume loading. Ultrastructural changes were minimal for both groups, and there were no major heart transplantation after 6 hours of ischemia; however, hearts retain their contractile capacity better after hypothermic perfusion than after simple hypothermic storage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low-Flow Hypothermic Crystalloid Perfusion Is Superior to Cold Storage During Prolonged Heart Preservation

BackgroundPreservation of donor hearts for transplantation has traditionally been performed with the use of static cold storage. We have developed and tested a novel gravity-powered system of cold crystalloid perfusion for prolonged donor heart preservation.MethodsGreyhounds were anesthetized; their hearts were arrested with cold cardioplegic solution and excised. Hearts were allocated to 12 hours of perfusion preservation (n = 6) or cold storage in ice (n = 5). Non-preserved hearts (n = 5) served as a normal reference group. Perfusion hearts were perfused (20 mL/min, 8–12°C) with a novel oxygenated nutrient-containing preservation solution. After preservation, the recovery of the hearts was assessed in a blood-perfused working heart rig over 2 hours in terms of function, blood lactate level, myocardial adenosine triphosphate, and histology.ResultsAfter 2 hours of reperfusion, in comparison with cold storage hearts, perfused heart function curves showed superior recovery of cardiac output (P = .001), power (P = .001), and efficiency (0.046 ± 0.01 vs 0.004 ± 0.003 joules/mL O₂, P = .034). Myocardial adenosine triphosphate content (mmol/mg protein) was reduced significantly from the normal level of 26.5 (15.9, 55.8) to 5.08 (0.50, 10.4) (P = .049) in cold storage hearts but not in perfused hearts. Over a period of 2 hours, lactate levels in the blood perfusate were significantly lower in the perfusion group than in the cold storage group (P < .05).ConclusionsContinuous hypothermic crystalloid perfusion provides myocardial preservation superior to cold storage for long-term heart preservation, with potential applicability to marginal and donation after circulatory death hearts.     

Successful extended hypothermic cardiopulmonary preservation for heart-lung transplantation

The inability to obtain sufficiently extended hypothermic organ preservation is a major restriction on clinical heart-lung transplantation. We used core cooling, nonrecirculating retrograde heart perfusion, and lung immersion with liposomal recombinant human superoxide dismutase in an attempt to provide effective 12-hour cardiopulmonary preservation. Donor dogs supported by cardiopulmonary bypass were rapidly cooled to 15 degrees C with cardioplegic arrest, and heterotopic heart and unilateral left lung transplantations were performed. In control dogs (n = 7), hearts and lungs, harvested after core cooling and cardioplegic arrest, were transplanted with a total mean ischemic time of 88 +/- 5 minutes. In group II (n = 7), heart-lung blocks were similarly excised but preserved at 4 degrees C for 12 hours (756 +/- 30 minutes) and then transplanted. During preservation, the lungs were immersed in hyperosmolar extracellular solution. For the heart, retrograde coronary sinus perfusion was performed with intracellular solution containing perfluorochemicals at a temperature of 4 degrees C and a rate of 30 ml/hr for 12 hours. In group III (n = 7), donor organs were similarly excised and preserved for 12 hours (726 +/- 39 minutes), except that liposomal recombinant human superoxide dismutase was administered during harvest, preservation, and reperfusion. Myocardial function, assessed by the ratio of end-systolic pressure to end-systolic dimension, after the 12-hour preservation period in both experimental groups was similar to that of the control group 4 and 6 hours after transplantation. The mean arterial oxygen capacity of the transplanted left lung during ventilation with an inspired oxygen concentration of 40% was also similar in each group. In contrast, the 12-hour preservation of pulmonary function assessed by pulmonary vascular resistance, the accumulation of extravascular lung water, and histologic evidence of alveolar wall injury, interstitial edema, and perivascular hemorrhage were significantly impaired in the absence of liposal recombinant human superoxide dismutase. These findings suggest that successful extended cardiopulmonary preservation for heart-lung transplantation is possible with core cooling, nonrecirculating retrograde heart perfusion, and hypothermic lung immersion incorporating liposomal recombinant human superoxide dismutase.     

持续低温氧合机械灌注对小鼠心脏死亡器官捐献供肝的保护作用

目的研究体外持续低温氧合机械灌注对小鼠心脏死亡器官捐献(donation after cardiac death,DCD)供肝的保护作用。方法雄性ICR小鼠根据灌注保存方式不同分为新鲜供肝低温保存组(FC组)、DCD供肝低温保存组(DC组)和DCD供肝低温氧合机械灌注组(DP组),每组6只。低温灌注保存供肝6h后,收集保存过供肝的威斯康星大学保存液(University of Wisconsin solution,UW液),检测丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)水平。收集3组小鼠肝组织,切片,行常规苏木素-伊红(HE)染色,在光学显微镜下观察病理改变,用原位末端脱氧核苷酸转移酶标记法介导的dUTP缺口末端标记(terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling,TUNEL)法观察3组小鼠肝细胞凋亡情况。结果保存6h后,DC组与DP组的UW液中的ALT、AST含量均明显高于FC组(均为P<0.01);DP组的ALT和AST含量均明显低于DC组(均为P<0.01)。光学显微镜下,FC组未见明显坏死区域,DC组肝细胞损伤严重,DP组肝组织未见明显损伤及坏死。荧光显微镜下,FC、DP两组肝细胞凋亡程度轻微,DC组肝细胞形态极不规则,肝细胞坏死严重。结论持续低温氧合机械灌注可减轻肝细胞损伤和凋亡,为DCD肝移植的器官保存研究提供了新的方法。     

Cryoprecipitated plasma perfusion preservation and cold storage preservation of duct-ligated pancreatic allografts.

It has been shown previously that, at least in dogs, a vascularized pancreatic allograft with ligation of the pancreatic duct can maintain normal beta-cell function for at least 5 years. In this study common organ preservation techniques, as used in human cadaveric kidney transplantation, were applied to canine pancreatic allografts to determine the influence of 24-hour preservation on beta-cell function, graft survival and histological appearances. Three groups of dogs were compared: group A consisted of 9 dogs with fresh grafts; group B consisted of 5 dogs who received grafts preserved for 24 hours by pulsatile hypothermic cryoprecipitated plasma perfusion; and group C was composed of 5 animals who received grafts that had been flushed with Collins' solution followed by hypothermic storage for 24 hours. It appeared that both preservation methods were equally effective and that preservation did not alter either the graft's function or its histological appearance. No significant differences after transplantation were observed in the endocrine function tests of the three groups when compared with the preoperative values; neither was there a significant difference in the mean graft survival time between the groups.     

Long-term preservation using a new apparatus combined with suppression of pro-inflammatory cytokines improves donor heart function after transplantation in a canine model.

OBJECTIVE: We developed a new apparatus for long-term heart preservation that combines simple immersion with coronary perfusion. In a previous study, we reported that suppression of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta), improved results after transplantation. In this study, we evaluated whether long-term preservation using our apparatus for continuous coronary perfusion, combined with suppression of pro-inflammatory cytokines, improves donor heart function after transplantation in a canine model. METHODS: We used adult mongrel dogs in this study. Coronary vascular beds were washed with University of Wisconsin (UW) solution after arresting hearts with glucose-insulin-potassium solution. The heart was then excised and preserved for 12 hours with a combination of immersion and coronary perfusion using a preservation apparatus. Adult mongrel dogs were divided into 2 groups: the coronary perfusion (CP) group (n = 7) and the FR167653 (FR-CP) group (n = 6). In the CP group, we used a 4 degrees C UW solution for immersion and coronary perfusion. In the FR-CP group, we used a 4 degrees C UW solution supplemented with 20 mg/liter of the anti-inflammatory agent FR167653 for immersion and coronary perfusion. At 2 and at 3 hours after orthotopic transplantation, we compared hemodynamic parameters with pre-operative values in donor animals, with right atrial pressure at 10 mm Hg and with 5 microg/kg/min dopamine infusion. We compared serum concentrations of TNF-alpha from the coronary sinus and compared electron microscopic studies between the 2 groups. RESULTS: Three hours after transplantation, cardiac output (CO), left ventricular pressure (LVP), and -LVdp/dt were significantly greater (p < 0.05) in the FR-CP group than in the CP group (CO, 178% +/- 65% vs 93% +/- 40%; LVP, 115% +/- 22% vs 73% +/-26%; -LVdp/dt, 168% +/- 13% vs 61% +/- 17%, respectively). Electron microscopic studies showed that glycogen was well preserved in the FR-CP group compared with the CP group. Serum concentrations of TNF-alpha were decreased significantly in the FR-CP group compared with the CP group at 3 hours after reperfusion (161 +/- 54 pg/dl vs 642 +/- 636 pg/dl, respectively). CONCLUSION: Hemodynamics after transplantation were significantly better in the FR-CP group than in the CP group. The combined preservation method of continuous perfusion and immersion using our apparatus in conjunction with suppression of pro-inflammatory cytokines improves donor heart function after transplantation.     

Cardiac transplantation after prolonged graft preservation with the University of Wisconsin solution.

We tested the ability of University of Wisconsin solution to extend hypothermic preservation of the nonperfused heart during orthotopic baboon allotransplantation. Seven baboons received hearts after cardioplegia and storage (4 degrees C) with University of Wisconsin solution, with a preservation time of 14.2 +/- 1.6 hours. One animal died as a result of a technical error. Six survivors were immunosuppressed for 45 days and then put to death. Preservation did not alter heart weight or histologic features according to light and electron microscopy. Animals were weaned from bypass and returned to their cages without intravenous support within 3.9 +/- 0.8 hours. Weekly biopsies, electrocardiograms, enzyme analyses, echocardiograms, and right heart catheterizations demonstrated excellent cardiac function. University of Wisconsin solution can extend hypothermic cardiac preservation and has no deleterious effects on long-term myocardial function (up to 45 days). This study validates the rationale for human trials with preservation and storage in University of Wisconsin solution toward the goal of improving and prolonging donor heart preservation.     

Lipid peroxidation results in compromised functional recovery of isolated rabbit hearts after low-pressure, hypothermic, perfused preservation for 24 hours.

Low-pressure, hypothermic perfusion of isolated rabbit hearts for 24 hours compromises contractile function. This occurs despite continuous recirculation of an oxygenated solution. This investigation tested the hypothesis that such functional impairment results from irreversible tissue damage consequent to ischemia-induced lipid peroxidation. Decreases in coronary flow were measured during preservation and related to concentrations of thiobarbituric acid reactive species (TBA+, primarily malondialdehyde, a by-product of lipid peroxidation) in the tissue after preservation. The concentration of TBA+ species and the percent decrease in coronary flow rates at 30 minutes and 24 hours were positively correlated (r = 0.591 and r = 0.646, respectively). India ink was used as a marker of microvascular perfusion. Hearts showing the greatest magnitude of ischemia (evidenced by decreased percentages of perfused microvessels) had the highest levels of TBA+ species (r = 0.924). Moreover, hearts that had the highest levels of TBA+ species in the tissue exhibited the lowest levels of left ventricular function (as measured on a modified Langendorff apparatus; r = 0.767). We conclude that impaired coronary flow rates during perfused preservation portend compromised myocardial contractility. Furthermore, these changes occur largely within the first 30 minutes of perfusion. It is likely that early decrements in microvascular perfusion and consequent tissue injury owing to lipid peroxidation underlie impaired myocardial function after preservation.     

The effect of fluorocarbon emulsion on 24-hour canine heart preservation by coronary perfusion

This study was designed to evaluate the effects of fluorocarbon emulsion as an oxygen carrier in myocardial preservation. The hearts were preserved for 24 hours by coronary perfusion with either oxygenated crystalloid cardioplegic solution (group C) or crystalloid cardioplegic solution with fluorocarbon added (group FC). The perfusion pressure was kept at 20 mm Hg, and myocardial temperature was maintained at 4 degrees C. Group FC demonstrated better recovery in developed pressure and maximum rate of rise of left ventricular pressure compared with group C. The postpreservation end-diastolic pressure in group C increased significantly compared with the baseline value (value obtained before preservation). On the other hand, group FC showed no significant increase of end-diastolic pressure after preservation. Group FC released a significantly lower level of creatine kinase into its perfusate than did group C. Ultrastructural changes after preservation in group C showed severe ischemic injury, but there was no evidence of ischemic injury in group FC. The use of fluorocarbon emulsion proved beneficial to myocardial protection in long-term preservation of canine hearts.     

Comparison of functional and metabolic assessments in preservation techniques for heart transplantation

The present study compares simple hypothermic storage and hypothermic perfusion in a swine model of heart transplantation using metabolic and functional assessments. In both groups the hearts were initially protected with iso-osmolar potassium Tyers' cardioplegia. The donor hearts of group A were placed in simple hypothermic storage for 5 h. The donor hearts of group B were placed onto a perfusion apparatus for 5 h with perfusion pressure maintained at 28 cm of H2O and a myocardial temperature of 8-10 degrees C. The perfustate consisted of Tyers' solution with the addition of 2 mg/L of mannitol, 12.5 mg/L of glucose, 5 units/L of insulin, and 95% oxygen. The ischemic interval within both groups was 6 h, including orthotoipic transplantation. Investigation was conducted at three time periods: prepreservation (T1) in the donor, and postpreservation (T2) and immediately after loading (T3) in the recipient. Following volume loading for the hypothermic perfusion group there was significant improvement of myocardial function (cardiac index, p less than .05; stroke index, p less than .05) with no significant change in systemic vascular resistance, systemic blood pressure, and heart rate. There was also significant improvement in myocardial performance (p less than .05) for the hypothermic perfusion group following volume loading. Results of fatty acid turnover using 15-p-iodo (123I)-phenylpentodecanoic acid indicate significantly greater increase in metabolic rate for the perfusion group than for the hypothermic storage group. (p less than .05). This indicates improved metabolic status of the heart treated with the hypothermic perfusion technique. We conclude that a combination of functional and metabolic assessments is a good method for deduction of ischemic-reperfusion injury. We also conclude that hypothermic perfusion is superior to hypothermic storage for in vitro preservation of hearts for heart transplantation.     

Safe orthotopic transplantation of hearts harvested 24 hours after brain death and preserved for 24 hours

Objectives. The aim of this study was to demonstrate safe orthotopic transplantation of porcine donor hearts harvested 24?hours after brain death and preserved for 24?hours before transplantation. Design. Circulatory normalization of brain dead (decapitated) pigs was obtained using a new pharmacological regimen (n?=?10). The donor hearts were perfused at 8?°C in cycles of 15?min perfusion followed by 60?min without perfusion. The perfusate consisted of an albumin-containing hyperoncotic cardioplegic nutrition solution with hormones and erythrocytes. Orthotopic transplantation was done in 10 recipient pigs after 24?hours’ preservation. Transplanted pigs were monitored for 24?hours, then an adrenaline stress test was done. Results. All transplanted pigs were stable throughout the 24-hour observation period with mean aortic pressure around 80?mmHg and normal urine production. Mean right and left atrial pressures were in the range of 3–6 and 5–10?mmHg, respectively. Blood gases at 24?hours did not differ from baseline values. The adrenaline test showed a dose dependent response, with aortic pressure increasing from 98/70 to 220/150?mmHg and heart rate from 110 to 185 beats/min. Conclusion. Orthotopic transplantation of porcine hearts harvested 24?hours after brain death and preserved for 24?hours can be done safely.     

UW solution for hypothermic machine perfusion of warm ischemic kidneys

BACKGROUND: Donation of kidneys from non-heart beating donors (NHBD) is increasingly being used to expand the donor pool. Warm ischemic injury of these kidneys suffered at harvest results in DGF at transplantation. In this study, we used hypothermic continuous machine perfusion preservation to mitigate this injury using two available solutions. METHODS: Dog kidneys (beagles) were exposed to 0, 60, or 75 min of in situ warm ischemia (37 degrees C), followed by 24 to 72 hr preservation by machine perfusion with Belzer MPS solution or the UW-solution (Viaspan). Auto-transplantation was performed with immediate contralateral nephrectomy. Survival and renal function (serum creatinine) were evaluated for up to 10 days posttransplant. RESULTS: Both solutions were equally effective for 72 hr machine perfusion preservation of dog kidneys giving 100% survival with only minor renal injury. Both solutions were also equally effective for preservation of kidneys exposed to 60 min of warm ischemia. However, only the UW solution gave reliable preservation (86% survival vs. 25% survival) in kidneys exposed to 75 min of warm ischemia and 24 hr machine perfusion. CONCLUSION: UW solution used with continuous hypothermic machine perfusion preservation can rescue canine kidneys from severe warm ischemic injury.     

Hypothermic perfusion of rabbit kidneys with solutions containing gelatin polypeptides.

Rabbit kidneys were perfused with a solution of extracellular electrolyte composition, made hypertonic with glucose and containing the gelatin polypeptide preparation Haemaccel (Hoechst) as the only colloid. Perfusions were carried out at 5 and 10 C for 19 hr, and function was tested by autografting. All of the kidneys perfused at the higher temperature showed immediate life-sustaining function after transplantation and contralateral nephrectomy, whereas only one graft of five perfused at the lower temperature showed any function. The suitability of the Haemaccel solution as a vehicle for introducing the cryoprotective agent glycerol was tested by perfusing kidneys for 4 hr with a solutiont containing 2% glycerol; the function of these organs was similar to that of kidneys transplanted without perfusion. Ultrastructural examination of kidneys perfused for 24 hr at 10 C showed excellent structural preservation, but measurements of water and ion contents and the penetration of marker molecules in nonmetabolizing kidneys showed 2.8% Haemaccel to be somewhat less effective than 6% bovine serum albumin in stabilizing these values. The Haemaccel perfusate is considered to be highly suitable for the introduction and removal of cryoprotective agents, and the results of hypothermic preservation by continuous perfusion are encouraging.