Celsior solution provides superior post-ischemic right ventricular function as compared with UW solution in a porcine heart transplantation model.

BACKGROUND: Use of the new cardioprotective Celsior solution has been suggested for organ preservation in cardiac transplantation, but selective data for right ventricular function, of special interest in the clinical setting, have not been evaluated. METHODS: Celsior solution was compared with the clinical standard University of Wisconsin solution (UW) in a porcine allogenic heart transplantation model with accurate isovolumic measurement of right ventricular (RV) function. RESULTS: Maximum RV developed pressures were significantly different between Celsior and UW groups (51.1 +/- 9.6 mm Hg vs 42.2 +/- 15.4 mm Hg after 1 hour, respectively, and 55.6 +/- 7.8 mm Hg vs 45.1 +/- 16.2 mm Hg after 2 hours, respectively; p = 0.02, 2-way analysis of variance). CONCLUSIONS: Celsior significantly improves post-ischemic right ventricular function when compared with UW solution in an experimental heart transplantation model.     

Improved preservation of coronary endothelial function with Celsior compared with blood and crystalloid solutions in heart transplantation.

BACKGROUND: Endothelial injury from preservation solutions has been implicated in acute coronary vasospasm and pathologic activation of the endothelium, which can contribute to the development of graft coronary vasculopathy after heart transplantation. Preservation solutions with a powerful antioxidant capacity may decrease the occurrence of these complications. MATERIALS and METHODS: This study was designed to evaluate the effect of Celsior (an anti-oxidant solution specifically designed for cardiac preservation) in a model of heart preservation (4 hours at 4 degrees C to reproduce the situation encountered in clinical heart transplantation) compared two commonly used cardioplegic and preservation strategies on coronary endothelial function. Endothelium-dependent relaxation of normal porcine epicardial coronary arteries to serotonin (5-HT, an agonist that activates 5-HT(1d) receptors coupled to Gi proteins) and bradykinin (BK, which activates B2 receptors coupled to Gq proteins) was studied in standard organ chamber experiments in the following groups: a control group was submitted to immediate excision without cardioplegia and preserved in saline solution (0.9% NaCl) for 4 hours (Group 1); two groups had cardioplegia induced with a crystalloid solution and were stored for 4 hours in saline (Group 2) or 4 hours in Celsior solution (Group 3); and two groups had cardioplegia induced with normothermic blood cardioplegia and were stored for 4 hours in the saline (Group 4), or 4 hours in Celsior solution (Group 5). Finally, two groups underwent cardioplegia with Celsior and were stored for 4 hours in saline (Group 6), or 4 hours in the Celsior solution (Group 7). All cardioplegia solutions were at 4 degrees C (except blood cardioplegia at 37 degrees C) and all preservations solutions were at 4 degrees C. RESULTS: Endothelium-dependent relaxations to serotonin were significantly decreased in all groups except the Celsior + Celsior group compared with the control group. There were no significant differences in relaxation to bradykinin except in one group. Use of the Celsior solution for induction of cardioplegia and storage better preserved endothelium-dependent G-protein-mediated relaxation compared with the other arrest and preservation strategies. CONCLUSIONS: The observed effect may be associated with an improvement in both short- and long-term outcome in heart transplantation, especially because these alterations may be further compounded by reperfusion.     

Effects of crystalloid, blood and Celsior solutions on porcine coronary endothelial function after heart transplantation.

BACKGROUND: Coronary endothelial dysfunction occurs early after heart transplantation and predicts the development of cardiac allograft vasculopathy. Cardioplegic solutions may cause endothelial injury. The present study aimed to assess the effects of cardioplegic solutions (crystalloid, blood and Celsior) used at the time of graft harvesting on endothelial function and intimal hyperplasia 1 month after heart transplantation. METHODS: A porcine heterotopic heart transplantation model was used. Three experimental groups were studied: crystalloid, blood and Celsior solutions were used for induction of cardiac arrest. Epicardial coronary arteries of native and allograft hearts were studied 1 month after transplantation in organ chambers. Endothelium-dependent relaxations to serotonin, bradykinin and calcium ionophore were assessed. Coronary neointimal proliferation was evaluated using histomorphometric studies. RESULTS: Endothelium-dependent relaxations to serotonin and to calcium ionophore were significantly decreased in all 3 experimental groups vs controls (p<0.05). Endothelium-dependent relaxations to bradykinin were significantly reduced in the crystalloid group compared with the Celsior and blood groups and controls (p<0.05). There was a significantly lower rate of severe intimal hyperplasia in the Celsior group compared to the crystalloid and blood groups (p<0.05). CONCLUSION: Celsior cardioplegic solution represents the solution of choice in terms of preservation of endothelial function and lower incidence of severe coronary intimal hyperplasia following transplantation compared with crystalloid and blood cardioplegia solutions. These early results could translate into a reduction of the long-term incidence of cardiac allograft vasculopathy and improve graft survival.     

Prolonged preservation of cadaver heart with Belzer UW solution: 24-hour storage system for asphyxiated canine hearts

The efficacy of Belzer UW solution was compared to Collins' solution in the preservation of asphyxiated cadaver hearts in a canine model. Donor hearts were stored for 24 h: 2 h of in situ hypothermic (15 degrees C) coronary perfusion plus 22 h of simple immersion in ice-cold solution. Verapamil, propranolol and prostacyclin were used for myocytoprotection in both groups. After orthotopic transplantation, all animals were weaned off bypass without inotropic support. After 1 h, however, the cardiac output was significantly higher in the Belzer UW solution group (128 +/- 28 vs. 67 +/- 13 ml/kg/min, p less than 0.01).     

The use of a nondepolarizing cardioplegic solution for cardiac preservation has a beneficial effect on the left ventricular diastolic function

We have developed a nondepolarizing solution (NDS) that retards myocardial calcium accumulation during cardioplegia. This study compares 1) the membrane resting potential (Em) in Purkinje fibers during cardioplegia induced by NDS or University of Wisconsin solution (UW) at normothermia and hypothermia for 6 h, 2) left ventricular (LV) diastolic function of isolated canine hearts preserved with NDS or UW for 6- and 12 h in hypothermia to elucidate the relationship between diastolic function and myocyte physiology (n = 8, each group), and 3) the effect of Non-depolarizing solution (NDS) compared with Bretschneider's HTK solution on LV diastolic function in isolated rabbit hearts using the Langendorff model in normothermia (n = 10, each group). The membrane resting potential (Em) was as follows: NDS in normothermia, –71 mV (2 min), –65 mV (30 min), and –52 mV (60 min); NDS in hypothermia, –40 mV (1 h) and –32 mV (6 h), while UW in hypothermia 0 mV (6 h). Myocardial calcium accumulation during reperfusion in the NDS groups was minimal and significantly lower than in the UW groups after the 6- and 12 h preservations. Postreperfusion myocardial cyclic adenosin monophosphate (cAMP) and adenosin tri-phosphate (ATP) concentrations in the NDS groups were closer to normal than in the UW groups after the 6- and 12 h preservations. The postreperfusion myocardial Ca concentration correlated with the cAMP (r = –0.68, n = 25, P = 0003) and cyclic guanosine monophosphate (cGMP) concentrations (r = –0.69, n = 25, P = 0.003). The left ventricular end-diastolic pressure (LVEDP) after reperfusion correlated with myocardial ATP (r = –0.65, n = 25, P = 0.003) and Ca concentrations (r = –0.68, n = 25, P = 0005). However, the parameter indicating LV elasticity (max LV –dp/dt) correlated with neither the Ca or ATP concentration following reperfusion. NDS prevented stiffness (increased LVEDP) better than HTK during normethermic cardioplegia for 30 min. These results in vitro suggest that NDS prevents myocardial Ca accumulation, depletion of ATP and cAMP, and preserves LV diastolic function, particularly stiffness after reperfusion, for up to 12 h. Furthermore, the mycoardial Ca concentration is inversely correlated with the cAMP and cGMP concentrations. Received: 14 October 1999 Revised: 30 October 2000 Accepted: 21 December 2000     

Superiority of the University of Wisconsin solution over simple crystalloid for extended heart preservation. A study of left ventricular pressure-volume relationship.

To compare the effects of the University of Wisconsin solution with those of an extracellular crystalloid solution, Krebs-Ringer bicarbonate, as cardiac preservation media, we studied 35 adult dogs in an isolated heart preparation. Four groups of seven hearts were preserved in University of Wisconsin solution for 6 or 12 hours or in Krebs-Ringer bicarbonate solution for 6 or 12 hours. An additional group of seven hearts with no ischemia was used for a control group. In the four preservation groups, hearts were arrested by electrolyte solution (Normosol with potassium chloride, 20 mEq/L, added, 4 degrees C), flushed with 200 ml of the preservation solution, and then stored in the same solution at 1 degree to 2 degrees C. The hearts were mounted on an isolated heart preparation equipped with a computer-controlled servo-pump system that used a mock arterial system to modulate the aortic input impedance presented to the left ventricle. Left ventricular pressure-volume loops were measured on-line for 2 hours of reperfusion with autologous warm oxygenated blood. Elastance was derived from the end-systolic pressure-volume relationship, and diastolic compliance was derived from the end-diastolic pressure-volume relationship. The total left ventricular performance was assessed by the preload recruitable stroke work area, the slope, and its x-intercept, all of which derived from the stroke work (pressure-volume area)-end-diastolic volume relationship. Extended global ischemia had more deleterious effects on the end-diastolic than the end-systolic pressure-volume relationship. In confirmation with other studies, elastance did not accurately reflect the level of ventricular contractile dysfunction because of the significant amount of diastolic dysfunction. The preservation of myocardial systolic and diastolic functions, as demonstrated by the preload recruitable stroke work area and diastolic compliance, was better in the University of Wisconsin solution groups than in the Krebs-Ringer bicarbonate solution groups after 6 and 12 hours of preservation. In addition, 6 hours of preservation with University of Wisconsin solution maintained normal systolic and diastolic functions as compared with those of the control group. Preservation with University of Wisconsin solution prevented any myocardial edema formation; by contrast, this was significantly increased after 12 hours in Krebs-Ringer bicarbonate solution. Groups preserved with University of Wisconsin solution had less reperfusion injury as evidenced by the release of coronary sinus creatine kinase during reperfusion; they also had improved oxygen use during reperfusion.(ABSTRACT TRUNCATED AT 400 WORDS)     

The immediate function of the kidney after 24-to 72-hr preservation. Hypothermic storage versus mechanical perfusion.

Seventy-two dog kidneys were stored under hypothermia as described by Collins and Sacks between 24 and 72 hr and then transplanted. The immediate function of the kidneys was measured by p-aminohippuric acid and inulin clearances. Twenty-four hr proved to be the maximum safe preservation time with both methods. The immediate function of the kidneys stored under hypothermia could not be improved by the addition of furosemide to the flushing solution. These results were compared with those gained by mechanical perfusion of the organ. Kidney function after 72 hr of hypothermic mechanical perfusion was significantly better than after 24 hr of hypothermic storage.     

Surfactant function in lung transplantation after 24 hours of ischemia: advantage of retrograde flush perfusion for preservation.

OBJECTIVE: Surfactant function was shown to be impaired in clinical and experimental lung transplantation. This study was designed to define the impact of retrograde flush perfusion on graft and surfactant function after an extended period of ischemia. METHODS: Left lung transplantation was performed after 24 hours of graft ischemia in 12 pigs. In half of the grafts antegrade cold flush perfusion (Perfadex) was used for preservation. In the second group grafts were flushed in a retrograde fashion via the left atrium. Graft function was monitored for 7 hours after transplantation. Before transplantation (basal) and after 2 hours of reperfusion, bronchoalveolar lavage fluid was obtained. Minimal surface tension of bronchoalveolar lavage fluid was determined and the ratio of small and large surfactant aggregates was calculated. Lung water content was analyzed online in the reperfusion period. RESULTS: Right-sided heart failure developed in 2 animals of group 1 (antegrade perfusion) within 2 and 4.5 hours of reperfusion, respectively. All other pigs survived the observation period. PO(2)/FIO(2) (P =.001) and dynamic lung compliance (P =.001) were superior in retrogradely flushed grafts. A comparable increase of minimal surface tension was found after reperfusion in both groups. Small/large surfactant aggregate ratio after reperfusion (P =.03), as well as extravascular lung water content, was higher in the antegrade perfusion group. CONCLUSION: Retrograde flush perfusion for 24-hour lung preservation with low-potassium dextran (Perfadex) solution led to better initial graft function than the standard antegrade perfusion technique. A moderate impairment of surfactant function was found in both groups, which was more pronounced in the antegrade perfusion group.     

Native heart complications after heterotopic heart transplantation: insight into the potential risk of left ventricular assist device.

BACKGROUND: In heterotopic heart transplantation, the donor heart is connected parallel to the recipient's diseased heart. Recipients continue to have risks, such as arrhythmia, thromboembolism, valvular heart disease, and ischemic heart disease which can develop in the native heart. It may serve as a clinical model to study long-term pathophysiologic processes in the native heart of patients with a left ventricular assist device. METHOD: We analyzed the prevalence of long-term complications related to the native heart in the heterotopic heart transplant and attempted to gain insight into the potential risk to a native heart after receiving a left ventricular assist device. RESULTS: Between December 1984 and December 1994, 16 patients (13 men, 3 women, ranging in age from 37 to 60 years) underwent heterotopic heart transplant at the University of Pittsburgh. The 1- and 5-year survival rate after the transplant was 81% and 44%, respectively. Actuarial freedom from complications related to the native heart after 1 year and 4 years was ventricular arrhythmia: 85%, 75%; ischemic disease: 85%, 64%; valvular disease: 100%, 88%; and thromboembolism: 85%, 58%. Of these complications, thromboembolism was not considered in determining actuarial freedom from complications because thromboembolism should be regarded as a device-related complication rather than as a native-heart-related complication for left ventricular assist device recipients. Consequently, actuarial freedom from all complications excluding thromboembolism was 70% after 1 year and 50% after 4 years. In addition, the hazard function curve remains constant up to 80 months after the operation without significant differences among the yearly ratios. CONCLUSIONS: This analysis suggests that cautious observation of the native heart's long-term performance is necessary for the left ventricular assist device recipient.     

Saphenous vein endothelial cell viability: a comparative study of endoscopic and open saphenectomy for coronary artery bypass grafting.

BACKGROUND: The use of endoscopic saphenous vein harvesting (ESVH) for coronary artery bypass grafting (CABG) is growing. This study was done to investigate the extent of endothelial injury in ESVH compared with that of the standard open method (OSVH), and under various physical and chemical preservation factors. METHODS: We endoscopically removed the saphenous vein from 45 consecutive patients undergoing saphenectomy for CABG together with a segment retrieved by the no-touch OSVH method. Vein samples from each group were divided into 8 subgroups of 5 samples each, and incubated in Plasma-Lyte solution with or without papaverine, at distending pressures of 100 or 300 mm Hg, and at either 4 degrees C or 28 degrees C, respectively. A ninth subgroup was preserved at room temperature without pressure or papaverine. The viability of cultured saphenous vein endothelial cells was assessed by counting the number of total cells and deriving the proportion of viable cells, following incubation for 72 hours. RESULTS: The median proportion of viable cells (PVC) showed a slight decline over days 0 to 4 for both harvesting methods. No significant difference existed in the median PVC between the two techniques (day 0: 75%, 72%, P = 0.8; day 1: 66.7%, 66.7%, P = 0.9; day 2: 66.7%, 66.7%, P = 0.3; day 3: 65.3%, 66.7%, P = 0.16, respectively). The mean PVC compared across temperatures of 4 degrees C, 28 degrees C, and room temperature for the ESVH was highly significant, with the highest value being for room temperature (69.5%, 56.4%, 70.3%, respectively, P = 0.0003). Results for the OSVH were not significant. The effect of distension pressure did not vary significantly for 0, 100, and 300 mm Hg for both techniques (70.3%, 63.2% and 63.4%, respectively, P = 0.46 for the ESVH; 66.5%, 68.4%, 67.4%, respectively, P = 0.94 for the OSVH). The addition of papaverine improved PCV slightly for the OSVH only (61.7%, 64.3%, respectively, P = 0.02), whereas that for the ESVH was not significant (67.3%, 72.5%, P = 0.12). CONCLUSION: The effect of ESVH on endothelial cell viability is comparable to that of the OSVH. Among the factors influencing endothelial viability during vein preparation, temperature had a major effect with lower temperatures in the range of 4 degrees C to room temperature being the most favorable one. Mechanical distension and papaverine had unimportant or inconsistent roles. We recommend the ESVH as the procedure of choice for saphenous vein harvesting due to the lower postoperative morbidity, and the lower incubation temperature needed for its better influence on potential graft patency.     

Optimal storage period for extended heart preservation with the University of Wisconsin Solution. A study of the left ventricular pressure-volume relationship.

To define the optimal and safe storage period in the use of the University of Wisconsin Solution (UWS) for extended heart preservation, 34 adult canine hearts were preserved under static and hypothermic conditions for 6, 12, 18, and 24 hours. A group of 10 hearts were used as a control of the preparation used in the study. Left ventricular functions were assessed in an isolated heart preparation equipped with a computerized servo-pump to measure the pressure-volume relationship. The systolic, diastolic and total ventricular performance were derived from the end-systolic pressure-volume relationship, end diastolic pressure-volume pressure relationship, and the stroke work-end diastolic volume relationship, respectively. Myocardial water content and coronary resistance during reperfusion were also analyzed. The study revealed that UWS was able to maintain normal levels of systolic and diastolic functions, and consequently normal level of total ventricular performance after 6 hours of storage. There was a reduction of diastolic function while the systolic function was still well maintained after 12 hours of preservation. The results after 12 hours were poor. There was no increase in the myocardial water content for up to 24 hours of storage; however, the coronary resistance during reperfusion significantly increased in the 18-hour group and the 24-hour group. The findings suggest that UWS may extend the safe period of myocardial preservation beyond the traditional 4 hours of storage closer to 12 hours of storage.