Combined heart-kidney transplantation with single-donor allografts.

OBJECTIVES: Combined heart-kidney transplantation with allografts from the same donor has been long proved to be a feasible approach for selected patients with coexisting end-stage cardiomyopathy and renal disease. The purpose of this retrospective study is to analyze our long-term results and compare these results with heart-only transplantation over a 7-year period. METHODS: Between June 1992 and April 1999, 10 patients underwent combined heart-kidney transplantation at Cedars-Sinai Medical Center. They were all men from 44 to 70 years old (mean age, 59 +/- 8.3 years) who had a mean left ventricular ejection fraction of 19.4% +/- 5.0% (range, 9%-25%) and a mean creatinine clearance of 25.4 mL/min (range, 10-39 mL/min). Four patients underwent pretransplantation dialysis. RESULTS: There was no operative mortality. The actuarial survival at 1, 2, and 5 years was 100%, 88% +/- 11.7%, and 55% +/- 20.1%, respectively. By comparison, the operative mortality of 169 patients who underwent heart-only transplantation during the same time interval was 2.4%, with an actuarial survival at 1, 2, and 5 years of 92% +/- 2.1%, 84% +/- 2.8%, and 71% +/- 3.9%, respectively (P =.37). Eight patients showed no evidence of significant (> or =1B) cardiac allograft rejection postoperatively, and the actuarial freedom from rejection at 30 days, 1 year, and 2 years was 90% +/- 9%, 80% +/- 13%, and 80% +/- 13%, respectively. Renal allograft survival was 90% at 1 and 2 years. CONCLUSIONS: Combined heart-kidney transplantation yields satisfactory long-term results similar to those for heart-only transplantation, with a low incidence of cardiac allograft rejection and renal allograft survival when both allografts are from the same donor. This approach effectively expands the selection criteria for heart-only and kidney-only transplantation in potential candidates with coexisting end-stage cardiac and renal disease.

Heart transplantation in patients seventy years of age and older: A comparative analysis of outcome.

OBJECTIVE: Advanced age has traditionally been considered a contraindication for heart transplantation because of the reported adverse effect of increased age on long-term survival. However, as the field of transplantation continues to evolve, the criteria regarding the recipient's upper age limit have been expanded and older patients are being considered as potential candidates. We analyzed the outcome of heart transplantation in patients 70 years of age and older and compared these results with those in younger patients (<70 years) over a 4-year period. METHOD: We retrospectively analyzed the results of 15 patients 70 years of age and older who underwent heart transplantation between November 1994 and May 1999 and compared them with results in 98 younger patients undergoing transplantation during the same period RESULTS: The older age group had a higher preoperative left ventricular ejection fraction (P =.02), higher incidence of female donors (P =.02), and longer cardiac allograft ischemic time (P =.01). No differences were found regarding incidence of diabetes mellitus, donor age, donor/recipient weight ratio, and mismatch (<0.80). The 30-day or to-discharge operative mortality was similar in both groups (0% in the older vs 5.1% in younger patients). Actuarial survival at 1 year and 4 years was not statistically different between the older and younger patients (93.3% +/- 6.4% vs 88.3% +/- 3.3% and 73.5% +/- 13.6% vs 69.1% +/- 5.8%, respectively). The length of intensive care unit stay and total post-transplantation hospital stay, incidence of rejection, and incidence of cytomegalovirus infection were similar between the groups. CONCLUSIONS: Heart transplantation in selected patients 70 years of age and older can be performed as successfully as in younger patients (<70 years of age) with similar morbidity, mortality, and intermediate-term survival. Advanced age as defined (> or =70 years) should not be an exclusion criterion for heart transplantation. The risks and benefits of transplant surgery should be applied individually in a selective fashion.

Is warm retrograde blood cardioplegia better than cold for myocardial protection?

BACKGROUND: This study tests the hypothesis that continuous normothermic retrograde blood cardioplegia is superior to cold intermittent blood cardioplegia in protecting the left and right side of the heart transmurally during an extended cross-clamping period. METHODS: Twelve anesthetized, open chest dogs were placed on cardiopulmonary bypass and randomized to receive continuous warm (n = 6) or intermittent cold cardioprotection (n = 6) during a 3-hour aortic cross-clamp period. Transmural left ventricular muscle biopsy specimens were taken before the initiation of cardiopulmonary bypass and 90 and 180 minutes after cross-clamping. Right ventricular (RV) biopsy specimens were taken 180 minutes after aortic cross-clamping. Biopsy specimens were analyzed for adenosine triphosphate, creatine phosphate, and lactate levels and for morphologic changes via electron microscopy. RESULTS: At the end of 180 minutes of cardiopulmonary bypass, the adenosine triphosphate contents of endocardial and epicardial halves of the left ventricular myocardium were only slightly degraded in both cardioplegia groups; a significantly greater reduction in adenosine triphosphate levels occurred in the RV of the warm compared with the cold group (p < 0.02). The difference in creatine phosphate values in the left ventricle between the cold group (35.2 +/- 23.4 nmol/mg cardiac protein) and the warm animals (64.4 +/- 24.9 nmol/mg cardiac protein) was not statistically significant, but the RV creatine phosphate stores were significantly better preserved in the warm compared with the cold cardioplegia group (p < 0.02). Lactate levels increased to a similar extent in both groups, but both values rose significantly over baseline (p < 0.03). Importantly the electron microscopic score of the left ventricle and RV indicated that cells were reversibly and not irreversibly damaged with both cardioplegic protections. CONCLUSIONS: These results suggest the following: (1) Chemical arrest is a major contributor of myocardial preservation during diastolic arrest as used in clinical cardiac surgery. (2) Both methods preserve the ultrastructure of the myocytes transmurally during 3 hours of aortic cross-clamping. (3) Both techniques protect the RV and left ventricle; however, to provide optimal protection of the RV, alternated retrograde and antegrade perfusion might be beneficial over retrograde cardioplegia flow alone, in particular with warm cardioplegia.

Fulminant hepatic failure in rats: survival and effect on blood chemistry and liver regeneration.

A reproducible experimental animal model of fulminant hepatic failure (FHF) resembling the clinical condition is needed. We have developed such a model in the rat by combining resection of the two anterior liver lobes (68% liver mass) with ligation of the right lobes pedicle (24% liver mass), resulting in liver necrosis; the remaining two omental lobes (8% liver mass) are left intact. Adult Sprague-Dawley rats (250-300 g) were used. Survival time was determined in 60 rats. Because maintenance of body temperature at 37 degrees C shortened survival time by half, FHF rats were not warmed during the postinduction period and were allowed to gradually enter a state of mild to moderate hypothermia (29-32 degrees C). Additionally, 42 FHF rats were killed in batches of six rats each 2, 6, 12, 18, 24, 30, and 36 hours postoperatively to evaluate changes in blood chemistry (glucose, lactate, liver function tests, prothrombin time) and to assess liver regenerative response in the residual omental liver lobes (weight, protein content, incorporation of bromodeoxyuridine [BrdU], expression of proliferation cell nuclear antigen [PCNA], mitotic activity), plasma levels of hepatocyte growth factor (HGF) and transforming growth factor beta (TGF-beta1), and tissue expression of the HGF and it's receptor c-met. Rats undergoing partial hepatectomy of 68% (PH; n = 42) and a sham operation (SO; n = 42) served as controls. All SO and PH controls survived. PH rats showed only transient decreases in body temperature, signs of modest early hepatic dysfunction (hyperlactemia, hyperammonemia, prolonged PT time), and normal restitution of liver mass. All FHF rats became comatose by 24 hours postoperatively. Most animals (90%) died within 24-48 hours postoperatively (mean, 39 +/- 11 hours). Changes in blood chemistry reflected rapid development of liver failure. Plasma HGF levels were markedly elevated and at all time points were higher than in PH controls (P < .05). At the same time, expression of HGF and c-met messenger RNA in the remnant liver was delayed. Plasma TGF-beta1 levels increased early (18 hours) and remained twofold to threefold higher than that of PH and SO controls (P < .05). There was only a 20% increase in the weight of the remnant liver lobes due to swelling. No hepatocytes stained positively for BrdU and PCNA, and none showed mitotic figures. In contrast, all PH controls showed vigorous liver regeneration. In conclusion, we have developed and characterized a novel model of FHF in rats that has a number of physiological and biochemical features seen clinically in FHF, including severely impaired ability of the residual liver tissue to regenerate.

Review: Artificial liver support systems.

Despite recent advances in medical therapy, patients with fulminant hepatic failure (FHF) have a mortality rate approaching 90%. Many patients die because of failure to arrest the progression of cerebral edema. Liver transplantation has improved survival to 65% to 75%. However, there is a shortage of donors and approximately one half of the patients with FHF will die while awaiting liver transplantation. There is thus a need to develop an extracorporeal liver assist system to help keep these patients alive and neurologically intact until either an organ becomes available for transplantation or the native liver recovers from injury. Such a system could also be used during the period of functional recovery from massive liver resection or to assist patients with decompensated chronic liver disease. Over the years, various methods utilizing charcoal and resin hemoperfusion, dialysis, plasma exchange, and other methods of blood detoxification have been developed and tested, but none have gained wide acceptance. This was due to: (i) incomplete understanding of the pathophysiology of liver failure; (ii) lack of accurate methods of assessment, quantitation, and stratification of the degree of liver dysfunction; and (iii) inadequate numbers of prospective controlled clinical trials examining the effects of specific therapeutic modalities. Liver support systems utilizing liver tissue preparations were developed in the 1950s, but it was not until recently that advances in hepatocyte isolation and culture, better understanding of hepatocyte-matrix interactions, and improved hollow-fiber technology have resulted in the development of a new generation of liver assist devices. Some of these devices are currently being tested in the clinical setting. In a preliminary clinical study, we have used a porcine hepatocyte-based liver support system to treat patients with acute liver failure as well as patients with acute exacerbation of chronic liver disease. Patients in the first group, who were candidates for transplantation, were successfully bridged to a transplant with excellent survival. No obvious benefit from bioartifical liver treatments was seen in the second group. It is possible that, in this group, patients will have to be treated earlier and for longer periods of time. Prospective controlled trials will be initiated as soon as the current phase I study is concluded to determine the efficacy of this system in both patients populations. (c) 1996 John Wiley & Sons, Inc.