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Biomedical subjects

R L Hardesty

Publications and source records attributed to R L Hardesty.

216 records · Page 12Linked to original sources
PubMedDate not supplied

Heart transplantation in patients with malignant disease.

We have traditionally pushed the limits of conservative candidate criteria for heart transplantation. We have been gratified by our results in the aged, the diabetic, and the mortally ill. Our inclusion of patients with malignant disease underscores our philosophy to include patients as candidates for transplantation for whom the procedure has reasonable expectation of success. We report here our early results of heart transplantation in 11 patients with malignant disease. Our survival rate in this group is 100%, and all patients are leading active lives with no evidence of recurrent or metastatic tumor. Immunosuppression protocols were adjusted on an individual basis determined by the chemotherapy dosage, duration, and relation to transplantation. Whenever possible a 1-year disease-free interval after completion of adequate cancer therapy is desired before transplantation.

Adult↗
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Posttransplantation diabetes mellitus in heart transplant recipients.

This study was undertaken to investigate the impact of diabetes, which develops after heart transplantation, on infection and patient survival. Nondiabetic patients (366) underwent heart transplantation at our institution between June 1, 1980 and January 12, 1988. Of these patients, 29 (8%) developed posttransplantation diabetes (PTD), defined as a continued need for hypoglycemic agents. The PTD group did not differ significantly from the nondiabetic recipients in age, sex, or human leukocyte antigen type. The average age in the PTD group was 49 years. Average length of follow-up was 21 months (range 4 to 46 months). Eighteen patients are maintained on insulin. Eight patients are on oral hypoglycemic agents. Three patients died while on insulin. The average prednisone dosage in this group is 0.23 mg/kg/day. There have been 18 minor infections and four potentially serious nonlethal infections in the 27 PTD recipients. One lethal infection occurred 33 months after heart transplantation. The only other fatality was related to metastatic bladder cancer. This lethal infection rate of 3% compares with a rate of 11% in all nondiabetic recipients who have follow-up for 21 months. The 3-year actuarial survival of the PTD group is 75%, which compares favorably with the survival of nondiabetic patients. PTD cannot be predicted by sex, age, or human leukocyte type before transplantation, and it does not significantly increase the incidence of mortality or serious infection.

Coronary Angiography↗
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Use of the total artificial heart as an interim device: initial experience in Pittsburgh with four patients.

The experimental use of the total artificial heart as an interim device before heart transplantation has demonstrated its potential usefulness. Once again there has been a reaffirmation of the basic principle in transplantation that careful selection of patients is a prerequisite for a high likelihood of success. Our experience suggests that advanced degrees of renal failure and liver dysfunction are not likely to be associated with a consistently useful interim support. Although our numbers of patients are quite small, we continue to be concerned by what appears to be the tendency for the development of severe thrombocytopenia not resulting from the use of heparin. Studies of platelet kinetics and deposition are planned for the future. Although no recipient has had direct evidence of thromboembolic events, systemic anticoagulation with heparin has been aggressively applied, and bleeding complications have been common. All Jarvik-7 hearts on which autopsies have been performed have demonstrated grossly evident platelet fibrin thrombi, especially around the inlet and outlet valve housings. It has not been our purpose to investigate the relative role for univentricular or biventricular assist. It is likely that a number of our patients might have benefited from left ventricular assistance alone. It would appear that additional patients are needed before strong conclusions can be formed regarding the potential benefits and risks of the current Jarvik-7 device or any total artificial heart as an interim method of support before heart transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Prostaglandin E1: an effective treatment of right heart failure after orthotopic heart transplantation.

Three patients are presented who had life-threatening postoperative pulmonary hypertension after orthotopic heart transplantation. This pulmonary hypertension was unresponsive to standard therapy but responded dramatically to treatment with prostaglandin E1. The problem of evaluating and treating heart transplant patients with pulmonary hypertension and the role of prostaglandins are discussed.

Alprostadil↗
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Management of cyclosporine toxicity by reduced dosage and azathioprine.

While cyclosporine immunosuppression has improved the results of heart transplantation, nephrotoxicity and hypertension occurred in a large percentage of surviving patients. The potential irreversibility of these toxicities was noted in patients chronically exposed to cyclosporine. The immunosuppressive protocol was modified in those patients with a serum creatinine greater than 2.5 mg/100 mL. Azathioprine was added to the immunosuppressive regimen, and the dose of cyclosporine was steadily decreased until the creatinine was lowered. The combination of low-dose cyclosporine and azathioprine provided effective immunosuppression and was associated with a significant decrease in serum creatinine level, in systolic and diastolic blood pressures. Although it is premature to assess the long-term results of this immunosuppressive protocol, the early results are encouraging.

Azathioprine↗
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Five years of heart transplantation in Pittsburgh.

Looking over the five years of HTx experience in Pittsburgh we conclude that a reasonable success has been achieved and that the promise of Cy superiority has been realized. Although certain naivete about the likely panacea property of Cy occurred early, major adjustments in the original immunosuppressive protocol were required and included the use of rescue ATG, the measurement of Cy levels in the blood, the use of less Cy, and the perioperative avoidance of Cy. We anticipate a continued 80% one year survival with a likely survival in excess of 66% at five years. Furthermore, it is believed that the avoidance of early nephrotoxicity combined with the use of less Cy chronically will result in far fewer problems with nephrotoxicity. While we have been conservative with our immunosuppression, we have aggressively broadened the criteria for candidacy to include patients mortally ill, patients with elevated pulmonary vascular resistances, and those in their sixth decade. We believe that challenges for the future will include the development of selective immunosuppressants and coordinated networks for donor procurement so that more patients will have the opportunity for cardiac replacement.

Age Factors↗
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Bronchoalveolar lavage in heart-lung transplantation.

Distinguishing lung rejection from infection in patients who have undergone heart-lung transplantation is difficult. Since bronchoalveolar lavage has been safely used to investigate other pulmonary conditions, its safety and the value of the cellular data obtained were evaluated on 44 occasions in ten heart-lung transplant recipients. This study established that bronchoalveolar lavage is safe after heart-lung transplantation, that it reliably diagnoses infection, and lastly that serial lavages are valuable in finding subclinical Pneumocystis carinii infections. The study failed to distinguish pulmonary infection from rejection. Nevertheless, the functional analysis of the cells obtained by bronchoalveolar lavage may yield information about the immune status of the allograft.

Bacterial Infections↗
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Lymphocytes of bronchoalveolar lavages from heart-lung transplant recipients.

Bronchoalveolar cells from 13 lavages done in six heart-lung transplant recipients were tested for spontaneous proliferation, Interleukin-2 response and secondary allogeneic proliferation measured by primed lymphocyte testing. In most instances the bronchoalveolar cells responded to Interleukin-2 suggesting the presence of activated T-cells in the lavage. The lavage cells from several patients exhibited primed lymphocyte testing responses suggesting the presence of alloreactive T-cells. A high degree of spontaneous cellular proliferation was observed in several lavages, which appeared to be due to a macrophage-lymphocyte reaction. Two mechanisms may be responsible for this reactivity; a macrophage-lymphocyte reaction as a result of recipient lymphocyte responses to donor macrophages in the lavage during the early post-transplant period, or a macrophage-lymphocyte reaction related to an ongoing infection. Thus, functional assays on bronchoalveolar lavage cells may have diagnostic value in monitoring heart-lung recipients for lung rejection and infection.

Bronchi↗
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HLA phenotype of lung lavage cells following heart-lung transplantation.

A transplanted lung contains a full complement of immunocompetent lymphocytes and macrophages that are able to react immunologically with recipient lymphocytes and macrophages. In this study, the origin of lymphocytes and macrophages recovered from sequential bronchoalveolar lavages of six heart-lung transplantation recipients was determined by histocompatibility phenotyping. We found that during the first four weeks after transplantation there is a rapid replacement of the donor cells with those of the recipient. Since lung rejection rarely occurs after this transition is complete, donor lymphocytes and macrophages may be an important component of the rejection process. Furthermore, the transition from donor to recipient phenotype indicates that the vast majority of human alveolar macrophages originate from bone marrow precursors.

HLA Antigens↗
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Blalock shunt: procedure of choice in infants.

This report summarizes our experience in 39 infants less than three months of age who underwent a Blalock anastomosis. Mortality in the 16 infants under one week of age was 25% (4/16) and the overall mortality was 26% (10/39). Early patency was 87% (34/39) and late, 83% (24/29). No patient developed congestive heart failure or pulmonary hypertension. For the infant with diminished pulmonary blood flow, the Blalock shunt is the procedure of choice.

Follow-Up Studies↗
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Development of an intravenous membrane oxygenator: a new concept in mechanical support for the failing lung.

An intravenous membrane oxygenator is being developed to supplement oxygen and carbon dioxide exchange in patients with temporary and potentially reversible lung failure in either a lung transplantation setting or in cases of acute respiratory distress from multiple causes. Our device incorporates a pulsatile balloon that is centrally located and around which are mounted microporous hollow fibers. Oxygen is vaccuumed through the fibers with resultant gas exchange. The rhythmic pulsations of the balloon enhance cross-flow and three-dimensional convective mixing at the blood-fiber interface and thus promote more efficient oxygen-carbon dioxide exchange. Seven intravenous membrane oxygenator prototypes have been designed and fabricated. Modifications in design have led to a progressive improvement in gas flux. Gas exchange performance measured in vitro and with both saline solution and fresh ox blood have shown gas exchange as high as 203 ml/min/m2 for oxygen and 182 ml/min/m2 for carbon dioxide. In vivo dog experiments with the device positioned in the inferior vena cava and right atrium have shown over a 50% increase in oxygen flux with balloon activation versus the static situation without changes in hemodynamics. The size of the prototype tested in animals can be scaled up fivefold for anticipated human trials. Our results indicate that our intravenous membrane oxygenator prototypes now under development may be an alternative to extracorporeal membrane oxygenation in the treatment of temporary respiratory failure.

Animals↗
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A clinical trial comparing University of Wisconsin solution and cold cardioplegic solution with load-independent mechanical parameters.

To evaluate the efficacy of University of Wisconsin solution for clinical heart transplantation, load-independent parameters were used to assess left ventricular function after transplantation. Donor hearts were arrested with and stored in buffered cold cardioplegic solution for control (n = 5) and University of Wisconsin solution for the experimental group (n = 5). Orthotopic transplantations were performed in a routine manner. Mean donor age (cardioplegic solution, 28 +/- 5.2 years; University of Wisconsin solution, 28 +/- 5.1 years) and ischemic times (cardioplegic solution, 181 +/- 27 minutes; University of Wisconsin solution, 224 +/- 23 minutes) were similar. Two hours after reperfusion of the heart, transesophageal echocardiography was used to image the left ventricle at the mid-papillary muscle level, and a high-fidelity catheter-tipped manometer was placed in the left ventricle to record left ventricular pressure simultaneously. These images were digitized during apneic baseline conditions and during an acute reduction in preload from inferior vena caval occlusion. The left ventricular cross-sectional areas were measured and matched with left ventricular pressure from the catheter-tipped manometer to reveal pressure-area relationships. The baseline parameters fractional area change and stroke force were calculated. End-systolic elastance, the slope of end-systolic pressure-area relationship and preload recruitable stroke force, the slope of stroke force versus end-diastolic area were calculated from the inferior vena cava occlusion measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗