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Biomedical subjects

W A Gay

Publications and source records attributed to W A Gay.

117 records · Page 7Linked to original sources
PubMedDate not supplied

Extracorporeal circulation in the fetal lamb. Effects of hypothermia and perfusion rate.

The poor prognosis of certain cardiac abnormalities detected prenatally by echocardiography has led some investigators to consider intrauterine cardiac surgery. Investigation into the efficacy of open cardiac procedures in-utero will require techniques for safe and effective fetal extracorporeal circulation and myocardial protection. We performed cardiopulmonary bypass in 8 fetal lambs to assess the feasibility of fetal cardiopulmonary bypass. Four fetuses underwent studies at 37 degrees C (Group I) and 4 at 25 degrees C (Group II). The aorta was clamped and cold crystalloid cardioplegia administered. Perfusion was carried out for 10 minutes each at high (95 +/- 18 cc/kg/min), moderate (67 +/- 10 cc/kg/min), and low (49 +/- 8 cc/kg/min) flow rates while hemodynamic and blood gas measurements were made. Total time on bypass averaged 57 min in Group I and 75 min in Group II. Four fetuses were successfully weaned from bypass following the study period. Fetal pO2 and oxygen saturation was very low at all flow rates in Group II and at low flow rates in Group I, indicating poor function of the placenta as an oxygenator at 25 degrees C and at low flow rates during normothermia. Lambs undergoing bypass at 37 degrees C had a progressive rise in pCO2 levels as flow decreased, while pCO2 was relatively normal at all flow rates at 25 degrees C. These studies serve as a starting point for the development of techniques to allow intrauterine correction of experimentally produced fetal cardiac lesions.

Animals↗
PubMedDate not supplied

Hypercholesterolemia after heart transplantation: amelioration by corticosteroid-free maintenance immunosuppression.

Most heart transplant recipients develop hypercholesterolemia, the cause of which is poorly understood. To test the hypothesis that corticosteroids contribute to the hypercholesterolemia, we reviewed 117 consecutive heart transplant recipients who survived more than 4 months, of whom 51 (44%) required and 66 (56%) did not require maintenance corticosteroids, chronic immunosuppression maintained with cyclosporine and azathioprine only. Fasting serum cholesterol levels were measured every 3 months and were found to be 21% to 26% lower during the first 18 months after heart transplantation in the group that did not require chronic corticosteroid administration (p less than 0.001). Beginning 3 months after transplantation, average serum cholesterol levels ranged from 199 +/- 8 mg/dl to 211 +/- 9 mg/dl in the corticosteroid-free group compared with 262 +/- 8 mg/dl to 272 +/- 8 mg/dl in patients requiring corticosteroid maintenance immunosuppression. Because serum cyclosporine levels did not differ between the groups, a contribution by cyclosporine to posttransplant hypercholesterolemia could not be substantiated. Although the hypercholesterolemia that occurs after heart transplantation is undoubtedly multifactorial, corticosteroid administration contributes importantly to its development.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Vascular (humoral) rejection in heart transplantation: pathologic observations and clinical implications.

We prospectively studied 551 sequential endomyocardial biopsies from 36 consecutive cardiac allografts. With the use of a combination of light microscopy (including careful evaluation of vascular changes) and immunofluorescence to detect the deposition of immunoglobulin and complement, we identified three patterns of allograft rejection, designated as cellular rejection, vascular (humoral) rejection, and mixed rejection. Cellular rejection was diagnosed with modified Billingham criteria. Vascular rejection was diagnosed by finding the combination of prominent endothelial cell swelling and/or vasculitis on light microscopy and the vascular deposition of immunoglobulin and complement by immunofluorescence. In such patients, cellular lymphoid infiltrates were uniformly absent at the time the vascular changes were detected. Mixed rejection consisted of findings of both cellular and vascular rejection occurring simultaneously. Twenty of 36 allografts exhibited cellular rejection; seven allografts showed vascular rejection, and nine allografts developed mixed rejection. The vascular (humoral) pattern of rejection was important to identify because the patients with this type of rejection had a significantly decreased survival compared with that of patients with cellular rejection (p less than 0.05). Survival in the mixed rejection category was intermediate. Positive donor-specific cross-match and/or panel-reactive antibody greater than or equal to 5% and systolic dysfunction were seen in three of the seven allografts with vascular (humoral) rejection but not in the other types. In the early period after transplant (up to 3 weeks after transplant), the only reliable identifying characteristics of patients with vascular (humoral) rejection were the presence of vascular immunoglobulin and complement assessed by immunofluorescence and endothelial cell swelling and interstitial edema as confirmed by histologic examination. We conclude that immunofluorescence should be routinely done on all heart biopsies for the first month after transplantation. Patients with vascular (humoral) rejection cannot be reliably identified by any other means.

Adult↗
PubMedDate not supplied

Increased cardiac allograft rejection in female heart transplant recipients.

To assess differences between male and female recipients after heart transplantation, we retrospectively reviewed 140 consecutive heart transplant recipients (119 males and 21 females) with regard to sex and characteristics before and after transplantation. Before transplantation, fewer female recipients had heart failure on the basis of coronary artery disease (14% versus 56%, p = 0.001), and more females required inotropic agents (71% versus 38%, p = 0.007). Although average follow-up (for females 430 +/- 73 days, range 12 to 1097 days; for males 412 +/- 27 days, range 1 day to 1103 days, mean +/- standard error of the mean), mortality (one female and nine males), and proportion of recipients with infectious complications (48% females and 52% males) did not differ between the groups, female recipients manifested a higher incidence of rejection during the first 4 months (2.39 +/- 0.27 episodes versus 1.67 +/- 0.11 episodes, p = 0.010) and during follow-up (3.24 +/- 0.44 episodes versus 2.20 +/- 0.21 episodes, p = 0.012). Although it was possible to discontinue maintenance dosages of corticosteroids in 65% of males, corticosteroid discontinuation was possible in only 17% of females (p less than 0.001). Furthermore, in a stepwise logistic regression analysis that included age, crossmatch (no female recipients with positive results, three males with positive results), cause of heart failure, and hemodynamic status before transplantation, females were more likely to experience a rejection episode than males (p less than 0.001). Although female recipients experience rejection episodes more than their male counterparts after heart transplantation and are more likely to require maintenance corticosteroid therapy, survival and the incidence of infectious complications are not different.

Antibodies, Monoclonal↗
PubMedDate not supplied

Early, aggressive open lung biopsy in heart transplant recipients.

Fourteen open lung biopsies were done in 13 patients out of a total of 63 heart transplant recipients. All of the patients were receiving cyclosporine and azathioprine (Imuran) and had received prophylactic antithymocyte globulin or murine antihuman mature T cell (OKT3). Eight of the patients were receiving steroids, and five of the patients had been weaned off steroids. A fever of greater than 38.5 degrees C was present in all 13 patients. Hypoxia, defined as PO2 less than 60 on room air, was present in 11 of the 13 patients. One patient had to be intubated before surgery for respiratory failure. The chest x-ray film most often revealed bilateral interstitial infiltrates. The operative approach was by a small anterior thoracotomy in 12 patients and a posterolateral thoracotomy in two patients. A definitive diagnosis was made in 11 of the 14 open lung biopsies: three patients had Legionella, one had cytomegalovirus (CMV), one had a Pseudomonas infection, three had Pneumocystis, one patient had CMV and Pneumocystis, one patient had a pulmonary infarct, and one patient had a pulmonary infarct and CMV. Specific therapy was instituted in all these patients. In the three patients in whom no specific diagnosis was made, therapy was also changed and the use of antibiotics discontinued. There was no mortality in this group. Morbidity was minimal. No patient had excessive bleeding, and none of the patients required the transfusion of blood or blood products. Three patients required mechanical ventilatory support for longer than 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Immunosuppressive efficacy of vincristine in heart transplantation: a preliminary report.

Because vincristine has immunosuppressive activity in animal models, has specific cytotoxic effects on lymphocytes, and does not have overlapping toxicity with other immunosuppressive agents, we designed a prospective randomized trial to evaluate the efficacy of the addition of vincristine to standard immunosuppressive therapy in heart transplantation. Patients received equine antithymocyte globulin for the first week or murine antihuman mature T cell (OKT3) monoclonal antibody for the first 2 weeks after transplantation and were maintained on azathioprine and cyclosporine. A steroid pulse was administered 1 day after completion of antithymocyte globulin or OKT3 monoclonal antibody and tapered off over 21 days. Vincristine was given at 0.025 mg/kg intravenously for eight dosages over 12 weeks, beginning 2 days after completion of antithymocyte globulin or OKT3 monoclonal antibody. Fifty-two patients were randomized (26 were given vincristine, and 26 were not). The addition of vincristine to the regimen of patients receiving antithymocyte globulin resulted in significantly fewer episodes of rejection at 1 month (vincristine, 0.2 +/- 0.1; no vincristine, 1.2 +/- 0.2; p less than 0.001), at 3 months (vincristine, 1.2 +/- 0.1; no vincristine, 2.5 +/- 0.3; p less than 0.001), and at 6 months (vincristine, 1.9 +/- 0.2; no vincristine, 2.9 +/- 0.3; p less than 0.001). It also resulted in significantly more patients being successfully weaned off daily steroids (vincristine, 67%; no vincristine, 20%; p = 0.04). The addition of vincristine to the regimen of patients receiving early rejection prophylaxis with OKT3 monoclonal antibody did not alter rejection incidence or steroid usage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Inotropic effects of histamine in human myocardium: differentiation between positive and negative components.

Histamine is known to enhance the contractility of the human myocardium in vitro. We have observed that when the H2-receptor antagonist cimetidine (or ranitidine) blocks the positive inotropic effect of histamine in spontaneously beating pectinate muscles isolated from human right atrial appendage, a negative inotropic effect is unmasked. This decrease in contractility is independent of changes in rate, as it occurs in preparations paced at constant rate, is mimicked by the H1-receptor agonist 2-(2-thiazolyl)-ethylamine (ThEA) and is abolished by the H1-antagonist pyrilamine. Thus, the negative inotropic effect of histamine appears to be mediated by H1-receptors. Our data indicate that the inotropic response of the human myocardium to histamine consists of two opposing components: an increase in contraction, mediated by H2-receptors, and a decrease in contraction, mediated by H1-receptors. Given the widespread use of H2-blockers and the multitude of clinical conditions in which histamine is released, there may well be circumstances in which an H1-response predominates. This could result in a decrease in myocardial contractility.

Cimetidine↗