Effect of hypothalamic stimulation on mucus production in vagally innervated and denervated gastric pouches.
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Animals↗
Biomedical subjects
J M Pearl
Publications and source records attributed to J M Pearl.
Hypothalamic influence on pancreatic blood flow and secretion.
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Animals↗
Leukocyte-depleted reperfusion of transplanted human hearts: a randomized, double-blind clinical trial.
Standard methods of myocardial preservation for heart transplantation have generally provided good results. Preservation times beyond 3 hours, however, have been associated with decreased survival. Leukocyte-mediated reperfusion injury is partly responsible for decreased graft function after prolonged graft ischemia. Leukocyte-depleted reperfusion has been shown experimentally to improve cardiac function after cold ischemic arrest. To determine the efficacy and safety of leukocyte-depleted reperfusion, 20 patients were enrolled in a randomized, double-blind clinical trial to be treated with either warm whole blood reperfusion (group I; n = 9) or warm leukocyte-depleted blood reperfusion (group II; n = 11). Reperfusion with leukocyte-depleted blood or whole blood was carried out for 10 minutes, with enriched cardioplegic solution added for the first 3 minutes of reperfusion. The mean donor and recipient age and the ischemic time (142 versus 153 minutes) were not significantly different between the two groups. Coronary sinus release of creatinine phosphokinase-MB 5 minutes after reperfusion was significantly less in group II (1.65 EU/min) than in group I (3.83 units/min; p = 0.05). Thromboxane B2 release was also significantly less (p = 0.05) in group II (33.6 pg/min) than in group I (67.0 pg/min). All hearts functioned adequately in both groups. The duration of inotropic support was shorter in group II than in group I, but the difference was not statistically significant. Postoperative hemodynamics, rejection episodes, and infectious complications were also not significantly different between groups in a mean follow-up of 9 months. Mean ejection fraction 1 month after operation was 65% in both groups. One early death occurred at 66 days secondary to infection; two late deaths occurred in group II, both from rejection. Leukocyte-depleted reperfusion is safe and easily applied in the operating room. Furthermore, leukocyte-depleted reperfusion decreases biochemical evidence of reperfusion injury. Although not influencing postoperative cardiac function when the ischemic time is short, less than 3 hours, leukocyte-depleted reperfusion may prevent significant reperfusion injury and improve posttransplantation graft function when ischemic times are long. Safe extension of the ischemic time would expand the donor pool and allow for better crossmatching.
Adult↗
Heart-lung xenotransplantation in primates.
Heart and heart-lung xenografts are a potential solution to the shortage of donors. Concern over the adequacy of conventional immunosuppression in prevention of xenograft rejection, however, has hindered their use. Cyclosporine has not been successful in suppressing the rejection process in cardiac xenotransplantation, and other methods of immunosuppression need to be investigated. Therefore we studied the effect of preoperative total lymphoid irradiation (TLI) in combination with cyclosporine in a primate heart-lung xenograft model using cynomolgus monkey donors and baboon recipients. Heart-lung grafts were harvested from donors and transplanted orthotopically in baboons with use of cardiopulmonary bypass. Recipients were treated in one of three groups: (1) cyclosporine and steroids (controls), (2) cyclosporine and steroids plus TLI 20 Gy, or (3) cyclosporine, steroids, antithymocyte globulin, and TLI 6 Gy. Mean survival time of the baboons treated with cyclosporine and steroids was 8 +/- 0.6 days. The group receiving 20 Gy TLI had prohibitive perioperative mortality; however, one baboon lived an additional 90 days, and at autopsy the heart showed minimal rejection. Treatment with TLI at 6 Gy in combination with cyclosporine, antithymocyte globulin, and steroids comparatively prolonged survival (16 +/- 7.8 vs 8 +/- 0.6 days; p less than 0.001), and all animals in this group died of infection, with only minimal evidence of heart rejection noted in animals surviving 30 days. We conclude that the addition of TLI and antithymocyte globulin to cyclosporine-based standard immunosuppression is a potent immunosuppressant in heart-lung xenotransplantation; nevertheless, infection remains a common complication.
Animals↗