Potential adaptations to acute hypoxia: Hct, stress proteins, and set point for temperature regulation.

Severe, intermittent hypoxia (hypoxic conditioning, HC) increases survival time during subsequent lethal hypoxia in mice. This protective effect was blocked by naloxone, suggesting an opioid-dependent mechanism. We proposed and evaluated three potential mechanisms of this acute adaptation: 1) increased hematocrit (Hct), 2) protein synthesis, and 3) decreased set point for temperature regulation (set point). Increased hematocrit is a well-studied adaptation to chronic hypoxia and could be acutely initiated by sympathetically mediated splenic contraction. Survival during stress can be prolonged by synthesis of stress proteins. We tested this hypothesis using two protein synthesis inhibitors, anisomycin and cycloheximide. Our third hypothesis is that set point is decreased after HC. A regulated decrease in body temperature would lower oxygen demand during hypoxia. Our studies indicate that hematocrit and protein synthesis are not dominant mechanisms of acute adaptation to hypoxia. However, we have observed a naloxone blockable decrease in set point after HC, supporting a mechanism in which acute adaptation involves an endogenous opioid-dependent decrease in set point. These studies also demonstrate that set point could be a more dominant contributor than body temperature to hypoxic tolerance.

Evolution of synchronous renal and pancreatic transplantation.

The utilization of pancreatic transplantation as a therapeutic option in type I diabetics is dependent on demonstrating its safety and efficacy. A protocol for synchronous renal and segmental pancreatic transplantation, utilizing pancreaticocystostomy, was initiated in February 1985, and through December 1988, 44 patients (mean age 34.8 years) received dual allografts. At last follow-up, 25 patients had functioning kidneys, and 17 patients were insulin independent 4 to 50 months after transplantation, with a mean fasting blood glucose level of 86 mg/100 ml. As our experience increased, three factors were identified as reducing pancreatic allograft and patient survival: vascular thrombosis, inadequate control of pancreatic secretions, and coronary artery disease. As a result, our protocol was modified to include postoperative heparin, external stenting of the pancreaticocystostomy, and dipyridamole thallium testing to screen for coronary artery disease. With these modifications, technical failures and postoperative morbidity were reduced with a resultant increase in 6-month graft and patient survival. These results provide impetus for considering synchronous renal and pancreatic transplantation as a therapeutic option for type I diabetics with end-stage renal disease.