Richard C. Lillehei

The modern treatment of shock based on physiologic principles

The hemodynamic disturbances resulting from shock due to hemorrhage or endotoxins and the results of several methods of treatment are presented. The experimental data indicate that vasopressors intensify the visceral vasoconstriction, ischemia, and loss of capillary integrity characteristic of severe shock. The benefical effects of corticosteroids or phenoxybenzamine combined with volume replacement are indicated.

Effects of allopurinol, propranolol and methylprednisolone on infarct size in experimental myocardial infarction

With use of a canine model of occlusion of the left anterior descending coronary artery and an intracellular lactic dehydrogenase stain to measure infarct size directly, the effects of allopurinol, methylprednisolone sodium succinate and propranolol were studied. Allopurinol did not influence the extent of myocardial necrosis, whereas both methylprednisolone and propranolol significantly reduced myocardial infarct size. Possible mechanisms of action and clinical applicability of these agents are discussed.

Late effect of pancreatic duct ligation on beta cell function

Abstract The effect of pancreatic duct ligation on endocrine function of the pancreas has been studied in the dog for a period of more than seven months. Endocrine insufficiencies were observed in ten of the fifteen dogs (67 per cent) between forty-five and 222 days after ductal ligation as assessed by fasting blood sugar levels, circulating plasma insulin levels, and intravenous glucose tolerance tests. It has been suggested that severe fibrotic degeneration of the exocrine tissue could lead to secondary endocrine dysfunction. The use of a pancreas with free drainage of the pancreatic secretion as an endocrine transplant for the treatment of diabetes mellitus is therefore recommended.

Ibuprofen inhibits granulocyte responses to inflammatory mediators. A proposed mechanism for reduction of experimental myocardial infarct size

The use of nonsteroidal antiinflammatory agents to reduce myocardial infarct size has demonstrated a dichotomy between ibuprofen, which reduces myocardial infarct size, and aspirin, which does not. A feline model of coronary ischemia using ligation of the anterior descending artery demonstrated that intravenous ibuprofen (2.5–20 mg/kg) given immediately and 2 h after ligation significantly decreased (by about 40%) myocardial infarct size. In contrast, aspirin did not diminish infarct size at any achieved dose; in fact, at some doses it tended to increase infarct size. In vitro studies with purified granulocytes demonstrated a similar dichotomy between ibuprofen and aspirin. Ibuprofen inhibits granulocyte aggregation, superoxide production, lysosomal enzyme release, and granulocytemediated endothelial cytotoxicity, while aspirin is without effect on these modalities. We propose that ibuprofens beneficial effect in experimental myocardial ischemia is related to its ability to inhibit activated granulocytes and thus to diminish myocardial cell death in experimental myocardial infarction.

Prevention of urological complications after kidney transplantation.

THE MORTALITY rate following kidney transplantation has been gradually reduced during the past few years, as knowledge of the management of the operative procedures and immunosuppressive agents has accumulated. Death in the early posttransplantation period is now almost completely preventable,14 particularly by the prevention of urological complications. The present report is an analysis of the urological complications associated with 200 consecutive kidney transplantations at the University of Minnesota, and an illustration of how a method of urinary tract reconstruction has eliminated death from this cause in the last 100 transplantations.

Orthotopic allotransplantation of the pancreas

Abstract A technic for orthotopic allotransplantation of the whole pancreas (including duodenum) has been successfully carried out with preservation of both endocrine and exocrine function of the transplant. The operative technic is described in detail and preliminary results with twenty-five transplantation procedures are given. Mean survival time of the dogs after orthotopic transplantation was five and a half days (range from four to nine days). Factors affecting the general condition of the recipient proved to be more decisive for survival than local complications.

PHYSIOLOGY AND THERAPY OF BACTEREMIC SHOCK. EXPERIMENTAL AND CLINICAL OBSERVATIONS.

OR THE past few years we have studied irreversible shock in the dog caused by prolonged hemorrhage, endotoxins or vasopressor agents. The dog has been used exclusively in these studies in an attempt to make a continuing study in one species; although there are many individual differences between the various species of mammals, the general physiologic principles are surprisingly constant among the mammals. Gram-negative bacterial shock or bacteremic shock was first described over 50 years ago in the German literature.’ Much has since been learned about this type of shock; but most important is the fact that the lipopolysaccharide or endotoxin within the cell wall is responsible for the hypotensive effects of these gram-negativ,e bacteria; hence the term endotoxin shock.2 Endotoxin causes shock by its sympathomimetic-like effect resulting in intense vasospasm in small arteries and veins in selected areas of the body, more particularlyin the I-isceral organs of a variety of species of

Problems in absorption and immunosuppression after entire intestinal allotransplantation

Abstract Orthotopic entire small intestine allografts were transplanted in twenty dogs. Ten of these animals received immunosuppressive drugs. Allograft function was compared with that of other dogs subjected to complete intestinal denervation and lymphatic interruption. Dogs with denervated intestine showed decreased d-xylose absorption with reversal to normal rates within four months. Groups receiving allografts also showed depressed function which persisted for up to five weeks. Interestingly, dogs with untreated allografts showed no significant pathologic changes even though survival ranged from one to four weeks. In contrast, some dogs who received immunosuppressive drugs showed manifestations of organ rejection. Although we could not clearly demonstrate a graft versus host reaction in untreated allografts, it appears that entire small intestinal allografts, in the absence of these immunosuppressive drugs, can precipitate such a reaction. This phenomenon is believed to be related to the abundant lymphatic tissue found in the intestine.

In vitro preservation of whole organs by hypothermia and hyperbaric oxygenation.

Abstract Canine whole organs (kidney, heart, small bowel) have been successfully preserved for 48 hours in an in vitro viable state by the combination of hypothermia (2 ° to 4 °C) and hyperbaric oxygen up to 7.9 atmospheres absolute. We have presented here the genesis of the method, described its purpose, and detailed the results of individual experiments, as well as citing pertinent historic data. Clinical applications have also been cited in human renal homotransplantation studies.

Pancreatic transplantation without duodenum in the dog

Abstract Our study has shown that it is possible to maintain normal exocrine and endocrine function in pancreatic heterotopic auto- and allotransplants without duodenum in the dog using a small periampullary duodenal cuff sutured directly to jejunal mucosa. The described technic has been used to prepare human cadaver donors and further clinical trials are anticipated.