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Biomedical subjects

R C Lillehei

Publications and source records attributed to R C Lillehei.

At least 19 recordsLinked to original sources

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 granulocyte-mediated endothelial cytotoxicity, while aspirin is without effect on these modalities. We propose that ibuprofen's 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.

Animals

Serum complement levels in canine endotoxin shock: relation to survival and to corticosteroid therapy.

Recent studies suggest prominent roles of the complement system in endotoxin shock and steroid-complement interactions in its treatment. To assess further the potential importance of the complement system in this condition, we measured serum total complement levels in dogs after an IV bolus of 1.5 mg/kg DIFCO E coli endotoxin. Dogs were assigned to control (C), dextran40 (LMD), or LMD + steroid groups. Corticosteroids, given IV 15 min after endotoxin, were 1) methylprednisolone sodium succinate (MPSS), 30 mg/kg; 2) dexamethasone sodium phosphate (DSP), 6 mg/kg; 3) hydrocortisone sodium succinate (HSS), 150 mg/kg; or 4) hydrocortisone sodium phosphate (HSP), 150 mg/kg. LMD was infused to maintain BP greater than 60% of preshock levels during the 4 h of monitoring. Survival rates at 48 h were C--7/24 (29%); LMD--3/12 (25%), MPSS--11/19 (59%) (P less than 0.1); DSP--9/14 (64%) (P less than 0.05); HSS--3/10 (30%) HSP--5/10 (50%). Within 15 min of endotoxin administration, serum complement titers fell at least 48% in all groups. Complement levels returned to the preshock range in only the LMD group. Mean complement levels of all survivors and nonsurvivors were nearly identical throughout the acute experiment. The results indicate that survival in canine endotoxin shock, with or without corticosteroid therapy, is not related to normalization of serum total complement titers during the first few hours after endotoxin injection.

Adrenal Cortex Hormones

Experiences with allopurinal in canine endotoxin shock.

Allopurinol, a xanthine-oxidase inhibitor and potential cell-stabilizing compound, was studied as a possible therapeutic agent in canine endotoxin shock. Circulatory collapse was produced in anesthetized mongrel dogs by IV administration of an LD75 dose of endotoxin. Treatment, with dextran alone, or with dextran and an IV bolus of allopurinol, was initiated 15 minutes after the onset of shock. The administration of 25, 50, or 100 mg/kg of IV allopurinol, accompanied by adequate volume replenishment, produced a significant reduction in the total peripheral vascular resistance and significant increases in cardiac output, blood glucose concentration, and arterial lactate concentration. Survival was not enhanced by allopurinol therapy, and allopurinol administration in normal dogs did not affect the vascular tone or the arterial lactic acid concentration. There was a transient hyperglycemic response and a decrease in the cardiac index in normal animals. The infusion of a postassium-insulin solution, in association with 100 mg/kg of allopurinol, did not significantly improve survival. In summary, although a number of potentially beneficial hemodynamic and metabolic effects were observed following allopurinol administration, survival in canine endotoxin shock was not enhanced.

Allopurinol

Basic requirements of pancreatic mass for transplantation.

In canine pancreas autografts, more than 20% (30% to 40%) of the pancreatic mass (body and distal head or proximal tail) is required for the establishment of a satisfactory endocrine response. Transplantation of 20% of the pancreatic mass did not result in an adequate restoration of the endocrine function. We believe that this study gives a practical answer to the question of how much pancreatic mass is necessary for the establishment of normal functional response after transplantation. This autotransplantation model precludes the determination of the content and volume of transplanted pancreatic islets. Thus, our model indicates the requirements of the pancreatic mass of the specific anatomic areas that were transplanted, but does not indicate the actual amount of transplanted islets.

Animals

Enhancement of local immune response in the treatment of experimental peritonitis.

We conclude from these experiments that the host defense in peritoneal infections rests largely on the phagocytic cells attracted into the peritoneal cavity by the offending organism, and that an increase in the number of available phagocytes by pretreatment with chemotactic substances protects against lethal peritoneal infections. There seems to be a direct relationship between the number of available phagocytes in the peritoneal cavity at the time of inoculation and the reduction of mortality in experimental peritonitis (Fig. 1).

Animals

Effects of pulsatile perfusion pressure and storage on hearts preserved for 24 hours under hypothermia, for transplantation.

Canine hearts preserved for 24 hours under hypothermic pulsatile perfusion at a systolic pressure of 25 mm Hg had better perfusion and transplantation survival results than hearts perfused at 50 or 80 mm Hg. Also, hearts perfused at a systolic pressure of 25 mm Hg did better than simple hypothermically stored hearts or fresh allografts. These findings indicate that hearts are adequately perfused for 24 hours under hypothermia for transplantation at a systolic pressure of 25 mm Hg.

Animals

Effects of glucocorticosteroids in patients undergoing coronary artery bypass surgery.

Glucocorticosteroid, methylprednisolone sodium succinate (MPSS), 30 mg/kg of body weight, or dexamethasone sodium phosphate (DSP), 6 mg/kg of body weight, were given intravenously to 60 patients, divided into two groups of 30 45 minutes prior to cardiopulmonary bypass for coronary artery bypass. These two groups were compared with 30 patients in a control group receiving a placebo and undergoing the same surgery. The study was carried out in a double-lind fashion. Patients receiving MPSS had a significantly higher cardiac index in both the preoperative and postoperative periods. This was accompanied by a decreased peripheral resistance. Patients receiving either MPSS or DSP also showed some evidence for the "washout" phenomenon indicating the possibility of better microcirculatory flow. Gluconeogenesis may have been enhanced in both groups receiving MPSS or DSP, but the evidence was greater in thos patients receiving MPSS. There were no hospital deaths in any of the three groups totaling 90 patients.

Adult

Preservation of the pancreas for transplantation.

Twenty-four hour hypothermic bloodless pulsatile perfusion of the canine pancreas did not have any detrimental effect on the survival rate of minimally immunosuppressed recipients. On the contrary, there was a favorable trend toward improved long term survival of perfused and transplanted pancreas. Fresh grafts or those stored under hypothermia survived for shorter periods of time than did the perfused grafts. Apancreatic dogs survived only for a few days after pancreatectomy. Hypothermic pulsatile perfusion appeared to be a better method of preservation than hypothermic storage of pancreatic allografts.

Amylases

Surgical treatment of pancreatic pseudocysts. Analysis of 119 cases.

A review was made of the hospital records of 119 patients with pancreatic pseudocysts. Alcoholism, biliary disease and abdominal trauma were the most common antecedent conditions. Abdominal pain was the most frequent symptom, and abdominal tenderness or mass were the most common physical findings. Abdominal echography and contrast study of the upper gastrointestinal tract were diagnostic in 90% of the patients examined. X-rays of the chest, colon, and biliary tract revealed pathology in 30--40% of the patients. Compared to patients with uncomplicated pseudocyst, patients who were acutely ill at the time of external drainage had twice the incidence of postoperative complications. Each subgroup experienced similar, high rates of postoperative death and pseudocyst recurrence. Both groups of patients treated by internal drainage had lower rates of postoperative morbidity, mortality, and pseudocyst recurrence than patients with uncomplicated pseudocysts undergoing external drainage. External drainage should be used in all patients with immature pseudocysts and in critically ill patients with mature pseudocysts not juxtaposed to a portion of the upper gastrointestinal tract. Internal drainage is a safer and more effective procedure in most other patients with mature pseudocysts, irrespective of the clinical status of the patient.

Adolescent

Septic shock associated with operations for colorectal disease.

The hospital records of 24 patients with septic shock associated with the need for surgical treatment of diseases of the colon and rectum were reviewed. In this group of patients shock was caused by gram-negative or anaerobic microorganisms. The sources or infection were the abdomen, chest, and urinary tract. Nineteen (79 per cent) patients survived the acute shock episode, but only four (16 per cent) were permanent survivors. The 15 patients who died following resuscitation from shock succumbed to continuing infection and/or multiple organ failure. Although the timing of treatment did not affect immediate survival, long-term survival occurred only among those patients treated early in the course of shock. Accordingly, the pathophysiology of early septic shock is presented, and the need to recognize and treat the condition at this stage is emphasized. In addition, the author's current treatment protocol, with which they have been able to achieve 85 per cent acute and 60 per cent long-term survival, is discussed.

Adolescent

Zymosan-induced resistance to endotoxin and hemorrhagic shock.

Improved surgical techniques and judicial use of available antibiotics have reduced the number of postoperative complications over the past decade. However, septic and hemorrhagic shock occur all too frequently, and each carries with it an appreciable morbidity and mortality. Endotoxins and hemorrhage are both known to suppress the phagocytic activity of the reticuloendothelial system (RES). On the other hand, zymosan, a yeast (Saccharomyces cerevisiae) cell wall preparation administered intravenously, results in temporary RES hyperplasia and increased phagocytic activity. Dogs were pretreated with zymosan to determine the degree of RES stimulation and protection against endotoxin and hemorrhagic shock attainable. Twenty-five dogs received intravenous zymosan (10 mg/kg) on days 1, 2, and 3. Another 24 dogs served as controls. On day four, one-half the animals in each group received E coli endotoxin (1.5 mg/kg) intravenously. The other animals underwent two hours of hemorrhagic shock at a mean blood pressure of 40 mm Hg. Seventy-two hour survival was as follows: Endotoxin treated, 66.7% (8/12); endotoxin control, 27% (3/11); hemorrhagic treated, 53.3% (8/15); and hemorrhagic control, 28.6% (4/14). Hemodynamic, metabolic, and lysosomal enzyme parameters were evaluated. No zymosan toxicity was observed. These findings suggest that an RES stimulant such as zymosan could be incorporated as preoperative adjunctive therapy to induce resistance to these shock syndromes in the elective surgical patient.

Animals