Louis D. Homer

Diminished pressor response to exogenous norepinephrine and angiotensin II in septic, unanesthetized rats: Evidence for a prostaglandin-mediated effect

Despite elevated plasma concentrations of norepinephrine (NE), septic patients generally have normal or low mean arterial pressure (MAP) and systemic vascular resistance. We tested the hypothesis that sustained sepsis in rats results in relative hyporesponsiveness to the pressor actions of NE and angiotensin II (AII). Sprague-Dawley rats were studied 48 hr after sepsis was induced by cecal ligation. Sham-operated rats served as controls. Carotid artery and jugular venous catheters were placed under halothane anesthesia and the rats were allowed to waken fully in restraining cages. Peak increments in MAP were measured after bolus iv doses of NE (0.125-8.0 micrograms/kg) or AII (0.0125-0.5 microgram/kg). Some rats were pretreated with indomethacin (5 mg/kg, iv) 30 min prior to the dose-response study. Data were fitted to a two-parameter hyperbolic function and the resulting curves were compared by analysis of variance. Compared with controls, sepsis decreased the pressor response to both NE (P less than 0.0001) and AII (P less than 0.0001). Indomethacin restored responsiveness toward normal for both pressor agents (P less than 0.0001). It is concluded that sepsis is associated with hyporesponsiveness to two chemically dissimilar vasopressors and that this phenomenon may be mediated by prostaglandins.

Benefits from improved oxygen delivery of blood in shock therapy.

Elevating erythrocyte 2,3-DPG and P50 has been proposed as a means of improving the delivery of oxygen by transfused blood. Fourteen baboons were resuscitated from hemorrhagic shock with either (A) 21-day-old blood with low P50 (20.2 mmHg ± SE 1.4) and 2,3-DPG (1.03 mm/liter ± 0.39), or (B) freshly shed autologous blood incubated 1 hr with pyruvate, inosine, glucose, phosphate, and adenine to elevate P50 (36.9 mmHg ± 1.2) and 2,3-DPG (5.00 mm/liter ± 0.33). Regressions of measured variables against P50 revealed: expected cardiac output down 18% for the observed increase in the P50 of the treated group; oxygen consumption up 9%; arterio-venous oxygen difference up 33%; and cardiac work down 24%. The P50 regression coefficients for these variables were different from zero (p < 0.05). It is concluded that administering blood with elevated 2,3-DPG and P50 furnished adequate tissue oxygenation at lower cardiac output and cardiac work than did 21-day-old blood.

Heparin versus citrate anticoagulation in autotransfusion.

Abstract Autotransfusion from controlled hemorrhage into a pelvic extraperitoneal pocket was performed in 19 baboons using a commercial autotransfusion apparatus. Nine heparinized animals (H) were compared to ten in which extracorporeal citrate plus cell-washing (CW) was employed. Serum hemoglobin levels were elevated in the H group but not in the CW group during autotransfusion. Elevated PT and PTT developed in both groups during autotransfusion with return to normal at 24 hr. Serum fibrinogen levels remained normal in the H group but were depressed in the CW group. Fibrin split products were more elevated in the H group than in the CW group. Interestingly, in the CW group total proteins were depressed with a disproportionate loss in the non-albumin fraction. The groups never differed from each other with respect to hematocrit, platelet aggregability, and serum total hemolytic complement levels. Both techniques provided adequate hypocoagulability for autotransfusion. The elevated PT, PTT , fibrin split products ( FSP ) and decreased fibrinogen represent a clear picture of disseminated intravascular coagulopathy in the H group. The lesser changes in the CW group suggest that the combination of citrate plus plasmaphoresis kept any intravascular coagulopathy at a more tolerable level in the CW group. The lower plasma hemoglobin levels in the CW group decreased the threat to renal function in the presence of marked hemolysis. These findings suggest that extracorporeal citrate plus cell-washing is an attractive alternative to heparinization of patients for autotransfusion.

The Relationship of Circulating Endogenous Endotoxin to Hemorrhagic Shock in the Baboon

Experiments were carried out to test the hypothesis that during hemorrhagic shock endotoxin enters the circulation from ischemic bowel by way of the portal venous system and is then associated with irreversibility of the hemorrhagic shock state. After placement of sampling catheters in the portal vein, right atrium, and aorta, 14 awake, restrained baboons were subjected to 1 hour of hemorrhagic shock at a mean arterial pressure (MAP) of 60 torr followed by a second hour at 40 torr MAP. Six animals were resuscitated with Ringers lactate and their shed blood; 8 were maintained hypotensive until death. Serial blood samples were analyzed for the presence of endotoxin. Endotoxemia was found infrequently, with no greater incidence (p > 0.6) in portal venous samples than in systemic blood, so these data were pooled for further analysis. Furthermore, endotoxemia was no more frequent (p > 0.6) late in shock than it was in early shock or during the baseline period. Autopsy showed no evidence of ischemic damage to the splanchnic viscera. It was concluded that spontaneous endogenous entotoxemia is not a common feature of hemorrhagic shock in baboons and is not related to the duration or degree of severity of hemorrhagic shock in this subhuman primate species.

Comparison of inulin and chromium-EDTA spaces in the nephrectomized baboon.

Summary The volumes of distribution of 14C-labeled inulin and Cr-EDTA have been compared in the nephrectomized baboon. The volume of distribution of inulin averaged 18.5 (±2.3)% of body weight with a range from 14.1 to 23%. Similar volumes for Cr-EDTA averaged 21.4 (±3.7)% of body weight with a range from 14.4 to 26.6%. No significant (p > 0.05) difference between the inulin and Cr-EDTA volumes was demonstrated. Plasma concentration of the isotope did not level off but continued to fall during the experiment. The gradual falling plasma-concentration curve was extrapolated to zero time in order to calculate extracellular fluid volume. It is concluded that when the extrapolation technique is used, the volumes of distribution of both inulin and Cr-EDTA adequately reflect the extracellular fluid volume in the nephrectomized baboon.