The American journal of physiology
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A volume-resuscitated porcine endotoxin shock model was used to evaluate the effect on organ blood flow of increasing systemic arterial blood pressure with vasopressors. Administration of 0.05-0.2 mg/kg of Escherichia coli endotoxin (E) reduced mean arterial blood pressure (MAP) to 50 mmHg, decreased systemic vascular resistance to 50% of control, and did not change cardiac output or heart rate. Blood flow to brain, kidney, spleen, and skeletal muscle was reduced during endotoxin shock, but blood flow to left ventricle, small and large intestine, and stomach remained at pre-endotoxin levels throughout the study period. ⋯ Kidney, splanchnic, and skeletal muscle blood flow did not change with vasopressor administration. The dose of norepinephrine required to increase MAP by 20-25 mmHg during E shock was 30 times the dose required for a similar increase in MAP in animals not receiving E. We conclude that hypotension in the fluid resuscitated porcine E shock model is primarily the result of peripheral vasodilatation, that the vascular response to vasoconstrictors in this model is markedly attenuated following E administration, that blood pressure elevation with norepinephrine, dopamine, and phenylephrine neither decreases blood flow to any organ nor increases blood flow to organs with reduced flow, and that norepinephrine, dopamine, and phenylephrine affect regional blood flow similarly in this model.
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Potentiated adrenal responses to the second of two identical hemorrhages spaced 24 h apart are seen in the pentobarbital sodium-anesthetized dog. Although pentobarbital effectively reduces environmental influences, barbiturates affect hemodynamic and hormonal responses and preclude normal daily feeding and activity patterns. To determine the role of anesthesia in these earlier results, we prepared awake trained dogs with chronic adrenal venous catheters. ⋯ No differences were detected in the hemodynamic response to bleeding on the 2 days. Whereas potentiation was seen in epinephrine and norepinephrine responses to a second 10% hemorrhage in anesthetized dogs, larger hemorrhage was needed to elicit this effect in awake dogs. Thus potential adrenal medullary responses to repeated hemorrhage occur in both awake and pentobarbital-anesthetized dogs, but important differences in the threshold and manifestation of this effect are seen.
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The effect of repetitive periods of coronary occlusion on myocardial adenine nucleotides, lactate, and infarct size was studied. In one series of dogs, the circumflex artery was occluded for one, two, or four 10-min episodes, each separated by 20 min of reperfusion. Hearts were excised and sampled for metabolic assays after one or more periods of ischemia before or after reperfusion. ⋯ Necrosis was observed in only one of six dogs and, in this dog, was only 1.5% of the anatomic area at risk. Thus intermittent reperfusion prevents cumulative metabolic deficits and myocardial ischemic cell death, perhaps by restoring the capacity for high-energy phosphate (HEP) production and/or washing out deleterious catabolites. A first episode of ischemia also slows HEP utilization in subsequent episodes.
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Assessment of cardiac protein metabolism in thyroxine-induced left ventricular hypertrophy requires measurements of both protein synthesis and degradation. In vivo protein degradative rates can best be measured as the difference between rates of protein synthesis and growth. Accordingly, rates of left ventricular protein accumulation were determined in growing rabbits, and in animals administered intravenous L-thyroxine (200 micrograms X kg-1 X day-1) for up to 15 days. ⋯ Thyroxine administration produced left ventricular hypertrophy by increasing the rate of total protein synthesis (35.7 +/- 2.0, 71.0 +/- 7.0, and 62.6 +/- 4.0 mg of left ventricular protein synthesized per day for 0-, 3-, and 9-day, thyroxine-treated rabbits, respectively). However, the increased rate of total protein synthesis was greater than the measured rate of total protein accumulation (8.1 vs. 15.9 mg protein/day for euthyroid and thyroxine-treated animals), indicating that left ventricular protein degradative rates were increased as well. These studies indicate that accelerated proteolysis may be important in the molecular and architectural remodeling of the rapidly hypertrophying heart during thyrotoxicosis.
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This study examined the effects of extracellular alkalosis on the metabolism and performance of perfused rat hindlimb muscles during electrical stimulation. Three acid-base conditions were used: control (C, normal acid-base state), metabolic alkalosis (MALK, increased bicarbonate concentration), and respiratory alkalosis (RALK, decreased PCO2). A one-pass system was used to perfuse the hindlimb via the femoral artery for 20 min at rest and during 5 min of tetanic stimulation via the sciatic nerve. ⋯ However, alkalosis resulted in an enhanced La- release from working muscle (peak La- release: C, 15.5 +/- 1.1; MALK, 19.7 +/- 1.6; RALK, 18.3 +/- 2.2 mumol/min), and a 15-20% reduction in intramuscular La- accumulation. Alkalosis had no effect on muscle creatine phosphate and ATP concentrations. Thus, in the perfused rat hindlimb, alkalosis was not associated with changes in tetanic force or glycolysis, but La- release from the working muscle was enhanced by increased extracellular pH and bicarbonate.