Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protamine sulfate (PS), used to neutralize the anticoagulant effect of heparin, is often associated with systemic hypotension. Whether this hypotension is secondary to a depression of myocardial function is not clear. The present study tested the hypothesis that systemic hypotension was accompanied by a depression in myocardial function and examined the possible role of histamine in mediating the cardiovascular response to PS. Seven conditioned dogs were chronically instrumented with pressure and ultrasonic dimension transducers. Studies were conducted under halothane anesthesia 7 to 10 days after instrumentation. Cardiac contractility was assessed using the slope, Ees, of the linear regression of the left ventricular end-systolic pressure-diameter relationship. Intravenous infusion of PS, 5 mg/kg, when given in periods of less than 30 seconds, decreased systemic arterial pressure by 45% (from 101 +/- to 54 +/- 5 mm Hg) without change in heart rate. Cardiac output decreased by 22% from control and the slope Ees decreased by 37% (from 14.5 +/- 1.2 to 8.7 +/- 1.4 mm Hg/mm). Systemic vascular resistance decreased by 34% (from 2581 +/- 121 to 1712 +/- 200 dyne.s.cm-5). The cardiovascular depression caused by PS was transient and could not be reproduced by a repeated dose given within a 60-minute period. Antagonists of histamine (diphenhydramine and cimetidine) could not attenuate the PS-induced cardiovascular depression. This depression was independent of preheparinization and did not occur when PS was infused slowly over a 2-minute period. The data clearly demonstrate negative inotropic and vasodilator effects of PS following rapid administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of hypotension following rapid infusion of protamine sulfate in anesthetized dogs. 156 2

Protamine sulfate often causes hypotension during heparin neutralization. The concept of ventricular-arterial coupling was applied to determine whether a negative inotropic effect or a vasodilating effect of protamine was the major contributing factor to this hypotension. Thirty-five patients who underwent cardiac operations were studied during operation by measuring instantaneous left ventricular pressure and aortic flow to examine the end-systolic pressure-volume relationship. We obtained end-systolic elastance and effective arterial elastance values in a beat-to-beat fashion with a single-beat estimation method. In 28 of the 35 patients (80%), mean arterial pressure decreased more than 10 mm Hg with protamine infusion. Parameters were compared at the following three points: before a decrease in mean arterial pressure (control), at maximally decreased mean arterial pressure (maximum), and at a middle point between control and maximum values (midpoint). At both midpoint and maximum, mean arterial pressure decreased significantly (control 79.6 +/- 12.6 mm Hg, midpoint 66.5 +/- 10.8 mm Hg, maximum 52.7 +/- 9.9 mm Hg; p < 0.01). Similar changes were observed in effective arterial elastance (control 2.00 +/- 0.75 mm Hg/ml, midpoint 1.60 +/- 0.53 mm Hg/ml, maximum 1.31 +/- 0.46 mm Hg/ml; p < 0.01). Although the decrease in end-systolic elastance at midpoint (control 3.08 +/- 1.61 mm Hg/ml, midpoint 2.92 +/- 1.68 mm Hg/ml) did not reach statistical significance, end-systolic elastance significantly decreased at maximum (2.63 +/- 1.46 mm Hg/ml; p < 0.01). Continuous measurements showed that the decreases in mean arterial pressure and effective arterial elastance always preceded the depression of end-systolic elastance and that afterload reduction by vasodilating effect of protamine was the mechanism most likely to have initiated the hypotension. Delayed decrease in contractility may be ascribed to reduced coronary perfusion pressure caused by vasodilation or to a direct effect of protamine.
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PMID:Protamine-induced hypotension in heart operations: application of the concept of ventricular-arterial coupling. 875 15