Relative contribution of preload and afterload to the reduction in cardiac output caused by nitric oxide synthase inhibition with L-NG-methylarginine hydrochloride 546C88
作者:
Robert Harrison,
Rajiv Thakkar,
Hideaki Senzaki,
Ulf Ekelund,
Edward Cho,
David Kass,
Joshua Hare,
期刊:
Critical Care Medicine
(OVID Available online 2000)
卷期:
Volume 28,
issue 5
页码: 1263-1268
ISSN:0090-3493
年代: 2000
出版商: OVID
关键词: cardiac output;L-NG-methylarginine hydrochloride;myocardial contractility;nitric oxide;nitric-oxide synthase;phenylephrine;septic shock;sepsis;vascular endothelium;vasoconstrictor agent
数据来源: OVID
摘要:
Objective:The nitric oxide synthase inhibitor L-NG-methylarginine hydrochloride (L-NMMA HC1 546C88) causes reductions in cardiac output (CO), a potential limitation to clinical application. This drop in CO exceeds that from phenylephrine at matched systemic arterial pressure. We tested the hypothesis that the greater fall in CO attributable to L-NMMA primarily reflects a difference in venoconstriction between agents, such that phenylephrine produces larger increases in preload (an independent determinant of CO).Design:Random infusion of phenylephrine or L-NMMA.Setting:An animal research laboratory.Subjects:Eight healthy, conscious, male dogs.Interventions:L-NG-methylarginine hydrochloride (20 mg/kg for 1 hr) and phenylephrine (0.5 to 3 μg/kg/min) were administered into eight dogs chronically instrumented to measure left ventricular pressure and dimension. Data were measured at a constant heart rate (140 beats/min) to render CO proportional to stroke dimension.Measurements and Main Results:At a matched increase in afterload (effective arterial elastance), L-NMMA increased preload (end-diastolic dimension) to a lesser degree (3.8% ± 1.5%,p< .05) than phenylephrine (9.6% ± 1.6%,p< .05 vs. L-NMMA). Neither L-NMMA nor phenylephrine affected the slope of the end-systolic pressure dimension relationship, although L-NMMA shifted the relationship rightward (1.7 ± 0.7 mm,p< .05), consistent with a mild negative inotropic effect. L-NMMA decreased the stroke dimension to a greater extent than phenylephrine (−24.1% ± 6.8% and −10.6% ± 3.4%, respectively,p< .05).Conclusions:Differential CO responses to phenylephrine and L-NMMA were primarily attributable to changes in preload. Variable venular vs. arteriolar constrictor effects must be considered when evaluating the integrated cardiovascular response to a vasoactive agent.
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