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Relative contribution of preload and afterload to the reduction in cardiac output caused by nitric oxide synthase inhibition with L-N(G)-methylarginine hydrochloride 546C88

Harrison, R W; Thakkar, R N; Senzaki, H; Ekelund, Ulf LU ; Cho, E; Kass, D A and Hare, J M (2000) In Critical Care Medicine 28(5). p.8-1263
Abstract
OBJECTIVE: The nitric oxide synthase inhibitor L-N(G)-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-N(G)-methylarginine hydrochloride (20 mg/kg for 1 hr) and phenylephrine... (More)
OBJECTIVE: The nitric oxide synthase inhibitor L-N(G)-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-N(G)-methylarginine hydrochloride (20 mg/kg for 1 hr) and phenylephrine (0.5 to 3 microg/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. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
in
Critical Care Medicine
volume
28
issue
5
pages
8 - 1263
publisher
Lippincott Williams & Wilkins
external identifiers
  • pmid:10834663
  • scopus:0034126937
ISSN
1530-0293
language
English
LU publication?
no
id
ac825737-14e8-4c58-88a2-09013e6d4bc1 (old id 1117169)
date added to LUP
2008-07-03 08:48:13
date last changed
2017-01-01 07:21:32
@article{ac825737-14e8-4c58-88a2-09013e6d4bc1,
  abstract     = {OBJECTIVE: The nitric oxide synthase inhibitor L-N(G)-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-N(G)-methylarginine hydrochloride (20 mg/kg for 1 hr) and phenylephrine (0.5 to 3 microg/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 &lt; .05) than phenylephrine (9.6%+/-1.6%, p &lt; .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 &lt; .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 &lt; .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.},
  author       = {Harrison, R W and Thakkar, R N and Senzaki, H and Ekelund, Ulf and Cho, E and Kass, D A and Hare, J M},
  issn         = {1530-0293},
  language     = {eng},
  number       = {5},
  pages        = {8--1263},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Critical Care Medicine},
  title        = {Relative contribution of preload and afterload to the reduction in cardiac output caused by nitric oxide synthase inhibition with L-N(G)-methylarginine hydrochloride 546C88},
  volume       = {28},
  year         = {2000},
}