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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1117169
- author
- Harrison, R W
; Thakkar, R N
; Senzaki, H
; Ekelund, Ulf
LU
; Cho, E
; Kass, D A
and Hare, J M
- publishing date
- 2000
- 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
- 2016-04-01 17:00:29
- date last changed
- 2022-02-28 01:10:08
@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 < .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.}},
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}},
}