Direct effects of hydralazine on cardiac contractile function, haemodynamics, and myocardial energetics in isolated myocardium

Stephen V. Rendig, Leigh D. Segel, Ezra A Amsterdam

Research output: Contribution to journalReview article

3 Citations (Scopus)

Abstract

The direct cardiac effects of hydralazine were studied in isolated working rat heart, isolated cat right ventricular papillary muscle, and isolated rabbit right atrium. The haemodynamics, myocardial energetics, and contractility of isolated hearts were measured at hydralazine concentrations of 0.01, 0.1, 0.5, 1.0, 10 and 100 μmol·litre-1. Coronary flow was significantly increased (≥21%, p<0.01) in paced (325 beats·min-1) rat hearts at ≥0.5 μmol·litre-1 hydralazine and in spontaneously beating hearts (≥37%; p<0.05) at ≥1.0 μmol·litre-1 hydralazine. The increases in coronary flow occurred without significant increases in heart rate, contractility (dP/dtmax), or coronary perfusion pressure. Myocardial oxygen consumption was not significantly changed at any hydralazine concentration in spontaneously beating hearts and was unaltered in paced hearts except for a small significant increase (9.8%) at 10 μmol·litre-1. A negative inotropic effect was apparent at 100 μmol·litre-1 hydralazine as indicated by a significant reduction of dP/dtmax (paced and non-paced hearts), peak aortic flow rate (non-paced), and maximum left ventricular pressure (paced). In isolated cat papillary muscles and rabbit right atria, cumulative hydralazine log dose-response curves (0.1-1000 μmol·litre-1) were obtained. A positive inotropic effect that could be abolished by beta adrenergic blockade was produced in papillary muscles only at concentrations ≥ 100 μmol·litre-1. A dose dependent negative chronotropic effect occurred at hydralazine concentrations ≥10 μmol·litre-1 in isolated rabbit atria. Thus hydralazine mediated increases in coronary flow may occur at therapeutic concentrations in the absence of an increase in coronary perfusion pressure or myocardial oxygen demand. Hydralazine did not induce direct positive inotropic or chronotropic effects at concentrations obtained clinically. At supratherapeutic drug concentrations species specific inotropic and chronotropic effects were apparent.

Original languageEnglish (US)
Pages (from-to)322-328
Number of pages7
JournalCardiovascular Research
Volume22
Issue number5
DOIs
StatePublished - Jan 1 1988

Fingerprint

Hydralazine
Myocardium
Hemodynamics
Papillary Muscles
Myocardial Contraction
Rabbits
Heart Atria
Cats
Perfusion
Pressure
Ventricular Pressure
Oxygen Consumption
Adrenergic Agents
Heart Rate
Oxygen

Keywords

  • Coronary flow
  • Hydralazine
  • Inotropic effect
  • Papillary muscle
  • Vasodilating drugs

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Direct effects of hydralazine on cardiac contractile function, haemodynamics, and myocardial energetics in isolated myocardium. / Rendig, Stephen V.; Segel, Leigh D.; Amsterdam, Ezra A.

In: Cardiovascular Research, Vol. 22, No. 5, 01.01.1988, p. 322-328.

Research output: Contribution to journalReview article

@article{6403bdbccfaa43fe8a8db014b204856c,
title = "Direct effects of hydralazine on cardiac contractile function, haemodynamics, and myocardial energetics in isolated myocardium",
abstract = "The direct cardiac effects of hydralazine were studied in isolated working rat heart, isolated cat right ventricular papillary muscle, and isolated rabbit right atrium. The haemodynamics, myocardial energetics, and contractility of isolated hearts were measured at hydralazine concentrations of 0.01, 0.1, 0.5, 1.0, 10 and 100 μmol·litre-1. Coronary flow was significantly increased (≥21{\%}, p<0.01) in paced (325 beats·min-1) rat hearts at ≥0.5 μmol·litre-1 hydralazine and in spontaneously beating hearts (≥37{\%}; p<0.05) at ≥1.0 μmol·litre-1 hydralazine. The increases in coronary flow occurred without significant increases in heart rate, contractility (dP/dtmax), or coronary perfusion pressure. Myocardial oxygen consumption was not significantly changed at any hydralazine concentration in spontaneously beating hearts and was unaltered in paced hearts except for a small significant increase (9.8{\%}) at 10 μmol·litre-1. A negative inotropic effect was apparent at 100 μmol·litre-1 hydralazine as indicated by a significant reduction of dP/dtmax (paced and non-paced hearts), peak aortic flow rate (non-paced), and maximum left ventricular pressure (paced). In isolated cat papillary muscles and rabbit right atria, cumulative hydralazine log dose-response curves (0.1-1000 μmol·litre-1) were obtained. A positive inotropic effect that could be abolished by beta adrenergic blockade was produced in papillary muscles only at concentrations ≥ 100 μmol·litre-1. A dose dependent negative chronotropic effect occurred at hydralazine concentrations ≥10 μmol·litre-1 in isolated rabbit atria. Thus hydralazine mediated increases in coronary flow may occur at therapeutic concentrations in the absence of an increase in coronary perfusion pressure or myocardial oxygen demand. Hydralazine did not induce direct positive inotropic or chronotropic effects at concentrations obtained clinically. At supratherapeutic drug concentrations species specific inotropic and chronotropic effects were apparent.",
keywords = "Coronary flow, Hydralazine, Inotropic effect, Papillary muscle, Vasodilating drugs",
author = "Rendig, {Stephen V.} and Segel, {Leigh D.} and Amsterdam, {Ezra A}",
year = "1988",
month = "1",
day = "1",
doi = "10.1093/cvr/22.5.322",
language = "English (US)",
volume = "22",
pages = "322--328",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "5",

}

TY - JOUR

T1 - Direct effects of hydralazine on cardiac contractile function, haemodynamics, and myocardial energetics in isolated myocardium

AU - Rendig, Stephen V.

AU - Segel, Leigh D.

AU - Amsterdam, Ezra A

PY - 1988/1/1

Y1 - 1988/1/1

N2 - The direct cardiac effects of hydralazine were studied in isolated working rat heart, isolated cat right ventricular papillary muscle, and isolated rabbit right atrium. The haemodynamics, myocardial energetics, and contractility of isolated hearts were measured at hydralazine concentrations of 0.01, 0.1, 0.5, 1.0, 10 and 100 μmol·litre-1. Coronary flow was significantly increased (≥21%, p<0.01) in paced (325 beats·min-1) rat hearts at ≥0.5 μmol·litre-1 hydralazine and in spontaneously beating hearts (≥37%; p<0.05) at ≥1.0 μmol·litre-1 hydralazine. The increases in coronary flow occurred without significant increases in heart rate, contractility (dP/dtmax), or coronary perfusion pressure. Myocardial oxygen consumption was not significantly changed at any hydralazine concentration in spontaneously beating hearts and was unaltered in paced hearts except for a small significant increase (9.8%) at 10 μmol·litre-1. A negative inotropic effect was apparent at 100 μmol·litre-1 hydralazine as indicated by a significant reduction of dP/dtmax (paced and non-paced hearts), peak aortic flow rate (non-paced), and maximum left ventricular pressure (paced). In isolated cat papillary muscles and rabbit right atria, cumulative hydralazine log dose-response curves (0.1-1000 μmol·litre-1) were obtained. A positive inotropic effect that could be abolished by beta adrenergic blockade was produced in papillary muscles only at concentrations ≥ 100 μmol·litre-1. A dose dependent negative chronotropic effect occurred at hydralazine concentrations ≥10 μmol·litre-1 in isolated rabbit atria. Thus hydralazine mediated increases in coronary flow may occur at therapeutic concentrations in the absence of an increase in coronary perfusion pressure or myocardial oxygen demand. Hydralazine did not induce direct positive inotropic or chronotropic effects at concentrations obtained clinically. At supratherapeutic drug concentrations species specific inotropic and chronotropic effects were apparent.

AB - The direct cardiac effects of hydralazine were studied in isolated working rat heart, isolated cat right ventricular papillary muscle, and isolated rabbit right atrium. The haemodynamics, myocardial energetics, and contractility of isolated hearts were measured at hydralazine concentrations of 0.01, 0.1, 0.5, 1.0, 10 and 100 μmol·litre-1. Coronary flow was significantly increased (≥21%, p<0.01) in paced (325 beats·min-1) rat hearts at ≥0.5 μmol·litre-1 hydralazine and in spontaneously beating hearts (≥37%; p<0.05) at ≥1.0 μmol·litre-1 hydralazine. The increases in coronary flow occurred without significant increases in heart rate, contractility (dP/dtmax), or coronary perfusion pressure. Myocardial oxygen consumption was not significantly changed at any hydralazine concentration in spontaneously beating hearts and was unaltered in paced hearts except for a small significant increase (9.8%) at 10 μmol·litre-1. A negative inotropic effect was apparent at 100 μmol·litre-1 hydralazine as indicated by a significant reduction of dP/dtmax (paced and non-paced hearts), peak aortic flow rate (non-paced), and maximum left ventricular pressure (paced). In isolated cat papillary muscles and rabbit right atria, cumulative hydralazine log dose-response curves (0.1-1000 μmol·litre-1) were obtained. A positive inotropic effect that could be abolished by beta adrenergic blockade was produced in papillary muscles only at concentrations ≥ 100 μmol·litre-1. A dose dependent negative chronotropic effect occurred at hydralazine concentrations ≥10 μmol·litre-1 in isolated rabbit atria. Thus hydralazine mediated increases in coronary flow may occur at therapeutic concentrations in the absence of an increase in coronary perfusion pressure or myocardial oxygen demand. Hydralazine did not induce direct positive inotropic or chronotropic effects at concentrations obtained clinically. At supratherapeutic drug concentrations species specific inotropic and chronotropic effects were apparent.

KW - Coronary flow

KW - Hydralazine

KW - Inotropic effect

KW - Papillary muscle

KW - Vasodilating drugs

UR - http://www.scopus.com/inward/record.url?scp=85047679554&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047679554&partnerID=8YFLogxK

U2 - 10.1093/cvr/22.5.322

DO - 10.1093/cvr/22.5.322

M3 - Review article

C2 - 3191517

AN - SCOPUS:85047679554

VL - 22

SP - 322

EP - 328

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 5

ER -