Systemic hypertension induces disparate localized left ventricular action potential lengthening and altered sensitivity to verapamil in left ventricular myocardium

John S. Cameron, Linda S. Miller, Shinichi Kimura, Charles J. Kaiser, David R. Campbell, Patricia L. Kozlovskis, Marion S. Gaide, Robert J Myerburg, Arthur L. Bassett

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Previously, we demonstrated that acute exposure to superfusate containing verapamil suppresses action potential plateau to a greater degree in cells at the tip of the anterior papillary muscle compared to those at its base in normal cat left ventricle (LV) studied in tissue bath. To determine the effects of chronic pressure overload brought about by renal hypertension on (1) papillary muscle electrophysiology and (2) regional sensitivity to verapamil, LV were isolated from cats subjected to unilateral nephrectomy and contralateral kidney wrapping. After 3 months, systemic hypertension (mean increase=60.2±1.4 mmHg) was associated with moderate LV hypertrophy of ≈18% (LV weight/body weight). Transmembrane action potentials recorded from the endocardial surface (including anterior papillary muscle) in pressure overloaded LV in vitro (800 ms stimulus cycle length) showed increased action potential duration at 25, 75 and 90% of repolarization (APD25, APD75 and APD90, respectively) relative to controls (LV from normal and sham operated cats). With respect to the anterior papillary muscle in pressure overloaded LV, APD25, APD75 and APD90 were increased to a greater extent in cells at the base of the muscle compared to those increases observed at the tip (P<0.05). In contrast to its effects in controls, verapamil (2 μg/ml) significantly reduced APD25 at both the base and the tip of the papillary muscle in pressure overloaded preparations, but particularly at the base; also, the disparities between the APD75 or APD90 at tip and base were decreased. Thus, (1) regional electrophysiologic disparities were induced in systemic hypertension, and (2) these differences were subsequently reduced by verapamil. Highly localized disparate effects of verapamil in normal and pressure overloaded LV myocardium indicate the need to assess drug action in diseased preparations.

Original languageEnglish
Pages (from-to)169-175
Number of pages7
JournalJournal of Molecular and Cellular Cardiology
Volume18
Issue number2
DOIs
StatePublished - Jan 1 1986

Fingerprint

Verapamil
Action Potentials
Heart Ventricles
Myocardium
Papillary Muscles
Hypertension
Pressure
Cats
Renal Hypertension
Electrophysiology
Nephrectomy
Baths
Membrane Potentials
Hypertrophy
Body Weight
Kidney
Weights and Measures
Muscles
Pharmaceutical Preparations

Keywords

  • Action potential duration
  • Anterior papillary muscle
  • Cardiac electrophysiology
  • Cat
  • Left ventricular pressure overload
  • Microelectrodes
  • Renal hypertension
  • Verapamil

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Systemic hypertension induces disparate localized left ventricular action potential lengthening and altered sensitivity to verapamil in left ventricular myocardium. / Cameron, John S.; Miller, Linda S.; Kimura, Shinichi; Kaiser, Charles J.; Campbell, David R.; Kozlovskis, Patricia L.; Gaide, Marion S.; Myerburg, Robert J; Bassett, Arthur L.

In: Journal of Molecular and Cellular Cardiology, Vol. 18, No. 2, 01.01.1986, p. 169-175.

Research output: Contribution to journalArticle

Cameron, John S. ; Miller, Linda S. ; Kimura, Shinichi ; Kaiser, Charles J. ; Campbell, David R. ; Kozlovskis, Patricia L. ; Gaide, Marion S. ; Myerburg, Robert J ; Bassett, Arthur L. / Systemic hypertension induces disparate localized left ventricular action potential lengthening and altered sensitivity to verapamil in left ventricular myocardium. In: Journal of Molecular and Cellular Cardiology. 1986 ; Vol. 18, No. 2. pp. 169-175.
@article{09ea897e97744dd5890ce4f98093d592,
title = "Systemic hypertension induces disparate localized left ventricular action potential lengthening and altered sensitivity to verapamil in left ventricular myocardium",
abstract = "Previously, we demonstrated that acute exposure to superfusate containing verapamil suppresses action potential plateau to a greater degree in cells at the tip of the anterior papillary muscle compared to those at its base in normal cat left ventricle (LV) studied in tissue bath. To determine the effects of chronic pressure overload brought about by renal hypertension on (1) papillary muscle electrophysiology and (2) regional sensitivity to verapamil, LV were isolated from cats subjected to unilateral nephrectomy and contralateral kidney wrapping. After 3 months, systemic hypertension (mean increase=60.2±1.4 mmHg) was associated with moderate LV hypertrophy of ≈18{\%} (LV weight/body weight). Transmembrane action potentials recorded from the endocardial surface (including anterior papillary muscle) in pressure overloaded LV in vitro (800 ms stimulus cycle length) showed increased action potential duration at 25, 75 and 90{\%} of repolarization (APD25, APD75 and APD90, respectively) relative to controls (LV from normal and sham operated cats). With respect to the anterior papillary muscle in pressure overloaded LV, APD25, APD75 and APD90 were increased to a greater extent in cells at the base of the muscle compared to those increases observed at the tip (P<0.05). In contrast to its effects in controls, verapamil (2 μg/ml) significantly reduced APD25 at both the base and the tip of the papillary muscle in pressure overloaded preparations, but particularly at the base; also, the disparities between the APD75 or APD90 at tip and base were decreased. Thus, (1) regional electrophysiologic disparities were induced in systemic hypertension, and (2) these differences were subsequently reduced by verapamil. Highly localized disparate effects of verapamil in normal and pressure overloaded LV myocardium indicate the need to assess drug action in diseased preparations.",
keywords = "Action potential duration, Anterior papillary muscle, Cardiac electrophysiology, Cat, Left ventricular pressure overload, Microelectrodes, Renal hypertension, Verapamil",
author = "Cameron, {John S.} and Miller, {Linda S.} and Shinichi Kimura and Kaiser, {Charles J.} and Campbell, {David R.} and Kozlovskis, {Patricia L.} and Gaide, {Marion S.} and Myerburg, {Robert J} and Bassett, {Arthur L.}",
year = "1986",
month = "1",
day = "1",
doi = "10.1016/S0022-2828(86)80469-2",
language = "English",
volume = "18",
pages = "169--175",
journal = "Journal of Molecular and Cellular Cardiology",
issn = "0022-2828",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Systemic hypertension induces disparate localized left ventricular action potential lengthening and altered sensitivity to verapamil in left ventricular myocardium

AU - Cameron, John S.

AU - Miller, Linda S.

AU - Kimura, Shinichi

AU - Kaiser, Charles J.

AU - Campbell, David R.

AU - Kozlovskis, Patricia L.

AU - Gaide, Marion S.

AU - Myerburg, Robert J

AU - Bassett, Arthur L.

PY - 1986/1/1

Y1 - 1986/1/1

N2 - Previously, we demonstrated that acute exposure to superfusate containing verapamil suppresses action potential plateau to a greater degree in cells at the tip of the anterior papillary muscle compared to those at its base in normal cat left ventricle (LV) studied in tissue bath. To determine the effects of chronic pressure overload brought about by renal hypertension on (1) papillary muscle electrophysiology and (2) regional sensitivity to verapamil, LV were isolated from cats subjected to unilateral nephrectomy and contralateral kidney wrapping. After 3 months, systemic hypertension (mean increase=60.2±1.4 mmHg) was associated with moderate LV hypertrophy of ≈18% (LV weight/body weight). Transmembrane action potentials recorded from the endocardial surface (including anterior papillary muscle) in pressure overloaded LV in vitro (800 ms stimulus cycle length) showed increased action potential duration at 25, 75 and 90% of repolarization (APD25, APD75 and APD90, respectively) relative to controls (LV from normal and sham operated cats). With respect to the anterior papillary muscle in pressure overloaded LV, APD25, APD75 and APD90 were increased to a greater extent in cells at the base of the muscle compared to those increases observed at the tip (P<0.05). In contrast to its effects in controls, verapamil (2 μg/ml) significantly reduced APD25 at both the base and the tip of the papillary muscle in pressure overloaded preparations, but particularly at the base; also, the disparities between the APD75 or APD90 at tip and base were decreased. Thus, (1) regional electrophysiologic disparities were induced in systemic hypertension, and (2) these differences were subsequently reduced by verapamil. Highly localized disparate effects of verapamil in normal and pressure overloaded LV myocardium indicate the need to assess drug action in diseased preparations.

AB - Previously, we demonstrated that acute exposure to superfusate containing verapamil suppresses action potential plateau to a greater degree in cells at the tip of the anterior papillary muscle compared to those at its base in normal cat left ventricle (LV) studied in tissue bath. To determine the effects of chronic pressure overload brought about by renal hypertension on (1) papillary muscle electrophysiology and (2) regional sensitivity to verapamil, LV were isolated from cats subjected to unilateral nephrectomy and contralateral kidney wrapping. After 3 months, systemic hypertension (mean increase=60.2±1.4 mmHg) was associated with moderate LV hypertrophy of ≈18% (LV weight/body weight). Transmembrane action potentials recorded from the endocardial surface (including anterior papillary muscle) in pressure overloaded LV in vitro (800 ms stimulus cycle length) showed increased action potential duration at 25, 75 and 90% of repolarization (APD25, APD75 and APD90, respectively) relative to controls (LV from normal and sham operated cats). With respect to the anterior papillary muscle in pressure overloaded LV, APD25, APD75 and APD90 were increased to a greater extent in cells at the base of the muscle compared to those increases observed at the tip (P<0.05). In contrast to its effects in controls, verapamil (2 μg/ml) significantly reduced APD25 at both the base and the tip of the papillary muscle in pressure overloaded preparations, but particularly at the base; also, the disparities between the APD75 or APD90 at tip and base were decreased. Thus, (1) regional electrophysiologic disparities were induced in systemic hypertension, and (2) these differences were subsequently reduced by verapamil. Highly localized disparate effects of verapamil in normal and pressure overloaded LV myocardium indicate the need to assess drug action in diseased preparations.

KW - Action potential duration

KW - Anterior papillary muscle

KW - Cardiac electrophysiology

KW - Cat

KW - Left ventricular pressure overload

KW - Microelectrodes

KW - Renal hypertension

KW - Verapamil

UR - http://www.scopus.com/inward/record.url?scp=0022618689&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022618689&partnerID=8YFLogxK

U2 - 10.1016/S0022-2828(86)80469-2

DO - 10.1016/S0022-2828(86)80469-2

M3 - Article

C2 - 3959090

AN - SCOPUS:0022618689

VL - 18

SP - 169

EP - 175

JO - Journal of Molecular and Cellular Cardiology

JF - Journal of Molecular and Cellular Cardiology

SN - 0022-2828

IS - 2

ER -