Spironolactone prevents the inducibility of ventricular tachyarrhythmia in rats with aldosteronism

Prajwal A. Deshmukh, Sripad R. Bellary, Frank T. Schwender, German Kamalov, Minoti Magotra, Amy Curry, Yao Sun, Karl Weber

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Myocardial fibrosis is considered a substrate for fatal ventricular arrhythmias (VAs). In rats receiving aldosterone/salt treatment (ALDOST) for ≥4 weeks, foci of myocardial scarring that replace necrotic cardiomyocytes appear scattered throughout the right and left sides of the heart. We hypothesized that this adverse structural remodeling would promote the inducibility of VA, which could be prevented by cotreatment with spironolactone (A+Spiro), an aldosterone receptor antagonist and cardioprotective agent. In controls and each treatment group, we monitored: (1) electrocardiogram, ventricular electrogram, and arterial pressure before, during, and after bipolar electrical stimulation of the right ventricular outflow tract and apex at a strength 3× the pacing threshold, using both programmed stimulation with premature extra stimuli and 50-Hz burst pacing for 3 different durations; and (2) myocardial collagen volume fraction (CVF) as a marker of cardiac fibrosis. We found that VA (duration >200 ms accompanied by declining arterial pressure) was more inducible (P < 0.05) at 4 weeks (4 of 6) and with even greater frequency at 6 weeks (9 of 10) of ALDOST versus controls (0 of 6) and A+Spiro for 6 weeks (2 of 11). CVF (%) was proportionally increased (P < 0.05) at 4 and 6 weeks (8.4 ± 0.74 and 13.9 ± 1.9, respectively) of ALDOST compared with control group (2.6 ± 0.4) and A+Spiro group (5.3 ± 0.7). However, the effective refractory period was indistinguishable between groups, whereas the probability of VA was nonlinearly related to CVF. Thus, in rats with aldosteronism, in which a reduction in effective refractory period was not evident, the mechanism for VA susceptibility is presumably linked to a decrease in conduction velocity and/or increased dispersion of refractoriness, probably caused by consequential myocardial fibrosis.

Original languageEnglish (US)
Pages (from-to)487-491
Number of pages5
JournalJournal of Cardiovascular Pharmacology
Volume58
Issue number5
DOIs
StatePublished - Nov 2011

Fingerprint

Spironolactone
Hyperaldosteronism
Tachycardia
Cardiac Arrhythmias
Aldosterone
Fibrosis
Collagen
Salts
Arterial Pressure
Mineralocorticoid Receptor Antagonists
Cardiotonic Agents
Ventricular Pressure
Cardiac Myocytes
Electric Stimulation
Cicatrix
Electrocardiography
Control Groups

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Spironolactone prevents the inducibility of ventricular tachyarrhythmia in rats with aldosteronism. / Deshmukh, Prajwal A.; Bellary, Sripad R.; Schwender, Frank T.; Kamalov, German; Magotra, Minoti; Curry, Amy; Sun, Yao; Weber, Karl.

In: Journal of Cardiovascular Pharmacology, Vol. 58, No. 5, 11.2011, p. 487-491.

Research output: Contribution to journalArticle

Deshmukh, Prajwal A. ; Bellary, Sripad R. ; Schwender, Frank T. ; Kamalov, German ; Magotra, Minoti ; Curry, Amy ; Sun, Yao ; Weber, Karl. / Spironolactone prevents the inducibility of ventricular tachyarrhythmia in rats with aldosteronism. In: Journal of Cardiovascular Pharmacology. 2011 ; Vol. 58, No. 5. pp. 487-491.
@article{87d0fdb44dcc4fd39460e9a302502c40,
title = "Spironolactone prevents the inducibility of ventricular tachyarrhythmia in rats with aldosteronism",
abstract = "Myocardial fibrosis is considered a substrate for fatal ventricular arrhythmias (VAs). In rats receiving aldosterone/salt treatment (ALDOST) for ≥4 weeks, foci of myocardial scarring that replace necrotic cardiomyocytes appear scattered throughout the right and left sides of the heart. We hypothesized that this adverse structural remodeling would promote the inducibility of VA, which could be prevented by cotreatment with spironolactone (A+Spiro), an aldosterone receptor antagonist and cardioprotective agent. In controls and each treatment group, we monitored: (1) electrocardiogram, ventricular electrogram, and arterial pressure before, during, and after bipolar electrical stimulation of the right ventricular outflow tract and apex at a strength 3× the pacing threshold, using both programmed stimulation with premature extra stimuli and 50-Hz burst pacing for 3 different durations; and (2) myocardial collagen volume fraction (CVF) as a marker of cardiac fibrosis. We found that VA (duration >200 ms accompanied by declining arterial pressure) was more inducible (P < 0.05) at 4 weeks (4 of 6) and with even greater frequency at 6 weeks (9 of 10) of ALDOST versus controls (0 of 6) and A+Spiro for 6 weeks (2 of 11). CVF ({\%}) was proportionally increased (P < 0.05) at 4 and 6 weeks (8.4 ± 0.74 and 13.9 ± 1.9, respectively) of ALDOST compared with control group (2.6 ± 0.4) and A+Spiro group (5.3 ± 0.7). However, the effective refractory period was indistinguishable between groups, whereas the probability of VA was nonlinearly related to CVF. Thus, in rats with aldosteronism, in which a reduction in effective refractory period was not evident, the mechanism for VA susceptibility is presumably linked to a decrease in conduction velocity and/or increased dispersion of refractoriness, probably caused by consequential myocardial fibrosis.",
author = "Deshmukh, {Prajwal A.} and Bellary, {Sripad R.} and Schwender, {Frank T.} and German Kamalov and Minoti Magotra and Amy Curry and Yao Sun and Karl Weber",
year = "2011",
month = "11",
doi = "10.1097/FJC.0b013e31822a78c1",
language = "English (US)",
volume = "58",
pages = "487--491",
journal = "Journal of Cardiovascular Pharmacology",
issn = "0160-2446",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Spironolactone prevents the inducibility of ventricular tachyarrhythmia in rats with aldosteronism

AU - Deshmukh, Prajwal A.

AU - Bellary, Sripad R.

AU - Schwender, Frank T.

AU - Kamalov, German

AU - Magotra, Minoti

AU - Curry, Amy

AU - Sun, Yao

AU - Weber, Karl

PY - 2011/11

Y1 - 2011/11

N2 - Myocardial fibrosis is considered a substrate for fatal ventricular arrhythmias (VAs). In rats receiving aldosterone/salt treatment (ALDOST) for ≥4 weeks, foci of myocardial scarring that replace necrotic cardiomyocytes appear scattered throughout the right and left sides of the heart. We hypothesized that this adverse structural remodeling would promote the inducibility of VA, which could be prevented by cotreatment with spironolactone (A+Spiro), an aldosterone receptor antagonist and cardioprotective agent. In controls and each treatment group, we monitored: (1) electrocardiogram, ventricular electrogram, and arterial pressure before, during, and after bipolar electrical stimulation of the right ventricular outflow tract and apex at a strength 3× the pacing threshold, using both programmed stimulation with premature extra stimuli and 50-Hz burst pacing for 3 different durations; and (2) myocardial collagen volume fraction (CVF) as a marker of cardiac fibrosis. We found that VA (duration >200 ms accompanied by declining arterial pressure) was more inducible (P < 0.05) at 4 weeks (4 of 6) and with even greater frequency at 6 weeks (9 of 10) of ALDOST versus controls (0 of 6) and A+Spiro for 6 weeks (2 of 11). CVF (%) was proportionally increased (P < 0.05) at 4 and 6 weeks (8.4 ± 0.74 and 13.9 ± 1.9, respectively) of ALDOST compared with control group (2.6 ± 0.4) and A+Spiro group (5.3 ± 0.7). However, the effective refractory period was indistinguishable between groups, whereas the probability of VA was nonlinearly related to CVF. Thus, in rats with aldosteronism, in which a reduction in effective refractory period was not evident, the mechanism for VA susceptibility is presumably linked to a decrease in conduction velocity and/or increased dispersion of refractoriness, probably caused by consequential myocardial fibrosis.

AB - Myocardial fibrosis is considered a substrate for fatal ventricular arrhythmias (VAs). In rats receiving aldosterone/salt treatment (ALDOST) for ≥4 weeks, foci of myocardial scarring that replace necrotic cardiomyocytes appear scattered throughout the right and left sides of the heart. We hypothesized that this adverse structural remodeling would promote the inducibility of VA, which could be prevented by cotreatment with spironolactone (A+Spiro), an aldosterone receptor antagonist and cardioprotective agent. In controls and each treatment group, we monitored: (1) electrocardiogram, ventricular electrogram, and arterial pressure before, during, and after bipolar electrical stimulation of the right ventricular outflow tract and apex at a strength 3× the pacing threshold, using both programmed stimulation with premature extra stimuli and 50-Hz burst pacing for 3 different durations; and (2) myocardial collagen volume fraction (CVF) as a marker of cardiac fibrosis. We found that VA (duration >200 ms accompanied by declining arterial pressure) was more inducible (P < 0.05) at 4 weeks (4 of 6) and with even greater frequency at 6 weeks (9 of 10) of ALDOST versus controls (0 of 6) and A+Spiro for 6 weeks (2 of 11). CVF (%) was proportionally increased (P < 0.05) at 4 and 6 weeks (8.4 ± 0.74 and 13.9 ± 1.9, respectively) of ALDOST compared with control group (2.6 ± 0.4) and A+Spiro group (5.3 ± 0.7). However, the effective refractory period was indistinguishable between groups, whereas the probability of VA was nonlinearly related to CVF. Thus, in rats with aldosteronism, in which a reduction in effective refractory period was not evident, the mechanism for VA susceptibility is presumably linked to a decrease in conduction velocity and/or increased dispersion of refractoriness, probably caused by consequential myocardial fibrosis.

UR - http://www.scopus.com/inward/record.url?scp=80955143019&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80955143019&partnerID=8YFLogxK

U2 - 10.1097/FJC.0b013e31822a78c1

DO - 10.1097/FJC.0b013e31822a78c1

M3 - Article

VL - 58

SP - 487

EP - 491

JO - Journal of Cardiovascular Pharmacology

JF - Journal of Cardiovascular Pharmacology

SN - 0160-2446

IS - 5

ER -