Pretreatment with angiotensin receptor blockade prevents left ventricular dysfunction and blunts left ventricular remodeling associated with acute myocardial infarction

Hoang Thai, Lisa Castellano, Elizabeth B Juneman, Huy Phan, Rose Do, Mohamed A. Gaballa, Steven Goldman

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

BACKGROUND - This study was designed to determine the effects of pretreatment with an angiotensin receptor blocker on left ventricular (LV) function and remodeling during acute myocardial infarction (MI). METHODS AND RESULTS - Sprague-Dawley rats were pretreated with candesartan (10 mg · kg · d) for 2 weeks and studied at 1, 3, and 6 minutes after MI. Compared with untreated rats, pretreatment with candesartan lowered (P<0.05) LV systolic pressure and the first derivative of LV pressure with respect to time but did not change LV end-diastolic pressure or improve LV regional function. With candesartan pretreatment, LV fractional shortening and ejection fraction increased (P<0.05) by 37% and 28%, and LV chamber dilation was attenuated (P<0.05). At 6 minutes after MI, LV endothelial nitric oxide synthase decreased in the infarcted and noninfarcted wall 47% (P=0.04) and 70% (P=0.002), and constitutive microtubulin increased 260% (P=0.0005) and 111% (P=0.003). Candesartan had no effect on LV tissue endothelial nitric oxide synthase levels but attenuated the increase in constitutive microtubulin by 77% (P=0.004) and 37% (P<0.05). CONCLUSIONS - Pretreatment with candesartan before an acute MI improves global LV function, prevents LV dilation, and blunts the increase in constitutive microtubulin, with minimal effects on LV hemodynamics, regional function, or tissue endothelial nitric oxide synthase. Thus, candesartan given before an MI attenuates LV remodeling and alters the cytoskeleton matrix of the left ventricle.

Original languageEnglish (US)
Pages (from-to)1933-1939
Number of pages7
JournalCirculation
Volume114
Issue number18
DOIs
StatePublished - Oct 2006

Fingerprint

Ventricular Remodeling
Angiotensin Receptors
Left Ventricular Dysfunction
Myocardial Infarction
Nitric Oxide Synthase Type III
Left Ventricular Function
Ventricular Pressure
Dilatation
Blood Pressure
Angiotensin Receptor Antagonists
Cytoskeleton
Heart Ventricles
Sprague Dawley Rats
candesartan
Hemodynamics

Keywords

  • Angiotensin
  • Heart failure
  • Myocardial infarction
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Pretreatment with angiotensin receptor blockade prevents left ventricular dysfunction and blunts left ventricular remodeling associated with acute myocardial infarction. / Thai, Hoang; Castellano, Lisa; Juneman, Elizabeth B; Phan, Huy; Do, Rose; Gaballa, Mohamed A.; Goldman, Steven.

In: Circulation, Vol. 114, No. 18, 10.2006, p. 1933-1939.

Research output: Contribution to journalArticle

@article{5f1eb69545d849f183c8442ad9a523ab,
title = "Pretreatment with angiotensin receptor blockade prevents left ventricular dysfunction and blunts left ventricular remodeling associated with acute myocardial infarction",
abstract = "BACKGROUND - This study was designed to determine the effects of pretreatment with an angiotensin receptor blocker on left ventricular (LV) function and remodeling during acute myocardial infarction (MI). METHODS AND RESULTS - Sprague-Dawley rats were pretreated with candesartan (10 mg · kg · d) for 2 weeks and studied at 1, 3, and 6 minutes after MI. Compared with untreated rats, pretreatment with candesartan lowered (P<0.05) LV systolic pressure and the first derivative of LV pressure with respect to time but did not change LV end-diastolic pressure or improve LV regional function. With candesartan pretreatment, LV fractional shortening and ejection fraction increased (P<0.05) by 37{\%} and 28{\%}, and LV chamber dilation was attenuated (P<0.05). At 6 minutes after MI, LV endothelial nitric oxide synthase decreased in the infarcted and noninfarcted wall 47{\%} (P=0.04) and 70{\%} (P=0.002), and constitutive microtubulin increased 260{\%} (P=0.0005) and 111{\%} (P=0.003). Candesartan had no effect on LV tissue endothelial nitric oxide synthase levels but attenuated the increase in constitutive microtubulin by 77{\%} (P=0.004) and 37{\%} (P<0.05). CONCLUSIONS - Pretreatment with candesartan before an acute MI improves global LV function, prevents LV dilation, and blunts the increase in constitutive microtubulin, with minimal effects on LV hemodynamics, regional function, or tissue endothelial nitric oxide synthase. Thus, candesartan given before an MI attenuates LV remodeling and alters the cytoskeleton matrix of the left ventricle.",
keywords = "Angiotensin, Heart failure, Myocardial infarction, Nitric oxide synthase",
author = "Hoang Thai and Lisa Castellano and Juneman, {Elizabeth B} and Huy Phan and Rose Do and Gaballa, {Mohamed A.} and Steven Goldman",
year = "2006",
month = "10",
doi = "10.1161/CIRCULATIONAHA.106.653329",
language = "English (US)",
volume = "114",
pages = "1933--1939",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "18",

}

TY - JOUR

T1 - Pretreatment with angiotensin receptor blockade prevents left ventricular dysfunction and blunts left ventricular remodeling associated with acute myocardial infarction

AU - Thai, Hoang

AU - Castellano, Lisa

AU - Juneman, Elizabeth B

AU - Phan, Huy

AU - Do, Rose

AU - Gaballa, Mohamed A.

AU - Goldman, Steven

PY - 2006/10

Y1 - 2006/10

N2 - BACKGROUND - This study was designed to determine the effects of pretreatment with an angiotensin receptor blocker on left ventricular (LV) function and remodeling during acute myocardial infarction (MI). METHODS AND RESULTS - Sprague-Dawley rats were pretreated with candesartan (10 mg · kg · d) for 2 weeks and studied at 1, 3, and 6 minutes after MI. Compared with untreated rats, pretreatment with candesartan lowered (P<0.05) LV systolic pressure and the first derivative of LV pressure with respect to time but did not change LV end-diastolic pressure or improve LV regional function. With candesartan pretreatment, LV fractional shortening and ejection fraction increased (P<0.05) by 37% and 28%, and LV chamber dilation was attenuated (P<0.05). At 6 minutes after MI, LV endothelial nitric oxide synthase decreased in the infarcted and noninfarcted wall 47% (P=0.04) and 70% (P=0.002), and constitutive microtubulin increased 260% (P=0.0005) and 111% (P=0.003). Candesartan had no effect on LV tissue endothelial nitric oxide synthase levels but attenuated the increase in constitutive microtubulin by 77% (P=0.004) and 37% (P<0.05). CONCLUSIONS - Pretreatment with candesartan before an acute MI improves global LV function, prevents LV dilation, and blunts the increase in constitutive microtubulin, with minimal effects on LV hemodynamics, regional function, or tissue endothelial nitric oxide synthase. Thus, candesartan given before an MI attenuates LV remodeling and alters the cytoskeleton matrix of the left ventricle.

AB - BACKGROUND - This study was designed to determine the effects of pretreatment with an angiotensin receptor blocker on left ventricular (LV) function and remodeling during acute myocardial infarction (MI). METHODS AND RESULTS - Sprague-Dawley rats were pretreated with candesartan (10 mg · kg · d) for 2 weeks and studied at 1, 3, and 6 minutes after MI. Compared with untreated rats, pretreatment with candesartan lowered (P<0.05) LV systolic pressure and the first derivative of LV pressure with respect to time but did not change LV end-diastolic pressure or improve LV regional function. With candesartan pretreatment, LV fractional shortening and ejection fraction increased (P<0.05) by 37% and 28%, and LV chamber dilation was attenuated (P<0.05). At 6 minutes after MI, LV endothelial nitric oxide synthase decreased in the infarcted and noninfarcted wall 47% (P=0.04) and 70% (P=0.002), and constitutive microtubulin increased 260% (P=0.0005) and 111% (P=0.003). Candesartan had no effect on LV tissue endothelial nitric oxide synthase levels but attenuated the increase in constitutive microtubulin by 77% (P=0.004) and 37% (P<0.05). CONCLUSIONS - Pretreatment with candesartan before an acute MI improves global LV function, prevents LV dilation, and blunts the increase in constitutive microtubulin, with minimal effects on LV hemodynamics, regional function, or tissue endothelial nitric oxide synthase. Thus, candesartan given before an MI attenuates LV remodeling and alters the cytoskeleton matrix of the left ventricle.

KW - Angiotensin

KW - Heart failure

KW - Myocardial infarction

KW - Nitric oxide synthase

UR - http://www.scopus.com/inward/record.url?scp=33750505876&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750505876&partnerID=8YFLogxK

U2 - 10.1161/CIRCULATIONAHA.106.653329

DO - 10.1161/CIRCULATIONAHA.106.653329

M3 - Article

C2 - 17060375

AN - SCOPUS:33750505876

VL - 114

SP - 1933

EP - 1939

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 18

ER -