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Effect of isoproterenol on myocardial perfusion, function, energy metabolism and nitric oxide pathway in the rat heart – a longitudinal MR study
Author(s) -
Desrois Martine,
Kober Frank,
Lan Carole,
Dalmasso Christiane,
Cole Mark,
Clarke Kieran,
Cozzone Patrick J.,
Bernard Monique
Publication year - 2014
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.3088
Subject(s) - phosphocreatine , medicine , malondialdehyde , endocrinology , chemistry , nitric oxide , nitric oxide synthase , creatine , perfusion , cardiac function curve , in vivo , ventricular pressure , oxidative stress , high energy phosphate , blood pressure , heart failure , energy metabolism , biology , microbiology and biotechnology
The chronic administration of the β‐adrenoreceptor agonist isoproterenol (IsoP) is used in animals to study the mechanisms of cardiac hypertrophy and failure associated with a sustained increase in circulating catecholamines. Time‐dependent changes in myocardial blood flow (MBF), morphological and functional parameters were assessed in rats in vivo using multimodal cardiac MRI. Energy metabolism, oxidative stress and the nitric oxide (NO) pathway were evaluated in isolated perfused rat hearts following 7 days of treatment. Male Wistar rats were infused for 7 days with IsoP or vehicle using osmotic pumps. Cine‐MRI and arterial spin labeling were used to determine left ventricular morphology, function and MBF at days 1, 2 and 7 after pump implantation. Isolated hearts were then perfused, and high‐energy phosphate compounds and intracellular pH were followed using 31 P MRS with simultaneous measurement of contractile function. Total creatine and malondialdehyde (MDA) contents were measured by high‐performance liquid chromatography. The NO pathway was evaluated by NO synthase isoform expression and total nitrate concentration (NO x ). In IsoP‐treated rats, left ventricular mass was increased at day 1 and maintained. Wall thickness was increased with a peak at day 2 and a tendency to return to baseline values at day 7. MBF was markedly increased at day 1 and returned to normal values between days 1 and 2. The rate–pressure product and phosphocreatine/adenosine triphosphate ratio in perfused hearts were reduced. MDA, endothelial NO synthase expression and NO x were increased. Sustained high cardiac function and normal MBF after 24 h of IsoP infusion indicate imbalance between functional demand and blood flow, leading to morphological changes. After 1 week, cardiac hypertrophy and decreased function were associated with impaired phosphocreatine, increased oxidative stress and up‐regulation of the NO pathway. These results provide supplemental information on the evolution of the different contributing factors leading to morphological and functional changes in this model of cardiac hypertrophy and failure. Copyright © 2014 John Wiley & Sons, Ltd.