Reduced mechanical efficiency of rat papillary muscle related to degree of hypertrophy of cardiomyocytes

Abstract

Isolated rat papillary muscles of the right ventricle were used to discover the origin of reduced myocardial efficiency in chronic heart failure. Right ventricular hypertrophy was induced by monocrotaline injection, causing pulmonary hypertension. Control (n = 7) and hypertrophied (n = 11) papillary muscles were subjected to sinusoidal length changes at 37 degrees C and 5 Hz with a peak-to-peak amplitude of 15% of the length giving maximum force (L(max)) after being stretched to 92.5% of L(max). Isometric tension at L(max) was similar in control and hypertrophied muscles. Work was assessed from the area encompassed by force-length loops. Work per loop was 0.93 +/- 0.11 and 0.84 +/- 0.11 microJ/mm(3) (means +/- SE) for control and hypertrophied muscles, respectively (P = 0.591). Suprabasal O(2) uptake per work loop was 5.7 +/- 0.7 pmol/mm(3) in control muscles and 8.7 +/- 1.7 pmol/mm(3) in hypertrophied muscles (P = 0.133). Net mechanical efficiency was calculated from the ratio of work output and suprabasal O(2) uptake. The efficiency of hypertrophied muscles was 29.1 +/- 3.7% and was smaller than in control muscles (43.7 +/- 2.2%, P = 0.016). The right ventricular cardiomyocyte cross-sectional area increased from 272 +/- 17 microm(2) in control muscles to 396 +/- 31 microm(2) in hypertrophied muscles (P < 0.003). Mechanical efficiency correlated negatively with right ventricular wall thickness and cardiomyocyte cross-sectional area [Spearman rank correlation coefficients of -0.50 (P = 0.039) and -0.53 (P = 0.024), respectively]. We conclude that efficiency decreases with increasing cardiomyocyte hypertrophy. Thus, the reduced efficiency of diseased whole hearts can be at least partly explained by reduced efficiency at the cardiomyocyte level.

Arrhythmogenic substrate in hearts of rats with monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy

“…Our observation that the RV MAP duration was prolonged is consistent with action potential and QT interval measurements in previous studies (9,26,32). The correlation between the degree of cardiac hypertrophy and APD is a novel observation in this model and is similar to that between impaired mechanical function and hypertrophy recently reported in MCT hearts (40). We also observed prolongation of LV action potentials by MCT, contrary to the findings of Lee et al (26).…”

Inadequate Myocardial Oxygen Supply/Demand in Experimental Pulmonary Hypertension

“…The oxygen demand of the right heart can increase threefold due to the increase in pulmonary artery pressure (Handoko et al, 2009) and by a similar factor due to a decrease of mechanical efficiency (Wong et al, 2010). Fig.…”

“…It is unlikely therefore, that the release of cytochrome c would cause a decrease of VO 2max and PO 2crit in failing myocardium. It is a possibility that mitochondrial damage is the reason for the reduced mechanical efficiency in observed in papillary muscles (Wong et al, 2010). Bache et al (1999) concluded that changes in energy rich phosphate concentrations that occur during high workload of hypertrophic hearts were not due to limited myocardial oxygenation using 1 H nuclear magnetic resonance to monitor myoglobin desaturation in situ in the anaesthetised dog.…”

“…Increased diffusion distances imply that the interstitial oxygen tension preventing core hypoxia in cardiomyocytes (PO 2crit ) increases, whereas reduced capillary density likely reduces interstitial PO 2 . In addition to the increased power output of the right ventricular myocytes, the rate of oxygen consumption of the cells also increases because their mechanical efficiency decreases (Wong et al, 2010). These changes can lead to oxidative stress (Redout et al, 2007) and may lead to apoptosis of RV cardiomyocytes (Ecarnot-Laubriet et al, 2002).…”

Muscle physiology: move to translation

“…In chronic heart failure, myocardial efficiency (cardiac work divided by oxygen consumption) is considerably diminished (Wong et al 2010), which may be due to altered catecholamine handling. van Eif et al (2013) tested the possibility that oxidation of catecholamines in failing hearts is induced by increased monoamine oxidase A (MAO-A) activity within cardiac myocytes and relate to increased number of intrinsic cardiac adrenergic (ICA) cells.…”