Myocardial ATP hydrolysis rates in vivo: a porcine model of pressure overload-induced hypertrophy

Am J Physiol Heart Circ Physiol. 2015 Aug 1;309(3):H450-8. doi: 10.1152/ajpheart.00072.2015. Epub 2015 May 29.

Abstract

Left ventricular (LV) hypertrophy (LVH) and congestive heart failure are accompanied by changes in myocardial ATP metabolism. However, the rate of ATP hydrolysis cannot be measured in the in vivo heart with the conventional techniques. Here, we used a double-saturation phosphorous-31 magnetic resonance spectroscopy-magnetization saturation transfer protocol to monitor ATP hydrolysis rate in swine hearts as the hearts became hypertrophic in response to aortic banding (AOB). Animals that underwent AOB (n = 22) were compared with animals that underwent sham surgery (n = 8). AOB induced severe LVH (cardiac MRI). LV function (ejection fraction and systolic thickening fraction) declined significantly, accompanied by deferent levels of pericardial effusion, and wall stress increased in aorta banded animals at week 1 after AOB, suggesting acute heart failure, which recovered by week 8 when concentric LVH restored LV wall stresses. Severe LV dysfunction was accompanied by corresponding declines in myocardial bioenergetics (phosphocreatine-to-ATP ratio) and in the rate of ATP production via creatine kinase at week 1. For the first time, the same linear relationships of the rate increase of the constants of the ATP hydrolysis rate (kATP→Pi) vs. the LV rate-pressure product increase during catecholamine stimulation were observed in vivo in both normal and LVH hearts. Collectively, these observations demonstrate that the double-saturation, phosphorous-31 magnetic resonance spectroscopy-magnetization saturation transfer protocol can accurately monitor myocardial ATP hydrolysis rate in the hearts of living animals. The severe reduction of LV chamber function during the acute phase of AOB is accompanied by the decrease of myocardial bioenergetic efficiency, which recovers as the compensated LVH restores the LV wall stresses.

Keywords: MR spectroscopy; adenosine triphosphate; heart failure; left ventricle hypertrophy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Animals
  • Creatine Kinase / metabolism
  • Female
  • Hydrolysis
  • Hypertrophy, Left Ventricular / metabolism*
  • Hypertrophy, Left Ventricular / physiopathology
  • Magnetic Resonance Spectroscopy
  • Phosphocreatine / metabolism
  • Swine
  • Ventricular Dysfunction, Left

Substances

  • Phosphocreatine
  • Adenosine Triphosphate
  • Creatine Kinase