title: Myocardial ATP hydrolysis rates in vivo: a porcine model of pressure overload-induced hypertrophy.
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.
authors.affiliation: Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xiong
authors.affiliation: Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota.
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota.
authors.forename: Cory
authors.initials: C
authors.lastname: Swingen
authors.affiliation: Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota.
authors.forename: Albert
authors.initials: A
authors.lastname: Jang
authors.affiliation: Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota zhang047@umn.edu.
authors.forename: Jianyi
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D005260:Female; D006868:Hydrolysis; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000503:physiopathology; D009682:Magnetic Resonance Spectroscopy; D010725:Phosphocreatine / Q000378:metabolism; D013552:Swine; D018487:Ventricular Dysfunction, Left
chemical_list: D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003402:Creatine Kinase
keywords: MR spectroscopy; adenosine triphosphate; heart failure; left ventricle hypertrophy