Key result
Catecholamine infusion increases myocardial ATP hydrolysis rates ~2.1-fold without altering creatine kinase flux.
Why the study?
Does high cardiac workload induced by catecholamines alter the transmural ATP hydrolysis rate or CK flux rate in normal porcine hearts?
Does high cardiac workload induced by catecholamines alter the transmural ATP hydrolysis rate or CK flux rate in normal porcine hearts?
Absolute Event Rate: 2.35% vs 1.11%
p-value: p=<0.01
Demonstrates a novel in vivo 31P MR spectroscopy method to measure transmural myocardial ATP kinetics, proving that healthy hearts manage increased workload through proportionally increased ATP hydrolysis across both inner and outer left ventricular layers.
Establishes baseline transmural energetics in healthy porcine hearts; leaves open relevance to human cardiovascular disease.
PURPOSE: Compare the transmural distribution of forward creatine kinase reaction (kf,CK ) and ATP hydrolysis rate (kr,ATPase ) in the myocardium of normal porcine heart. Rate constants were extracted from partially relaxed spectra by applying the T1nom method, effectively reducing data acquisition time by up to an order of magnitude. THEORY AND METHODS: T1nom method for double saturation of PCr and Pi is introduced and validated through simulations. Bioenergetics was measured in vivo utilizing one-dimensional chemical shift imaging (1D-CSI) magnetic resonance (31) P spectroscopy. RESULTS: At basal conditions, there was no significant difference between subepicardial layers (EPI) vs. the subendocardial layers (ENDO) for both fluxf,CK and fluxr,ATPase . At high cardiac workload (HWL), where the rate pressure product increased 2.6-fold, PCr/ATP ratio and fluxf,CK showed no significant change in both EPI and ENDO layers, while fluxr,ATPase increased significantly (baseline: 1.11 ± 0.12 and 1.12 ± 0.13 μmol/g/s, EPI and ENDO, respectively; to HWL: 2.35 ± 0.27 and 2.21 ± 0.08 μmol/g/s, EPI and ENDO, respectively, each P < 0.01 vs. baseline). CONCLUSION: In the normal heart, increase of cardiac work state is accompanied by an increase in ATP hydrolysis rate with no changes in CK flux rate. There are no significant differences between EPI vs. ENDO concerning the ATP hydrolysis rate or CK flux rate in both baseline and high cardiac work states.
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Jang et al. (2016) studied Normal porcine heart. High cardiac workload (catecholamine infusion) vs. Baseline cardiac workload was evaluated on ATP hydrolysis rate (fluxr,ATPase) in the subepicardial layer (EPI) (p=<0.01). Increasing cardiac work state via catecholamine infusion significantly increased ATP hydrolysis rates in normal porcine hearts without changing creatine kinase flux rates, with no significant differences between subepicardial and subendocardial layers.
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