Study objective - The aim was to study the in vivo interaction and regulation of myocardial perfusion, metabolism, and pump function in an open chest canine model using a combination of potentially non-invasive and clinically useful techniques.Design - To assess potential regulatory mechanisms and the interaction of myocardial perfusion, metabolism, and contractile function responses during changes in cardiac workload, noradrenaline (1 μg·kg-1·min-1) was infused and hypoxia was produced by increasing the inspired ratio of nitrogen to oxygen to produce a Pao2 of 2.6-4.0 kPa in separate interventions.Subjects - Nine mongrel dogs of either sex, age 2-5 years, weight 8.5(SD 2.2) kg, were studied in separate interventions.Measurements and main results - Myocardial perfusion was determined using 2H nuclear magnetic resonance (NMR) measured washout of deuterium oxide from the left ventricle interpreted with a one component Kety-Schmidt exponential model. High energy phosphate bioenergetics were determined by 31P NMR measurements of the phosphocreatine/ATP ratio. Redox state was estimated by nicotinamide adenine dinucleotide fluorometry expressed as percent change from the baseline, normalised to maximum response measured at 100% inspired N2. Mechanical function was evaluated using heart rate × systolic blood pressure and oxygen consumption measurements. During both noradrenaline infusion and hypoxia, mechanical function increased significantly from control values: heart rate × systolic blood pressure = 1.9(SD 0.5), 3.6(0.1), and 2.6(0.4), respectively; oxygen consumption = 0.9(2), 1.6(0.1), and 1.2(0.6) ml·min-1·100 g-1. Myocardial perfusion increased to support the increased workloads, from 87(10) to 131(20), and from 60(12) to 182(14) ml·min-1·100 g-1, respectively. ADP, estimated by the phosphocreatine/ATP ratio, did not change during noradrenaline infusion [2.4(0.2) to 2.4(0.7)], but decreased during hypoxia [2.4(0.4) to 1.7(0.5)]. Redox state decreased during noradrenaline infusion, from 100% to 84(0.7)%, and increased during hypoxia, from 100% to 140(10)%.Conclusions - Similar changes in workload induced by different physiological stimuli are associated with different biochemical responses even though changes in perfusion are similar. The data suggest that myocardial function is regulated by different biochemical mechanisms under different physiological conditions, ie, there is probably no universal regulator of myocardial function. It is now possible to evaluate potential metabolic regulators of myocardial function in an in vivo animal model.
Bibliographical noteFunding Information:
The authors would like to thank Jeannette Forte and Evelyn Robles for their excellent secretarial assistance and Christopher Duska and Ihor Ponomarenko for their technical assistance. This work was supported by NIH R01 HL39208-02, the Council for Tobacco Research, New York, the WW Smith Foundation, Philadelphia, and the Sklarow Fund, Buffalo. Dr Osbakken was an Established Investigator of the American Heart Association during the tenure of this work.
- 31P NMR
- Deuterium NMR
- Mechanical function