A number of cardiac metabolic intermediates, namely, adenosine triphosphate (ATP), H+, phosphocreatine (PCr), inorganic phosphate (P(i)), adenosine diphosphate (ADP), and related functions of these intermediates, Gibbs' free energy of ATP hydrolysis (DELTAG) and phosphorylation ratio [ATP/(ADP.P(i))], are thought to adjust mitochondrial oxidative phosphorylation rates to conform to mechanical demand. The effects of hypothermia and altered perfusion pressure on these parameters were evaluated in 12 hearts from Sprague-Dawley rats perfused in the Langendorff mode. P-31-nuclear magnetic resonance (NMR) spectra were obtained at cardiac temperatures between 20 and 37-degrees-C, and coronary perfusion pressures between 20 and 145 cm H2O. Coronary flow varied between 0.5 and 15 ml/min throughout this range of intervention. Heart rate (HR), left ventricular systolic pressure (LVSP), and specific volumetric coronary flow (SCF) were determined for each temperature and perfusion pressure. The product HR x LVSP directly correlated with perfusion pressure at all temperatures. The temperature dependence could be represented by an overall activation energy of 72.7 kJ/M. In the constant temperature experiment, SCF and HR x LVSP fell linearly with decreasing perfusion pressure. Quantitative evaluation of the relationship between cardiac function and the metabolic intermediates described above defined these intermediates as nonregulatory with the possible exception of H+.

The present study was performed to determine whether 31 P NMR relaxation times ( T 1 ) of adenosine triphosphate (ATP) might be used to monitor the resultant altered myocardial physiology produced by ischemia and possibly to explain mechanisms of altered physiology. To this end, pre‐and post‐ischemic T 1 s were determined in hearts perfused in the Lan‐gendorff mode, using 31 P NMR inversion recovery methods. In hearts without any pretreatment (CON), post‐ischemic ATP Ti values were significantly decreased compared with pre‐isch‐emic values ( P <0.05): Pre‐isch: γ = 0.58 ± 0.08; α = 62 ± 0.06; β = 0.38 ± 0.08; Post‐isch: γ = 0.33 plusmn; 0.05; α = 0.43 ± 0. 03; β = 0. 23 plusmn; 0.05. In groups pretreated with creatine (CR), cyclocreatine (CY), or superoxide dismutase plus catalase (SOD‐CAT) before ischemia, the post‐ischemic ATP T 1 values were simlilar and were not significantly changed from pre‐ischemic values. These combined data suggest that T 1 s of ATP might be used to monitor altered myocardial physiology and could provide insight into mechanisms of alteration.

Metabolic regulatory mechanisms are designed to maintain stable myocardial function during extremes in physiological insult; they can now be studied in vivo and may provide insight into mechanisms of altered myocardial functional decompensation during disease processes. To determine mechanisms of myocardial stability during hypoxia and acute pressure loading, creatine kinase (CK) kinetics (forward rate constant, Kf, and flux of phosphocreatine, PCr, to adenosine triphosphate, ATP), and nicotinamide adenine dinucleotide (NADH) redox state were determined with 31P nuclear magnetic resonance (NMR) and NADH fluorometry, respectively, and correlated with heart work (heart rate x systolic blood pressure, HR x SBP), cardiac output (CO) and O2 consumption (MVO2) in 15 anesthetized open chest dogs. Hypoxia (PaO2 of 30-35 mm Hg) was produced in 6 dogs with an inspired O2/N2 of 200/3,000. Cardiac loading was produced in 9 dogs by administration of norepinephrine (NE, 1 micrograms/kg/min). Each dog acted as its own control. Baseline NADH fluorometry, 31P-NMR saturation transfer and cardiac function measurements were performed simultaneously in each dog, after which the experimental interventions were made. Similar increases in HR x SBP, CO, and MVO2 which occurred during both interventions were associated with different bioenergetic responses. During NE infusion, the Kf of CK increased from control; during hypoxia, the Kf decreased from control (p less than 0.05). Flux of PCr----ATP was significantly lower during hypoxia than during NE infusion (p less than 0.05). PCr was decreased significantly during NE infusion (p less than 0.05). In addition, NADH redox state increased (from baseline of 100%) during hypoxia (140 +/- 10%) and decreased during NE infusion (78 +/- 6%).(ABSTRACT TRUNCATED AT 250 WORDS)