Mechanical function and substrate oxidation in the neonatal pig heart subjected to pacing-induced tachycardia

Isolated, paced, isovolumically beating, neonatal pig ( approximately 2 days) hearts were perfused with a crystalloid solution during four periods: (1) baseline, HR 150 bpm; (2) HR-response curves, HR 150-360 bpm; (3) tachycardia, HR 300 bpm; and (4) posttachycardia, HR 150 bpm. Group I was studied with glucose (5. 5 mM) as the sole substrate. During baseline, left ventricular peak systolic pressure (PSP) averaged 123 +/- 7 mm Hg; end diastolic pressure (EDP), 4.9 +/- 0.4 mm Hg; relaxation time constant (Tau), 29.5 +/- 3.9 ms; glucose oxidation (14CO2 from [14C]glucose), 1535 +/- 96 nmol/min/gdry; and myocardial oxygen consumption (MVO2), 17.4 +/- 0.4 micromol/min/gdry. During tachycardia, PSP was 83 +/- 4* mm Hg; EDP, 9.8 +/- 1.7* mm Hg; Tau, 29.9 +/- 5.4 ms; glucose oxidation, 1921 +/- 136* nmol/min/gdry; and MVO2, 21.1 +/- 0.7* micromol/min/gdry (*different from baseline, P < 0.05). Posttachycardia, all parameters returned to near baseline values, except EDP, which remained elevated. Group II was studied with glucose (5.5 mM) and palmitate (0.55 mM). When compared to those of Group I, the mechanical responses were similar. During baseline, glucose oxidation was 149 +/- 24 nmol/min/gdry; palmitate oxidation, 343 +/- 28 nmol/min/gdry; and MVO2, 18.4 +/- 0.7 micromol/min/gdry. Both oxidation rates increased significantly during tachycardia, indicating aerobic metabolic reserve. Posttachycardia, glucose oxidation returned to baseline, but palmitate oxidation remained elevated, suggesting enhanced beta oxidation. Group III was perfused with glucose (5.5 mM) and pyruvate (5.5 mM), along with iodoacetate (50 microM) to inhibit glycolysis. PSP was maintained, but Tau (HRs >/= 270 bpm) and EDP (HRs >/= 180 bpm) markedly increased. In conclusion, for the isovolumically beating, neonatal pig heart stressed with tachycardia: (1) PSP decreases, EDP increases, and Tau remains relatively constant; (2) substrate oxidation is enhanced; and (3) glycolysis, rather than glucose oxidation, appears to be important for supporting ventricular diastolic function.