MECHANICAL AND METABOLIC CHARACTERIZATION OF ISCHEMIC CONTRACTURE IN THE NEONATAL PIG-HEART

Isolated, paced, isovolumetrically beating piglet hearts (n = 37) unde rwent retrograde aortic perfusion with a crystalloid solution during t hree periods: 1) baseline (coronary perfusion pressure 60 mm Hg), 2) i schemia (coronary flow 10% of baseline for approximate to 80 min), and 3) reperfusion (perfusion pressure returned to baseline). In one grou p of hearts, glycolysis (using (H2O)-H-3 formation from [H-3]glucose) was assessed. During baseline, peak systolic pressure (PSP) was 101.1 +/- 5.0 mm Hg, end diastolic pressure (EDP) 4.4 +/- 0.5 mm Hg, glycoly sis 970.5 +/- 65.3 nmol/min/g(wet), and myocardial glycogen 234.8 +/- 12.0 mu mol/g(dry). During ischemia, PSP decreased to 23.3 +/- 2.7 mm Hg, EDP increased to 12.3 +/- 0.7 mmHg, myocardial glycogen decreased to 181.5 +/- 30.3 mu mol/g(dry) and lactate (approximate to 154 mu mol /g(wet)) and glycerol (approximate to 930 nmol/g(wet)) were released. Myocardial contracture correlated with a decrease in lactate release. Glycolysis decreased to approximate to 400 nmol/min/g(wet) and remaine d stable, accounting for approximate to 50% of the lactate produced. D uring reperfusion, PSP recovered to 79.8 +/- 3.5 mmHg, EDP 6.6 +/- 1.7 mm Hg, and glycolysis 1103.9 +/- 81 nmol/min/g(wet). In a second grou p of hearts, with similar mechanical responses, glucose oxidation (usi ng (CO2)-C-14 formation from [C-14]glucose) was evaluated. During base line, glucose oxidation was 165.4 +/- 15.9 nmol/min/g(wet) and correla ted closely (r = 0.957) with mechanical activity. With ischemia, gluco se oxidation decreased to approximate to 17 nmol/min/g(wet), yet accou nted for approximate to 42% of the ATP produced. Upon reperfusion, glu cose oxidation returned to baseline values, but now correlated poorly (r = 0.574) with mechanical activity. We conclude that for neonatal he arts undergoing severe low-flow ishcemia: 1) myocardial contracture is associated with a decline in lactate release, implying impaired lacta te production and/or clearance; 2) glycolysis may not full account for the lactate released, suggesting nonglycolytic sources for energy pro duction; 3) glycerol release is stimulated, indicating hydrolysis of t riacylglycerols; 4) glucose oxidation provides an important source of ATP; and 5) glycolysis and glucose oxidation return to baseline values upon reperfusion, despite depressed contractile function, indicating dissociation between mechanical and metabolic recovery.