Importance of fatty acid oxidation in the neonatal pig heart with hypoxia and reoxygenation.
We investigated mechanical and metabolic responses in isolated, isovolumically-beating, pig hearts (n = 7), 12 h to 2 days of age; subjected to hypoxia followed by reoxygenation. Hearts were perfused with an erythrocyte-enriched (hematocrit approximately 15%) solution during 3 consecutive 30-min periods: pre-hypoxia, arterial perfusate [O2] = 7.6 +/- 0.2 vol% (PO2 approximately 270 torr); hypoxia, [O2] = 0.6 +/- 0.1 vol% (approximately 10% hemoglobin saturation) and reoxygenation. Prehypoxia parameters averaged: left ventricular peak systolic pressure, 107.1 +/- 2.9 mmHg and end-diastolic pressure, 0.9 +/- 0.3 mmHg; coronary flow, 2.8 +/- 0.2 ml/min per g; myocardial O2 consumption, 59.4 +/- 1.6 microliters/min per g and fatty acid oxidation, 37.1 +/ 1.1 nmol/min per g. Fatty acid oxidation was determined using [14C]palmitate. Early in hypoxia, coronary flow increased 3-4 fold but then decreased. Throughout hypoxia, hearts released lactate yet continued to oxidize fatty acids (45-50% of myocardial O2 consumption). By the end of the hypoxia period, hearts exhibited mechanical failure (peak systolic pressure approximately 55 mmHg and end-diastolic pressure approximately 19 mmHg). After 30 min of reoxygenation, peak systolic pressure recovered to 80.6 +/- 2.6 mmHg and end-diastolic pressure remained elevated at 6.1 +/- 1.9 mmHg. However, fatty acid oxidation rates were 90-95% above pre-hypoxia values. Thus, during 30 min of severe hypoxia neonatal pig hearts exhibited mechanical dysfunction, yet continued to oxidize exogenously supplied fatty acids. Moreover, fatty acid oxidation was enhanced during reoxygenation.
Ascuitto
R J
RJ
Tulane University School of Medicine, Department of Pediatrics, New Orleans, Louisiana.
Ross-Ascuitto
N T
NT
Ramage
D
D
McDonough
K H
KH
D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure; D002245:Carbon Dioxide / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D006321:Heart / Q000502:physiology*; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D007773:Lactates / Q000096:biosynthesis; D019344:Lactic Acid; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D013552:Swine
D005227:Fatty Acids; D007773:Lactates; D010169:Palmitic Acids; D002245:Carbon Dioxide; D019308:Palmitic Acid; D019344:Lactic Acid; D010100:Oxygen