Changes in myocardial substrate utilisation and protection of ischemic stressed myocardium by oxfenicine [(S)-4-hydroxyphenylglycine].
Potential protective effects of oxfenicine [(S)-4-hydoxyphenylglycine] in ischemic stressed canine myocardium have been studied. This compound is characterized as a drug leading to metabolic inhibition of free fatty acid (FFA) metabolism. The drug (0.06 mmol . kg-1 body weight) caused no changes in hemodynamics or energy demand (Et) but depressed myocardial oxygen consumption (MVO2) by 11% (P less than 0.02). Significant changes in FFA and lactate metabolism were observed: lactate extraction (EX) increased from 22.5-37.1 mumol/Min, extraction ratio (EXR) from 16.5-30% and oxygen extraction ratio (OER) from 24.8-38%; EX of FFA decreased from 6900-5000 nmol/min, EXR from 48.2-31.4% and OER from 59.7-46.6%. Arterial concentrations of FFA and lactate remained unchanged. EX, EXR and OER of glucose were not affected under basic conditions. In the same collective, repeated ischemia (3 min) was produced by proximal occlusion of the left anterior descending artery (LAD). The efficiency of the drug was examined by (a) the amounts of ischemia metabolites released in the early reperfusion and (b) quantification of O2-debt and O2-repayment in the occlusion- and reperfusion periods. Compared to control occlusions, premedication led to a reduced O2-debt (P less than 0.01) combined with a reduced amount of oxygen additionally taken up in the early reperfusion (P less than 0.05). Furthermore, release of potassium increased (+7.1%; P less than 0.05); release of lactate (-32%, P less than 0.001) and inorganic phosphate (-34%, P less than 0.01) decreased. These data give support to the concept that a pharmacologically induced shift of cardiac metabolism with reduction of FFA utilisation may be favourable in circumstances with limited oxygen supply.
D000818:Animals; D050260:Carbohydrate Metabolism; D003327:Coronary Disease / Q000378:metabolism*; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects
D005230:Fatty Acids, Nonesterified; D007773:Lactates; D019344:Lactic Acid; C023010:4-hydroxyphenylglycine; D005998:Glycine