Effects of acylcarnitine transferase blockade on metabolism and function in the normally and underperfused canine myocardium.
The acylcarnitine transferase blocking agent, sodium 2(5-(4-chlorophenyl)-pentyl)-oxirane-2-carboxylate (Clomoxir, INN), effectively inhibits free fatty acid oxidation, thereby decreasing myocardial oxygen consumption in the normally perfused myocardium without influencing cardiodynamic parameters. As a consequence, however, arterial free fatty acid levels increase significantly. In an acute dog model, we investigated the hypothesis that the sodium 2(5-(4-chlorophenyl)-pentyl)-oxirane-2-carboxylate-induced decrease in myocardial oxygen consumption may also improve the energetic situation in the underperfused myocardium. Regional myocardial function was assessed by means of subendocardially inserted ultrasonic crystals, and changes in metabolism were measured regionally by means of a catheter inserted into a local myocardial vein in the underperfused area. The flow in the circumflex coronary artery was reduced on average by 53.5% followed 30 min later by an infusion of sodium 2(5-(4-chlorophenyl)-pentyl)-oxirane-2-carboxylate (dosage: 20 mg/kg over 20 min). Arterial free fatty acid levels continuously increased, whereas arterial glucose levels decreased. In accordance with the situation in the normally perfused myocardium, free fatty acid uptake and oxygen uptake were also reduced in the underperfused area. However, sodium 2(5-(4-chlorophenyl)-pentyl)-oxirane-2-carboxylate induced a further, transient increase in end-diastolic segment length and a sustained decrease in systolic shortening in the underperfused area, indicating a further deterioration in regional myocardial function. Control experiments with infusion of 9 g/l sodium chloride showed no change in the degree of regional myocardial dysfunction throughout the observation period.(ABSTRACT TRUNCATED AT 250 WORDS)
Seitelberger
R
R
II. Department of Surgery, University of Vienna, Austria.
Huber
S
S
Schwarzacher
S
S
Raberger
G
G
D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors*; D003327:Coronary Disease / Q000503:physiopathology; D004285:Dogs; D004852:Epoxy Compounds / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*
D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D005230:Fatty Acids, Nonesterified; C035111:B 807-27; D000217:Acyltransferases; D002334:Carnitine O-Palmitoyltransferase