Accumulation and excretion of long-chain acylcarnitine by rat hearts; studies with aminocarnitine.
During Langendorff perfusion of rat heart with aminocarnitine, long-chain acylcarnitine (LCAC) accumulates in heart cells, from which it is excreted by the heart. The heart function remains intact during this process. The accumulation of LCAC can be inhibited by the simultaneous addition of an inhibitor of the outer membrane carnitine palmitoyl-coenzyme A transferase (CPT-1), indicating that aminocarnitine is a specific inhibitor of the inner membrane isoenzyme (CPT-2). LCAC accumulation is associated with glycogen depletion. After 60 min perfusion with aminocarnitine, electron microscopy shows large multilamellar lipid vesicles, especially in cardiomyocytes, which are depleted in glycogen granula. Multilamellar lipid vesicles are also found in the blood vessels. Extraction of the perfusate shows the presence of LCAC, fatty acid and phosphatidylethanolamine. Morphological analysis with freeze fracturing and thin sectioning furthermore reveals that the sarcolemma is not deteriorated during the export of LCAC to the coronary vessels. Since cardiac structures and functions are intact, LCAC alone is not the clue for ischemic damage. Therefore the present work supports the hypothesis that acidosis rather than LCAC is of primary importance to ischemic damage.
Hülsmann
W C
WC
Thorax Centre, Erasmus University Rotterdam, The Netherlands.
Schneijdenberg
C T
CT
Verkleij
A J
AJ
D000818:Animals; D001622:Betaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002331:Carnitine / Q000378:metabolism*; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors*; D003327:Coronary Disease; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000648:ultrastructure; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012508:Sarcolemma / Q000648:ultrastructure*
D001622:Betaine; C045761:emeriamine; D002334:Carnitine O-Palmitoyltransferase; D002331:Carnitine