Changes in myocardial substrate and energy metabolism by S-(4)-hydroxyphenylglycine and an N-(6)-derivative of adenosine.
In 15 mongrel open chest dogs oxidative myocardial carbohydrate utilization was stimulated by activation of pyruvatedehydrogenase with S-(4)-hydroxyphenylglycine (HPG) or by inhibition of lipolysis with N(6)-allyl-N(6)-cyclohexyladenosine (PAA). HPG and PAA shifted cardiac respiratory quotients (RQ) from 0.83 to 0.89 and 0.99, respectively. Oxygen extraction ratio of lactate was significantly increased by both interventions. Arterial nonesterified fatty acids (NEFA) concentration decreased significantly only by PAA. The oxygen saving potency of both interventions was quantified over a wide hemodynamic range by comparing the directly measured myocardial oxygen consumption (MVO2) with the myocardial energy requirements calculated from its hemodynamic determinants according to the Bretschneider formula during base conditions and beta-stimulation. Inhibition of peripheral lipolysis with PAA reduced MVO2 by 14%, enzyme activation with HPG by 8%. The results show that the efficiency of the myocardial energy supply can be influenced by manipulation of the oxidative substrate metabolism.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D050260:Carbohydrate Metabolism; D003326:Coronary Circulation; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects*; D004789:Enzyme Activation; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006439:Hemodynamics; D008066:Lipolysis / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D013268:Stimulation, Chemical
D011768:Pyruvate Dehydrogenase Complex; C050057:N(6)-allyl-N(6)-cyclohexyladenosine; C023010:4-hydroxyphenylglycine; D000241:Adenosine; D005998:Glycine