FUNCTIONAL-SIGNIFICANCE OF ENERGY PATHWAY S IN CARDIOMYOCYTES

To study the relative roles of creatine kinase (CK) and adenylate syst ems in cardiac energy turnover, the effect of CK inhibitor, iodoacetam ide-(IAA, 0,5 mM), and 2-deoxyglucose-(DOG, 2 mM) induced) 65% depleti on of adenine nucleotides at slightly decreased CK flux was determined in isolated rat heart. Both substances did not substantially affect c ontractile parameters of the isovolumic heart. However, an augmentatio n of cardiac work induced by isoproterenol addition was feable and tra nsient in IAA-treated hearts while the response of DOG-treated hearts was well preserved: The cardiac failure after IAA treatment was associ ated with unreversible fall in myocardial ATP content as evidenced by P-31-NMR technique. Furthermore, these hearts were unable to perform c ardiac pump function due to insufficient cardiac filling and distensib ility. The DOG-treated hearts exhibited 50 % reduction in the pump fun ction and were able to increase their work in elevated resistance. The results suggest that CK pathway is extremely important for both full cardiac relaxation and maximal contractile function.