EFFECTS OF 2-DEOXYGLUCOSE, A METABOLIC INHIBITOR, ON SPONTANEOUS CONTRACTION AND ADRENOCEPTOR RESPONSIVENESS IN CULTURED RAT VENTRICULAR MYOCYTES

Although it is well known that myocardial ischemia induces the depleti on of myocardial ATP and sustained myocardial dysfunction, the mechani sms causing impaired myocardial function have not been elucidated comp letely. To clarify the relationship between ATF depletion and myocardi al contractility, we investigated the influence of myocardial ATP depl etion on spontaneous beating in cultured rat ventricular myocytes. Fur thermore, because catecholamines have been used to improve myocardial contraction in the ischemic heart, we attempted to determine whether t he ATP depletion per se alters the contractile responses to alpha(1)- and beta-adrenoceptor stimulation. After 24 hr of culture in the prese nce of a metabolic inhibitor, 2-deoxyglucose (2DG, 5mM), myocardial co ntractility decreased to 19% of the vehicle level, and returned to nor mal after the removal of 2DG. The beating rate did not show any altera tions in the vehicle, in the presence of 2DG (2DG [+/+]) or after the removal of 2DG (2DG [+/-]). Norepinephrine (NE) caused significant dec reases in beating rate and increases in contractility in all groups. I soproterenol (ISP) caused significant increases in beating rate and co ntractility in all groups. In the 2DG (+/+) group, the contractility w as significantly lower as compared to other groups during NE or ISP st imulation. However, the percent change of contractility was similar to those of other groups after NE or ISP stimulation in the 2DG (+/+) gr oup. These results suggest that decreased myocardial ATP causes the de creased contractility and does not affect the alpha(1)- or beta-adreno ceptor-mediated responses.