Use of isolated adult myocytes to evaluate cardiotoxicity. I. sugar uptake and protein synthesis

Abstract

The usefulness of isolated adult cardiac myocytes, both in suspension and in culture, as a model system for measuring cardiotoxicity is evaluated. It has been suggested that isolated adult myocytes should preferably be cultured for such experimentation, as this restores the cells to a physiological preference for fatty acids as a substrate rather than glucose. We show here that the restoration of Ca2+ to cells immediately after isolation results in an artifically enhanced glucose metabolism, as measured by an elevated rate of deoxyglucose uptake. Early restoration of Ca2+ during cell isolation, on the other hand, results in cells with a normal low level of deoxyglucose uptake. We, thus, conclude that cells can be ready for valid toxicity studies immediately after isolation, without the need for culture. The culture of adult feline ventricular cells is also described. These cells, like rabbit but unlike rat, are particularly promising for toxicity studies because they remain quiescent in culture and do not round up. On exposure to norepinephrine, they beat spontaneously and increase their rate of protein synthesis.