A CARDIODEPRESSANT FACTOR ISOLATED FROM BLOOD BLOCKS CA-2+ CURRENT IN CARDIOMYOCYTES

A cardiodepressant factor (CDF) was isolated (salt free) from the plasma of dogs after hypovolemic-traumatic shock by column chromatography. CDF was found to exert a concentration-dependent negative inotropic effect in guinea pig papillary muscle; it reduced the amplitude of cell wall motion, the contraction and relaxation velocity, and the frequency of spontaneously beating rat cardiomyocytes in culture, effects that were rapidly reversible upon washout. By means of electrophysiological methods (whole cell recording with patch electrodes and voltage clamp) we tested the effect of CDF on adult guinea pig cardiomyocytes: application of CDF initially decreased the plateau by 7 mV (150 ms after peak of action potential) and reduced the action potential duration by 93 ms (76% of control action potential duration) at 50% and 88 ms (79%) at 90% of repolarization. The plateau was further reduced by 13 mV and the action potential duration was prolonged by 25 ms (106%) at 50% and was prolonged drastically by 156 ms (137%) at 90% of repolarization compared with control. Voltage-clamp experiments have shown that the most prominent effect of CDF is a strong reduction of I(Ca) accompanied by inhibition of I(K) and subsequent repolarization. Similar results have been obtained with neonatal rat cardiomyocytes. Blockage of the calcium inward current can explain the negative inotropic and chronotropic effect of CDF in cardiomyocytes.