In undiseased human ventricular myocytes, I(Ks) exhibits slow activation and fast deactivation kinetics. Therefore, in humans I(Ks) differs from that reported in guinea pig, and it best resembles I(Ks) described in dog and rabbit ventricular myocytes.

Endothelins have been reported to exert a wide range of electrophysiological effects in mammalian cardiac cells. These results are controversial and human data are not available. Our aim was to study the effects of endothelin-1 (ET-1, 8 nmol/l) on the L-type calcium current (ICa-L) and various potassium currents (rapid component of the delayed rectifier, IKr; transient outward current, Ito; and the inward rectifier K current, IK1) in isolated human ventricular cardiomyocytes. Cells were obtained from undiseased donor hearts using collagenase digestion via the segment perfusion technique. The whole-cell configuration of the patch-clamp technique was applied to measure ionic currents at 37 degrees C. ET-1 significantly decreased peak ICa-L from 10.2+/-0.6 to 6.8+/-0.8 pA/pF at +5 mV (66.7% of control, P<0.05, n=5). This reduction of peak current was accompanied by a lengthening of inactivation. The voltage dependence of steady-state activation and inactivation was not altered by ET- 1. IKr, measured as tail current amplitudes at 40 mV, decreased from 0.31+/-0.02 to 0.06+/-0.02 pA/pF (20.3% of control, P<0.05, n=4) after exposure to ET-1. ET-1 failed to change the peak amplitude of Ito, measured at +50 mV (9.3+/-4.6 and 9.0+/-4.4 pA/pF before and after ET-1, respectively), or steady-state IK1 amplitude, measured at the end of a 400-ms hyperpolarization to -100 mV (3.6+/-1.4 and 3.7+/-1.4 pA/pF, n=4). The present results indicate that in undiseased human ventricular myocytes ET-1 inhibits both ICa-L and IKr; however, the degree of suppression of the two currents is different.

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Determinants of early, late and event-free survival of combined valve and coronary artery bypass graft (CABG) surgery were studied in 420 patients using multivariate analysis. It was found that the risk of hospital death increases 5 times when the preoperative NYHA class was > or = IV, 3 times when left ventricular (LV) function is significantly impaired and is double when mitral regurgitation is present. The survival probability of hospital survivors was 91% (87.3-94.5%) at 5 years. Late mortality was determined by advanced preoperative NYHA class ( > or = IV) and the presence of mitral regurgitation. The event-free survival probability of hospital survivors, i.e. total events including death, valve-related complications, ischemic complications and recurrent NYHA class > or = IV, was 73.0% (66.7-79.5%) at 5 years. Postoperative events were determined by the presence of preoperative NYHA class > or = IV, impaired ventricular function, mitral regurgitation and non-sinus rhythm. It is concluded that these parameters can be considered as the most important predictors of clinical outcome after combined valve and CABG surgery.