Calcium- and sodium-dependent modulation of stretch-induced arrhythmias in isolated canine ventricles.

Gadolinium-sensitive stretch-activated channels have been implicated in the process of mechanotransduction signaling of ventricular myocardium. Such channels nonspecifically transport Na+ and Ca2+ in the inward direction. We tested the hypothesis that Na+ and Ca2+ influx are important in the genesis of stretch-induced arrhythmias (SIAs) in an isolated, blood-perfused canine ventricle. To elicit SIAs, left ventricular volume was transiently increased in early diastole using a computerized servo-pump system. Monophasic action potential recordings revealed stretch-induced depolarizations (SIDs) that preceded the arrhythmias. In five ventricles, raising the perfusate Ca2+ concentration from 1 to 3 mM increased ventricular sensitivity to SIAs, manifested by a decrease in the volume change required to precipitate an arrhythmia 50% of the time (delta V50) from 19.5 +/- 2.7 to 15.2 +/- 1.9 ml (P < 0.05). When the perfusate Na+ concentration was decreased from 150 to 90 mM in seven ventricles, delta V50 greatly increased (31.1 +/- 14.4 vs. 17.7 +/- 5.3 ml, P < 0.05), and SID amplitude decreased by 47% (P = 0.002). The suppression of SIAs with low extracellular Na+ is unlikely to be mediated by voltage-gated Na+ channels because lidocaine (5 mg/dl) did not alter SID amplitude. Thus the transsarcolemmal Na+ gradient (and probably that of Ca2+) modulates the amplitude of SIDs, which, in turn, initiate SIAs. These data provide initial evidence that Na+ and Ca2+ help mediate the mechanotransduction processes that underly the genesis of SIAs.

Characteristics of left-ventricular isovolumic pressure waves in isolated dog hearts.

The peak pressure which a chamber would develop in isovolumic contraction at end-diastolic distention (peak source pressure) is an expression of contractile vigor and a determinant of systolic performance. One can predict source pressure of an ejecting beat by fitting its isovolumic phases with a model isovolumic-wave function. Characteristics of the left-ventricular isovolumic pressure wave (amplitude, duration, shape) were studied in isolated, perfused, artificially loaded dog hearts, where strictly isovolumic conditions could be obtained over a wide range of cavity volumes at constant heart rate and approximately constant contractile state. The characterization involved two steps: (1) beginning and ending points were identified by a transition-locating algorithm, and (2) Fourier analysis was performed on points in between. The amplitude of the isovolumic pressure wave increased with cavity volume as expected, the duration of contraction increased with cavity volume, and the shape of the wave (normalized Fourier coefficients) depended slightly on the cavity volume. Duration of contraction declined slightly with increasing heart rate, but the shape of the isovolumic pressure wave was independent of heart rate. The mean shape was similar to that found in dog hearts subjected to one-beat aortic-root clamping in vivo-the wave being less sharply peaked than a cosine wave and tilted to the left because relaxation was slower than contraction. When ejecting beat duration declined linearly with increasing ejection fraction. This relation could be used to predict the duration of the isovolumic beat corresponding to the duration of an ejecting beat. Source pressure could then be predicted by fitting a model isovolumic wave of predicted duration to the isovolumic contraction phase of the ejecting beat. In 270 comparisons, the ratio of predicted peak source pressure to observed peak source pressure was 1.04 +/- 0.10 (SD). This method provides a reasonably accurate prediction of an important determinant of systolic performance.