CONTRACTION-EXCITATION FEEDBACK IN AN EJECTING WHOLE HEART MODEL - DEPENDENCE OF ACTION-POTENTIAL DURATION ON LEFT-VENTRICULAR DIASTOLIC AND SYSTOLIC PRESSURES

Study objective - Contraction-excitation feedback may play a role in arrhythmogenesis in heart failure. The aims of this study were to determine whether contraction-excitation feedback has a significant effect on action potential duration within a physiological range of pressures, and to investigate the individual effects of left ventricular end diastolic and peak systolic pressures on action potential duration. Design - A new model was developed for studying contraction-excitation feedback in a physiologically ejecting isolated heart preparation. Hearts were perfused via the left atrium, ejecting against an aortic afterload. By varying left atrial and aortic pressures, left ventricular end diastolic pressure and left ventricular peak systolic pressure were controlled independently. Intracellular potentials were recorded from the epicardium. Experimental material - Hearts (n = 33) were obtained from guinea pigs weighing 300-350 g. Measurements and main results - Increasing left ventricular end diastolic pressure from 0.3 to 1.1 kPa (2.2 to 8.3 mm Hg), at constant left ventricular peak systolic pressure, shortened action potential duration by 11.3(SEM 1.5) ms (p < 0.0005). Action potential duration achieved a new steady state within 30 s of a change in end diastolic pressure. The changes were fully reversible. The effects of left ventricular peak systolic pressure variation at constant left ventricular end diastolic pressure were less marked. Increasing left ventricular peak systolic pressure from 10.3 to 13.1 kPa (75 to 100 mm Hg) shortened action potential duration by 2.1(0.7) ms (p < 0.01). Reduction of aortic pressure below 8 kPa had variable effects on action potential duration, reflecting the development of ischaemia. Conclusion - The results show the existence of contraction-excitation feedback in a physiologically ejecting whole heart preparation and suggest that raised end diastolic pressure may contribute to arrhythmogenesis in heart failure.