K O Ryder1, S M Bryant, G Hart. 1. Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Headington, United Kingdom.
Abstract
OBJECTIVE: The aim was to look for membrane current changes as a basis for the prolongation of action potential duration in left ventricular myocytes following abdominal aortic coarctation. METHODS: Immature female guinea pigs underwent laparotomy and an aortic coarctation was fashioned immediately distal to the renal arteries. After 20 weeks the hearts were removed and single myocytes were isolated from the left ventricles by standard enzymatic techniques. The switch-clamp technique was used. RESULTS: Heart weight:body weight ratio was increased by 7% in the coarctation group (p < 0.01). Systolic left ventricular pressure was 59(SEM 4) mm Hg in control and 76(7) mm Hg in coarctation animals (p < 0.05). Cell capacity was increased by 21% in the coarctation group (p < 0.05), and mean resting potential was 4.6 mV more negative in this group (p < 0.001). Action potential duration at 90% repolarisation was 310(17) ms in the control group (n = 22) and 358(13) ms in the coarctation group (n = 34, p < 0.05). Peak density of L-type calcium current was -8.6(0.4) pA.pF-1 in control and -11.1(0.7) pA.pF-1 in coarctation cells (p < 0.01). The regression line for calcium current versus cell capacity was shifted to higher calcium currents in the coarctation group. The half inactivation potential for this current was shifted by 11.5 mV (p < 0.01). Calcium-activated tail currents were larger and the envelope of tail currents was prolonged in the coarctation cells. No significant differences were found in the amplitude of IK or of IKl. CONCLUSIONS: After infrarenal aortic coarctation, action potential duration of left ventricular myocytes is prolonged. This prolongation may be attributed to an increase in calcium current density and a shift of its inactivation variable, together with an increased magnitude and prolonged time course of sodium-calcium exchange current. These current changes are potentially arrhythmogenic.
OBJECTIVE: The aim was to look for membrane current changes as a basis for the prolongation of action potential duration in left ventricular myocytes following abdominal aortic coarctation. METHODS: Immature female guinea pigs underwent laparotomy and an aortic coarctation was fashioned immediately distal to the renal arteries. After 20 weeks the hearts were removed and single myocytes were isolated from the left ventricles by standard enzymatic techniques. The switch-clamp technique was used. RESULTS: Heart weight:body weight ratio was increased by 7% in the coarctation group (p < 0.01). Systolic left ventricular pressure was 59(SEM 4) mm Hg in control and 76(7) mm Hg in coarctation animals (p < 0.05). Cell capacity was increased by 21% in the coarctation group (p < 0.05), and mean resting potential was 4.6 mV more negative in this group (p < 0.001). Action potential duration at 90% repolarisation was 310(17) ms in the control group (n = 22) and 358(13) ms in the coarctation group (n = 34, p < 0.05). Peak density of L-type calcium current was -8.6(0.4) pA.pF-1 in control and -11.1(0.7) pA.pF-1 in coarctation cells (p < 0.01). The regression line for calcium current versus cell capacity was shifted to higher calcium currents in the coarctation group. The half inactivation potential for this current was shifted by 11.5 mV (p < 0.01). Calcium-activated tail currents were larger and the envelope of tail currents was prolonged in the coarctation cells. No significant differences were found in the amplitude of IK or of IKl. CONCLUSIONS: After infrarenal aortic coarctation, action potential duration of left ventricular myocytes is prolonged. This prolongation may be attributed to an increase in calcium current density and a shift of its inactivation variable, together with an increased magnitude and prolonged time course of sodium-calcium exchange current. These current changes are potentially arrhythmogenic.
Authors: Jochen Rose; Antonis A Armoundas; Yanli Tian; Deborah DiSilvestre; Miroslava Burysek; Victoria Halperin; Brian O'Rourke; David A Kass; Eduardo Marbán; Gordon F Tomaselli Journal: Am J Physiol Heart Circ Physiol Date: 2005-01-06 Impact factor: 4.733