Kaoru Yanagihara

Quinapril with High Affinity to Tissue Angiotensin-Converting Enzyme Reduces Restenosis after Percutaneous Transcatheter Coronary Intervention

Experimental studies have demonstrated that vascular injury resulted in an induction of vascular angiotensin-converting enzyme (ACE), and have suggested that inhibition of vascular ACE might be important in the prevention of restenosis. The present study aimed to determine the effect of quinapril, an ACE inhibitor with high affinity to tissue ACE, on restenosis following coronary intervention. The design of this study was a prospective, randomized, open, and non-placebo controlled trial. Patients with ischemic heart disease were enrolled after successful percutaneous transluminal coronary angioplasty or stent implantation at 7 participating institutions. Two hundred and fifty-three patients with 294 lesions were randomly assigned to the quinapril (10–20 mg per day) group or control group. Administration of quinapril was continued for 3–6 months of the follow-up. Quantitative coronary angiography was performed before and after angioplasty and at follow-up. Core laboratory measurements were performed independently and blinded. Follow-up angiography was performed in 108 patients with 124 lesions in the quinapril group and in 107 patients with 130 lesions in the control group. The baseline characteristics and findings of angioplasty showed no significant differences between the two groups. However, in the quinapril group, restenosis per patient and per lesion was significantly lower (34.3% vs. 47.7%, p < 0.05 and 30.6% vs. 43.8%, p < 0.05). Multivariable analysis revealed that administration of quinapril independently contributed to reducing the restenosis per patient and per lesion (odds ratio, 0.73; 95% confidence interval, 0.54–0.99 and odds ratio, 0.75; 95% confidence interval, 0.57–0.99). In conclusion, quinapril significantly reduces restenosis following coronary intervention.

Mathematical simulation of the Wenckebach phenomenon in Purkinje fibers

SummaryWe were able to simulate the Wenckebach phenomenon using a model of a one-dimensional cable, consisting of 20 serially connected Purkinje fiber cells represented by the model of McAllister, Noble, and Tsien. The internal resistance between the 10th and 11th cells was modified to five times the normal. To reconstruct the action potential, the derivative equation was solved using a fourth-order Runge-Kutta algorithm. When the first cell of the cable was stimulated, periodically, at an interval of 610ms, a 9:8 Wenckebach pattern was elicited in the conduction between the tenth and 11th cells. Lower order 5:4, 4:3, 3:2 Wenckebach patterns were observed at pacing cycle length of 605, 600—595, and 590—575 ms, respectively. At a pacing cycle length of 570ms or less, 2:1 block was elicited. In another simulation, only whenINa was 0 could the Wenckebach phenomenon be elicited in a cable model, in which internal cell resistance and membrane capacitance were uniformly set, but in which theINa of the center two cells of the cable were alternated between 1 and 0. A localized increase in internal resistance, a relatively long time constant of deactivation of the delayed rectifier outward current, and a relatively rapid rate of pacing cycle length was necessary to evoke the Wenckebach phenomenon. The conductance of the delayed rectifier current at the end of an action potential increased progressively, except after a dropped beat when it was allowed to decrease. It was concluded that the change of conductance affected the cable property of the fiber and consequently evoked the Wenckebach phenomenon.