Pathophysiology and Natural History Coronary Artery Disease

The effect of pacing-induced ischemia on early left ventricular filling and regional myocardial lengthening was studied in 11 patients with coronary artery disease (CAD) and six control patients with normal coronary arteriograms. All of the 11 patients with CAD developed typical anginal pain during pacing tachycardia, and in the postpacing beat, the left ventricular end-diastolic pressure (LVEDP) rose from 13 4 to 26 + 4 mm Hg (mean ± SD, p < .01), the relaxation time constant increased from 43 9 to 59 + 7 msec (p < .01), and the ejection fraction diminished from 62.1 + 6.7 to 51.6 + 10.6% (p < .01). However, the peak rate of early left ventricular filling (LVPF) obtained from frame-by-frame analysis of left ventriculograms and the LVPF normalized for the stroke volume and for the end-diastolic volume did not change significantly. In the ischemic segment, the peak rate of lengthening (PL) decreased by 45% with ischemia, and the PL normalized for the end-diastolic segment length decreased by 42%. However, the PL normalized for the extent of systolic shortening did not change. In the control segment there was a tendency for these three variables to increase, but the changes were not statistically significant. The time difference from the PL to the LVPF increased significantly in the ischemic segment (31 28 vs 75 + 48 msec, p < .05). Although the LVEDP rose slightly but significantly from 9 + 3 to 12 + 5 mm Hg (p < .05) in the control patients in the postpacing beat, the other global hemodynamic variables and the variables of regional myocardial dynamics did not change. The administration of nifedipine in six patients with CAD resulted in the disappearance or diminution of anginal pain even with the same duration and rate of pacing and was associated with restoration of global systolic function and regional myocardial shortening and lengthening in the ischemic segment. In the control segment, the three variables of segmental lengthening increased with administration of nifedipine. Thus, the segmental myocardial lengthening rate decreased with ischemia due to a decrease in segmental shortening and impairment of myocardial distensibility. The LVPF did not decrease with ischemia despite impairment in isovolumetric relaxation, accentuation of asynchrony in left ventricular filling, and a decrease in the PL in the ischemic segment because of an increase in the PL in the nonischemic segment secondary to an increase in left ventricular filling pressure. Administration of nifedipine resulted in improvement in segmental lengthening in the ischemic as well as in the control segment in the postpacing beat. Circulation 76, No. 6, 1232-1244, 1987. PREDOMINANT left ventricular filling occurs during so-called rapid ventricular filling in the early phase of diastole. Effective early ventricular filling is important for ventricular ejection, and the rate of early ventricular filling is thought to be influenced by left ventricular From The Third Division, Department of Internal Medicine, Faculty of Medicine, Kyoto University, Kyoto, Japan. Address for correspondence: Chuichi Kawai, M.D., The Third Division, Department of Internal Medicine, Faculty of Medicine, Kyoto University, Shogoin, Sakyo-ku, Kyoto 606, Japan. Received May 7, 1986; revision accepted Aug. 13, 1987. *Present address: The Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, 930-01 Japan. 1232 performance, relaxation, and the pressure gradient between the left atrium and the left ventricle during this period.'-Therefore, factors that can alter ventricular ejection, relaxation, and left atrial pressure may have an indirect as well as a direct effect on early ventricular filling.5 Myocardial ischemia has been known to depress ventricular systolic function and relaxation6 7; however, its effect on early ventricular filling is controversial.3, 4 8, 9 Most previous studies have paid attention to overall ventricular filling. Since an ischemic insult is mostly regional in nature, the analysis of CIRCULATION by gest on A ril 4, 2017 http://ciajournals.org/ D ow nladed from PATHOPHYSIOLOGY AND NATURAL HISTORY-CORONARY ARTERY DISEASE regional myocardial function in addition to the determination of global ventricular performance is crucial. 1012 Furthermore, many previous studies have not focused on the interaction between ventricular filling and ejection or relaxation. The present study was designed to investigate regional myocardial dynamics in addition to global ventricular filling in patients with coronary artery disease (CAD) during postpacing ischemic periods. In some of the patients studied, we tested the effects of a calcium-channel blocker, nifedipine, on regional and global ventricular function with special attention to early ventricular filling during ischemia. The results for early ventricular filling were analyzed in relation to ventricular systolic function and relaxation.