Endothelial dysfunction and effectiveness of treatment of calcium antagonists are suggestive of coronary artery spasm as an underlying disorder in dilated cardiomyopathy (DCM). The aim of this study is to determine whether or not the epicardial coronary artery spasm can induce severe cardiac dysfunction like DCM. Thirty-four consecutive patients with angiographically normal coronary arteries and diffuse left ventricular hypokinesis whose causes had been unknown underwent acetylcholine provocation test and left ventricular biopsy. Eight patients were excluded according to the clinical and laboratory data and biopsy findings suggesting myocarditis or other systemic diseases. According to the results of the acetylcholine provocation test, 17 patients were finally diagnosed as having DCM, and nine patients (35% of the study patients), who had acetylcholine-induced diffuse and multivessel coronary spasm, were diagnosed as having DCM-like vasospastic angina pectoris (VSA). Clinical and cardiac catheterization data including hemodynamics and biopsy findings were similar between the two groups except that left ventricular end-systolic volume was significantly greater in DCM than in DCM-like VSA. After the acetylcholine provocation test, DCM patients received both a beta blocker and an angiotensin-converting enzyme inhibitor, and DCM-like VSA patients received antianginal drugs. In echocardiographic findings at predischarge and those after 6-month drug treatment, both DCM-lke VSA and DCM showed significant reduction in end-diastolic and end-systolic diameters and significant increase in fractional shortening and ejection fraction, whereas changes in ejection fraction and fractional shortening were significantly greater in DCM-like VSA than those in DCM. Epicardial coronary artery spasm can induce diffuse and severe left ventricular dysfunction like DCM in VSA. Although antianginal drugs markedly improve left ventricular function of these patients, only the acetylcholine provocation test can identify DCM-like VSA.

Background-We reported that digoxin abolishes the infarct size (IS)-limiting effect of ischemic preconditioning (IPC).Because ATP-sensitive K ϩ (K ATP ) channels are involved in IPC, we studied whether Na ϩ ,K ϩ -ATPase and K ATP channels functionally interact, thereby modulating IPC. Methods and Results-Rabbits received 30 minutes of coronary artery occlusion followed by 3 hours of reperfusion. IPC was elicited by 5 minutes of occlusion followed by 10 minutes of reperfusion. The IS, expressed as a percentage of the area at risk, was 40.2Ϯ2.8% in control and 39.8Ϯ5.0% in digoxin pretreatment rabbits. Both IPC and pretreatment with cromakalim, a K ATP channel opener, reduced IS to 11.8Ϯ1.8% and 13.4Ϯ2.6% (PϽ0.05 versus control). Digoxin abolished the reduction in IS induced by IPC (33.5Ϯ3.3%), whereas it did not change that induced by cromakalim (18.8Ϯ3.0%). In patch-clamp experiments, digoxin was found to inhibit the opening of K ATP channels in single ventricular myocytes in which ATP depletion had been induced by metabolic stress. In contrast, digoxin had little effect on the channel opening induced by cromakalim. Moreover, the inhibitory action of digoxin on channel activities was dependent on subsarcolemmal ATP concentration. Conclusions-The IS-limiting effect of IPC is modulated by an interaction between K ATP channels and Na ϩ ,K ϩ -ATPase through subsarcolemmal ATP. (Circulation. 1998;98:2905-2910.)

Calcium preconditioning (CPC), like ischemic preconditioning (IPC), reduces myocardial infarct size in dogs and rats. ATP-sensitive potassium (KATP) channels induce cardioprotection of IPC in these animals. To determine whether KATP channels mediate both IPC and CPC, pentobarbital sodium-anesthetized rabbits received 30 min of coronary artery occlusion followed by 180 min of reperfusion. IPC was elicited by 5 min of occlusion and 10 min of reperfusion, and CPC was elicited by two cycles of 5 min of calcium infusion with an interval period of 15 min. Infarct size expressed as a percentage of the area at risk was 38 ± 3% (mean ± SE) in controls. IPC, CPC, and pretreatment with a KATP channel opener, cromakalim, all reduced infarct size to 13 ± 2, 17 ± 2, and 12 ± 3%, respectively ( P < 0.01 vs. controls). Glibenclamide, a KATP channel blocker administered 45 min (but not 20 min) before sustained ischemia, attenuated the effects of IPC and CPC (31 ± 4 and 41 ± 6%, respectively). Thus KATP channel activation appears to contribute to these two types of cardioprotection in rabbits.

No abstract

Preconditioning preserves the ischemia-induced reduction in sarcolemmal Na+,K+-ATPase activity in the early phase of ischemia in rabbit hearts. Inhibition of Na+,K+-ATPase activity reduces the infarct size-limiting effect of preconditioning with a loss of increased Na+-Ca2+ exchange activity, implying that this preservation is responsible for the cardioprotective effect of preconditioning.