Kazuya Hayasaki

Tissue Factor Expression on Macrophages in Coronary Plaques in Patients with Unstable Angina

Tissue factor is a membrane-bound glycoprotein that functions in the extrinsic pathway of blood coagulation by acting as a cofactor for factor VII, and the resulting complex leads to thrombin production in vivo. The purpose of the present study is to determine whether macrophages express tissue factor in human coronary atherosclerotic plaques. We examined directional coronary atherectomy specimens from 24 patients with unstable angina and 23 with stable exertional angina. In these specimens, macrophages were detected in 22 (92%) of 24 patients with unstable angina versus 12 (52%) of 23 with stable exertional angina (P = .003). The percentage of macrophage infiltration area was significantly larger in patients with unstable angina than in those with stable exertional angina (17 +/- 3% versus 6 +/- 2%, P = .008). The immunohistochemical double staining revealed the expression of tissue factor on macrophages in 18 (75%) of 24 patients with unstable angina versus 3 (13%) of 23 with stable exertional angina (P < .0001). Thrombus was identified in 20 (83%) of 24 patients with unstable angina versus 12 (52%) of 23 with stable exertional angina (P = .02). Fibrin deposition was mainly observed around macrophages expressing tissue factor in the patients with unstable angina. We have shown that tissue factor expression on macrophages was more frequent in coronary atherosclerotic plaques in patients with unstable angina. Tissue factor expressed on macrophages may play an important role in the thrombogenicity in coronary atherosclerotic plaques of these patients.

ATRIAL ECTOPY ORIGINATING FROM THE POSTEROINFERIOR ATRIUM DURING RADIOFREQUENCY CATHETER ABLATION OF ATRIOVENTRICULAR NODAL REENTRANT TACHYCARDIA

Atrial ectopy sometimes appears during RF ablation of the slow pathway in patients with atrioventricular nodal reentrant tachycardia (AVNRT). However, its origin, characteristics, and significance are still unclear. To examine these issues, we analyzed 67 consecutive patients with AVNRT (60 with slow‐fast AVNRT and 7 with fast‐slow AVNRT), which was successfully eliminated by RF ablation to the sites with a slow potential in 63 patients and with the earliest activations of retrograde slow pathway conduction in 4 patients. During successful RF ablation, junctional ectopy with the activation sequence showing H‐A‐V at the His‐bundle region appeared in 52 patients (group A) and atrial ectopy with negative P waves in the inferior leads preceding the QRS and the activation sequence showing A‐H‐V at the His‐bundle region appeared in 15 patients (group B). Atrial ectopy was associated with (10 patients) or without junctional ectopy (5 patients). Before BF ablation, retrograde slow pathway conduction induced during ventricular burst and/or extrastimulus pacing was more frequently demonstrated in group B than in group A (9/15 [60%] vs 1/52 [2%], P < 0.001). Successful ablation site in group A was distributed between the His‐bundle region and coronary sinus ostium, while that in group B was confined mostly to the site anterior to the coronary sinus ostium. In group B, atrial ectopy also appeared in 21 % of the unsuccessful RF ablations. In conclusion, atrial ectopy is relatively common during slow pathway ablation and observed in 8% of RF applications overall and 22% of RF applications that successfully eliminated inducible AVNRT. Atrial ectopy appears to be closely related to successful slow pathway ablation among patients with manifest retrograde slow pathway function.

Effects of angiotensin-converting enzyme inhibitor alacepril in patients with stable effort angina during chronic isosorbide dinitrate treatment

Nitrate tolerance has been reported to be reversed by certain types of angiotensin-converting enzyme (ACE) inhibitors. We examined whether alacepril, a new long-acting oral ACE inhibitor, has beneficial effects against exercise-induced angina in patients with stable effort angina after substantial isosorbide dinitrate (ISDN) treatment. Thirteen men with stable effort angina were treated with oral ISDN (80 mg/d) for >3 weeks. After this period, efficacy of single oral administration of either alacepril (50 mg) or its placebo on exercise-induced angina and electrocardiographic changes was examined by treadmill exercise test in a double-blind crossover design. Alacepril significantly improved the exercise duration by 9.1% (p=0.03), the time to 1 mm ST-segment depression by 19% (p<0.01), and the maximal ST-segment depression by 33% (p=0.015) compared with placebo. Alacepril did not significantly alter the rate-pressure product, a marker of myocardial oxygen demand, during exercise test compared with placebo. Plasma renin activity was significantly increased (p<0.05) after administration of alacepril, indicating that alacepril significantly blocked ACE activity in our patients. In conclusion, a single oral administration of the ACE inhibitor alacepril (50mg) elicited beneficial effects against exercise-induced myocardial ischemia in patients with stable effort angina during chronic nitrate treatment. These effects may be mediated by increased coronary blood flow.

Facilitation of Localized conduction block with procainamide during entrainment of sustained ventricular tachycardia

Intravenous administration of procainamide is widely used for the management of ventricular tachycardia (VT). Although its efficacy has been clinically established,’ the precise mechanism by which the drug interrupts VT still remains unclear. An experimental study on VT induced in the canine myocardial infarction model has suggested that a class I antiarrhythmic drug (lidocaine) causes conduction block preferentially within the reentry circuit and this interrupts the tachycardia.2 We recently suggested3 that transient entrainment of a tachycardia allows a selective examination of antiarrhythmic drug effect on the area of slow conduction within the reentry circuit of VT. This report presents data that suggest the possible mechanism of action of procainamide in its slowing and interruption of VT in man.

Effects of antecedent anginal episodes and coronary artery stenosis on left ventricular function during coronary occlusion

We evaluated the effects of antecedent anginal episodes and coronary artery stenosis on left ventricular function during coronary occlusion and the role of collateral filling in 33 patients with angina pectoris who underwent angioplasty. Wall motion abnormalities were investigated by echocardiography and classified into hypokinesia and akinesia. Collateral filling during angioplasty was evaluated by using a second artery catheter. Akinesia was observed as follows: 24% of the patients had > 30 anginal episodes, 38% had 5 to 30, and 87% of the patients had < 5 (p < 0.01); 12% of patients had a lesion of 99%, 47% had a lesion of 90%, and 83% had a lesion of 75% (p < 0.05). Akinesia was observed in none of the patients with grade 3 collaterals, 57% with grade 2, and 67% with grade 1 or 0 (p < 0.01). These observations suggest that the patients with antecedent frequent anginal episodes and severe coronary stenosis have less left ventricular dysfunction during coronary occlusion. This finding may be the result of more extensive collateral development.

RIGHT VENTRICULAR WALL MOTION DISTURBANCE AND DETERMINANTS OF THE APPEARANCE OF HEMODYNAMIC RIGHT VENTRICULAR INFARCTION

In order to elucidate the mechanisms of the appearance of hemodynamic right ventricular infarction (RVI), we studied right and left ventriculograms and hemodynamic findings in 52 patients with acute inferior myocardial infarction. Right ventricular wall motion disturbance (RVWMD) was detected in 69% of patient but hemodynamic RVI was observed only in 16%. Among patients with RVWMD, there was no significant difference in right ventricular ejection fraction between those with (group III) and without (group II) hemodynamic RVI, suggesting that right ventricular (RV) systolic dysfunction does not independently produce hemodynamic RVI. Right ventricular end-diastolic volume index was similar in groups II and III in spite of higher mRA in group III. The result suggested that the RV compliance of group III was decreased. Heart rate (HR) was significantly lower in group III than in group II. Not only physiologic pacing but also VVI pacing significantly improved hemodynamics in patients with hemodynamic RVI. A positive correlation between HR and cardiac index was observed (r = 0.56, p < 0.001) in patients with RVWMD. Decreased RV compliance and bradycardia were considered to be determinants of the appearance of hemodynamic RVI. Volume loading did not improve hemodynamics significantly in patients with hemodynamic RVI.

Effect of nisoldipine on variant angina: Assessment by 24-hour holter monitoring

Abstract Nisoldipine, a newly developed coronary vasodilating agent, was administered to 12 patients with variant angina to assess its efficacy in this condition. A placebo was administered during an observation period of ⩾2 days, after which nisoldipine 10 mg/day was administered as a single daily dose during a 3- to 4-day treatment period. The number of angina attacks significantly decreased from 5.4 ± 1.4 times/day/patient during the observation period to 1.1 ± 0.4 times/day/patient during the treatment period ( P P

Usefulness of reinjection image for evaluating viable myocardium in the infarcted zone on exercise thallium-201 SPECT

Reinjection images were obtained in 23 patients with myocardial infarction by the additional injection of 37 MBq of thallium-201 after obtaining 4 hour delayed images on exercise thallium-201 SPECT (TSPECT). A redistribution index (RI) was derived of the changes in perfusion defects between immediate and 4 hour delayed images as well as immediate and reinjection images on polar bull’s eye maps. The RI of reinjection images (46±27%) was significantly greater than that of 4 hour delayed images (26±26%) in patients with myocardial infarction (p< 0.01). Significant redistribution after reinjection occurred in 4 of 9 patients (44%) without significant redistribution on 4 hour delayed images. Improvement in redistribution on reinjection images correlated significantly to the small extent of coronary artery disease and collateral development. The appearance of redistribution from 4 hour delayed imaging to reinjection imaging also might reflect the function of collateral development in the resting state in patients without significant redistribution on 4 hour delayed images. It has been demonstrated that underestimated viable myocardium on 4 hour delayed images in the infarcted zone can be better assessed on reinjection images. This reinjection technique is recommended in patients with no or partial redistribution on 4 hour delayed images.