To examine whether nicardipine, a dihydropyridine derivative, limits size of myocardial infarction, and to compare the protective effects of nicardipine administered before and early and late after coronary artery occlusion, 99mTc-labeled albumin microspheres were injected into the left atrium during 5 min temporary coronary artery occlusion to determine the extent of the hypoperfused zone (the area at risk). The coronary arteries were then reperfused for 45 min before 6 hr permanent coronary artery occlusion. Fifteen minutes before permanent occlusion, dogs were randomly assigned to (1) a control group (n = 11), (2) a pretreatment group (n = 9), which received at this point 10 ,g/kg of nicardipine as a loading dose followed by a continuous infusion of 8 p.g/kg/hr for 6 hr, (3) an early treatment group (n = 9), in which nicardipine treatment was initiated 15 min after occlusion, or (4) a late treatment group (n = 8), in which nicardipine administration was delayed for 3 hr. Six hours after coronary artery occlusion, the hearts were excised and the left ventricle of each was cut into 3 mm thick slices and stained with triphenyltetrazolium chloride. The extent of myocardial necrosis was measured by planimetry of the unstained areas. Thereafter, the same slices were autoradiographed and the extent of the hypoperfused zone was measured by planimetry of the "cold spot." The extent of the hypoperfused zone was identical among the four groups. In the control group, the ratio of the extent of myocardial necrosis to the extent of the hypoperfused zone was 95.8 3.8% (mean SEM). However, it was significantly smaller in the pretreatment group (59.9 + 13.3%, p < .05) and the early treatment group (49.0 + 10.6%, p < .01) than in the control group. In the late treatment group, this value was not different from that in the control group (86.5 + 7.1%). There was a close inverse correlation between reduction of infarct size and the extent of the hypoperfused zone in the pretreatment and early treatment groups. Thus, nicardipine administered before or early after coronary artery occlusion limited infarct size by 37% to 49%, whereas when administration was delayed for 3 hr infarct size was not reduced. Furthermore, nicardipine had more striking effects on the ischemic myocardium of dogs with small hypoperfused zones than on that of dogs with large hypoperfused zones. Circulation 74, No. 2, 420-430, 1986. IN 1969

CHST6 mutations may be responsible for the pathogenesis of MCD in Chinese patients. The Q298X mutation detected in 5 of 19 families (6 of 38 alleles, 15.8%) may be the founder mutation in Chinese patients. However, our findings also indicate a high level of allelic heterogeneity of the CHST6 gene in Chinese patients and in other ethnic groups.

The extremely prominent negative U wave occasionally appears during a cardiac attack in variant angina pectoris. The clinical profile of the negative U wave was therefore studied in 80 patients with variant angina pectoris (VA) and 33 controls with resting angina pectoris (RA). The prominent negative U wave appeared in 55 of the patients with VA (68.8% of patients) and in 10 of the patients with RA (30.3%); thus, there was a significant difference in the appearance of the wave between the 2 groups of patients (p<0.001). The leads in which the negative U wave appeared were mostly consistent with those in which the ST segment was elevated. The negative U wave began to appear at about the time when ST-segment elevation began to improve; the wave then gradually became very prominent and then eventually disappeared. The patients with VA and also those with RA on whose ECGs the negative U wave appeared during exercise testing also had negative U waves during spontaneous episodes of angina. An investigation of the frequency of appearance of ST deviation and negative U waves during exercise testing, regardless of the type of angina pectoris, disclosed that the negative U wave appeared in 14 of 20 patients with ST-segment elevation (70% of patients), while the negative U wave appeared in only 52 of 519 patients with either no ST change or ST-segment depression (10.4%); thus, there was a significant difference in the appearance of the negative U wave between these 2 groups (p<0.001). Coronary cinearteriography failed to disclose any apparent difference between the appearance of the negative U wave and the presence of stenosis. The prognosis of VA and RA in patients with negative U waves was less favorable compared to those without negative U waves. In particular, we noted that of the 10 patients with RA associated with negative U waves, 4 died. Al-From the

The disposition of aprindine following a single oral dose can best be described by a two-compartment open model. The mean plasma half-life (t 1/2 beta) increased from 8.0 +/- 2.1 h (SD) after a 25 mg dose of 9.4 +/- 2.9 h after 50 mg and to 15.8 +/- 2.6 h after 100 mg, with a decrease in total plasma clearance (Cl/F) and volume of distribution at steady state (V dss/F) and during beta-phase (V d beta/F). The area under plasma concentration-time curve (AUC), maximum plasma concentration (C max) and the amount of unchanged aprindine excreted in the urine increased in a non-linear fashion with the increase in dose. The t 1/2 beta after multiple oral doses showed a 3-fold increase over the single dose value. These results indicate that aprindine shows dose-dependent non-linear kinetics.

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