To reveal the presence of atherogenic potential in the blood serum obtained from patients with angiographically assessed coronary atherosclerosis we used primary cultures of subendothelial cells isolated by collagenase from unaffected human aortic intima. Earlier, we have demonstrated that such cultures are made up mostly of typical and modified smooth muscle cells. Within 24 hours of cultivation with a 40% sera of patients suffering from coronary atherosclerosis, the total intracellular cholesterol level increased twofold to fivefold. Cultivation with the sera of healthy subjects had no effect on the intracellular cholesterol level. The sera of patients were separated by ultracentrifugation into two fractions: total lipoprotein fraction containing the main classes of lipoproteins and a lipoprotein-deficient fraction. The former, but not the lipoprotein-deficient fraction, was characterized by atherogenicity (i.e., the ability to induce the accumulation of intracellular cholesterol). Lipoproteins of the patients' serum were separated into main classes: low density lipoproteins (LDL), very low density lipoproteins (VLDL), and high density lipoproteins (HDL2 and HDL3). An atherogenic component of the serum capable of stimulating the deposition of intracellular cholesterol was represented by LDL and, in one case, by VLDL, but not by other classes of lipoproteins. LDL and other lipoproteins isolated from the blood serum of healthy subjects failed to raise the cholesterol content in cultured cells; that is, they were nonatherogenic.(ABSTRACT TRUNCATED AT 250 WORDS)

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SUMMARY Ethmozin, a phenothiazine derivative, is an antiarrhythmic drug synthesized in the USSR. Preliminary data suggest that it is effective against a diversity of ectopic arrhythmias. The present study, carried out in the USSR, was designed to assess efficacy and patient tolerance of this new drug. Thirty-seven patients with chronic, persistent, frequent and symptomatic ventricular premature complexes (VPCs) were studied. VPCs were exposed by means of 24-hour ambulatory monitoring and exercise stress testing. Two drug schedules were used. Group 1, consisting of 11 patients, received 225 mg/day of ethmozin, while group 2, consisting of 26 patients, received 600 mg/day. Acute drug testing with a single large dose of ethmozin was followed by multiple dosing for a minimum of 4 days. Placebo was given in a single-blind fashion only to responders.Only two patients in group 1 had a significant reduction in VPCs as evaluated by both monitoring and exercise testing. Fourteen patients in group 2 (54%) showed striking suppression of VPCs. Mild and transient effects were encountered in only four of the 37 patients. We conclude that ethmozin appears to be a welltolerated, relatively effective agent for controlling VPCs.PATIENTS with ventricular arrhythmias are being detected in increasing numbers because of the widespread use of ambulatory monitoring and exercise stress testing. Currently available antiarrhythmic drugs, however, are not consistently effective, safe, or well tolerated. There is an urgent need for drugs that suppress ventricular arrhythmias, cause minimal adverse reactions and have a prolonged duration of action so as to gain patient acceptance and adherence.In 1965, the Institute of Pharmacology of the USSR Academy of Medical Sciences synthesized a new antiarrhythmic drug, ethmozin, the hydrochloride of 1 0-(3-morpholinopropionyl)-phenothiazine-2-carbamic acid, ethylester ( fig. 1). Early reports in the USSR have shown that ethmozin effectively controls From the