4,071 consecutive cardiac catheterizations were reviewed retrospectively to obtain 56 cases of pure mitral regurgitation among whom chest X-ray, electrocardiography and echocardiography had been performed within 10 days of catheterization. Mitral regurgitation was mild to moderate (1-2+) in 7 of the 56 cases while 49 had more severe regurgitation (3-4+). Left atrial size as measured by echocardiography was found to be enlarged in all but 2 cases. A positive correlation between left atrial size and severity of mitral regurgitation, irrespective of the height of the pulmonary capillary wedge pressure V wave was demonstrated. There was no demonstrable, predictive relationship between left atrial size and pulmonary capillary wedge pressure or electrocardiographic or chest X-ray findings. We conclude that knowledge of left atrial size is predictive of the severity of mitral regurgitation; however, it is not possible to predict the pulmonary capillary wedge pressure or height of the V waves based on a knowledge of left atrial dilatation in patients with pure mitral regurgitation.

Enhanced dietary omega-3 fatty acid consumption is thought to be associated with a reduced incidence of atherothrombotic disorders. This effect may be mediated in part through suppression of in vivo platelet activity by omega-3 fatty acids. We observed that platelet survival, a sensitive indicator of in vivo platelet activity was prolonged from 6.4 +/- 1.5 days to 7.7 +/- 1.4 days by moderate amounts of dietary omega-3 fatty acid supplementation for 6 weeks in a group of hyperlipidemic patients with preexisting, established atherothrombotic disorders. This effect on platelet survival was associated with a decrease in platelet arachidonic acid levels from 26.7 +/- 3.5% to 20.9% +/- 2.5% and a rise in platelet eicosapentaenoic and docosahexaenoic acid measurements from essentially undetectable to 2.8% +/- 1.6% and 1.9% +/- 1.0%. Plasma total cholesterol, low-density lipoprotein cholesterol, and serum apolipoprotein B levels rose significantly during the omega-3 fatty acid supplementation period. Platelet aggregation did not change. This study demonstrates that a modest amount of dietary omega-3 fatty acid supplementation can significantly effect in vivo platelet activity in a population at high risk for recurrent atherothrombotic disorders.

The transfer of patients with acute myocardial infarction from community hospitals to tertiary care facilities for further intervention has become increasingly more frequent due to the emerging role of thrombolytic therapy and percutaneous transluminal coronary angioplasty. To assess the feasibility and safety of early transfer, a prospective analysis of 57 patients who were transported by ground ambulance or helicopter to the University of Massachusetts Medical Center, Worcester, for acute intervention during the early hours of myocardial infarction was conducted. Before transport, the majority (46 [81%]) of patients were having chest discomfort, 13 (23%) were hypotensive, and 12 (21%) were electrically unstable (defined as high-grade ventricular ectopia or nonsustained ventricular tachycardia). During transport, the majority (41 [72%]) continued to have some chest discomfort; however, only two (4%) remained hypotensive. Although five patients (9%) were electrically unstable during transport, the instability was considered noncritical. The distance traveled or the mode of transportation did not adversely impact on these clinical complications. All patients survived transport, and 53 patients (93%) were eventually discharged from the receiving hospital.

Lipid-laden macrophages, which are predominantly derived from blood monocytes, are present at sites of active multiple sclerosis demyelination and are assumed to be involved in the demyelinating process. These inflammatory cells produce a variety of toxic oxygen metabolites which can mediate host tissue destruction. We measured production of two oxygen metabolites by monocytes and polymorphonuclear leukocytes in MS patients and controls. Stimulated monocytes produced significantly more hydrogen peroxide, superoxide, and chemiluminescence in the MS group than controls. The polymorphonuclear leukocyte, an inflammatory cell that appears to contribute little to MS demyelination, did not demonstrate increased production of toxic oxygen metabolites in the MS patients as compared to controls. These results suggest that blood monocytes in MS patients are primed to produce increased amounts of cytotoxic oxygen metabolites when exposed to inflammatory stimuli.

We studied the effect of cod-liver oil on the development and progression of coronary artery disease in swine subjected to coronary balloon abrasion and fed an atherogenic diet for eight months. Sections from serial 3-mm segments of the coronary arteries were analyzed morphometrically in 7 pigs given a cod-liver-oil supplement and 11 control animals not given the supplement. Significantly less disease was seen in the sections from the animals fed cod-liver oil. The mean lesion area per vessel, mean luminal encroachment per vessel, and mean maximal luminal encroachment per vessel were reduced in animals fed cod-liver oil, as compared with controls, (P = 0.05, P = 0.016, and P = 0.011, respectively). Both groups of animals had severe hyperlipidemia throughout the study. Differences in the extent of coronary atherosclerosis were not related to differences in plasma lipid levels. Platelet arachidonate was markedly reduced, platelet eicosapentaenoic acid was increased, and serum thromboxane was decreased in the oil-fed group as compared with the control group. We conclude that in our animal mode, dietary cod-liver oil retarded the development of coronary artery disease, possibly through changes in prostaglandin metabolism.

The pharmacokinetics of intravenous bepridil (1-[2-(N-benzylanilino)-1-(isobutoxymethyl)ethyl]pyrrolidine ) were studied in 16 patients undergoing cardiac catheterization for evaluation of coronary disease, all with normal base-line hemodynamic and renal functions. Ten patients received 3 mg/kg and six patients received 4 mg/kg of bepridil infused over a period of 30 min. Plasma bepridil concentrations were measured by HPLC and analyzed by model-dependent and model-independent methods. The mean (+/- SD) maximum plasma bepridil concentrations at the end of the infusion were 2047 +/- 820 ng/mL (3 mg/kg) and 2478 +/- 1426 ng/mL (4 mg/kg). Postinfusion bepridil concentrations were best described by a two-compartment open model. The model-dependent harmonic mean distribution and elimination half-lives were 1.7 h (range: 1.1-2.2 h) and 19.7 h (range: 8.0-61.9 h), respectively. The harmonic mean elimination half-life from model-independent analysis was 14.9 h (range: 7.4-64.0 h). The arithmetic means of other model-independent kinetic parameters were systemic clearance, 0.524 +/- 0.215 L X kg-1 X h-1; Vd, 15.3 +/- 10.9 L/kg; and Vdss, 10.1 +/- 6.0 L/kg. Model-dependent and model-independent estimates of half-life and clearance agreed reasonably well. Bepridil was well tolerated, effecting little or no change in central hemodynamics or EKG intervals. The extensive distribution and relatively slow clearance of bepridil account for its long elimination half-life. Intravenous bepridil appears to be a safe calcium (II) antagonist that is suitable for once-a-day dosing.

Vegetarians have an apparent diminished risk for the development of ischemic coronary heart disease. This may be secondary to dietary effects of plasma lipids and lipoproteins, but platelets, which may also play a role, have also been observed to have aberrant functions in vegetarians. We measured plasma lipid and lipoprotein levels, platelet function, platelet fatty acid levels, and platelet active prostaglandins in ten strict vegetarians (vegans), 15 lactovegetarians, and 25 age- and sex-matched omnivorous controls. The most striking observations were a highly significant rise in platelet linoleic acid concentration and a decline in platelet arachidonic acid concentration in both vegetarian subgroups as compared with omnivorous controls. Serum thromboxane and prostacyclin levels as well as results of platelet aggregation studies did not differ among the groups tested. Cholesterol levels were significantly lower in both vegetarian groups as compared with controls, but plasma high- and low-density lipoprotein levels were lower only in the vegan subgroup as compared with omnivores. If diet produces these changes in platelet fatty acid and plasma lipid levels it may contribute to the decreased risk of coronary heart disease and possibly atherosclerosis in vegetarians.

Coronary atherosclerosis was induced in Yorkshire swine by diet-induced hyperlipidemia and balloon intimal abrasion of a coronary artery. Severe stenoses pathologically similar to the lesions of human atherosclerosis were seen after 8 months of the atherogenic regimen. To examine the relationship between the angiogram and pathology in the assessment of the extent and location of coronary atherosclerosis, antemortem angiographic results were compared with results of pathologic examination. Vernier caliper measurements of the coronary angiogram were compared with results of morphometric evaluation of perfusion-fixed coronary arteries. Isolated focal stenoses were correctly localized and quantified, as were focal lesions within vessels diffusely diseased. Both overestimation and underestimation of lesions occurred at bifurcation sites. Diffuse disease without focal stenoses was not well demonstrated angiographically. Vessels that were angiographically thought to be normal or only minimally diseased demonstrated significantly larger lumens angiographically than pathologically. This is believed to be due to fixation and paraffin-processing artifact, even though fixation was performed by perfusion at physiologic pressure. The demonstration of an excellent correlation between the luminal size as determined angiographically and morphometrically at sites of focal obstruction confirms the value of quantitation of coronary angiograms in vivo as a diagnostic tool in coronary atherosclerosis.

Calcium-channel blockers are known to have depressant effects on atrioventricular (AV) nodal conduction and myocardial contractility. Because of these known depressant effects, bepridil hydrochloride, a new, long-acting, antianginal and antiarrhythmic calcium-channel blocker, was administered intravenously to patients without heart failure to determine acute hemodynamic effects. The patients studied had normal ventricular function, were without electrocardiographic conduction disturbances and were taking no drug except sublingual nitroglycerin for at least 24 hours before bepridil infusion. The study protocol included right- and left-sided cardiac catheterization with infusion of bepridil at 2 mg/kg for 15 minutes followed by 1 mg/kg for 15 minutes in 10 patients, and infusion of bepridil at 3 mg/kg for 15 minutes followed by 1 mg/kg for 15 minutes in 8 patients. Pressures, Fick cardiac output, resistances, left ventricular (LV) dP/dt, LV stroke work index and rate-pressure product of the left ventricle were monitored. There were no significant changes during bepridil infusion at either dose for cardiac output, systemic vascular and pulmonary vascular resistances, LV stroke work index, heart rate, arterial blood pressure and rate-pressure product. There was mild depression of LV dP/dt during bepridil infusion. Further, LV end-diastolic pressure, pulmonary capillary wedge pressure and pulmonary arterial pressures were significantly increased during bepridil infusion. There were no apparent changes in AV nodal or intraventricular conduction during bepridil infusion. We conclude that bepridil appears to be a safe drug for intravenous administration despite mild depression of myocardial function in patients with normal baseline hemodynamic function who are not receiving concomitant beta-blocker therapy.