Although thromboxane A2 is a potent platelet agonist and vasoconstrictor in vitro, our knowledge of its pathophysiologic importance in human disease is limited. To facilitate the elucidation of its role in vivo, we sought to define a human syndrome in which pharmacologic interventions designed to inhibit the biosynthesis or biologic actions of thromboxane A2 might be appropriately assessed. Patients with severe peripheral vascular disease were selected on the basis of elevated plasma beta-thromboglobulin and circulating platelet aggregates and compared with healthy, age-matched control subjects. In addition to the platelet indexes, their bleeding time was shorter and excretion of 2,3-dinor-thromboxane B2, a noninvasive index of thromboxane formation in vivo, and 2,3-dinor-6-keto-prostaglandin F 1 alpha, the major urinary metabolite of prostacyclin, was markedly increased. A selective inhibitor of thromboxane synthase, imidazo (1,5-2) pyridine-5-hexanoic acid, was administered to these patients under randomized, double-blind, controlled conditions. Platelet aggregation ex vivo, the circulating platelet aggregate ratio, and the bleeding time were all unaltered, despite almost maximal inhibition of platelet thromboxane formation 1 hr after dosing. By contrast, pronounced inhibition of aggregation was observed when platelet cyclooxygenase was inhibited by aspirin. During long-term dosing with the synthetic inhibitor, inhibition of thromboxane biosynthesis was incomplete, which would permit continued thromboxane-dependent platelet aggregation to occur. However, the failure of enzyme blockade to influence platelet function at the time of maximal drug action, despite efficient inhibition of serum thromboxane B2, suggests that accumulation of proaggregatory endoperoxides is also likely to have contributed to the persistence of platelet activation. We have characterized a human preparation in which platelet activation coexists with increased thromboxane biosynthesis. In this setting, platelet activation persists despite long-term administration of a thromboxane synthase inhibitor in a dosing regimen representative of that employed in clinical trials. Prolongation of drug action and combination with antagonists of the shared endoperoxide/thromboxane A2 receptor may be necessary to assess the potential of selective inhibition of thromboxane synthase as a therapeutic strategy in man.

The goal of this study was to verify whether myocardial protection could be achieved via the intracoronary administration of propranolol in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Accordingly, 21 patients undergoing PTCA were randomly assigned to receive either intracoronary placebo (group A, n = 10) or intracoronary propranolol (group B, n = 11). Three balloon inflations (i.e., coronary artery occlusions) were performed in each patient. Inflations I and II (maximum duration 60 sec) served as control occlusions. Inflation III (maximum duration 120 sec) was performed either after intracoronary administration of saline (2 ml) or propranolol (1.1 +/- 0.2 mg). The following electrocardiographic index of myocardial ischemic injury were measured: (1) time to development of ST segment elevation equal to 0.1 mV and (2) magnitude of ST segment elevation after 60 sec of coronary artery occlusion. Both indexes did not differ significantly between the groups during inflations I and II. In group A the time to development of ST segment elevation of 0.1 mV remained unchanged between the second and third occlusions (25 +/- 5 and 26 +/- 4 sec during inflations II and III, respectively). In group B subselective injection of propranolol into the affected coronary artery significantly prolonged the time to ST segment elevation of 0.1 mV from 19 +/- 4 sec (inflation II) to 53 +/- 9 sec (inflation III; p less than .001). Administration of placebo did not change the magnitude of ST segment elevation 60 sec after coronary artery occlusion between the second and third occlusion in group A (0.16 +/- 0.02 and 0.18 +/- 0.03 mV, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

The incidence of congestive heart failure was studied in the Beta Blocker Heart Attack Trial in which postmyocardial infarction patients between the ages of 30 and 69 years, with no contraindication to propranolol, were randomly assigned to receive placebo (n = 1921) or propranolol 180 or 240 mg daily (n = 1916) 5 to 21 days after admission to the hospital for the event. Survivors of acute myocardial infarction with compensated or mild congestive heart failure, including those on digitalis and diuretics, were included in the study. A history of congestive heart failure before randomization characterized 710 (18.5%) patients: 345 (18.0%) in the propranolol group and 365 (19.0%) in the placebo group. The incidence of definite congestive heart failure after randomization and during the study was 6.7% in both groups. In patients with a history of congestive heart failure before randomization, 51 of 345 (14.8%) in the propranolol group and 46 of 365 (12.6%) in the placebo group developed congestive heart failure during an average 25 month follow-up. In the patients with no history of congestive heart failure, 5% in the propranolol group developed congestive heart failure and 5.3% in the placebo group developed congestive heart failure. Baseline characteristics predictive of the occurrence of congestive heart failure by multivariate analyses included an increased cardiothoracic ratio, diabetes, increased heart rate, low baseline weight, prior myocardial infarction, age, and more than 10 ventricular premature beats per hour.(ABSTRACT TRUNCATED AT 250 WORDS)

Fifty patients with congestive heart failure received, by infusion, 15 ml/kg body weight water load, and systemic hemodynamic, renal function, and neurohumoral parameters values were measured before, 2 days, and 1 month after randomly allocating patients to prazosin or captopril therapy. Both prazosin and captopril caused similar and persistent hemodynamic changes, but important differences existed between their renal and neurohumoral effects. After 1 month of continuous therapy, captopril increased creatinine clearance from 71 to 84 ml/min/1.73(2) (p less than .05), increased the water load excreted in 5 hr from 50% to 71% (p less than .005), and increased 5 hr sodium excreted from 6.8 to 14.7 meq (p less than .005), Captopril also caused a decrease in plasma norepinephrine from 568 to 448 pg/ml (p less than .005), in plasma epinephrine from 94 to 73 pg/ml (p less than .05), and in plasma aldosterone from 57 to 28 ng/dl (p less than .005), without changing plasma vasopressin. These beneficial effects were greater after 1 month of therapy than after 2 days. The only beneficial effect of prazosin was to increase water excretion from 49% to 59% (p less than .05). The long-term response to captopril was similar in patients with higher (greater than 2.5 ng/ml/hr) and lower renin levels. However, in patients with lower renin levels, prazosin decreased pulmonary capillary wedge pressure (24.8 to 21.8 mm Hg, p less than .05), decreased plasma arginine vasopressin (1.16 to 0.75 pg/ml, p less than .05), increased water excretion (62% to 85%, p less than .005), and decreased plasma epinephrine (81 to 46 pg/ml, p less than .05), while in patients with higher renin levels none of these beneficial effects were noted. We conclude that captopril produces long-term beneficial renal and neurohumoral effects that prazosin does not despite similar hemodynamic changes with the two drugs, that these effects are at least partially dependent on the initial neurohumoral and hemodynamic status of the patient, and that through hemodynamic improvement vasodilators may chronically interrupt vasopressin overstimulation.

The value of the addition of beta-blockers to coronary vasodilator therapy in the treatment of patients with unstable angina at rest is controversial. We conducted a double-blind, randomized, placebo-controlled 4 week trial of propranolol in 81 patients with unstable angina, 39 of whom were assigned to placebo and 42 of whom received propranolol in a dose of at least 160 mg daily. All patients were also treated with coronary vasodilators, including 80 mg nifedipine daily and long-acting nitrates. The incidences of cardiac death, myocardial infarction, and requirement for bypass surgery or coronary angioplasty did not differ between the two groups (propranolol = 16; placebo = 18). The propranolol group had a lower cumulative probability of experiencing recurrent resting angina than the placebo group (p = .013), and over the first 4 days of the trial the mean number of clinical episodes of angina (propranolol 0.9 +/- 0.2, placebo 1.8 +/- 0.3, p = .036), duration of angina (propranolol 15.1 +/- 4.3 min, placebo 38.1 +/- 8.4, p = .014), and nitroglycerin requirement (propranolol 1.1 +/- 0.3 tablets, placebo 3.5 +/- 0.8, p = .003) were also fewer. Continuous electrocardiographic recording for ischemic ST segment changes revealed fewer daily ischemic episodes in the propranolol group (2.0 +/- 0.5) than in the placebo group (3.8 +/- 0.7, p = .03), and a shorter duration of ischemia (propranolol 43 +/- 10 min, placebo 104 +/- 28 min, p = .039). Thus propranolol, in patients with unstable angina, in the presence of nitrates and nifedipine is not detrimental and reduces the frequency and duration of symptomatic and silent ischemic episodes.

To study the prevention of occlusion of aortocoronary-artery bypass grafts, we conducted a prospective, randomized, double-blind trial comparing long-term administration of dipyridamole (begun 2 days before operation) plus aspirin (begun 7 hr after operation) with placebo in 407 patients. Results at 1 month and at 1 year showed a reduction in the rate of graft occlusion in patients receiving dipyridamole and aspirin. On the basis of our clinical trial and our experimental studies in dogs and pigs, we describe four consecutive phases of aortocoronary artery bypass vein-graft disease: an early postoperative phase of platelet thrombotic occlusion, which is significantly prevented by platelet inhibitor therapy when started in the perioperative period; in addition, occlusion rates are presently decreasing, perhaps related to better surgical and technical experience; an intermediate phase of platelet-related intimal hyperplasia, within the first postoperative year, which is not prevented with platelet inhibitor therapy; a late phase of occlusion, toward the end of the first postoperative year, in which intimal hyperplasia or complicating platelet thrombi superimposed on the intimal hyperplasia may contribute to occlusion; platelet inhibitor therapy is of significant benefit in the prevention of this thrombotic type of occlusion; a phase of atherosclerotic disease, after the first postoperative year, in which the role of platelets and of platelet inhibitor therapy is under investigation.

The effects of four levels of activity on heart rate, blood pressure, cardiac index, total peripheral resistance index (TPRI), norepinephrine (NE) spillover rate, insulin sensitivity, and levels of lipids and some hormones were studied in 12 normal subjects. The randomized periods were (1) 4 weeks of below-sedentary activity, (2) 4 weeks of sedentary activity, (3) 4 weeks of 40 min of bicycling three times per week, and (4) 4 weeks of similar bicycling seven times per week. Exercise three times per week reduced resting blood pressure by 10/7 mm Hg (p less than .01) and it was reduced by 12/7 mm Hg after exercise seven times per week (both p less than .01). This was associated with reduction in TPRI, an increase in cardiac index, and cardiac slowing. At the highest level of activity, NE spillover rate, an index of sympathetic activity, fell to 35% of the sedentary value (p less than .001) in eight of 10 subjects. In two other subjects NE spillover rate rose, although blood pressure and TPRI were reduced. Metabolic changes included lowering of total cholesterol, but high-density lipoprotein level was unchanged. Insulin sensitivity rose by 27% after exercise three times per week, but declined to sedentary levels with seven times per week exercise. Maximum oxygen uptake increased linearly with activity. Exercise performed three times per week lowers blood pressure and should reduce cardiovascular risk. The same exercise seven times per week enhances physical performance with little further reduction in cardiovascular risk factors. Exercise is potentially a major nonpharmacologic method of lowering blood pressure.

This report from the European Prospective Randomised Study presents 8 year results on survival and 5 year results on myocardial infarction and employment status. The 768 recruited patients were all men under age 65 with mild or moderate angina, 50% or greater stenosis in at least two major coronary arteries, and a left ventricular ejection fraction of 50% or greater. One "surgical" patient was lost to follow-up immediately after randomization and is therefore excluded from the statistical analysis. Thus 394 patients allocated to surgery were compared with 373 patients allocated to medical treatment, regardless of what subsequently happened to the patients. The policy of early surgery improved survival significantly compared with the conventional medical treatment policy in the total population (89% to 80%, respectively; p = .0013) and in the subgroup with three-vessel disease (92% and 77%, respectively; p = .00015). Reclassification of vessel disease by greater than 75% instead of 50% or greater stenosis as the criterion was undertaken to facilitate comparison of these results with those of other studies, which apply 70% or greater stenosis as the criterion of significant disease. Of the 767 patients, a cohort of 711 were identified as having greater than 75% obstruction in one, two, or three vessels. A significant improvement in survival with surgery was found in the total cohort (89% and 80%, respectively; p = .0022), the subgroup with three-vessel disease (91% and 73%, respectively; p = .0044), and that with two-vessel disease in which one of the diseased vessels was the proximal segment of the left anterior descending artery (LAD) (90% and 79%, respectively; p = .013). There was no significant difference in survival between the two treatments in patients with one-vessel disease and those with two-vessel disease without proximal LAD stenosis. Four noninvasive prognostic variables were independently predictive of the effect of surgery: resting electrocardiogram (in 767 patients), ST segment response to exercise (in 656), history and physical signs of peripheral arterial disease (in 722), and age (in 767). A reduction in cardiac deaths was entirely responsible for the improved survival with surgery. The incidence of myocardial infarction in the medical group (11%) was not significantly different from that in the surgical group (15%). Repeat angiography in 71 patients showed 6% graft closure between 1 and 5 years of follow-up. Surgery did not influence the gradually increasing annual rate of retirement from work.

The long-term effect of coronary artery bypass grafting on mortality and the incidence of nonfatal myocardial infarction was evaluated in 686 patients in the randomized Veterans Administration study of medical vs surgical treatment for stable angina. Average follow-up was 11.2 years. The 11 year cumulative mortality rates for all patients and for the 595 patients without left main diseases were not significantly different in the two treatment groups. The 7 year mortality rates were 30% in medically assigned and 23% in surgically assigned patients (p = .043) and the 11 year rates were 43% and 42% (p = .45), respectively. The rates in patients without left main disease were 28% for medical and 23% for surgical treatment policy at 7 years (p = .267) and rose to 42% in both groups at 11 years (p = .813). A statistically significant reduction in mortality with surgical policy was found both at 7 and 11 years in high-risk patients without left main disease who had multiple clinical or angiographic risk factors or both. In the subgroup with angiographic high risk, the 7 year mortality rates were 48% in medically assigned and 24% in surgically assigned patients (p = .002); the 11 year rates were 62% and 50%, respectively (p = .026). Corresponding rates in the clinically defined high-risk group were 48% vs 28% (p = .003) at 7 years and 64% vs 51% (p = .015) at 11 years for medical vs surgical policy, respectively. For the subgroup of patients with combined angiographic and clinical high risk, the 7 year mortality rates were 64% for medical and 24% for surgical policy (p = .002); the 11 year rates were 76% and 46%, respectively (p = .005).(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise electrocardiographic stress testing was performed in 81% of the 780 patients randomized in the Coronary Artery Surgery Study at entry. The cumulative survival at the end of 7 year follow-up was 90% for those assigned to surgical treatment and 88% for those assigned to medical therapy (p = NS). These survival rates did not differ significantly from either those of the entire randomized cohort or those of the 149 patients who did not have a qualifying exercise test at baseline. No differences in important baseline characteristics existed between those who were exercised and not exercised at entry. Stratification of patients according to the degree of ST segment depression (less than 1 mm, greater than or equal to 1 mm, greater than 2 mm) and final exercise stage achieved during a Bruce protocol treadmill test (final stage less than or equal to 1, stage 2 and greater than or equal to stage 3) failed to show any significant differences in 7 year survival rates between medically and surgically assigned patients. Additionally no differences in survival were noted within either the medical or surgical groups regardless of the degree of ST segment depression or the final stage achieved. The presence of exercise-induced angina, however, identified patients who had a survival advantage if assigned to surgical therapy, with a 7 year survival rate of 94% compared with 87% for medically assigned patients (p = .007).(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized, double-blind clinical trial in 1266 men with unstable angina showed that 324 mg of aspirin daily for 12 weeks reduced the incidence of myocardial infarction by 51% (p = .001), and the data suggested a similar reduction in mortality. The only other therapy for unstable angina that has been studied in randomized trials of adequate size to evaluate mortality and rate of infarction is aortocoronary bypass surgery. Results with heparin therapy have been encouraging, but the studies in which this drug has been tested have been flawed. Nitrates, beta-blockers, calcium blockers, fibrinolytic therapy, and coronary angioplasty have not been adequately evaluated. Randomized trials of aortocoronary bypass surgery have not demonstrated decreased mortality or rates of myocardial infarction in patients with unstable angina. Although surgical techniques have improved since these trials were conducted, medical management has also improved. Mortality and infarct rate in patients with unstable angina are now lower than in the early 1970s. New well-controlled clinical trials are needed.

Beta-Adrenergic blockers have not been widely used in patients with peripheral vascular disease because these drugs have been reported to worsen the symptoms of intermittent claudication. To test this assumption we studied the effects of a beta 1-selective and a nonselective beta-adrenergic blocker on postexercise calf blood flow and symptoms of claudication in 19 patients with mild-to-moderate peripheral vascular disease. Subjects received placebo for 3 weeks, and then were randomized to 120 mg/day propranolol or 150 mg/day metoprolol with the use of a crossover design. Blood flow in the calf was measured by strain-gauge plethysmography at rest and immediately after exercise on a bicycle ergometer at a low and a high workload. The symptoms of claudication were monitored during bicycle exercise and by patient diaries maintained between visits. Maximal exercise heart rate was reduced an equivalent amount by metoprolol (19 beats/min) and propranolol (16 beats/min). Mean arterial pressure was reduced by propranolol at rest and by both drugs with exercise. Calf blood flow was not affected by either drug compared with placebo at rest or at either workload. In addition, the symptoms of claudication were not worsened by either drug. We conclude that despite evidence of beta 1-adrenergic blockade and a lowering of arterial pressure, neither beta-adrenergic blocker adversely affected the peripheral circulation.

After 30 min rest in the lying position, 12 healthy male volunteers (average age 22 years) received, in a randomized double-blind cross-over protocol, either saline or naloxone (10 mg iv followed by a continuous infusion of 10 mg/hr). Thereafter they rested for a further 30 min in the recumbent position and for 15 min sitting on a bicycle ergometer; they then exercised to exhaustion. At rest plasma levels of adrenocorticotropin (ACTH), cortisol, and aldosterone increased during infusion of naloxone, while body temperature decreased. During exercise the difference in plasma ACTH between naloxone and saline periods was abolished, while the differences in plasma cortisol and aldosterone lost statistical significance. Intra-arterial pressure, heart rate, ventilation, O2 uptake, and CO2 output were continuously monitored throughout the experiment and were not affected by naloxone. This was also the case for several hormonal and biochemical measurements, including those of plasma renin, angiotensin II, norepinephrine, 13,14-dihydro-15-keto-prostaglandin F2 alpha, glucose and lactate, and serum insulin and growth hormone. Exercise performance was not changed by naloxone. In conclusion (1) during exhaustive graded exercise of short duration opioidergic inhibition of the pituitary-adrenocortical axis is probably not sustained, (2) apart from the latter mechanism, the present study does not support the hypothesis that endogenous opioids are involved in various hemodynamic, respiratory, and hormonal responses to this type of exercise.

In a prospective, randomized, parallel study, two regimens of platelet-suppressant therapy (PST)--dipyridamole-aspirin and pentoxifylline-aspirin--were compared with standard oral anticoagulation with warfarin in the prevention of prosthetic heart valve thromboembolism. In the entire group of 254 patients followed for 395.6 patient-years, the thromboembolic rate was significantly less in the warfarin group (warfarin vs dipyridamole-aspirin, p less than .005; warfarin vs pentoxifylline-aspirin, p less than .05). Subgroup analysis disclosed that, in patients with isolated mitral valve replacement, warfarin was superior to both of the PSTs with respect to the prevention of thromboembolism (warfarin vs dipyridamole-aspirin, p = .005; warfarin vs pentoxifylline-aspirin, p less than .05). Furthermore, a significant number of our patients could not tolerate the antiplatelet agents. However, in the rare situation in which repeated significant bleeding occurs despite careful adjustment of the dosage of warfarin, PST may be an acceptable alternate method of thromboembolism prophylaxis.

Cyclosporine has gained acceptance as the immunosuppressive agent of choice in cardiac transplantation, but the validity of this assumption has yet to be established. Since January 1983, 25 patients have been randomly assigned to receive either conventional immunosuppression (azathioprine/antithymocyte globulin/prednisone) and pretransplant transfusion (PAAP, n = 11) or cyclosporine immunosuppression (cyclosporine and prednisone [CyA], n = 14). There was no difference in the age distribution (41 +/- 9 vs 38 +/- 11 years), indications for transplantation, preoperative serum creatinine level (1.2 +/- 0.2 vs 1.4 +/- 0.3 mg/dl), or postoperative follow-up time (13.5 +/- 5.4 vs 13.5 +/- 5.2 months). Mortality was not different (PAAP = 2, CyA = 3) and there was no difference in rejection episodes per patient (PAAP = 1.8, CyA = 1.9). Patients in the PAAP group had more serious infections (PAAP = 8, CyA = 3; P less than .02), but those in the CyA group developed a greater incidence of systemic hypertension (PAAP = 1, CyA = 10; p less than .02), pericardial effusion (PAAP = 0, CyA = 6; p = .05), and impaired renal function (creatinine 1.5 mg/dl, PAAP = 2, CyA = 11; p less than .02). Thus it appears that in this small series, cyclosporine is not associated with a significant increase in early survival. It does appear that patients on PAAP immunosuppression develop a greater number of serious infections, but the incidence of rejection episodes appears to be the same. Renal dysfunction and hypertension in patients receiving cyclosporine continue to be long-term concerns and may add to the morbidity and mortality of patients treated with this immunosuppressive regimen.

It has been suspected that the increased sympathetic activity seen in patients with chronic congestive heart failure from dilated cardiomyopathy may be harmful. We therefore tested the long-term effect of metoprolol on eight patients in a double-blind, randomized protocol and 12 patients in an unblinded, crossover protocol who were treated for 12 months (range 10 to 24), and compared them with 16 similar subjects who were treated with placebo for 10 months (range 6 to 12) in a double-blind, randomized protocol. Patients were followed by serial clinical assessment, treadmill testing, radionuclide ventriculography, and echocardiography. Metoprolol-treated patients had an improvement in mean exercise capacity by 3 mets (p less than .0001) while experiencing a significant improvement in functional classification (p less than .001) during both the double-blind and open-label crossover studies and had an improved ejection fraction during the double-blind study (p less than .02). These improvements were not seen in matched control subjects receiving placebo. Seven of 20 patients receiving long-term metoprolol therapy had resolution of nearly all symptoms of heart failure, doubled their exercise capacity, and had progressive improvement in resting radionuclide left ventricular ejection fraction (12.6 +/- 3% to 26.9 +/- 6%) and echocardiographic left ventricular end-diastolic dimension (7.7 +/- 0.5 to 6.5 +/- 0.5 cm). Only one of 21 patients treated was intolerant of metoprolol. We conclude that metoprolol can be given safely to a select group of patients with dilated cardiomyopathy in doses that substantially reduce both resting and exercise heart rates. Long-term beta-blockade improved functional class and exercise capacity in 14 of 20 patients while producing an exceptional clinical response in seven that was accompanied by improved resting parameters of left ventricular function.

The relationships among clinical variables, coronary anatomy, and left ventricular function during the early hours of acute myocardial infarction (AMI) were evaluated from data acquired in the Western Washington Intracoronary Streptokinase Trial. All patients had symptoms and electrocardiographic changes typical of AMI. All data were obtained before treatment with streptokinase. Mean time to catheterization was 4.1 hr after onset of symptoms. Coronary angiograms (n = 245) were analyzed for location of infarct-related occlusion and collateral flow to the infarct bed. Left ventricular ejection fraction and regional left ventricular function were quantitated in 227. Sixty-two percent of occlusions were in the most proximal segment of the involved coronary artery. Collateral circulation was seen in 42% overall, in 31% with left anterior descending artery (LAD) occlusion, and in 52% with right coronary artery (RCA) occlusion (p less than .005). Left ventricular ejection fraction was lowest and regional function was most abnormal in the group with proximal LAD occlusion. Hyperkinesis was present in 32%; in those with hyperkinesis, hyperkinetic segment length was longest in those with RCA or circumflex occlusion. Multivariate analysis identified proximal LAD occlusion as the factor most closely associated with left ventricular ejection fraction and with measures of left ventricular regional hypofunction. We conclude that (1) AMI is usually caused by occlusion or subtotal occlusion in the most proximal portion of the involved coronary artery, (2) collateral circulation is more frequent with RCA than with LAD occlusion, and (3) location of the infarct-related occlusion is the most important determinant of global and regional left ventricular function in the early hours of AMI.

We performed a prospective, randomized crossover study to evaluate the comparative efficacy of transvenous cardioversion and rapid ventricular pacing for termination of induced ventricular tachycardia in patients with spontaneous ventricular tachycardia and organic heart disease. Sixty-two episodes of ventricular tachycardia were induced in 15 patients, mean age 60 +/- 10 years, during electrophysiologic studies. All patients underwent a preselected electrical therapy protocol in a randomized crossover sequence. Transvenous cardioversion was performed by an incremental protocol of three sequential shocks (0.5, 1.1, and 2.7 J). Six asynchronous sequential bursts of rapid ventricular pacing (10 and 15 paced stimuli at 90%, 75%, and 65% of ventricular tachycardia cycle length) were used. Mean cycle length of ventricular tachycardia for the study population was 391 +/- 85 msec. The morphology of the tachycardia was left bundle branch block in 27, right bundle branch block in 32, and indeterminate in three. Characteristics of ventricular tachycardia terminated by the two techniques were comparable. Rate of success for termination of tachycardia with the two methods was also comparable (transvenous cardioversion 83%, rapid ventricular pacing 80%; p greater than .1) and these responses were concordant in 78%. The modes of termination of ventricular tachycardia were similar. The incidence of acceleration of ventricular tachycardia per episode with these preselected protocols was also comparable (transvenous cardioversion 11%, rapid ventricular pacing 6%; p greater than .2). Transient supraventricular tachyarrhythmias were more frequent after transvenous cardioversion (23%) than after rapid ventricular pacing (3%). Significant patient discomfort occurred only after transvenous cardioversion (incidence of 57%).(ABSTRACT TRUNCATED AT 250 WORDS)

One hundred forty-seven consecutive coronary bypass patients were enrolled in a randomized, double-blind, risk-stratified, placebo-controlled prospective trial evaluating the effect on graft patency of 325 mg tid aspirin (ASA) plus 75 mg tid dipyridamole (DP) or ASA alone. One hundred twenty-seven patients (399 total grafts) underwent surgery, initiation of drug therapy 67 +/- 27 (SD) hr postoperatively, five clinic visits, and repeat angiography at 1 year. A logistic regression statistical model was used to determine the effects of 28 different measured variables on graft patency and to adjust for these effects in determining the relationship between antiplatelet therapy and graft occlusion. No patient-specific variable contributed significantly to the prediction of occlusion in either the placebo or the treated group. Six graft-specific variables (arterial diameter, severity of stenosis, graft flow, reactive hyperemia, presence or absence of collaterals, and graft type) did contribute and were included in the model. Twenty-one percent of placebo-treated grafts became occluded. Compared with placebo, the relative risk of graft occlusion with ASA was 0.47 (p = .04); with ASA + DP, it was 0.50 (p = .04). This benefit was principally due to reduction of occlusion in the most common and presumably most important groups of grafts, those in which flow exceeded 40 ml/min, or supplying arteries having luminal diameters greater than 1.5 mm. Grafts lacking reactive hyperemia had a 32% occlusion frequency in placebo-treated patients; relative risk of their occlusion averaged 0.26 (p less than .01) with platelet-inhibiting therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of orally administered diltiazem combined with maximally tolerated doses of beta-blockers and nitrates were assessed in 12 patients, who during stress testing exhibited persistent effort angina and continued objective evidence for inducible myocardial ischemia. Patients performed multistage semisupine exercise on a bicycle ergometer during equilibrium-gated radionuclide angiography after consecutive 2 week treatment periods of placebo or diltiazem 90 mg qid (mean dose 340 mg/day) combined with maximally tolerated propranolol (mean dose 178 mg/day) and isosorbide dinitrate (mean dose 137 mg/day). All medications (including diltiazem or placebo) were administered four times daily for the duration of the study. Diltiazem or placebo was administered according to a double-blind design, with randomized cross-over at the end of each 2 week treatment period. The average number of angina attacks decreased during the double-blind cross-over phase of the trial (7 +/- 7 episodes/week at baseline vs 4 +/- 3 on placebo vs 2 +/- 2 on diltiazem; p = .08). Angina pectoris was abolished during peak exercise in eight of 12 patients on diltiazem (p less than .05 vs placebo). Diltiazem increased total exercise duration from 276 +/- 92 to 310 +/- 78 sec (p less than .005 vs baseline). Diltiazem likewise increased the time to onset of angina from 231 +/- 84 sec at baseline to 305 +/- 77 sec (p less than .005), as well as the time to the onset of 1 mm ischemic ST segment depression (p = .01). Diltiazem decreased heart rate at rest, during submaximal workload, and at peak exercise (p less than .05), and decreased systolic blood pressure at peak exercise only (p less than .05). A significant decline in rate-pressure product at submaximal and peak exercise was noted (p less than .05). At any given workload there was significantly less ST segment depression during submaximal (p = .05) and peak exercise (p less than .025).(ABSTRACT TRUNCATED AT 250 WORDS)