Effects of diltiazem and long-term beta 1-adrenergic blockade on hemodynamics and blood flow during exercise in patients with stable angina pectoris

The short-term effects of oral diltiazem on hemodynamics and distribution of cardiac output at rest and during semiupright bicycle exercise were evaluated in eight patients with stable effort angina on long-term beta 1-adrenergic blockade. Cardiac output and iliofemoral blood flow were measured using thermodilution. The patients were exercised to the same work load on a bicycle before and 2 h after oral diltiazem (60 mg in two patients and 120 mg in six). At maximal exercise, diltiazem reduced heart rate from 94 +/- 5 to 88 +/- 6 beats/min (p less than 0.01), mean arterial pressure from 139 +/- 5 to 127 +/- 4 mm Hg (p less than 0.01) and systemic vascular resistance from 9.7 +/- 0.7 to 8.4 +/- 0.4 x 10(2) dynes.s.cm-5 (p less than 0.05) compared with control. During exercise, cardiac output, iliofemoral blood flow, mean pulmonary wedge pressure and mean right atrial pressure were not altered, but stroke volume increased from 119 +/- 11 to 131 +/- 10 ml (p less than 0.05). Maximal ST segment depression during exercise was decreased and angina was less. Diltiazem does not alter the distribution of the cardiac output during exercise but improves ischemia.     

Comparison of bevantolol and atenolol in chronic stable angina

A randomized, double-blind, parallel-group study design was used to compare the antianginal efficacy of bevantolol (200 to 400 mg) and atenolol (50 to 100 mg) each administrated once daily for 8 weeks in 39 patients with chronic stable angina. Assessments were made using 24-hour ambulatory monitoring and treadmill exercise testing performed 22 to 24 hours after the last dose of medication. Both groups were comparable at the end of the placebo phase. In the bevantolol group, exercise time increased from 7.9 +/- 0.7 minutes with placebo to 9.3 +/- 0.7 minutes with bevantolol (mean +/- standard error of the mean) (p less than 0.05). Time to 1 mm ST depression was unaltered. Rest and exercise heart rate decreased (p less than 0.0001 and less than 0.0005, respectively) as did exercise double product (p less than 0.0001). In the atenolol group exercise time increased from 7.1 +/- 0.7 minutes with placebo to 8.2 +/- 0.8 minutes with atenolol (p less than 0.02). Time to 1 mm ST depression increased (p less than 0.005) and rest and exercise heart rate and double product decreased (p less than 0.0001 and less than 0.05, respectively). When within-group differences between placebo and active drug were compared for bevantolol and atenolol, no significant differences were detected. Both drugs were well tolerated and reduced ambulatory heart rate throughout the 24 hours. This study confirms that both bevantolol and atenolol are effective antianginal agents. Bevantolol compares well with atenolol in the treatment of patients with chronic angina, and there was a similar response to exercise testing with the 2 drugs.     

Hemodynamic and radionuclide effects of acute captopril therapy for heart failure: changes in left and right ventricular volumes and function at rest and during exercise

Although the resting hemodynamic effects of captopril in congestive heart failure are known, little information is available about the hemodynamic response to captopril during exercise or about changes in noninvasive measurements of the size and function of both ventricles. In this study, 14 stable New York Heart Association class III patients were given 25 mg or oral captopril. Rest and exercise hemodynamic measurements and blood pool scintigrams were performed simultaneously before and 90 minutes after captopril. The radionuclide studies were analyzed for left and right ventricular end-diastolic volumes, end-systolic volumes, ejection fractions and pulmonary blood volume. The primary beneficial responses at rest were decreases in left and right ventricular end-diastolic volumes from 388 +/- 81 to 350 +/- 77 ml (p less than 0.01) and from 52 +/- 26 to 43 +/- 20 volume units (p less than 0.01), respectively, and in their corresponding filling pressures, from 24 +/- 10 to 17 +/- 9 mm Hg and 10 +/- 5 to 6 +/- 5 mm Hg (both p less than 0.001). Although stroke volume did not increase significantly, both left and right ventricular ejection fractions increased slightly, from 19 +/- 6% to 22 +/- 5% and from 25 +/- 9% to 29 +/- 11%, respectively (both p less than 0.01). During exercise, similar changes were noted in both hemodynamic and radionuclide indexes. Thus, in patients with moderate symptomatic limitation from chronic heart failure, captopril predominantly reduces ventricular volume and filling pressure, with a less significant effect on cardiac output. These effects persist during exercise, when systemic vascular resistance is already very low. Radionuclide techniques are valuable in assessing the drug effect in these subjects, particularly when ventricular volumes are also measured.     

Effects of isosorbide-5-mononitrate on exercise-induced hemodynamic changes in angina pectoris

Hemodynamic effects of isosorbide-5-mononitrate (ISMN) were studied in 14 patients with effort angina pectoris. Hemodynamic and echocardiographic data were obtained by angina-limited supine multistage bicycle ergometer exercise testing before and 120 minutes after single oral administration of 20 mg of ISMN. Compared with control exercise testing, the ST segment at peak exercise showed less depression after administration of ISMN (p less than 0.001). At rest, systolic and diastolic blood pressure decreased significantly after administration of ISMN (p less than 0.001 and p less than 0.01, respectively). At rest and at peak exercise, pulmonary artery wedge pressure (both p less than 0.001), left atrial volume (both p less than 0.001) and left ventricular end-diastolic volume (both p less than 0.05) decreased, whereas cardiac index, pressure-rate product and systemic vascular resistance did not change significantly after administration of ISMN. Average time to peak plasma ISMN concentration was 90 minutes and average peak plasma concentration was 460 ng/ml with an elimination half-life of 7 hours. These data suggest that the main mechanism of the antianginal action of ISMN is a reduction in left ventricular preload followed by diminution of myocardial oxygen requirements.     

Antianginal efficacy of carvedilol, a beta-blocking drug with vasodilating activity

The efficacy of carvedilol, a new vasodilating beta-blocking drug, was evaluated in 20 patients with chronic angina using a single-blind, placebo-controlled protocol. A 2-week placebo phase was followed by therapy with carvedilol, 25 mg twice daily for 2 weeks, after which the dose was doubled. There was then a second placebo phase lasting 2 weeks. Treadmill exercise testing, 24-hour ambulatory electrocardiographic monitoring and drug blood level assays were performed at the end of each phase. Exercise time (mean +/- standard error of mean) increased from 7.4 +/- 0.5 minutes during placebo to 9.0 +/- 0.5 minutes carvedilol, 25 mg twice daily (p less than 0.001), and to 9.2 +/- 0.4 minutes with 50 mg twice daily (p less than 0.001). Mean time to 1 mm of ST depression in both bipolar leads CM5 and CC5 increased significantly, but peak ST depression did not change. Heart rate at rest was reduced at both dose levels, from 86 +/- 4 beats/min during placebo to 70 +/- 2 beats/min with 25 mg twice daily (p less than 0.001) and to 67 +/- 3 beats/min with 50 mg twice daily (p less than 0.001). Systolic blood pressure at rest was significantly reduced at both doses (p less than 0.05; p less than 0.01), but blood pressure during exercise was decreased only with the larger dose (p less than 0.001). The exercise rate-pressure product was 182 +/- 9 with placebo and decreased to 153 +/- 5 with 25 mg twice daily (p less than 0.001) and to 138 +/- 6 with 50 mg twice daily (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of captopril in chronic aortic insufficiency

In 16 patients with chronic aortic regurgitation, we studied the acute hormonal and hemodynamic effects of 12.5 to 25 mg captopril; in 12 patients the changes after a 4 to 8 week treatment period (mean 6.3 +/- 2 weeks; doses: 3 times 12.5 to 3 times 25 mg/day) were investigated. The following baseline variables were evaluated: the radionuclide left ventricular ejection fraction (EF) at rest and during exercise, left ventricular end-diastolic volume (EDV), regurgitant blood volume (RBV); and plasma renin activity (PRA). Repeated determinations of EF, EDV and RPA were carried out 90 minutes after application of the drug. In patients with chronic therapy, EF at rest and during exercise, EDV, RBV and PRA were reinvestigated at the end of the study. Acute administration of captopril was followed by an increase of EF (from 49 +/- 12 to 55 +/- 12%, p less than 0.001) and a slight decrease of EDV (from 389 +/- 160 to 376 +/- 146 ml, p less than 0.05). PRA significantly increased (from 1.6 to 3.1 ng/ml/h, p less than 0.05). Chronic therapy resulted in a moderate decrease of systolic and diastolic blood pressure (from 156/70 +/- 31/15 to 140/63 +/- 23/15 mm Hg, p less than 0.01). However, no significant changes were observed in EF at rest and during exercise (51 +/- 9 vs. 53 +/- 10% and 45 +/- 14 vs. 47 +/- 14%), EDV (433 +/- 179 vs. 422 +/- 179 ml) and RBV (136 +/- 81 vs. 129 +/- 77 ml). PRA was significantly increased (6.3 ng/ml/h, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Combined effects of nitrates on the coronary and peripheral circulation in exercise-induced ischemia

We compared the effects of isosorbide dinitrate (ISDN) administered by intracoronary and intravenous routes in 10 patients with severe coronary artery disease, stable effort angina, and very low exercise tolerance. Supine bicycle ergometer exercise was performed under four conditions: 1) control, 2) after intracoronary administration of 0.4 mg ISDN, 3) 1 hour later (control 2), and 4) after administration of intravenous 4 mg ISDN. At rest, intracoronary ISDN caused no significant hemodynamic effects, whereas intravenous infusion of ISDN resulted in a decline in left ventricular (LV) systolic pressure (-20 +/- 5 mm Hg), LV end-diastolic volume (-27 +/- 3%), and LV end-systolic volume (-30 +/- 4%). After intracoronary infusion of ISDN, ST segment depression and the increase in LV end-diastolic pressure and LV end-systolic volume induced by exercise were significantly less abnormal than during control (0.20 +/- 0.09 vs. 0.14 +/- 0.08 mV, 36 +/- 7 vs. 24 +/- 8 mm Hg, and 91 +/- 40% vs. 40 +/- 29%, respectively). When exercise was performed after intravenous infusion of ISDN, the above-mentioned parameters were significantly improved even further: ST segment depression to 0.05 +/- 0.07 mV, end-diastolic pressure to 14 +/- 7 mm Hg, and LV end-systolic volume to 5 +/- 11% (all p less than 0.01 compared with intracoronary ISDN). Thus, in patients with severe coronary artery disease, it is suggested that intracoronary nitrates increase coronary blood supply during effort-induced ischemia, based on significant improvements in the indirect measures of ST segment depression, LV end-diastolic pressure, and LV volume.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of the cardiac output and stroke volume response to upright exercise in children with valvular and subvalvular aortic stenosis

Cardiac output and stroke volume were evaluated in 17 children (mean age 11.5 +/- 3 years) with discrete, membranous subvalvular (Group I, n = 7) and valvular (Group II, n = 10) aortic stenosis during submaximal and maximal (greater than 75% predicted maximal oxygen consumption) upright cycle ergometry. Patients with valvular aortic stenosis were further subdivided on the basis of their aortic valve gradient at rest determined by cardiac catheterization (Group IIA, gradient less than 40 mm Hg; Group IIB, gradient greater than or equal to 40 mm Hg). These patients were matched with 17 control subjects on the basis of age, sex, height and intensity of exercise during maximal exertion. Cardiac and stroke indexes were determined by the acetylene rebreathing method at each exercise level. Stroke volume index in Group I was significantly greater at rest when compared with that in control subjects (69 +/- 13 versus 53 +/- 11 ml/m2, alpha = 0.01, p less than 0.05) and that in patients in Group II (69 +/- 13 versus 47 +/- 12 ml/m2, alpha = 0.01, p less than 0.05). Patients with subvalvular aortic stenosis were unable to increase their stroke volume index from rest to submaximal exercise and also decreased their stroke volume index at maximal exercise levels. In contrast, patients with mild valvular aortic stenosis (Group IIA) displayed a normal exercise response. Patients with severe valvular aortic stenosis (Group IIB) had a blunted stroke volume response at rest and at each level of exercise, as well as signs of myocardial ischemia (ST segment depression) during maximal exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of ST segment depression in upright treadmill and supine bicycle exercise testing

Significant differences in the hemodynamic response to upright and supine exercise have been reported in patients with coronary artery disease. The purpose of the present study was to compare the degree of myocardial ischemia as assessed by ST segment depression during upright treadmill and supine bicycle exercise in 98 patients with coronary artery disease and in 34 patients with normal coronary arteries. The amount of ST segment depression at maximal exercise in patients with coronary artery disease was 0.90 +/- 0.80 mm for treadmill and 1.34 +/- 1.09 mm for supine bicycle (p less than 0.001). The amount of ST segment depression during treadmill and supine bicycle exercise tests was also compared at highest similar heart rates (0.68 +/- 0.77 versus 1.17 +/- 1.01, p less than 0.001), at highest similar rate-pressure products (0.71 +/- 0.77 versus 1.08 +/- 1.04, p less than 0.001), at highest similar metabolic equivalents of oxygen consumption (MET) levels (0.69 +/- 0.75 versus 1.20 +/- 1.05 mm, p less than 0.001) and at the onset of angina (0.84 +/- 0.73 versus 1.18 +/- 0.88 mm, p less than 0.001). The rate-pressure product achieved at maximal exercise was similar in both tests (18.74 +/- 5.80 x 10(3) versus 18.81 +/- 5.17 x 10(3), p = NS). The occurrence of angina during treadmill and supine bicycle exercise tests was similar (47 of 98 versus 48 of 98, respectively, p = NS). For the detection of coronary artery disease, the sensitivity was 50.0% for treadmill and 63.3% for supine bicycle (p less than 0.05) and the specificity was 73.5 versus 70.6%, respectively (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of clinical and treadmill variables for the prediction of outcome after myocardial infarction

To assess the relative prognostic merits of 15 clinical and 10 predischarge exercise test variables, 226 patients who had sustained an acute myocardial infarction were studied. A submaximal treadmill test was performed on 205 patients to a mean work load of 5.7 +/- 2.9 METS. Testing was performed an average of 11.7 (range 6 to 33) days after myocardial infarction. During the first year of observation, major cardiac events were noted in 33 patients (16%), unstable angina in 7 (3.4%), recurrent myocardial infarction in 14 (6.8%) and death in 12 patients (5.9%). Cardiac mortality correlated with mean peak serum creatine kinase (CK) (p less than 0.05), history of previous myocardial infarction (p less than 0.01) and ST segment depression at rest (p less than 0.01). The only exercise variable that correlated with cardiac mortality was poor exercise endurance (p less than 0.05). Multivariate risk stratification of clinical and treadmill variables from these 205 patients using linear discriminant analysis produced a function that correctly classified 95% of those who were event-free and 80% of those who died. The first four discriminant variables that contributed independent information for the prediction of cardiac mortality were: 1) ST segment depression at rest; 2) CK greater than 1,280 IU/liter; 3) exercise duration less than 3 minutes; and 4) a history of previous myocardial infarction. ST segment depression on the predischarge treadmill test did not predict any event, nor did it improve the predictive accuracy of the clinical variables. It is concluded that a history of previous myocardial infarction and ST segment depression on the rest electrocardiogram indicate a poor prognosis after acute myocardial infarction. Poor endurance is the only exercise variable that suggests a future cardiac event. Prognosis after acute myocardial infarction is more accurately predicted by these clinical data than by variables derived from the predischarge treadmill test.     

Beneficial effects of high-dose diltiazem in patients with persistent effort angina on beta-blockers and nitrates: a randomized, double-blind, placebo-controlled cross-over study

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)     

Improved left ventricular performance during exercise with verapamil or nifedipine in patients with chronic stable angina

To examine the effects of chronic oral therapy with verapamil, 120 mg three times a day, and nifedipine, 20 mg four times daily, on left ventricular ejection fraction and regional wall motion at rest and exercise, 10 patients with chronic stable angina pectoris underwent serial rest and exercise radionuclide angiography. Pre drug control study revealed a resting left ventricular ejection fraction (LVEF) of 0.62 +/- 0.08, falling to 0.54 +/- 0.12 at peak exercise (p less than 0.05). Wall motion score deteriorated from a resting value of 13.8 +/- 2.3 to 10.6 +/- 1.8 (p less than 0.01) with exercise. Patients were subsequently randomized to verapamil or nifedipine for 4 weeks each in an open-labeled crossover design. Rest and exercise radionuclide angiography were repeated at the end of each 4-week period. Neither verapamil nor nifedipine had a significant effect on resting LVEF (verapamil LVEF = 0.61 +/- 0.10, nifedipine LVEF = 0.64 +/- 0.02). Likewise, they had no significant effect on resting wall motion score (verapamil = 14.2 +/- 2.2, nifedipine = 14.4 +/- 1.6). Both verapamil and nifedipine significantly increased LVEF at peak exercise (verapamil = 0.63 +/- 0.09, nifedipine = 0.65 +/- 0.08, p less than 0.05 vs pre drug control) and improved peak exercise wall motion score (verapamil = 13 +/- 1.9, nifedipine = 13.8 +/- 1.6, p less than 0.05 vs pre drug control). Both drugs significantly reduced maximal ST depression at peak exercise and prolonged exercise duration. Episodes of angina and nitroglycerin use were also significantly reduced. In summary, verapamil and nifedipine improved left ventricular performance at exercise in patients with angina pectoris.     

Sustained release verapamil, a once daily preparation: objective evaluation using exercise testing, ambulatory monitoring and blood levels in patients with stable angina

The efficacy of a once daily, sustained release formulation of verapamil (Verapamil SR, 360 mg) was evaluated in 19 patients with chronic angina pectoris using a double-blind placebo-controlled crossover protocol. Evaluation by exercise testing, 24 hour electrocardiographic ambulatory monitoring and blood drug level assays was performed at the end of each 2 week phase, 21 to 23 hours after the last dose. After the crossover protocol, all patients were given sustained release verapamil for 4 weeks and the evaluation was repeated. Exercise time (mean +/- SEM) increased from 7.4 +/- 0.6 minutes with placebo to 9.6 +/- 0.8 minutes with verapamil (p less than 0.001) and to 9.5 +/- 0.7 minutes (p less than 0.001) after 4 weeks of therapy. The mean time to 1 mm ST depression also increased significantly, from 4.5 +/- 0.4 and 4.8 +/- 0.5 minutes in bipolar leads CM5 and CC5, respectively, with placebo, to 5.5 +/- 0.6 (p less than 0.05) and 6.2 +/- 0.5 minutes (p less than 0.01) with verapamil. Maximal ST depression and rest and peak heart rates were not altered significantly. The mean rate-pressure product was 208 +/- 9.9 with placebo and decreased to 189 +/- 7.7 (p less than 0.05) with verapamil but rose to 200.6 +/- 10.4 (p = NS) after 4 weeks of therapy. The mean hourly heart rates were lower with the drug than with placebo throughout the 24 hour period but there was no significant bradycardia, arrhythmia or heart block.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of a benzodiazepine (alprazolam) on plasma epinephrine and norepinephrine levels during exercise stress

To determine whether a benzodiazepine central nervous system depressant, alprazolam, inhibits sympathetic discharge during exercise stress, 11 healthy men, aged 21 to 35 years, performed symptom-limited treadmill tests before and on the third day of drug therapy (0.5 mg 3 times daily). Plasma epinephrine and norepinephrine levels were measured at rest and at 8 minutes, 11 minutes and maximal exercise. Owing to catheter malfunction during vigorous exercise, paired samples could be obtained from only 8 subjects at 8 minutes and from only 4 subjects at 11 minutes of exercise. During drug treatment, the plasma epinephrine level was lower at rest (30 +/- 4 vs 53 +/- 7 pg/ml, p less than 0.01), and at 8 minutes (60 +/- 13 vs 117 +/- 19 pg/ml, p less than 0.01), 11 minutes (120 +/- 39 vs 193 +/- 52 pg/ml, p less than 0.05), and maximal exercise (520 +/- 125 vs 970 +/- 324 pg/ml, p = 0.13). Plasma norepinephrine was unchanged at rest (452 +/- 57 vs 413 +/- 45 pg/ml) but lower at 8 minutes (730 +/- 75 vs 886 +/- 82 pg/ml, p less than 0.01), 11 minutes (1,077 +/- 197 vs 1,447 +/- 301 pg/ml, p less than 0.05) and at maximal exercise (3,453 +/- 487 vs 5,590 +/- 1,100 pg/ml, p = 0.09). Exercise duration (17 +/- 1 and 17 +/- 1 minutes) was unchanged on drug. Thus, alprazolam reduces the plasma catecholamine response to exercise stress, possibly by inhibiting centrally mediated sympathetic discharge. Blunting of sympathetic activation may be beneficial in cardiac disorders in which increased sympathetic tone is potentially deleterious.     

Effects of nicorandil on exercise tolerance in patients with stable effort angina: a double-blind study

Effects of nicorandil, a recently introduced 2-nicotinamidethyl nitrate, on exercise performance were studied in 11 patients with stable effort angina. The duration of exercise before the onset of angina and time to the onset of ischemic ST depression 30 minutes after 20 mg of oral nicorandil were compared with events 30 minutes after oral placebo and 5 minutes after 0.3 mg of sublingual nitroglycerin. Nicorandil and placebo were given according to the randomized double-blind method. Nicorandil prolonged the duration of exercise in all 11 patients by 2.3 +/- 2.2 minutes (mean +/- SD, p less than 0.01) and delayed the onset of ischemic ST depression by 2.3 +/- 1.7 minutes compared to placebo (p less than 0.01). The increment of the duration of exercise and the time to the onset of ischemic ST depression following 20 mg of oral nicorandil were almost equivalent to findings after sublingual nitroglycerin (by 2.0 +/- 1.8 and 2.5 +/- 1.7 minutes, respectively). Nicorandil also increased the pressure-rate product at the time of angina compared with placebo (20,420 +/- 480 vs 17,480 +/- 370, p less than 0.05). These results indicate that oral administration of nicorandil should be considered for the clinical treatment of effort angina.     

Dose response effects of diltiazem on treadmill tolerance in chronic stable angina: a randomized double-blind, placebo-controlled crossover trial

Sixteen patients with stable angina underwent treadmill exercise on 4 separate days prior to and at 1, 2, 4 and 8 hours following a single dose of 30 mg, 60 mg or 90 mg of diltiazem or identical placebo. Prolongation of exercise time to the onset of angina, 0.1 mV ST depression and to maximal exercise developed within 2 hours, peaked at 4 hours and persisted for 8 hours. Time to angina at control with placebo and 90 mg of diltiazem was 399 +/- 176 and 368 +/- 193 seconds respectively (X +/- SD) and 4 hours post drug was 474 +/- 216 and 635 +/- 209 seconds respectively (p less than 0.001). The pressure-rate product at angina 4 hours following 90 mg of drug was higher than after placebo (189 +/- 48 and 168 +/- 44 mmHg-1 X 10(-2) respectively). Heart rate increased (127 +/- 24 vs. 117 +/- 19 bpm) while systolic pressure was unchanged (147 +/- 17 and 142 +/- 21 mmHg). During submaximal exercise at a fixed work load, diltiazem, 90 mg, decreased heart rate from 114 +/- 14 to 97 +/- 18 bpm (p less than 0.005), systolic blood pressure from 148 +/- 19 to 135 +/- 18 mmHg (p less than 0.005) and rate-pressure product from 169 +/- 37 to 131 +/- 36 mmHg-1 X 10(-2) (p less than 0.005). Peak diltiazem plasma levels occurred at 4 hours, being 37 +/- 34, 74 +/- 67 and 106 +/- 68 ng/ml for 30, 60 and 90 mg respectively. Drug levels paralleled increased exercise tolerance when mean data were considered; however, correlation on an individual basis was poor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Significance of hyperventilation-induced ST segment depression in patients with coronary artery disease

To investigate the significance of hyperventilation-induced ST segment depression, 329 consecutive patients with angina and documented coronary artery disease who underwent hyperventilation and exercise tests during pharmacologic washout were studied. The hyperventilation test induced ST segment depression in 79 patients. In 36 of these 79 patients, the electrocardiographic changes occurred early during overbreathing (Group I), whereas in 26 they occurred late during recovery (Group II). Seventeen patients developed ST segment depression both during over-breathing and during recovery (Group III). Group I patients had a higher frequency of history of angina during exercise, multivessel disease and lower tolerance to exercise as compared with patients in Group II. In Group I, the rate-pressure product at the time to onset of ST depression during overbreathing was similar to that during exercise (152 +/- 24 versus 148 +/- 42; p = NS), whereas in Group II the rate-pressure product at the time to onset of ST depression during recovery was comparable with that under control conditions (104 +/- 30 versus 98 +/- 27; p = NS) and far less than that required to produce ischemia during exercise (104 +/- 30 versus 201 +/- 56; p less than 0.0011). In nine Group III patients, the acute administration of propranolol prevented the early hyperventilation-induced ST segment depression, whereas nifedipine abolished the delayed hyperventilation-induced ST segment depression. These findings suggest that early hyperventilation-induced ST segment depression is due to increased oxygen demand in patients with poor coronary reserve and may be prevented by beta-adrenergic blockers, which are useful for lowering oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prognostic value of profound ST segment depression during treadmill stress test in coronary heart disease: nine years follow-up study.

To define the prognostic significance of profound ST segment depression (greater than or equal to 3mm) during exercise test, 106 patients of definite coronary heart disease enrolled in a prospective study were followed for up to 9 years. Group A (56 patients) had profound (greater than or equal to 3mm) ST segment depression (3.56 +/- 0.74mm) and Group B (50 patients) had less than 3mm ST segment depression (1.23 +/- 0.35mm, P less than 0.01) during treadmill testing. Group A patients tolerated exercise for a lesser duration in comparison to group B patients (7.22 +/- 3.35 vs. 10.18 + 4.07 minutes, p less than 0.01). At the end of the study, 21 (37.5%) group A patients either died or underwent coronary artery bypass surgery as compared to 8 (16.0%) group B patients (p = 0.02). The difference in the incidence of cardiac deaths between the two groups was not statistically significant (19.6% in group A and 14.0% in group B). However, sudden deaths were significantly more common in group A as compared to group B patients (10 of 11 (90.9%) vs 4 of 7 (57.1%), p = 0.02). These data suggest that profound ST segment depression (greater than 3mm) during treadmill stress test indicates an adverse long term prognosis with the risk in particular, of sudden cardiac death.     

Dynamic mitral regurgitation. An important determinant of the hemodynamic response to load alterations and inotropic therapy in severe heart failure

Cardiac performance and mitral regurgitation were measured by Doppler echocardiography and right heart catheterization in 12 patients with severe congestive heart failure who performed isometric exercise during control and intravenous administration of dobutamine and nitroglycerin. During control isometric exercise, mitral regurgitant volume increased from 18 +/- 13 to 31 +/- 17 ml (p less than 0.01), while forward stroke volume, by both thermodilution and Doppler echocardiography, substantially decreased. At rest, dobutamine decreased mitral regurgitant volume from 18 +/- 13 to 11 +/- 10 ml (p less than 0.05), while forward stroke volume increased from 46 +/- 13 to 55 +/- 15 ml (p less than 0.05). During isometric exercise, dobutamine tended to decrease mitral regurgitant volume (24 +/- 12 vs. 31 +/- 17 ml; NS) when compared with control exercise. At rest, nitroglycerin decreased mitral regurgitant volume from 18 +/- 13 to 11 +/- 11 ml (p less than 0.05), while forward stroke volume, by both thermodilution and Doppler echocardiography, substantially increased. Similarly, during isometric exercise, nitroglycerin decreased mitral regurgitant volume from 31 +/- 17 to 20 +/- 14 ml (p less than 0.05), while significantly increasing forward stroke volume. At control rest, the median mitral regurgitant fraction was 24% for the 12 patients. Neither dobutamine nor nitroglycerin changed significantly forward stroke and mitral regurgitant volumes at rest and during isometric exercise in the six patients with resting mitral regurgitant fraction below the median. In contrast, dobutamine and nitroglycerin significantly decreased mitral regurgitant volume and increased forward stroke volume both at rest and during isometric exercise in the six patients with mitral regurgitant fraction greater than the median.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of nicardipine and propranolol for chronic stable angina pectoris

In a double-blind, randomized, crossover clinical trial, a new calcium antagonist, nicardipine (90 mg/day in 3 divided doses), was compared with propranolol (120 mg/day in 3 divided doses) in 25 patients with chronic stable angina. The mean weekly frequency of angina episodes decreased from 7.8 +/- 1.2 (+/- standard error of the mean) with placebo to 3.8 +/- 1.2 with nicardipine treatment and 3.5 +/- 1 with propranolol treatment (p less than 0.001). With exercise testing, 5 patients receiving nicardipine and 3 receiving propranolol had no angina or ST-segment changes. Comparing paired samples of both drugs with placebo, significant improvement occurred in exercise duration (nicardipine, 1.3 +/- 0.3 minutes, p less than 0.001; propranolol, 1.0 +/- 0.4 minutes, p less than 0.01), time to onset of angina (nicardipine, 1.5 +/- 0.4 minutes, p less than 0.001; propranolol, 1.5 +/- 0.5 minutes, p less than 0.001), maximal ST-segment changes (nicardipine, 0.7 +/- 0.1 mm, p less than 0.01; propranolol, 0.06 +/- 0.1 mm, p less than 0.01) and time to 1 mm of ST depression (nicardipine, 2.5 +/- 0.4 minutes, p less than 0.01; propranolol, 2.0 +/- 0.3 minutes, p less than 0.01). One patient receiving propranolol and 2 receiving nicardipine withdrew from the study because of transient side effects. Mild side effects occurred in 10 patients receiving propranolol and 5 receiving nicardipine. Nicardipine proved to be safe and effective for patients with chronic stable angina; it had fewer side effects than propranolol in the doses used.