Erwin A. Rodrigues

Effects of a new vasodilating beta-blocking drug, carvedilol, on left ventricular function in stable angina pectoris

The effects of a new vasodilating beta-blocking drug, carvedilol, were studied in 20 patients with chronic stable angina using a single-blind, placebo-controlled protocol. Two doses of carvedilol, 25 mg twice daily and 50 mg twice daily, were compared with placebo using analysis of variance. The study design consisted of 2 weekly phases of initial placebo followed by carvedilol, 25 mg twice daily and then 50 mg twice daily, and a second placebo period. Supine rest and exercise radionuclide ventriculography was performed at the end of each phase. Carvedilol produced a significant dose-related reduction in rest and exercise heart rate and blood pressure (p less than 0.01 to less than 0.0001). Ejection fraction at rest increased significantly, from a mean (+/- standard error) of 53 +/- 3% with placebo to 58 +/- 3% with carvedilol, 50 mg twice daily, but no improvement was noted in ejection fraction on exercise. Relative, counts-based end-systolic and end-diastolic volumes were significantly reduced at rest (p less than 0.001). Rest peak filling rate index, first-third filling fraction and ejection rate index increased significantly with carvedilol. A dose-related change was observed with rest ejection fraction, peak filling rate index and ejection rate index. Exercise-induced ST-segment depression improved significantly with both doses of carvedilol compared with placebo. Carvedilol was well tolerated and produced significant hemodynamic improvement. This salutary effect on left ventricular function may confer advantages in long-term treatment of patients with chronic stable angina.

Acute and sustained effects of isosorbide 5-mononitrate in stable angina pectoris

Isosorbide 5-mononitrate (IS 5-MN) is an active metabolite of isosorbide dinitrate and is widely used as an antianginal agent. The acute and subacute (2 weeks) effects of IS 5-MN, 40 mg twice daily, were evaluated in 18 patients with stable angina pectoris using computerized exercise testing and a placebo-controlled, double-blind, randomized trial protocol. There were 2 phases of 2 weeks each in which patients received placebo or active IS 5-MN. Acute testing (8 patients) was performed 2 hours after the first dose and subacute testing 2 hours after the morning dose on day 14. Acute testing showed an increase in exercise time from a mean (+/- standard error of mean) of 8.2 +/- 0.6 minutes to 11.1 +/- 0.5 minutes (p less than 0.001) after a single dose of IS 5-MN. Time to 1 mm of ST depression increased significantly and peak exercise ST-segment depression decreased significantly. Rest and peak exercise heart rate increased significantly during acute testing with IS 5-MN; blood pressure did not change significantly. After 2 weeks of therapy, exercise time had not changed (9.9 +/- 0.6 with placebo to 9.7 +/- 0.6 minutes). The beneficial effects on ST-segment variables were sustained at 2 weeks. The data suggest that there is an attenuation of effect with respect to exercise time and sustained beneficial effect on the ST-segment variables. This may be a result of development of partial tolerance to IS 5-MN after 2 weeks of therapy.

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)

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)

Comparison of nicardipine and verapamil in the management of chronic stable angina

Twenty-two patients with stable angina were studied in a randomised double-blind, placebo-controlled crossover trial to compare the antianginal effects of nicardipine (30 mg) and verapamil (120 mg), each given three times a day. Efficacy was assessed using treadmill exercise testing and 24-hour ambulatory electrocardiographic monitoring performed after an initial 2-week placebo phase and at the end of each 4-week active treatment period. Exercise time (mean +/- standard error of mean) increased from 7.4 +/- 0.5 min on placebo to 8.4 +/- 0.7 min on nicardipine (P less than 0.05) and to 9.9 +/- 0.7 min on verapamil (P less than 0.001). Resting heart rate was decreased by verapamil (P less than 0.002) and increased by nicardipine (P less than 0.02). Exercise heart rate was increased on nicardipine (P less than 0.005) but heart rate gain was higher on verapamil (P less than 0.01). Blood pressure and peak ST segment depression were unaltered by either drug but the time to 1 mm ST segment depression increased on both drugs. Ambulatory heart rates were lower on verapamil than on nicardipine and patient subjective preference was in favour of verapamil. This study confirms that both nicardipine and verapamil improve exercise capacity, but verapamil produces a greater improvement in exercise tolerance and indices of myocardial ischaemia whilst nicardipine is associated with an increase in the number of episodes of ST segment depression on ambulatory monitoring.

An objective evaluation of once-daily sustained-release verapamil (480 mg) in chronic stable angina

Verapamil in a daily dose of 360 mg is an effective antianginal agent [11 but its short plasma half-life (4 h) necessitates thrice daily administration. In a previous study we demonstrated a 40% improvement in exercise tolerance, 60% of patients becoming angina-free on exercise [2]. Verapamil SR 360 mg is a new sustained-release formulation of verapamil with a systemic availability profile that is suitable for once-daily administration [3]. Whilst preliminary studies have confirmed its antianginal efficacy, we were only able to demonstrate a 23% improvement in exercise tolerance in a recent placebo-controlled study [4]. A further double-blind, placebo-controlled, crossover study was therefore undertaken to determine whether higher dosing (480 mg per day) with the once-daily formulation could improve exercise capacity further. We recruited 20 men and three

Is high body mass index associated with increased risk of groin complications using manual compression after diagnostic coronary angiography

There is a common perception that high body mass index (BMI) is associated with an increased risk of bleeding complications at the site of femoral puncture when manual compression is used for achieving hemostasis. Because of lack of evidence to support or refute this, we conducted a study to assess whether raised BMI is associated with increased risk of groin complications. 15 cases of groin complications after manual compression over 2 years and 40 controls were each divided into 3 groups according to BMI. Baseline characteristics of cases and controls were similar. High BMI was not found to be associated with increased risk of groin complications, suggesting that manual compression is safe and effective in patients with raised BMI.

A new method of imaging the right ventricle using peripheral vein infusion of xenon 127

We report the development of a new method for obtaining right ventriculograms using the peripheral intravenous infusion of a new tracer, 127Xe dissolved in saline. This tracer has a half life of 36 days, emits 172 keV and 203 keV photons, and is completely cleared by the lungs during pulmonary transit. The right ventricle can therefore be imaged free from interfering activity in the systemic circulation. The technique was used in 11 normal subjects and the results compared with those obtained using first pass and gated equilibrium blood pool angiography with 99mTc. Excellent images of the right ventricle were obtained and the tricuspid and pulmonary valve planes could be easily identified. This imaging technique has significant advantages over existing methods for the noninvasive assessment of right ventricular function.