Evaluation of left ventricular mass and diastolic function in the treatment of hypertension with beta blockers [abstract]

Arterial hypertension is associated with left ventricular hypertrophy (LVH), and LVH increases the risk for cardiovascular morbidity and mortality. Selected antihypertensive agents have been shown to reverse LVH. In this study, the effects of celiprolol, a selective á1 blocker with partial agonist activity on á2 receptors and propranolol, a non-selective á-blocker, on blood pressure, left ventricular mass of diastolic function were compared. In a prospective study, twenty-nine patients with mild to moderate hypertension were randomly allocated to treatment with either celiprolol or propranolol for twelve weeks, after a three-week drug washout period. Cross-sectional doppler echocardiography was performed for the measurement of left ventricular mass and pulse doppler studies done for evaluation of left ventricular diastolic function. At the end of the study, both celiprolol and propranolol significantly reduced the diastolic blood pressure, while only celiprolol significantly reduced the systolic blood pressure. In the celiprolol group, there was a greater decrease in the left ventricular mass (7.9 percent) compared to the propranolol group (0.3 percent), but this was not significant. Doppler studies established that propranolol caused no significant change in the E/A ratio, while celiprolol caused a significant increase in the E/A ratio (p= 0.01). Propranolol increased the deceleration time (DT) (p= 0.001), while celiprolol decreased the isovolumetric relaxation time (IVRT) (p= 0.002) and increased the pulmonary venous A wave width (P= 0.02). In conclusion, short-term treatment with celiprolol demonstrated a trend towards decreasing the left ventricular mass, and caused significant improvement in left ventricular diastolic function, while propranolol did not. This may be due to the observation that celiprolol reduces total peripheral resistance by vasodilation. Treatment with celiprolol over a longer interval may result in significant reduction of left ventricular mass. (AU)

[Safety and efficacy of celiprolol in hypertensive patients with chronic obstructive lung disease]. / Seguridad y eficacia de celiprolol en hipertensos con enfermedad pulmonar obstructiva crónica.

BACKGROUND: Third generation beta blockers have an intrinsic simpatico-mimetic activity and are cardioselective. Therefore, they should not have adverse bronchial effects and could even have a slight bronchodilator activity. AIM: To test the efficacy and safety of celiprolol in hypertensive patients with chronic obstructive lung disease. PATIENTS AND METHODS: Uncomplicated hypertensive patients with chronic obstructive lung disease received celiprolol during 12 weeks. They were subjected to monthly clinical assessment and ventilatory function was measured on the basal period and at the end of the trial. RESULTS: During the study period, blood pressure fell significantly from 179 +/- 6/112 +/- 8 to 161 +/- 4.7/98 +/- 1.6 mmHg. No changes were observed in forced expiratory volume in 1 s or in forced expiratory flow between 25 and 75% of the vital capacity. No subjective changes in respiratory function were reported during the trial. CONCLUSIONS: No changes in ventilatory function were observed in these patients with chronic obstructive lung disease, treated with celiprolol during 12 weeks.

Seguridad y eficacia de celiprolol en hipertensos con enfermedad pulmonar obstructiva crónica / Safety and efficacy of celiprolol in patients with chronic obstructive lung disease

Background: Third generation beta blockers have an intrinsic simpatico-mimetic activity and are cardioselective. Therefore, they should not have adverse bronchial effects and could even have a slight bronchodilator activity. Aim: To test the efficacy and safety of celiprolol in hypertensive patients with chronic obstructive lung disease. Patients and methods: Uncomplicated hypertensive patients with chronic obstructive lung disease received celiprolol during 12 weeks. They were subjected to monthly clinical assessment and ventilatory function was measured on the basal period and at the end of the trial. Results: During the study period, blood pressure fell significantly from 179ñ6/112ñ8 to 161ñ4,7/98ñ1.6 mmHg. No changes were observed in forced expiratory volume in 1 s or in forced expiratory flow between 25 and 75 percent of the vital capacity. No subjective changes in respiratory function were reported during the trial. Conclusions: No changes in ventilatory function were observed in these patients with chronic obstructive lung disease, treated with celiprolol during 12 weeks

[A comparative study of celiprolol and nicardipine in stable angina of effort]. / Efecto comparativo de celiprolol y nicardipina en angina de esfuerzo estable.

Seventeen patients with effort angina, a positive exercise test and at least one stenosed vessel in coronary angiography were studied. Following a crossover blind-design, each patient received at random either 400 mg/day oral celiprolol or 120 mg/day oral nicardipine. A treadmill exercise test and 24 hour Holter monitoring were accomplished at the end of each treatment period. Both drugs significantly prolonged exercise time and reduced maximum ST segment depression at similar stages of control testing. Nicardipine reduced resting diastolic blood pressure a mean of 18 mm Hg (p less than 0.005) and also systolic blood-pressure 11 mm Hg (p less than 0.005) while celiprolol only reduced systolic pressure 10 mm Hg (p less than 0.01). Resting heart-rate was lowered by celiprolol a mean of 9 beats/min (p less than 0.0001) while nicardipine slightly increased it. The double product at maximum effort decreased with celiprolol and increased with nicardipine. Six patients with 3 vessel disease continued having transient ischemic episodes during treatment with celiprolol and 5 had them with nicardipine. Both drugs were well tolerated by the patients. In conclusion celiprolol and nicardipine proved to be effective in the treatment of myocardial ischemia specially when coronary heart disease is not very advanced.

[Celiprolol in the treatment of chronic stable angina]. / Celiprolol en el tratamiento de la angina crónica estable.

Celiprolol is a third generation beta blocking drug with intrinsic vasodilator effect. We evaluated the effect of this drug at a fixed dose of 400 mg daily in 20 patients with coronary artery disease and stable angina having 2 to 40 episodes of pain a week. All patients had positive exercise stress test with greater than 1 mm ST depression. Compared to the 1 month baseline placebo phase, patients after 3 months of treatment with celiprolol had less episodes of angina (2.4 vs 7.2 a week, p less than 0.001), higher angina threshold (667 vs 337 sec, p less than 0.025), higher ischemia threshold (614 vs 401 sec, p less than 0.001) and were able to perform more work (3937 vs 2403 kgm/min. p less than 0.01). 9 patients had no pain during exercise. A decrease in blood pressure, heart rate and double product was evident in the stress tests of the active phase. Adverse effects included headache (4 patients), sweating (1) and fatigue (1) not requiring modification of drug dose. No adverse effects were seen in 13 patients. Thus, celiprolol is effective to decrease angina during daily life and increase exercise tolerance in patients with chronic stable angina pectoris.

Celiprolol, a compound which attenuates myocardial acidosis and improves regional segmental function following ischemia in dogs: a comparison with propranolol.

Celiprolol, propranolol or saline were administered to separate groups (n = 5-6) of anesthetized dogs in which a critical stenosis was applied to the circumflex coronary artery for 90 min and then reperfused for 30 min. Test drugs were administered at 30 min poststenosis and the effects on pH, regional function and endocardiogram were monitored. A reduction in coronary flow of 54 +/- 2% (n = 27) yielded marked increases in hydrogen ion concentration (H+) of 17 +/- 2 X 10(-8) and ischemic endocardial ST segment of 6 +/- 1 mV while ischemic segmental shortening decreased 75 +/- 9%. Heart rate, arterial pressure and normal regional function were not altered. Celiprolol 0.1 and 1 mg/kg, i.v., reversed the alterations in H+ and ischemic ST segment to prestenosis values while improving ischemic segmental shortening 20 and 38%, respectively, and not affecting heart rate. Propranolol 0.1 and 1 mg/kg, i.v., reversed the alterations in H+ and ischemic ST segment to prestenosis values while further decreasing ischemic segmental shortening 66 and 30%, respectively. Upon reperfusion, ischemic segmental shortening returned to prestenosis values in the group treated with celiprolol 1 mg/kg, i.v., while the propranolol- and saline-treated groups further decreased. It is concluded that celiprolol is efficacious in normalizing myocardial function and ischemia-induced electrophysiological changes following coronary artery stenosis.