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  • 1
    ISSN: 1432-1440
    Keywords: Congestive heart failure ; Left ventricular ejection fraction ; Vasodilating β-blocker
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Several studies in the past have shown the long-term beneficial effects of β-blockers in congestive heart failure. Despite the interest in this mode of therapy, their clinical application has been limited due to their negative inotropic effect. A subset of the heart failure patients do not show any improvements with standard β-blocker therapy. Carvedilol, a new, non-selective β-blocking agent with concurrent α-blocking properties, was evaluated in 17 patients with chronic heart failure secondary to ischaemic heart disease. All had resting left ventricular ejection fraction ≤45% and were maintained on diuretic therapy. Acute haemodynamic measurements were made after intravenous carvedilol (2.5–7.5 mg) and also after chronic therapy for 8 weeks (carvedilol 12.5–50 mg b.d.). Radionuclide ventriculography, ambulatory intra-arterial blood pressure monitoring and right heart catheterization were performed before and after 8 weeks of chronic therapy. Twelve patients completed the study and 5 were withdrawn. Symptomatic and haemodynamic improvement was demonstrated in 11 of the 12 patients after 8 weeks of therapy. Mean±standard error systolic intraarterial blood pressure (133 ± 6 to 114 ± 5 mmHg, P 〈0.005), heart rate (81 ± 3 to 61 ± 1 beats/min, P 〈0.0001), pulmonary artery wedge pressure (19 ± 2 to 12 ± 1 mmHg, P 〈0.001) and systemic vascular resistance (1748 ± 115 to 1497 ± 89 dynes/ s/cm5/m2, P 〈 0.02) were reduced with an increase in mean ± SE of stroke volume index (31 ± 1.8 to 40 ± 1.6 ml/m2/beat, P 〈 0.0005) and left ventricular ejection fraction (25 ± 3 % to 32 ± 3 %, P 〈 0.01) after 8 weeks of therapy with carvedilol. This is in contrast to the acute haemodynamic effects of carvedilol, which only showed a reduction in heart rate (81 ± 3 to 74 ± 3 beats/min, P 〈 0.0001), systolic intra-arterial blood pressure (133 ± 6 to 117 ±6 mmHg, P 〈 0.0005) and pulmonary artery wedge pressure (19 ± 2 to 14 ± 2 mmHg, P 〈 0.002) at 10 min post-injection. The systemic vascular resistance, left ventricular ejection fraction and stroke volume index failed to show any significant improvement. Thus intravenous carvedilol produces a reduction in filling pressure, which is maintained after chronic treatment. This property is clearly beneficial for chronic heart failure patients and differs from standard β-blockers. The discrepancy of the haemodynamic changes between the acute and chronic long-term response to carvedilol lends further support to the concept of upregulation of β-adrenoceptors in cognestive heart failure.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: Ranolazine ; angina ; stress testing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ranolazine (RS-43285) has been shown to possess significant anti-ischaemic properties in a canine model of reversible myocardial ischaemia. The clinical efficacy of this new agent was assessed by a single blind, placebo controlled study of 14 patients with chronic stable angina. A 2 week placebo phase was followed by therapy with 30 mg and 60 mg of ranolazine tid for 2 weeks each. Graded, symptom limited treadmill exercise tests were performed at the end of each phase, 1.5 h (AM) and 7 h (PM) after the morning dose. An additional exercise test 1.5 h after the first dose of 30 mg was included to assess the acute dose response. In the AM study, the mean exercise time increased from 6.9 min (placebo) to 7.8 min after the first dose of 30 mg and to 8.2 min and 8.5 min respectively at the end of 30 mg and 60 mg phases. In the PM study, exercise time improved from 6.5 min (placebo) to 8.2 min and 7.8 min respectively at the end of 30 mg and 60 mg phases. The time to onset of angina showed a similar improvement. No significant changes were observed in the resting and peak exercise heart rates and blood pressure. This preliminary study suggests that ranolazine may significantly prolong exercise time in patients with stable coronary artery disease without altering heart rates and blood pressure.
    Type of Medium: Electronic Resource
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