Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · Mar 1997
Efficacy and proarrhythmia with the use of d,l-sotalol for sustained ventricular tachyarrhythmias.
This study prospectively evaluated the clinical efficacy, the incidence of torsades de pointes, and the presumable risk factors for torsades de pointes in patients treated with d,l-sotalol for sustained ventricular tachyarrhythmias. Eighty-one consecutive patients (54 with coronary artery disease, and 20 with dilated cardiomyopathy) with inducible sustained ventricular tachycardia or ventricular fibrillation received oral d,l-sotalol to prevent induction of the ventricular tachyarrhythmia. During oral loading with d,l-sotalol, continuous electrocardiographic (ECG) monitoring was performed. ⋯ Other ECG parameters before the application of d,l-sotalol did not identify patients at increased risk for torsades de pointes. Recurrence rates of ventricular tachyarrhythmias are high despite complete suppression of the arrhythmia during programmed stimulation. Therefore programmed electrical stimulation in the case of d,l-sotalol seems to be of limited prognostic value.
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J. Cardiovasc. Pharmacol. · Jan 1997
Randomized Controlled Trial Clinical TrialThe practical assessment of compliance with ACE-inhibitor therapy--a novel approach.
Poor compliance may be responsible for symptomatic decompensation or neurohormonal "escape" in patients with heart failure treated over the long term with angiotensin-converting enzyme-1 (ACEI) drugs. Serum ACE activity is a poor index of neurohormonal suppression or haemodynamic effect after ACE-inhibitor treatment. Serum ACE activity may, however, be a useful index of compliance with treatment, as serum ACE is sensitive to the presence of an ACE inhibitor in the blood. ⋯ With this long-acting ACEI in a dose relevant to congestive heart failure management, we suggest that 4-6 h after-dosing serum ACE (< 5 EU/L) and elevated ANG I (> 300 pg/ml) can be used to confirm compliance with treatment. These absolute values may be altered in patients treated concomitant with loop diuretics. In principle, however, this may be a useful tool in clinical trials or in clinical practice after further work has been done to assess the limits in patients across the doses and across the range of available drugs used.
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J. Cardiovasc. Pharmacol. · Jan 1997
Clinical Trial Controlled Clinical TrialEffect of methylprednisolone on complement activation during heparin neutralization.
During cardiac surgery, steroids are frequently administered before the initiation of cardiopulmonary bypass (CPB), termed "pre-treatment," to reduce "first phase" complement activation during cardiopulmonary bypass (CPB). "Second phase" complement activation also occurs during heparin neutralization with protamine, although the effects of steroid pretreatment on such activation are unknown. This study was performed in patients undergoing coronary artery bypass graft surgery to determine whether high-dose methylprednisolone pretreatment affected complement activation during heparin-protamine interaction after termination of CPB. In eight patients (group MP), methylprednisolone, 30 mg/kg, was administered before CPB commencement, whereas another eight patients received placebo (group C). ⋯ C5a was not detected in any samples. These results demonstrate that the effect of pretreatment persists beyond the period of CPB and that methylprednisolone inhibits second-phase complement activation during heparin-protamine interaction. These findings have implication for patients with severe anaphylactoid reactions to protamine.
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J. Cardiovasc. Pharmacol. · Jul 1996
Comparative StudyCyclooxygenase inhibition and vascular reactivity in a rat model of hyperdynamic sepsis.
We postulated that the attenuated pulmonary and systemic vascular contractility observed in sepsis was secondary to the release of vasodilator prostaglandins. We used the cyclooxygenase inhibitor meclofenamate to inhibit prostaglandin synthesis in an unanesthetized, chronically instrumented model of hyperdynamic sepsis. Sixteen male Sprague-Dawley rats (300-350 g) were randomized to either sepsis induced by cecal ligation and perforation (CLP, n = 8) or a sham procedure (Sham, n = 8). ⋯ The attenuated pressor response to phenylephrine was not changed in either the pulmonary or the systemic circulation after the administration of meclofenamate. These data suggest that vasodilator prostaglandins may contribute to the attenuated pulmonary pressor response in sepsis. However, the mechanism of the attenuated HPV may be different than the attenuated response to exogenous catecholamines since meclofenamate had no effect on either the pulmonary or systemic response to a phenylephrine infusion in septic animals.
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J. Cardiovasc. Pharmacol. · Mar 1996
Antifibrillatory effect of esmolol alone and in combination with lidocaine.
The primary objective of this study was to determine the effect of esmolol, administered alone and in combination with lidocaine, on ventricular fibrillation threshold (VFT) in pigs. A secondary objective was to determine the relationship between blood esmolol concentrations and VFT. We determined VFT using a train of electrical stimuli delivered to the right ventricle after eight paced beats at a basic cycle length of 285 ms. ⋯ The relationship between blood esmolol concentrations and VFT was described by a counterclockwise hysteresis curve, suggesting delay in equilibration of esmolol between blood and site of effect. The antifibrillatory efficacy of esmolol is significantly greater than that of lidocaine in this model. Administration of the two agents in combination resulted in significantly greater antifibrillatory efficacy than that associated with either drug administered alone.