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[Hemodynamic and electrophysiologic effects of the new calcium antagonist Ro 11-1781 (author's transl)]
Insights
The novel calcium-channel blocker Ro 11-1781 effectively reduced blood pressure and ventricular rate in patients. It demonstrated antiarrhythmic properties by slowing atrioventricular nodal conduction and converting arrhythmias to sinus rhythm.
Area of Science:
- Cardiology
- Pharmacology
Context:
- Ro 11-1781 is a new calcium-channel antagonist.
- Cardiac electrophysiology and hemodynamics are crucial for understanding cardiac function and arrhythmias.
Purpose:
- To investigate the hemodynamic, electrophysiologic, and antiarrhythmic effects of Ro 11-1781.
- To assess the impact of Ro 11-1781 on left ventricular performance, sinus node function, and atrioventricular nodal conduction.
Summary:
- Ro 11-1781 significantly decreased systolic and diastolic blood pressure, leading to sympathetic activation and increased heart rate.
- The drug demonstrated a negative dromotropic effect on the atrioventricular node, increasing conduction times and decreasing maximal 1:1 conduction.
- Ro 11-1781 showed antiarrhythmic effects, reducing ventricular rate in patients with supraventricular tachycardias and converting some to sinus rhythm.
Impact:
- Ro 11-1781 exhibits potential as an antiarrhythmic agent by modulating cardiac electrophysiology.
- The study provides insights into the cardiovascular effects of novel calcium-channel blockers.
- Further research may explore Ro 11-1781's therapeutic applications in managing cardiac arrhythmias.
Abstract:
In a 3-part study the new calcium-antagonist Ro 11-1781 was investigated in respect to hemodynamic, electrophysiologic and antiarrhythmic effects. In the first part of the investigation, systolic time intervals were determined as an indicator of left ventricular performance in 10 patients without cardiac disease before and 5 min after i.v. injection of Ro 11-1781 (1 mg/kg/body weight). At the same time blood pressure was measured. There was a significant decrease in systolic and diastolic blood pressure (p < 0.01). Due to the resulting activation of the sympathetic nervous system by baroreflex, heart rate increased by 7 bpm (p < 0.01), there was a shortening of the pre-ejection period PEPc by 15 ms (p < 0.01), whereas left ventricular ejection time LVETc was not changed significantly. The ratio PEPc/LVETc decreased significantly (p < 0.01), reflecting the increase of left ventricular contractility, which results from the activation of the sympathetic nervous system. The PQ interval was increased (16 ms, p less than 0.01), an atrioventricular block however was not seen. In the second part of the investigation, sinus node function was studied in 8 patients by His-bundle electrography and programmed stimulation of the right atrium. There was no significant change in sinus-node recovery time, sinu-atrial conduction time, sinus-node rate and atrial conduction time in response to Ro 11-1781. However, in 2 patients with sinus-bradyarrhythmia a second-degree sinu-atrial block was provoked by the calcium-antagonist. The drug was shown to have a negative dromotrope effect to the AV node, reflected by an increase of the PQ interval (p < 0.01), AH interval (p < 0.01) and a decrease (p < 0.01) of the maximal 1:1 conduction of the AV node, whereas the HV interval was not changed significantly. The antiarrhythmic effects of Ro 11-1781 were studied in 13 patients with atrial flutter, atrial fibrillation or paroxysmal supraventricular tachycardia: In 10 patients the injection of the calcium-antagonist produced a marked decrease in ventricular rate for a short time reflecting a neagative dromotrope effect in the AV node. In 5 patients conversion to sinus rhythm was observed.