Ro 40-5967, in contrast to diltiazem, does not reduce left ventricular contractility in rats with chronic myocardial...

Area of Science:

• Cardiology
• Pharmacology

Background:

• Calcium antagonists are crucial in cardiovascular therapy.
• Verapamil and diltiazem are established calcium antagonists with known inotropic effects.
• Ro 40-5967 is a new calcium antagonist with a distinct pharmacological profile.

Purpose of the Study:

• To compare the inotropic effects of Ro 40-5967 and diltiazem.
• To evaluate these effects in both healthy and myocardial infarction models.
• To assess contractility in vitro and in vivo.

Main Methods:

• Isolated perfused rat hearts for in vitro assessment.
• Conscious rats with induced chronic myocardial infarction for in vivo assessment.
• Measurement of left ventricular dP/dtmax and dP/dt at P40 to assess contractility.

Main Results:

• Neither Ro 40-5967 nor diltiazem reduced contractility in vitro at doses causing AV block.
• In vivo, diltiazem significantly decreased left ventricular contractility.
• Ro 40-5967 exhibited a less negative inotropic effect compared to diltiazem in vivo.

Conclusions:

• Ro 40-5967 shows a more favorable inotropic profile than diltiazem in preclinical models.
• Ro 40-5967 may represent a safer therapeutic option than diltiazem.
• Further clinical trials are warranted to confirm these findings, especially for patients with left ventricular dysfunction.