Temperature dependence of calcium antagonist action

Area of Science:

• Cardiology
• Pharmacology
• Physiology

Background:

• Ventricular myocytes exhibit temperature-dependent contraction frequencies.
• Calcium antagonists are used in cardiac procedures, including cardioplegia during hypothermia.

Purpose of the Study:

• To investigate the effect of calcium antagonists on the maximal contraction frequency (fm) of rat ventricular myocytes at varying temperatures.
• To analyze the temperature-dependent behavior of these drugs in relation to the Arrhenius equation.

Main Methods:

• Electrical stimulation of calcium-tolerant adult rat ventricular myocytes.
• Determination of maximal contraction frequency (fm) across a range of temperatures (7–39.5°C).
• Analysis of Arrhenius plots in the presence and absence of calcium antagonist drugs (verapamil, nifedipine, diltiazem, fendiline).

Main Results:

• In drug-free conditions, fm followed the Arrhenius equation from 7 to 39.5°C.
• Calcium antagonists introduced a discontinuity in Arrhenius plots between 27°C and 30°C.
• These drugs reduced fm more significantly above the transition temperature, with lower concentrations required for effect compared to below the transition or at 37°C.

Conclusions:

• Calcium antagonists exhibit temperature-dependent effects on myocyte contraction frequency.
• A transition temperature around 27-30°C was identified for the action of these drugs.
• Findings may have implications for the clinical use of calcium antagonists in cardiac surgery, particularly during deep hypothermia protocols.