Effects of gallopamil, diltiazem and nifedipine on the loss of K from ischaemic pig hearts

K⁺ release into the extracellular space was investigated during repeated 6-min coronary occlusions before and after the intravenous administration of cardiovascular active doses of gallopamil (0.02; 0.05 mg/kg), diltiazem (1.0; 2.0 mg/kg) or nifedifine (0.01; 0.05 mg/kg) to anaesthetized pigs. K⁺]_e was measured epicardially using silver valinomycin electrodes calibrated in vivo. During control occlusions K⁺]_e rose steeply in all groups, from a pre-ischaemic baseline value of about 3.5 mmol/1 reaching a plateau value within the ischaemic period. This response was reproducible in an untreated control group. Gallopamil reduced the ischaemic K⁺ efflux dose dependently and significantly 10 min after injection; the higher dose also did 60 min after injection. Diltiazem had less effect on K⁺ efflux 10 min after administration and an effect was no longer detectable after 60 min. Nifedipine did not significantly inhibit the ischaemic K⁺ loss. Besides these differences in the direct protection of the ischaemic myocardium, the Ca²⁺ antagonists also had the following effects on the haemodynamic profile. Diltiazem and gallopamil significantly prolonged PQ intervals whereas nifedipine caused a shortening accompanied by a significant increase in heart rate. Blood pressure and LV dP/dt_max were significantly reduced by all compounds, but to a different degree. Diltiazem reduced blood pressure to a greater extent than did nifedipine and gallopamil. LV dP/dt_max was comparably reduced by gallopamil and diltiazem, while nifedipine had less effect. Thus, gallopamil exerted pronounced protective effects on the ischaemic pig heart.