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 nifedipine (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/l 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/dtmax 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/dtmax was comparably reduced by gallopamil and diltiazem, while nifedipine had less effect. Thus, gallopamil exerted pronounced protective effects on the ischaemic pig heart.
Kirchengast
M
M
Department of Cardiovascular Pharmacology, Ludwigshafen, F.R.G.
Raschack
M
M
D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy / Q000503:physiopathology; D004110:Diltiazem / Q000494:pharmacology*; D004566:Electrodes; D005711:Gallopamil / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D013552:Swine
D005711:Gallopamil; D004110:Diltiazem; D009543:Nifedipine; D011188:Potassium