Diastolic tension and contraction amplitude in calcium-loaded rat ventricular myocardium are differently affected by drugs.
1. To obtain a measure of drug effects on myocardial function during diastole, the following experimental protocol was designed: rapid electrical stimulation (5 Hz) at high Ca02+ caused an elevated diastolic tension, which could be subjected to drug-induced alterations. 2. Antiarrhythmic drugs (quinidine, propafenone, procainamide, mexiletine) were able to lower diastolic force without appreciably decreasing contraction amplitude. Calcium antagonists (nifedipine, verapamil) lowered both parameters in parallel. 3. Veratridine and Bay K 8644 both enhanced diastolic tension, but only Bay K 8644 concomitantly elevated contraction amplitude. 4. These findings may be explained when taking into account differential actions of sodium- and calcium channel modulating drugs, respectively, on cellular Ca2+ movements. In quantitative terms, the non-linear dependence of myocardial force on Cai2+ also had to be considered.
Herzig
S
S
Department of Pharmacology, University of Kiel, Fed. Rep. Germany.
Mohr
K
K
Schmidt
S
S
Splieth
J
J
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003864:Depression, Chemical; D003971:Diastole / Q000502:physiology; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D016276:Ventricular Function / Q000187:drug effects; D014701:Veratridine / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D014701:Veratridine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium