A comparison of tests for antifibrillatory action
Abstract:
THE OBJECT OF THE EXPERIMENTS WAS TWOFOLD: first, to choose the most satisfactory test for antifibrillatory action; secondly, to place several drugs with reputed antifibrillatory activity in an order of potency as a preliminary to investigating their mode of action. Measurements were made on isolated rabbit atria at 34 degrees C of (1) the maximum driving frequency the atria would follow, (2) conduction velocity, (3) contractions, and of the threshold for the production of (4) extrasystoles, (5) flutter and (6) fibrillation. Log dose-response curves were plotted for quinidine, papaverine, procaine, dibenamine and procaine amide. The maximum frequency test and fibrillation threshold test gave similar results with all the drugs, and the results gave the order quinidine 1.0, procaine 0.53, Dibenamine 0.47, papaverine 0.43 and procainamide 0.26. Thresholds for extrasystoles and flutter were much more variable. The regressions relating changes in conduction velocity and contraction to log dose were different from those for maximum driving frequency and fibrillation threshold for procaine, papaverine and dibenamine, but the regressions for quinidine and procaine amide were nearly parallel in all tests. Serpajmaline contained a substance with antifibrillatory activity as great as that of quinidine and with no greater depressant action on contractions.
Insights
This study identified reliable tests for antifibrillatory drug action, ranking quinidine, procaine, and others by potency. Results guide future research into antifibrillatory mechanisms.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
Background:
- Antifibrillatory drugs are crucial for managing cardiac arrhythmias.
- Standardized testing is needed to compare drug efficacy and potency.
Purpose of the Study:
- To determine the most effective test for assessing antifibrillatory action.
- To rank several reputed antifibrillatory drugs by potency.
Main Methods:
- Experiments utilized isolated rabbit atria at 34°C.
- Measurements included maximum driving frequency, conduction velocity, contractions, and thresholds for extrasystoles, flutter, and fibrillation.
- Log dose-response curves were generated for quinidine, papaverine, procaine, dibenamine, and procaine amide.
Main Results:
- Maximum frequency and fibrillation threshold tests yielded consistent results, establishing a drug potency order: quinidine > procaine > dibenamine > papaverine > procainamide.
- Extrasystole and flutter thresholds showed higher variability.
- Serpajmaline exhibited antifibrillatory activity comparable to quinidine without increasing contractile depression.
Conclusions:
- The maximum driving frequency and fibrillation threshold tests are reliable indicators of antifibrillatory activity.
- Drug potency varies significantly, with quinidine and procaine amide showing distinct dose-response relationships compared to other tested agents.
- Further investigation into the mode of action of these antifibrillatory compounds is warranted.
