Effect of KRN2391 on canine ventricular arrhythmia models
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1Pharmaceutical Research Laboratory, Kirin Brewery Co. Ltd, Gunma, Japan.
Abstract:
1. KRN2391 (3-30 micrograms/kg, i.v.) produced a decrease in mean blood pressure (MBP) with concomitant increase in heart rate (HR) and change in electrocardiogram (ECG) such as the shortening of PP and PQ intervals and the prolongation of QTc and these changes in HR and ECG were attenuated by pretreatment with propranolol (1 mg/kg) in normal dogs. 2. KRN2391 at 30 micrograms/kg induces neither suppression nor aggravation of ventricular arrhythmias caused by adrenaline and digitalis. 3. In two-stage coronary ligation-induced arrhythmia, KRN2391 inhibited arrhythmia at 48 hr. 4. These results suggest that KRN2391 may be effective on arrhythmia related to ischemia. In addition, it is considered that arrhythmia is not induced even by a high dose of KRN2391 in the normal condition.
Insights
KRN2391 effectively treats ischemia-related arrhythmia in dogs without inducing arrhythmias in normal conditions. Pretreatment with propranolol mitigated KRN2391's cardiovascular effects, suggesting its potential therapeutic value.
Area of Science:
- Pharmacology
- Cardiovascular Research
- Veterinary Medicine
Background:
- Arrhythmia is a significant clinical concern.
- Investigating novel anti-arrhythmic agents is crucial.
- Understanding drug effects on cardiovascular parameters is essential.
Purpose of the Study:
- To evaluate the anti-arrhythmic efficacy of KRN2391.
- To assess the cardiovascular effects of KRN2391 in normal dogs.
- To determine KRN2391's effect on drug- and ischemia-induced arrhythmias.
Main Methods:
- Intravenous administration of KRN2391 (3-30 micrograms/kg) in normal dogs.
- Monitoring of mean blood pressure (MBP), heart rate (HR), and electrocardiogram (ECG).
- Assessment of KRN2391's effect on adrenaline/digitalis-induced and coronary ligation-induced arrhythmias.
Main Results:
- KRN2391 decreased MBP and increased HR, with ECG changes (shortened PP/PQ, prolonged QTc) that were attenuated by propranolol.
- KRN2391 did not induce or worsen ventricular arrhythmias in normal dogs or those challenged with adrenaline/digitalis.
- KRN2391 inhibited arrhythmia in a two-stage coronary ligation model at 48 hours.
Conclusions:
- KRN2391 demonstrates potential efficacy in treating ischemia-related arrhythmias.
- KRN2391 appears safe at high doses in normal conditions, not inducing arrhythmia.
- Cardiovascular effects of KRN2391 warrant further investigation, particularly its interaction with beta-blockers.