Antiarrhythmic Efficacy of Selective Blockade of the Cardiac Slowly Activating Delayed Rectifier Current, I Ks , in Canine Models of Malignant Ischemic Ventricular Arrhythmia
| Autor: | Harold G. Selnick, Nigel J. Liverton, David A. Claremon, Melanie S. Houle, David B. Gilberto, Andrew J. Tebben, Audrey A. Wallace, Smith Garry R, George E. Billman, Hossain Jahansouz, Gary L. Stump, Joseph J. Lynch |
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| Rok vydání: | 1999 |
| Předmět: |
medicine.medical_specialty
Sympathetic Nervous System Heart disease medicine.medical_treatment Myocardial Ischemia Ischemia Antiarrhythmic agent QT interval Electrocardiography Dogs Physiology (medical) Internal medicine Acetamides Ventricular Dysfunction medicine Animals cardiovascular diseases Myocardial infarction Fibrillation Benzodiazepinones business.industry Arrhythmias Cardiac medicine.disease Blockade Disease Models Animal Heart Block Anesthesia Ventricular fibrillation cardiovascular system Cardiology medicine.symptom Cardiology and Cardiovascular Medicine business Anti-Arrhythmia Agents |
| Zdroj: | Circulation. 100:1917-1922 |
| ISSN: | 1524-4539 0009-7322 |
| Popis: | Background —To date, the lack of potent and selective inhibitors has hampered the physiological assessment of modulation of the cardiac slowly activating delayed rectifier current, I Ks . The present study, using the I Ks blocker L-768,673, represents the first in vivo assessment of the cardiac electrophysiological and antiarrhythmic effects of selective I Ks blockade. Methods and Results —In an anesthetized canine model of recent (8.5±0.4 days) anterior myocardial infarction, 0.003 to 0.03 mg/kg L-768,673 IV significantly suppressed electrically induced ventricular tachyarrhythmias and reduced the incidence of lethal arrhythmias precipitated by acute, thrombotically induced posterolateral myocardial ischemia. Antiarrhythmic protection afforded by L-768,673 was accompanied by modest 7% to 10% increases in noninfarct zone ventricular effective refractory period, 3% to 5% increases in infarct zone ventricular effective refractory period, and 4% to 6% increases in QTc interval. In a conscious canine model of healed (3 to 4 weeks) anterior myocardial infarction, ventricular fibrillation was provoked by transient occlusion of the left circumflex coronary artery during submaximal exercise. Pretreatment with 0.03 mg/kg L-768,673 IV elicited a modest 7% increase in QTc, prevented ventricular fibrillation in 5 of 6 animals, and suppressed arrhythmias in 2 additional animals. Conclusions —The present findings suggest that selective blockade of I Ks may be a potentially useful intervention for the prevention of malignant ischemic ventricular arrhythmias. |
| Databáze: | OpenAIRE |
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