Antiarrhythmic efficacy of selective blockade of the cardiac slowly activating delayed rectifier current, I-Ks, in canine models of malignant ischemic ventricular arrhythmia
Jj. Lynch et al., Antiarrhythmic efficacy of selective blockade of the cardiac slowly activating delayed rectifier current, I-Ks, in canine models of malignant ischemic ventricular arrhythmia, CIRCULATION, 100(18), 1999, pp. 1917-1922
Citations number
31
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Background-To date, the lack of potent and selective inhibitors has hampere
d the physiological assessment of modulation of the cardiac slowly activati
ng delayed rectifier current, I-Ks. The present study, using the I-Ks block
er L-768,673, represents the first in vivo assessment of the cardiac electr
ophysiological 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 sign
ificantly suppressed electrically induced ventricular tachyarrhythmias and
reduced the incidence of lethal arrhythmias precipitated by acute, thrombot
ically induced posterolateral myocardial ischemia, Antiarrhythmic protectio
n afforded by L-768,673 was accompanied by modest 7% to 10% increases in no
ninfarct zone ventricular effective refractory period, 3% to 5% increases i
n infarct zone ventricular effective refractory period, and 4% to 6% increa
ses in QTc interval, In a conscious canine model of healed (3 to 4 weeks) a
nterior myocardial infarction, ventricular fibrillation was provoked by tra
nsient occlusion of the left circumflex coronary artery during submaximal e
xercise, Pretreatment with 0.03 mg/kg L-768,673 IV elicited a modest 7% inc
rease in QTc,prevented ventricular fibrillation in 5 of 6 animals, and supp
ressed arrhythmias in 2 additional animals.
Conclusions-The present findings suggest that selective blockade of I-Ks ma
y be a potentially useful intervention for the prevention of malignant isch
emic ventricular arrhythmias.