Laszlo Szekeres

Coronary artery ligation, early arrhythmias, and determination of the ischemic area in conscious rats

A method for studying the acute phase of myocardial infarction in conscious rats has been developed. In preliminary surgery, a loose ligature of atraumatic silk was understitched around the left coronary artery. Its ends were pulled through a polyethylene tube placed within the thorax and fixed under the skin. Seven days later, coronary occlusion was performed by tightening the ligature in conscious animal. Lidocaine and pindolol pretreatment increased the survival rate and attenuated the life-threatening arrhythmias during the first 20 min, but did not influence the infarct size 16 hrs later. An ex vivo perfusion technique for determining the ischemic area has also been developed. 3, 6, and 20 min after coronary ligation, the hearts were excised and perfused with 4% formaldehyde. The ischemic area could not be perfused and remained dark red with a sharp border-line. At the 3rd and 20th min its size was as same as that of the 16-hr infarcted area; however at the 6th min it increased by 50%. Lidocaine and pindolol eliminated this transitory increase. These methods appear to be valuable for large-scale determination of drug effects on the acute phase of experimental myocardial infarction in conscious rats, and for estimating their action on the size of ischemic area very early after coronary occlusion.

Electrophysiological effects of GYKI-23 107, a new antiarrhythmic compound, in isolated rabbit and canine cardiac preparations

The cellular cardiac electrophysiological effects of GYKI-23 107 (I-/2.6-dimethylamino/-2-dimethylaminopropane dihydrochloride). a new investigational antiarrhythmic drug, were studied in rabbit and canine ventricular muscle and Purkinje fibers. For comparison, mexiletine was used. GYKI-23 107. like mexiletine, did not affect the resting membrane potential and slightly reduced the action potential amplitude in both fiber types. The time for repolarization was shortened, but the ratio of effective refractory period to action potential duration was increased by both drugs. The maximum rate of depolarization (Vmax) was depressed by the drugs in a frequency-dependent (“use-dependent”) manner. GYKI-23 107 slowed the recovery kinetics of Vmax in the canine ventricular muscle (Tc = 229.9 ± 5.6 ms; n = 7) and Purkinje fiber (Tc = 149.6 ± 33.8 ms; n = 7) in the same way as mexiletine. The kinetics of restitution of action potential duration during premature and postmature stimulation were slowed to similar degrees in the presence of both GYKI-23 107 and mexiletine in canine Purkinje fibers. It is concluded that, on the basis of its cardiac cellular electrophysiological effects. GYKI-23 107 can be categorized as a class 1b antiarrhythmic agent.