ABSTRACT
To assess flecainide's ability to suppress ventricular fibrillation during reperfusion, we compared flecainide acetate (2 mg/kg i.v.) with saline placebo in 50 pentobarbital-anesthetized dogs undergoing proximal anterior descending coronary artery occlusion for 20 min followed by sudden release. Treatment selection was blinded and randomized. Flecainide (1 mg/kg) was given for 5 min before ligation and 1 mg/kg over the 20 min occlusion period. Heart rate, blood pressure, myocardium at risk, and QRS duration before drug infusion were similar between treatment groups. Flecainide prolonged the QRS duration 12% with no effect on heart rate or blood pressure. Dogs successfully cardioverted from ventricular fibrillation during occlusion were subjected to reperfusion. One of the 25 dogs treated with placebo fibrillated during occlusion, whereas 13 of the 25 dogs treated with flecainide fibrillated during occlusion and 10 of these 13 could not be resuscitated. Thirteen of the 25 dogs in the placebo group fibrillated during reperfusion, whereas 3 of the remaining 15 dogs in the flecainide treatment group fibrillated during reperfusion. The proarrhythmic effects of flecainide during occlusion confound interpretation of its antiarrhythmic activity during reperfusion. Thus, although flecainide may have prevented ventricular fibrillation during reperfusion, it clearly caused ventricular fibrillation during occlusion in this preparation of acute myocardial ischemia.
Subject(s)
Coronary Disease/drug therapy , Flecainide/therapeutic use , Myocardial Reperfusion Injury/drug therapy , Ventricular Fibrillation/drug therapy , Animals , Blood Pressure/drug effects , Coronary Disease/physiopathology , Dogs , Electrocardiography , Flecainide/blood , Heart Rate/drug effects , Myocardial Reperfusion Injury/physiopathology , Ventricular Fibrillation/physiopathologyABSTRACT
Standard and ion-sensitive microelectrodes were used to identify the basis of electrophysiologic changes that occur in canine cardiac Purkinje fibers superfused with "ischemic" solution (40 min) and then returned to standard Tyrode's solution. Maximum diastolic potential (EMDP) decreased (-92.6 +/- 2.4 to -86.0 +/- 4.0 mV; n = 19; P less than 0.001) during exposure to "ischemia," and after reperfusion, rapidly hyperpolarized to -90.0 +/- 4.7 (2 min) and then depolarized to -47.0 +/- 7.5 mV (10 min; P less than 0.001). No significant change in intracellular K activity (alpha ik) was noted throughout. Extracellular K activity (alpha ek) changed only during reperfusion, reaching a nadir at 5 min (3.5 +/- 0.4 to 2.6 +/- 0.5 mM, P less than 0.03), and thus can not account for the decrease in EMDP during reperfusion. Mean alpha iNa increased (8.7 +/- 1.3 to 10.9 +/- 1.9 mM; n = 10; P less than 0.01) during ischemia, but rapidly declined during reperfusion to 5.1 +/- 2.2 mM (10 min; P less than 0.01). Exposure to acetylstrophanthidin (4-5 x 10(-7) M) during the final 10 min of ischemia increased alpha iNa to 19.9 +/- 3.8 mM (n = 5), which was unchanged at 5 min of reperfusion. This suggests that Na-K pump inhibition during ischemia was minimal and that the pump was stimulated early during reperfusion, accounting for the initial transient hyperpolarization. Resting tension did not change significantly during exposure to ischemia; however, return to control Tyrode's solution caused a marked rise to 11.3 +/- 9.9 mg/mm2 (n = 13, P less than 0.001). This is consistent with a calcium overload state during reperfusion. The depolarization seen during reperfusion may result from activation of a Ca-activated, nonselective cation channel or enhanced electrogenic Na/Ca exchange.
Subject(s)
Coronary Disease/metabolism , Electrophysiology , Heart Conduction System/metabolism , Ion Channels/metabolism , Myocardium/metabolism , Perfusion , Purkinje Fibers/metabolism , Animals , Coronary Disease/physiopathology , Disease Models, Animal , Dogs , Extracellular Space/metabolism , Extracellular Space/physiology , Hydrogen-Ion Concentration , Intracellular Fluid/metabolism , Intracellular Fluid/physiology , Ion Channels/physiology , Membrane Potentials , Myocardial Contraction , Potassium/metabolism , Purkinje Fibers/physiology , Sodium/metabolismABSTRACT
The effect of 60 minutes of exposure to high-frequency (10- to 40-kHz), high-intensity (115-dB) noise on the cochlear blood flow (CoBF) was investigated in adult gerbils. The CoBF was measured with a newly improved microsphere method. The number of microspheres in cochlear tissue that had been dissected by the surface preparation technique was assessed by direct counting. Our experiments have indicated that the CoBF is elevated even after 60 minutes of noise exposure. This was true particularly in the areas where these frequencies stimulate the cochlea. The noise also increased CoBF in the opposite ear in areas not corresponding to the stimulation frequencies (second and third turn). This phenomenon is under further investigation.
