Arrhythmogenicity of Low‐Flow Reperfusion Following Acute Local Ischemia in Excised Rat Hearts

Abstract

Clinical studies show that impaired myocardial reperfusion following thrombolytic therapy for coronary occlusions increases the incidence of ventricular arrhythmias; however the mechanisms are poorly understood. We studied arrhythmias during controlled low‐flow reperfusion (LFRP) in excised Langendorff‐perfused hearts (n=6). The left anterior coronary artery (LAD) was cannulated. An HPLC pump delivered perfusate to the LAD at a rate of 2 mL/min, followed by 20 min of local ischemia (0 mL/min) and then 20 min of LFRP (0.2 mL/min). The electrical response at each flow rate was monitored using an ECG and fluorescence imaging of epicardial potentials. We found that the highest heart rates and lowest heart rate variability occurred during LFRP (p<0.05). LFRP also resulted in the highest incidence of VF (p<0.05). During ischemia heart rate variability was highest and the incidence of VF was much lower than during LFRP (p<0.05). Fluorescence images revealed periodic ectopic beats during ischemia and numerous ectopic beats during LFRP. During LFRP, frequent episodes of monomorphic VT were driven by a single rotor and VF was driven by multiple transient rotors. In summary, LFRP fuels the continuous generation of ectopic beats that precede VT/VF. These findings match with our previous in‐vitro studies where we hypothesized that microreperfusion of ischemic border zones could result in ectopic beats and arrhythmias.