Electrophysiological Properties of the Infarcted Rodent Myocardium

Abstract

The objective of this study was to establish whether altered electromechanical and Ca2+ cycling properties of surviving myocytes of the infarcted heart contribute to the deterioration of ventricular function following MI. Thus, permanent coronary artery ligation was performed in female mice and echocardiography, pressure-volume (PV) and electrocardiographic analysis were performed after ∼2 weeks. Action potential (AP) duration and propensity to arrhythmia in Langendorff perfused hearts were assessed using a monophasic AP probe with programmed electrical stimulation (PES). Electrical, Ca2+ cycling and contractile properties of isolated LV myocytes were determined by patch-clamp and field stimulation. By echocardiography, the free wall of the LV at the level of the papillary muscles was akinetic in infarcted hearts. In comparison to non-infarcted, diastolic and systolic LV chamber diameters were increased by 1.8- and 2.9-fold, respectively, resulting in a significant decline of fractional shortening and ejection fraction. The slope of the end-diastolic PV relations was significantly higher in infarcted hearts compared to control, whereas slope of the end systolic PV relations was decreased. Thus, both diastolic and systolic functions were compromised. EKGs presented inverted R wave and longer QRS and QT intervals in respect to non-infarcted. Ex-vivo, infarcted hearts displayed prolonged APs and higher propensity to develop arrhythmia following PES. In isolated cells, myocyte volume distribution was shifted toward larger size following MI. By patch-clamp, hypertrophied myocytes obtained from the surviving myocardium of MI hearts were characterized by prolonged APs with high occurrence of early afterdepolarizations (EADs). Moreover, Ca2+ transient amplitude was 1.4-fold larger in cells from infracted hearts in respect to control. This was accompanied by longer transient decay and enhanced shortening in infarcted cells. Consistent with the incidence of EADs, myocytes from infarcted hearts displayed extra-systolic Ca2+ release coupled with after-contractions. In conclusion, MI results in hypertrophy of surviving myocytes together with prolongation of the AP and potentiated Ca2+ transients and contractility. These cellular adaptations did not prevent the deterioration of ventricular function secondary to the loss myocardial tissue. The objective of this study was to establish whether altered electromechanical and Ca2+ cycling properties of surviving myocytes of the infarcted heart contribute to the deterioration of ventricular function following MI. Thus, permanent coronary artery ligation was performed in female mice and echocardiography, pressure-volume (PV) and electrocardiographic analysis were performed after ∼2 weeks. Action potential (AP) duration and propensity to arrhythmia in Langendorff perfused hearts were assessed using a monophasic AP probe with programmed electrical stimulation (PES). Electrical, Ca2+ cycling and contractile properties of isolated LV myocytes were determined by patch-clamp and field stimulation. By echocardiography, the free wall of the LV at the level of the papillary muscles was akinetic in infarcted hearts. In comparison to non-infarcted, diastolic and systolic LV chamber diameters were increased by 1.8- and 2.9-fold, respectively, resulting in a significant decline of fractional shortening and ejection fraction. The slope of the end-diastolic PV relations was significantly higher in infarcted hearts compared to control, whereas slope of the end systolic PV relations was decreased. Thus, both diastolic and systolic functions were compromised. EKGs presented inverted R wave and longer QRS and QT intervals in respect to non-infarcted. Ex-vivo, infarcted hearts displayed prolonged APs and higher propensity to develop arrhythmia following PES. In isolated cells, myocyte volume distribution was shifted toward larger size following MI. By patch-clamp, hypertrophied myocytes obtained from the surviving myocardium of MI hearts were characterized by prolonged APs with high occurrence of early afterdepolarizations (EADs). Moreover, Ca2+ transient amplitude was 1.4-fold larger in cells from infracted hearts in respect to control. This was accompanied by longer transient decay and enhanced shortening in infarcted cells. Consistent with the incidence of EADs, myocytes from infarcted hearts displayed extra-systolic Ca2+ release coupled with after-contractions. In conclusion, MI results in hypertrophy of surviving myocytes together with prolongation of the AP and potentiated Ca2+ transients and contractility. These cellular adaptations did not prevent the deterioration of ventricular function secondary to the loss myocardial tissue.