Improved left ventricular function and reduced necrosis after myocardial ischemia/reperfusion in rabbits treated with ranolazine, an inhibitor of the late sodium channel.
Ranolazine is an inhibitor of the late sodium current and, via this mechanism, decreases sodium-dependent intracellular calcium overload during ischemia and reperfusion. Ranolazine reduces angina, but there is little information on its effects in acute myocardial infarction. The aim of this study was to test the effects of ranolazine on left ventricular (LV) function and myocardial infarct size after ischemia/reperfusion in rabbits. Ten minutes before coronary artery occlusion (CAO), anesthetized rabbits were assigned to vehicle (n=15) or ranolazine (2 mg/kg i.v. bolus plus 60 microg/kg/min i.v. infusion; n=15). Hearts received 60 min of CAO and 3 h of reperfusion. CAO caused LV dysfunction associated with necrosis. However, at the end of reperfusion, rabbits treated with ranolazine had better global LV ejection fraction (0.42+/-0.02 versus 0.33+/-0.02; p<0.007) and stroke volume (1.05+/-0.08 versus 0.78+/-0.07 ml; p<0.01) compared with vehicle. The fraction of the LV wall that was akinetic or dyskinetic was significantly less in the ranolazine group at 0.23+/-0.03 versus 0.34+/-0.03 in vehicle-treated group; p<0.02. The ischemic risk region was similar in both groups; however, infarct size was significantly smaller in the treated group (44+/-5 versus 57+/-4% vehicle; p<0.04). There were no significant differences among groups in heart rate, arterial pressure, LV end-diastolic pressure, or maximum-positive or -negative first time derivative of LV pressure (dP/dt). In conclusion, the results of this study show that ranolazine provides protection during acute myocardial infarction in this rabbit model of ischemia/reperfusion. Ranolazine treatment led to better ejection fraction, stroke volume and less wall motion abnormality after reperfusion, and less myocardial necrosis.
Hale
Sharon L
SL
The Heart Institute, Good Samaritan Hospital, 1225 Wilshire Blvd., and the Keck School of Medicine, Division of Cardiovascular Medicine, University of Southern California, Los Angeles, CA 90017, USA. sharon.hale@netscape.com
Leeka
Justin A
JA
Kloner
Robert A
RA
D000083:Acetanilides; D000818:Animals; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D009336:Necrosis / Q000188:drug therapy / Q000503:physiopathology; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D000069458:Ranolazine; D026941:Sodium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D015222:Sodium Channels / Q000502:physiology*; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
D000083:Acetanilides; D010879:Piperazines; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D000069458:Ranolazine