PREISCHEMIC EFFERENT VAGAL STIMULATION INCREASES THE SIZE OF MYOCARDIAL INFARCTION IN RABBITS BY THE ACTIVATION OF MUSCARINIC RECEPTORS.

BRUNO BUCHHOLZ; JOSE M RODRÍGUEZ; FLAVIO C IVALDE; NADEZDA SIACHOQUE; MARTIN DONATO; RICARDO J. GELPI

Estocolmo

Congreso; European Congress of Cardiology, 2010; 2010

European Society of Cardiology

It has been shown that vagal stimulation (VS) induces cardioprotective protein overexpression, attenuates arrhythmias and improves survival in post myocardial infarction chronic heart failure. Also, the administration of exogenous acetylcholine mimics ischemic preconditioning.  However, there are no conclusive data in regards to the effects of in vivo VS on the infarct size induced by ischemia and reperfusion. The objective of this study was to evaluate the effects of VS on the infarct size performing VS before ischemia.  Methods: Male rabbits subjected to 45 min of regional myocardial ischemia followed by 4 hours of reperfusion were used (Group 1, G1, n=13). In group 2 (G2, n=9) G1 protocol was repeated but, in addition, right efferent VS was performed during 10 min to an intensity enough to reduce heart rate (HR) between 10 to 20%.  In group 3 (G3, n=4) the G2 protocol was repeated but atropine was administered during the stimulation, at a dose necessary to block the effect of VS on HR. In group 4 (G4, n=5) the G2 protocol was repeated but a beta 1 receptor blocker (Esmolol; 3 mg/kg bolus followed by 9.5 mg/kg/min) was administered during the stimulation. To eliminate the efferent stimulation, the vagus nerve was sectioned at the cervical level.  A catheter was placed in the left ventricle (LV) to measure the left ventricular systolic pressure (LVSP), the LV end diastolic pressure (LVEDP), the LV +dP/dt and the HR. The risk area and infarct zone were measured with Evans Blue and triphenyl tetrazolium chloride, respectively. Results: In G1, G2 and G3 the LVEDP increased during ischemia and slightly decreased during reperfusion. LVEDP was not altered in G4. No significant changes were observed in LVSP, LV+dP/dt and HR during ischemia and reperfusion in either group. The VS increased the infarct size from 43,38 ± 2,87% (G1) to 60,67 ± 4,39% (G2) (p<0.05). The administration of atropine during VS (G3) reverted this effect reducing the infarct size to 41,25 ± 2,37% (p<0.05 vs G2).  However, Esmolol administration (G4) only reduced the infarct size to 51.8 ± 5.46%.  Conclusions: Efferent VS performed before ischemia significantly increased the infarct size by a muscarinic cholinergic mechanism. This deleterious effect is also partially reverted by beta 1-adrenergic blockade.