Introduction: In acute myocardial infarction (AMI), the extent of unsalvaged myocardium determines the progression to heart failure in the long-term. Therefore, reducing the unsalvaged myocardium is essential to prevent chronic heart failure. Recently we developed a transvenous intravascular vagal nerve stimulation (iVNS) and demonstrated that in a dog of 180 min ischemia/60 min reperfusion model, iVNS started 90 min after the onset of ischemia strikingly reduced infarct size by 61%, and prevented heart failure (HF). However, the question remains what if the ischemia already lasted for 180 min. Does iVNS remain effective over simple reperfusion? Thus we examined if iVNS 180 min after the onset of ischemia overperforms simple reperfusion in reducing infarct size and preventing HF in the long-term.
Methods: In 13 mongrel dogs, we occluded the left anterior descending coronary artery (LAD) to create ischemia. In Control (n=6), 180 minutes of LAD occlusion was followed by 60 minutes of reperfusion. In delayed iVNS (DiVNS; n=7), we applied iVNS 180 min after the LAD occlusion for 60 min, and delayed reperfusion for 30 min (Fig.1). We maximized the intensity of iVNS to the point where hemodynamics remained stable (7.5±2.5 V, frequency; 10 Hz). Four weeks after MI, we compared the infarct size, left ventricular (LV) function in 2 groups.
Results: In comparison with Control, despite the delay in reperfusion, DiVNS increased LV ejection fraction (47.2±5.4 vs. 57.4±4.1%, p<0.01) and end-systolic elastance (3.8±0.5 vs 10.0±3.4 mmHg/ml, p<0.01) and decreased LV end-diastolic pressure (17.9±6.3 vs 4.5±1.8 mmHg, P<0.01). DiVNS nearly halved the infarct size (13.3±2.7 vs. 6.1±4.1%, p<0.01) (Fig.2).
Conclusion: iVNS after the 180 min of ischemia markedly reduced the infarct size, preserved LV function and prevented HF despite delaying reperfusion. Delayed iVNS may contribute to improve long-term cardiac function and thus may serve as a therapeutic option in the management of AMI.