Abstract
Vagal nerve stimulation (VNS) started prior to, or during, ischemia has been shown to reduce infarct size. Here, we investigated the effect of VNS when started just prior to, and continued during early, reperfusion on infarct size and no-reflow and studied the underlying mechanisms. For this purpose, swine (13 VNS, 10 sham) underwent 45 min mid-LAD occlusion followed by 120 min of reperfusion. VNS was started 5 min prior to reperfusion and continued until 15 min of reperfusion. Area at risk, area of no-reflow (% of infarct area) and infarct size (% of area at risk), circulating cytokines, and regional myocardial leukocyte influx were assessed after 120 min of reperfusion. VNS significantly reduced infarct size from 67 ± 2 % in sham to 54 ± 5 % and area of no-reflow from 54 ± 6 % in sham to 32 ± 6 %. These effects were accompanied by reductions in neutrophil (~40 %) and macrophage (~60 %) infiltration in the infarct area (all p < 0.05), whereas systemic circulating plasma levels of TNFα and IL6 were not affected. The degree of cardioprotection could not be explained by the VNS-induced bradycardia or the VNS-induced decrease in the double product of heart rate and left ventricular systolic pressure. In the presence of NO-synthase inhibitor LNNA, VNS no longer attenuated infarct size and area of no-reflow, which was paralleled by similarly unaffected regional leukocyte infiltration. In conclusion, VNS is a promising novel adjunctive therapy that limits reperfusion injury in a large animal model of acute myocardial infarction.Electronic supplementary materialThe online version of this article (doi:10.1007/s00395-015-0508-3) contains supplementary material, which is available to authorized users.
Highlights
The single most effective therapy to limit myocardial infarct size and improve clinical outcome after acute myocardial infarction is early coronary reperfusion via primary percutaneous coronary intervention [41, 43]
The main findings were that (1) vagal nerve stimulation (VNS) significantly limited infarct size and extent of no-reflow; (2) these effects were accompanied by reductions in regional infiltration of neutrophils and macrophages; (3) Inhibition of NO-synthase prevented the cardioprotection by VNS against necrosis, no-reflow and leukocyte influx
The present study in a porcine model of acute myocardial infarction demonstrated that vagal nerve stimulation (VNS) started just prior to reperfusion and continued during early reperfusion-limited infarct size and the extent of no-reflow
Summary
The single most effective therapy to limit myocardial infarct size and improve clinical outcome after acute myocardial infarction is early coronary reperfusion via primary percutaneous coronary intervention [41, 43]. No-reflow refers to inadequate myocardial reperfusion following opening of the culprit coronary lesion, despite lack of angiographic evidence of epicardial vessel obstruction and may be present in 30–40 % of patients [34]. Since both infarct size [30] and extent of no-reflow [17, 33, 38] are independent predictors of clinical outcome, strategies to limit these two components of reperfusion injury have significant therapeutic potential. Since none of the aforementioned studies assessed the effects of VNS on no-reflow, despite its prognostic potential in the clinical setting [17, 33, 38], the second aim of the present study was to investigate the effects of VNS on no-reflow
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