Cardioprotective effects of low-level carotid baroreceptor stimulation against myocardial ischemia-reperfusion injury in canine model

Purpose The modulation of the autonomic nervous system (ANS) has been shown to prevent myocardial ischemia-reperfusion injury (MIRI). Carotid baroreceptor stimulation modulates the ANS by sympathetic withdrawal and vagal activation. The aim of this study was to assess whether low-level carotid baroreceptor stimulation (LL-CBS) attenuated MIRI and test its underlying molecular mechanisms. Methods Forty adult healthy mongrel dogs were randomly assigned to three groups as follows: (1) I/R group (n=15): left anterior descending artery (LAD) was occluded for 1 h and allowed for 1 h reperfusion; (2) LL-CBS group (n=15): I/R plus LL-CBS; and (3) sham group (n = 10): sham surgery without stimulation. The voltage-reducing blood pressure by 5% was defined as the threshold. LL-CBS was performed at a voltage that is 80 % below the threshold. Infarct size was assessed with Evans blue and TTC staining. The inflammatory cytokines, biomarker of oxidative stress and apoptosis, and connexin 43 (Cx43) expression were measured to assess the injury. Results The number of ventricular tachycardia/ventricular fibrillation (VT/VF) episodes was significantly decreased in the LL-CBS group compared with the I/R group (2.8 +/- 0.8 vs. 7.0 +/- 2.6, P<0.05). LL-CBS reduced tumor necrosis factor a, interleukin (IL)-1, IL-6, and malondialdehyde levels but increased superoxide dismutase level compared with the I/R group (P<0.05). Meanwhile, LL-CBS significantly decreased the percentage of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL)-positive cardiomyocytes (20 +/- 8 vs. 47 +/- 12, P<0.05). Western blotting and real-time polymerase chain reaction (RT-PCR) in Cx43 revealed that LL-CBS caused an increase, respectively, compared with the I/R group (0.75 +/- 0.3 vs. 0.3 +/- 0.2 and 1.0 +/- 0.3 vs. 0.4 +/- 0.1, respectively, both P<0.05). Conclusions LL-CBS exerted cardioprotective effects during ischemic reperfusion period potentially by inhibiting inflammation, oxidative stress, and apoptosis and modulating the Cx43 expression.