Sympathetic Nerve Innervation and Metabolism in Ischemic Myocardium in Response To Remote Ischemic Conditioning

Background Multiple potential interventions have been tested to protect the heart against myocardial ischemia/reperfusion (MIR) injury. Remote ischemic conditioning (RIC), an endogenous cardioprotective approach, could markedly improve cardiac function post-myocardial ischemia injury. In this study, we aimed to assess the effects of RIC on cardiac sympathetic nerve innervation and metabolism in the association with Chondroitin sulfate proteoglycans (GSPG). Methods Transient myocardial ischemia (30 min) is induced by ligature of the left anterior descending coronary artery ligation (LAD) in male Sprague Dawley rats (250-350 g), in vivo cardiac [11C]mHED and 2-[18F]FDG PET scans were performed at 14 days after ischemia. Remote ischemic preconditioning (RIPerc) was induced by three cycles of five-minute-long unilateral hind limb ischemia and intermittent five minutes of reperfusion during LAD occlusion period. The quantitative parameters were quantified in parametric polar maps. This standardized format facilitates the regional radioactive quantification of parameters in deficit regions to remote areas. The ex vivo radionuclide distribution was additionally identified using autoradiography. Myocardial neuron density and GSPG expression were assessed by immunohistochemistry. Results There was no significant difference in the metabolism-defected to the remote activity ratio (44.6±4.8% vs. 45.4±4.4%) between control rats (MIR) and treated (MIR+RIPerc) rats (P>0.05). Additionally, the mean nervous activity of denervated myocardium activity was significantly elevated in rats with RIPerc coupled with reduced denervated myocardium size compared to the rats MIR group (35.9±7.1% vs. 28.9±2.3% of the left ventricular (LV) remote area (P<0.05). These findings were associated with preserved LV systolic function and a significant reduction in GSPG expression in the myocardium. Conclusion RIPerc presented the effect on cardiac sympathetic nerve innervation following ischemia, but there is no significant effect on myocardial metabolism. A long-term outcome study is warranted.

Activation of the carotid body increases directly recorded cardiac sympathetic nerve activity and coronary blood flow in conscious sheep

Activation of the carotid body (CB) using intracarotid potassium cyanide (KCN) injection increases coronary blood flow (CoBF). This increase in CoBF is considered to be mediated by co-activation of both the sympathetic and parasympathetic nerves to the heart. However, whether cardiac sympathetic nerve activity (cardiac SNA) actually increases during CB activation has not been determined previously. We hypothesized that activation of the CB would increase directly recorded cardiac SNA, which would cause coronary vasodilatation. Experiments were conducted in conscious sheep implanted with electrodes to record cardiac SNA and diaphragmatic electromyography (dEMG), flow probes to record CoBF and cardiac output and a catheter to record arterial pressure. Intracarotid KCN injection was used to activate the CB. To eliminate the contribution of metabolic demand on coronary flow, the heart was paced at a constant rate during CB chemoreflex stimulation. Intra-carotid KCN injection resulted in a significant increase in directly recorded cardiac SNA frequency (from 24±2 to 40±4 bursts/minute; p<0.05) as well as a dose-dependent increase in mean arterial pressure (79±15 to 88±14 mmHg; p<0.01) and CoBF (75±37 Vs 86±42 mL/min; p<0.05). The increase in CoBF and coronary vascular conductance to intracarotid KCN injection was abolished after propranolol infusion, suggesting that the increased cardiac SNA mediates coronary vasodilatation. The pressor response to activation of the CB was abolished by pre-treatment with intravenous atropine but there was no change in the coronary flow response. Our results indicate that CB activation increases directly recorded cardiac SNA which mediates vasodilatation of the coronary vasculature.

Long-term serial changes of cardiac sympathetic nerve dysfunction in acute decompensated heart failure patients with reduced, mid-range and preserved left ventricular ejection fraction

Background Cardiac sympathetic nerve dysfunction, which is assessed by I-123 metaiodobenzylguanidine (MIBG) imaging, is associated with the poor outcomes in patients with chronic heart failure (CHF). Serial evaluation of cardiac MIBG imaging was shown to be useful for predicting adverse outcome in CHF. However, there was no information available on long-term serial changes of cardiac sympathetic nerve dysfunction after discharge of acute decompensated heart failure (ADHF) hospitalization. Purpose We aimed to clarify the serial change of cardiac MIBG imaging parameter in long-term after discharge of heart failure hospitalization, especially relating to HFrEF (LVEF&lt;40%), HFmrEF (40%≤LVEF&lt;50%) and HFpEF (LVEF≥50%). Methods We studied 112 patients (HFrEF; n=44, HFmrEF; n=23 and HFpEF; n=45) who were admitted for ADHF, discharged with survival and without heart failure hospitalization during follow-up period. All patients underwent cardiac MIBG imaging at the timing of discharge, in 6–12 months and in 18–24 months after discharge. The cardiac MIBG heart to mediastinum ratio (H/M) was calculated on the early image and the delayed image (late H/M). The cardiac MIBG washout rate (WR) was calculated from the early and delayed planar images after taking radioactive decay of I-123 into consideration. Results In HFrEF patients, late H/M was significantly improved from discharge to 6–12 months data (1.60±0.24 vs 1.75±0.31, p&lt;0.0001). Late H/M of HFmrEF patients was also significantly improved from discharge to 18–24 months data (1.71±0.27 vs 1.84±0.29 p=0.043). On the other hand, late H/M of HFpEF patients was not significantly changed. As for WR, WR in HFrEF and HFmrEF patients was significantly improved from discharge to 18–24 months data, although WR of HFpEF was not significantly changed. Conclusion The improvement in cardiac sympathetic nerve dysfunction was observed in patients with HFrEF and HFmrEF, not in HFpEF, after the discharge of acute heart failure hospitalization. Funding Acknowledgement Type of funding source: None