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Background: Abnormal respiration during exercise is one of the major manifestations and a powerful predictor of survival in chronic heart failure (CHF). There have not been proposed the appropriate animal model to investigate the mechanism of respiratory abnormalities in CHF during exercise. In this study, we developed an experimental model using anesthetized CHF rats to evaluate exercise-induced abnormal respiration and central chemoreflex control function during exercise in CHF. Methods: We used anesthetized 16 weeks old rats with/without myocardial infarction induced CHF. To mimic exercise, we induced muscle contraction by stimulating bilateral distal sciatic nerves. We recorded the respiratory change in response to sciatic nerve stimulation (SNS) with ramp (5 Hz, 0.01 Volts/sec) and step (5 Hz, 0.5 Volts) protocols. We also evaluated the change of the central chemosensitivity (ventilatory response to partial pressure of carbon dioxide in arterial blood; PaCO2) by CO2 gas inhalation (0, 3 and 5%) during exercise in normal and CHF. Results: In ramp protocol, SNS significantly increased minute ventilation (VE) in CHF to a greater extent than in that of normal (normal 155.2±27.9, CHF 211.2±48.6 mL/min, p Conclusion: Anesthetized rat exercise model simulated respiratory abnormalities in CHF reasonably well. It will provide us an opportunity to clarify the physiological mechanisms of exercise-induced abnormal respiration in CHF.

Background: The inflammatory response plays a pivotal role in the pathogenesis of chronic heart failure (CHF). Although vagal nerve stimulation (VNS) improves CHF, the central mechanism remains unclear. Since VNS exerts powerful anti-inflammatory effects, we investigated how VNS impacts on the inflammatory regulation and the development of CHF. Methods: In 8 weeks old Sprague-Dawley rats, we created large myocardial infarction (MI) and started VNS 2 weeks after MI. We adjusted the intensity of VNS below the threshold of bradycardia (20 Hz, 1.5±0.9 volts, 10 sec on, 50 sec off). In the first group (EARLY) (CHF: n=8, VNS: n=13), we continued VNS for 3 days and evaluated the early impact of VNS on inflammation on the 3rd day. In the second group (LATE) (CHF: n=13, VNS: n=13), we continued VNS for 4 weeks and evaluated cardiac remodeling and function on the last day. Results: In EARLY, hemodynamic parameters or plasma BNP as an index of CHF did not change significantly. In contrast, VNS halved the invasion of CD 68 positive cells in the left ventricle (LV) (CHF: 295.1±142.1, VNS: 110.7±59.6 counts/mm2, p Conclusion: VNS significantly decreased the invasion of macrophage, IL-1β and TGF-β production from the beginning of VNS initiation, and resulted in the decrease of cardiac fibrosis and the improvement of cardiac remodeling as well as cardiac function. VNS induced early suppression of the excessive inflammatory response may lead to its late beneficial effects on CHF.

Introduction: Carotid body denervation (CBD) abolishes the carotid body hypersensitivity induced sympathoexcitatory hypertension. Since the carotid body hypersensitivity is a salient feature and predicts poor outcome of chronic heart failure (CHF), we hypothesized that CBD restores normal autonomic balance, thus improves CHF in rats after large myocardial infarction (MI). Methods: We created MI in 8 weeks Sprague-Dawley rats. Surviving rats at 2 weeks after MI were randomized into CBD (n=11) and sham-operated (Sham; n=13) groups. We removed the tissues around the carotid bifurcation and established CBD. In some rats (Sham; n=5, CBD; n=5), we telemetrically recorded heart rate (HR). One month after CBD, we compared physiological, histological and immunochemical findings between CBD and Sham. Results: CBD significantly reduced HR (337±15 vs. 364±12 bpm, p Conclusions: CBD restores normal autonomic balance and prevents the worsening of heart failure in rats after large myocardial infarction. CBD may serve as a novel neuro-modulatory therapy for CHF patients.