Development of a rat model of exercise under anesthesia capable of reproducing abnormal respiratory responses in chronic heart failure (882.5)

Abstract

Background: Abnormal ventilation during exercise is one of the major manifestations of chronic heart failure (CHF). However the lack of good animal models under anesthesia makes it difficult to investigate underlying mechanisms of respiratory abnormality. In this study, we developed a rat model of cardio‐respiratory exercise testing (CPX) under anesthesia.Methods: We used 16 weeks old rats with/without CHF. CHF was created by myocardial infarction. We induced muscle contraction by stimulating bilateral distal sciatic nerves (SNS) and mimicked exercise under anesthesia. We recorded breath‐by‐breath respiration with gas analysis. We ran a ramp protocol and a step protocol while recording respiratory responses.Results: In the ramp protocol, SNS increased minute ventilation (VE) more in CHF in normal rats (NRM). The increase in VE with the production of carbon dioxide (VE/VCO2 slope) was 23.0% more in CHF than in NRM (p<0.05).The increase in tidal volume with the respiratory rate was 16.5% less in CHF than in NRM reflecting the rapid and shallow breathing in CHF. In the step protocol, the time constant (TC) of oxygen uptake (VO2) was 78.7% longer in CHF than in NRM. Conclusion: These data indicated the model simulated respiratory abnormalities in CHF reasonably well. This novel CPX model will provide us an opportunity to clarify the mechanisms of exercise‐induced abnormal ventilation in CHF.