Diaphragm Dysfunction In Isoproterenol-Induced Heart Failure

Background: In addition to primary cardiocirculatory alterations, heart failure (HF) patients are characterized by diaphragm weakening. Although the HF rodent model based on infusion of isoproterenol (ISO) is widely used, whether the diaphragm is altered in this model is unknown. Aim: Given that some indirect data suggest that ISO increases diaphragm contractibility, our aim was to test the hypothesis that the widespread rodent model of HF based on ISO infusion results in increased diaphragmatic contractility. Methods: Forty C57BL/6J male mice were randomized into 2 groups: HF and healthy controls (C). After 30 days of ISO infusion to establish HF, in vivo diaphragmatic excursion and ex vivo contractility in a bath preparation were conventionally measured. Gene expression of myosin was assessed by qPCR. Results: As expected, HF showed significant changes in structural and functional echocardiographic parameters respect to C. HF increased echo-diaphragmatic excursion (2.8-fold change, p<0.01). Ex vivo force testing HF showed an increase in peak specific force (p<0.05), in tetanic force (p<0.05), at almost all frequencies 10-100 Hz (p<0.05) respect C. Fatigue resistance testing showed reduced time to half-maximum force (p<0.01) in HF vs C. Gene expression of MYH4 was higher in HC as compared with C (p<0.05). Conclusion: The conventional ISO-induced rodent model of HF increases diaphragm contraction, which is contrary to what is observed in patients with HF. Therefore, this model seems limited for translational-integrative HF research, especially when exercise and other respiratory aspects of HF are investigated.