Rapid screen for heart failure autonomic nervous system imbalance in cardiomyopathic BIO TO‐2 hamsters

Abstract

The cardiomyopathic BIO TO-2 hamster is a recognized model for heart failure including autonomic nervous system dysfunction. Recent studies using BIO TO-2 hamster that has a large deletion in the -sarcoglycan gene have provided promising results showing the efficacy of gene therapy in heart failure. Methods to accelerate preclinical testing of gene therapy and new drugs for heart disease are urgently needed. This study demonstrates a rapid non-invasive screen for characterizing autonomic nervous system imbalance in BIO TO-2 hamsters thus showing its usefulness in the preclinical testing of drugs for heart failure. EKGs were recorded non-invasively through the underside of the paws in conscious BIO TO-2 hamsters and controls (BIO F1-B) using an electrode-embedded platform. Each recording took only a few minutes. Heart rate was significantly higher in BIO TO-2 hamsters. Time domain heart rate variability, an index of parasympathetic tone, was significantly lower, as was the coefficient of variance of the RR interval. Power spectrum analysis showed a reduced high-frequency power spectrum and an increased low/high-frequency ratio, indicating autonomic imbalance with an increased sympathetic tone and a decreased parasympathetic tone in BIO TO-2 hamsters. Thus, autonomic nervous system dysfunction of the heart in hamsters can be quickly and noninvasively quantified. This technique and the findings are of practical significance in accelerating the testing of new therapeutic modalities in the treatment of heart failure.