Heart failure canine model

All animal procedures were approved by the Institutional Animal Care and Use Committee of the Ohio State University, conforming to the NIH Guide for the Care and Use of Laboratory animals. A total of 43 adult mixed breed dogs of either sex with normal cardiac function were used. Dogs were verified to have normal cardiac function by transthoracic two-dimensional and M-mode echocardiographic examinations during butorphanol tartrate (0.5 mg kg ⁻¹ intravenously) sedation. Dogs had an RV pacemaker lead implanted in the RV apex, and HF was induced (n=19, baseline weight 21.4±1.3 kg; mean±SEM) by tachypacing for four months as previously described[17] . Echocardiograms were measured at baseline and 4 months of pacing (with pacer temporarily turned off during the echocardiographic studies). Left atrial and left ventricular end-diastolic dimensions were significantly increased in HF dogs and left ventricular fractional shortening was reduced from 37.4±1.4% pre-pacing to 17.4±1.2% (p<0.01) post-tachypacing. An age matched group of 24 healthy dogs (weight, 21.7±1.2 kg) were used as controls (CTL) and studied in parallel.