“Pacing Bigeminal”

Abstract

SummaryA rapid pacing-induced heart failure model is commonly used in developing dilated cardiomyopathy (DCM). Traditionally, the right ventricular lead was connected with a single chamber pacemaker specific for animals that had a high frequency. However, the pacemaker used in this model is commercially unavailable. We developed a "pacing bigeminal" method using a commercially available dual-chamber (DDD) pacemaker to achieve high-frequency pacing. Twenty beagles were assigned to group A (n = 10) (pacing bigeminal method) and group B (n = 10) (traditional method). Echocardiographic measurements and electrocardiograms were obtained at baseline, at two weeks of pacing, and at 4 weeks of end pacing. LV anterior wall cardiac samples were obtained at 2 weeks of pacing and 4 weeks of end pacing for myocardial microscopic evaluation. Clinical manifestation and exposure time were also observed. After pacing for 10.5 ± 2.3 (7-14) days, the beagles in group B experienced heart failure, whereas in group A, only 7.9 ± 2.5 (5-12) days (P < 0.05) were needed to reach heart failure. Both methods could induce wide QRS duration, heart rate elevation, and myocardial microscopic changes (P > 0.05). In conclusion, this pacing bigeminal-induced heart failure method is feasible and can induce heart failure faster than the traditional method, which makes it a promising alternative method. (Int Heart J 2016; 57: 747-752) Key words: Animal model, Cardiac resynchronization therapy, Dilated cardiomyopathy D ilated cardiomyopathy (DCM) is an important cause of heart failure that is characterized by unexplained left ventricular (LV) dilatation and impaired systolic function.1) Cardiac resynchronization therapy (CRT) is a device therapy for end-stage HF, especially that caused by idiopathic DCM. In the wide application of CRT, the establishment of a suitable big-animal heart failure model is essential in basic research on DCM and CRT, because the devices are not easily used in small-animal models.Current DCM heart failure models of large animals include myocardial infarction, coronary microembolization, pacing-induced tachycardia, and toxic injury, 2,3) described in detail in the AHA Scientific Statement. 4) Regional myocardial infarction models mimic human ischemic cardiomyopathy, which mainly uses pigs instead of dogs because dogs have a well-developed collateral circulation, 5) which can result in higher variability in infarct size and subsequent remodeling. Coronary microembolization also resembles human ischemic cardiomyopathy, but it is time consuming and requires repeated injection with polystyrene microspheres. The limitations of the toxic model include variability of the response to doxorubicin and the degree of LV dysfunction and animal mortality caused by arrhythmias. 4)Chronic tachycardia-mediated DCM is a recognized clinical condition. 6,7) This disease model closely replicates the mechanical, structural, neurohormonal, and myocyte functional alterations of DCM in humans. [8][9][10][11] The predictability and reproducibility...