Chronic Heart Failure Induced by Multiple Sequential Coronary Microembolization in Sheep

Abstract

Objective Although a large variety of animal models for acute ischemia and acute heart failure exist, valuable models for studies on the effect of ventricular assist devices in chronic heart failure are scarce. We aimed to establish a stable and reproducible animal model of chronic heart failure in sheep. Methods Sheep (n=8, 77 ± 4 kg) were anesthesized and a 5F sheath was implanted into the left carotid artery. The left main coronary artery was catheterized under flouroscopic guidance and bolus injection of polysterol microspheres (90 μm, n=25.000) was performed. Microembolization (ME) was repeated up to three times in two to three week intervals until animals started to develop stable clinical signs of heart failure. Clinical and echocardiographic data were analyzed at baseline (base) and at three months (3 mo) after first ME. All animals were followed for 3 months after first microembolization and then sacrificed for histological examination. Another four healthy sheep (79±6 kg) served as control animals. Results All animals developed clinical signs of heart failure as indicated by increased heart rate at rest (68±4 bpm (base) to 93 ± 5 bpm (3 mo) (p<0.05)), increased respiratory rate at rest (28±5 (base) to 38 ± 7 (3 mo) (p<0.05)) and increased body weight 77 ± 2 kg to 81 ± 2 kg (p<0.05) due to pleural effusion, peripheral edema and ascites. Echocardiographic evaluation revealed significantly an increase of left ventricular enddiastolic diameter from 46 ± 3 mm (base) to 61 ± 4 mm (3 mo) (p<0.05). Clinically and echocardiographically no significant changes were revealed in healthy control animals. Conclusions We conclude that multiple sequential intracoronary microembolization can effectively induce myocardial dysfunction with clinical and echocardiographical signs of chronic ischemic cardiomyopathy. The present model may be suitable in experimental work on heart failure and left ventricular assist devices, e.g. for studying the impact of mechanical unloading, mechanisms of recovery and reverse remodeling.

Large Animal Models of Chronic Heart Failure (CHF)

“…Schmitto et al used a similar approach in sheep to produce small sequential myocardial lesions, which cumulatively are sufficient to produce CHF but most likely would have been lethal if established in a single intervention [19,20]. An important feature of Schmitto et al's model is the lack of recovery of LV-function after coronary embolizations are completed [25].…”

“…The disadvantages, on the other hand, include fatal arrhythmias despite prophylactic administration of anti-arrhythmic agents, the development of postoperative adhesions and scar tissue, which make subsequent operations more dangerous and difficult, and the need for personnel capable of surgical procedures. In summary, coronary ligation creates a robust, replicable model of ischemic heart failure in several species [31,35] including dogs [32], sheep [19,20,30,33,34], and pigs [36].…”

Should Chronic Total Occlusion Be Treated With Coronary Artery Bypass Grafting?

“…The occurrence of these complications is not surprising and probably should be expected considering the level of coronary invasiveness applied during CTO-PCI, the off-label use of stents designed for non-CTO lesions, the CTO-PCI-related activation of pathophysiological mechanisms triggering acute thrombosis, chronic inflammation, and repeated intracoronary microembolization in the relevant viable myocardial territory, which may impair Lv function, in line with the principles of established models of chronic heart failure. 68 In a meta-analysis of 18 061 pooled CTO patients with 18 941 target CTOs, Patel et al 55 reported a rate of coronary perforation of 3.65% versus 10.70% in successful versus failed CTO-PCIs (P<0.001), with a related incidence of tamponade of 0% versus 1.65% (P<0.001). These numbers are equal to hundreds of patients suffering poor health outcome caused by CTO-PCI procedures.…”

Letter by Schmitto et al Regarding Article “Large Animal Models of Heart Failure: A Critical Link in the Translation of Basic Science to Clinical Practice”

“…This produced left ventricular-dysfunction, but the mortality was high, however. To create a stable and reproducible animal of chronic heart failure, Schmitto et al 9,10 were the first to describe a novel chronic heart failure model induced by multiple, repetitive, and sequential coronary microembolization in sheep.…”