Comparative Analysis of Methods to Induce Myocardial Infarction in a Closed-Chest Rabbit Model.
OBJECTIVE
To develop a rabbit model of closed-chest catheter-induced myocardial infarction. Background. Limitations of rodent and large animal models justify the search for clinically relevant alternatives.


METHODS
Microcatheterization of the heart was performed in 47 anesthetized 3-4 kg New Zealand rabbits to test five techniques of myocardial ischemia: free coils (n = 4), interlocking coils (n = 4), thrombogenic gelatin sponge (n = 4), balloon occlusion (n = 4), and alcohol injection (n = 8). In order to limit ventricular fibrillation, an antiarrhythmic protocol was implemented, with beta-blockers/amiodarone before and xylocaine infusion during the procedure. Clinical, angiographic, and echographic data were gathered. End points included demonstration of vessel occlusion (TIMI flow grades 0 and 1 on the angiogram), impairment of left ventricular function at 2 weeks after procedure (by echocardiography), and pathologically confirmed myocardial infarction.


RESULTS
The best arterial access was determined to be through the right carotid artery. The internal mammary guiding catheter 4-Fr was selected as the optimal device for selective intracoronary injection. Free coils deployed prematurely and tended to prolapse into the aorta. Interlocking coils did not deploy completely and failed to provide reliable results. Gelatin sponge was difficult to handle, adhered to the catheter, and could not be clearly visualized by fluoroscopy. Balloon occlusion yielded inconsistent results. Alcohol injection was the most efficient and reproducible method for inducing myocardial infarction (4 out of 6 animals), the extent of which could be fine-tuned by using a coaxial balloon catheter as a microcatheter (0.52 mm) to achieve a superselective injection of 0.2 mL of alcohol. This approach resulted in a 20% decrease in LVEF and infarcted myocardium was confirmed histologically.


CONCLUSIONS
By following a stepwise approach, a minimally invasive, effective, and reproducible rabbit model of catheter-induced myocardial infarction has been developed which addresses the limitations of rodent experiments while avoiding the logistical and cost issues associated with large animal models.
Department of Cardiology, Hôpital Européen Georges Pompidou, Assistance Publique des Hôpitaux de Paris, France ; Université Paris Descartes, Paris, France.
Marc-Antoine
MA
Isorni
INSERM U970, Paris Cardiovascular Research Center PARCC, Paris, France.
Amaury
A
Casanova
INSERM U970, Paris Cardiovascular Research Center PARCC, Paris, France.
Julie
J
Piquet
INSERM U970, Paris Cardiovascular Research Center PARCC, Paris, France.
Valérie
V
Bellamy
National Veterinary School of Alfort, Maisons-Alfort, France.
Charly
C
Pignon
Department of Cardiology, Hôpital Européen Georges Pompidou, Assistance Publique des Hôpitaux de Paris, France ; Université Paris Descartes, Paris, France ; INSERM U970, Paris Cardiovascular Research Center PARCC, Paris, France.
Etienne
E
Puymirat
Université Paris Descartes, Paris, France ; INSERM U970, Paris Cardiovascular Research Center PARCC, Paris, France ; Department of Cardiovascular Surgery, Hôpital Européen Georges Pompidou, Assistance Publique des Hôpitaux de Paris, France.
Philippe
P
Menasche
D000818:Animals; D006328:Cardiac Catheterization; D004195:Disease Models, Animal; D004452:Echocardiography; D008297:Male; D009203:Myocardial Infarction; D009206:Myocardium / Q000473:pathology; D011817:Rabbits