ICS 2012 Report – A method of studying the course of myocardial ischemia and reperfusion in rats in vivo

by Edel O’Connell reporting on a presentation by Dr. Darrach O h-Ici.

O h-Ici D, Thore D, Titus K, Messroghli D

Apre-implanted balloon occluder could enhance the study of the effects of myocardial ischemia and reperfusion with MRI in real-time in a closed-chest rat model.

“The use of MRI for the study of ischemia and its consequences in small animals has been limited by the need for a thoracotomy and operative occlusion of the coronary arteries,” explained Dr O h-Ici  of the Department of Congenital Heart Disease and Pediatric Cardiology in Berlin,

“The trauma of the surgery may be an important confounder in this open-chest model. The closure of the coronaries with a suture does not allow multiple occlusion-reperfusion cycles, and has limited the study of ischemia/reperfusion in small animals,” he added.

The purpose of the study was to develop a “closed chest” model of ischemia/reperfusion, which would allow ischemia and infarction to be studied in real-time while the rat is in the MRI environment.

“The main problems with the current models are, are we studying the effects of myocardial infarction or are we studying the effects of surgery? We have anaesthesia, analgesia, surgical trauma, lack of integrity of the chest wall. We have metabolic abnormalities, abnormal hemodynamic and excess catecholamines. We are not able to study the initial stages of ischemia- those first 15 or 20 minutes or so and we have limited ability to study reperfusion. If you tie a suture around the chest you have to reopen it, which makes reperfusion difficult,” Dr O h-Ici commented.

He purported an ideal model would allow animals to fully recover from a surgical procedure allowing various striations of ischemia to be studied while also allowing for the study of the early stages of ischemia without the necessity to move the animal.

“We developed a method of implanting a balloon occluder to the left anterior descending coronary artery,” explained Dr O h-Ici.

For this study, male Sprague Dawley rats were anaesthetised and then intubated.

The heart was exposed by an incision between the fourth to fifth rib space. The occluder was then secured loosely to the myocardium with a 6-0 non-absorbable suture. Occlusion and reperfusion of the coronary artery was confirmed by visual inspection (blanching of the left ventricle) and by ECG on brief inflation and deflation of the balloon.

The tubing of the occluder was then tunnelled to the back of the rat and exposed in the intra scapular area. The animals were then allowed to recover from the operation for at least five days.

For coronary occlusion and MRI scanning, rats were again anaesthetised, the tubing was connected to a syringe, and the animals were placed in the MRI scanner.

“There was a very low mortality rate for the implantation of the coronary occlude at 8.3per cent,” explained Dr O h-Ici

Inflation of the occluder on the MRI table resulted in myocardial ischemia in all animals as documented by ECG, and allowed the effects of ischemia and reperfusion on myocardial oedema and function to be studied serially before, during, and after coronary occlusion.

The study showed how the use of a pre-implanted balloon occluder allows for the study of the effects of single or repeated myocardial ischemia and reperfusion with MRI in real-time in a closed-chest rat model.

“We are hopeful it could also be used for Echo, PET and CT and should hopefully provide an improved model for the study of improved myocardial infarction and ischemia,” concluded Dr O h-Ici