Comparison of Established Cardial Infarctionion Models in Rats

Cloud-Clone Corp.

Cardial infarctionion is a kind of serious disease, which refers to a pathological processes of irreversible myocardial necrosis, mainly due to a sustained coronary ischemia. More than 90% cardial infarctionion is resulted from coronary atherosclerosis, based on thrombosis caused less seen in coronary artery spasm, stenosis and occlusion caused by a small number of embolism, inflammation, deformity, severe and persistent myocardial ischemia can also lead to myocardial necrosis. The main causes of cardial infarctionion include fatigue, agitation, bleeding, shock, dehydration, surgery or serious arrhythmia. The incidence of cardial infarctionion is about 1.5 million per year in US. While in China, in recent years, the incidence of cardial infarctionion was significantly increased, besides at least 2 million of existing patients there are more than 500,000 new patients every year.

In order to screen effective drugs against cardial infarctionion and study the pathogenesis of cardial infarctionion, researchers usually use rat, rabbit or experimental miniature pig to establish standardized cardial infarctionion models. Compared to other experimental animals, rat has many advantages:

1. Rat has certain strains, no significant differences among groups;

2. The cost of feeding and reproduction is low, it’s easy to cultivate during the modeling;

3. The coronary collateral circulation system in rat is relatively simple, it can form a relatively fixed ischemic area after ligation, which will significantly improve the success rate of modeling;

4. One person is enough to handle this surgery.

Here we will summarize three types of cardial infarctionion modeling in rats.

A. coronary ligation

CAL(Coronary artery ligation) is the most common method, which includs the following steps: After ammonia with chlorine, using one small animal anesthesia ventilator, cut the skin from the left 4th intercostal, blunt separation of muscle tissue, open the chest, squeeze out the heart, threading between the left atrial appendage and the pulmonary cone, ligation of the left anterior descending coronary artery (a branch of the starting point for about 1-2 mm), recording ECG by Ⅱ polygraph, which shows ST segment elevation cardial infarction, suggesting the modeling is successful. Then put the heart quickly back into the chest, and then suturing the skin. Sham group (negative control group) is done similarly except no coronary artery ligation, the last step is giving local gentamicin treatment.

b. Isoproterenol injection

Besides CAL, drug injection method is also used to establish a myocardial infarction model in rats. Rats were anesthesia with 1% sodium pentobarbital 20-25 mg/kg body weight, then treated subcutaneously 4% isoproterenol (ISO), or directly intraperitoneal injection, 5 mg / kg body weight, once a day, 2-8 days can cause myocardial infarction, heart failure, coronary artery spasm, usually 4-8 weeks after onset of the injection

c. Repeated freezing

Along cut the skin from the left 4th intercostal, blunt separation of muscle tissue, open the chest, squeeze out the heart, using a 6mm diameter copper soaked in liquid nitrogen to contact left ventricular free wall, duration 5s, then closed the chest, after spontaneous breathing, operators can repeat the freezing step for 5-8 times.

Those three methods have their own advantages and disadvantages, it depends on disease types, surgical experiments technical requirements, laboratory equipment requirements, postoperative mortality and modeling stability. Here we summarized these modeling methods (Table 1).

Table 1. Comparison of three classic cardial infarctionion models

name type technical requirements respirator mortality rate stability
CAL acute MI high need relatively high high
freezing acute MI relatively high need relatively high low
drug injection chronic MI low no low relatively high

Seen from the table, CAL and freezing method are similar, both of them can cause acute MI in rats, while these two methods involve anesthesia, thoracotomy, intercostal separation and other experimental procedures. In particular, since the determination of ligation site and wound closure require some surgical experiences, unskilled persons have risk of postoperative pneumothorax, resulting in high mortality in rats. However, after training, this method has high stability, the severity of myocardial infarction is positively correlated with the size of infarct size ligation site, thus it is a well-known method in established cardial infarctionion models. In contrast, freezing method can also cause acute MI, and the operation method is much simpler than CAL, but whether the onset of freezing or not depends on the site and freezing time, it is difficult to ensure the stability and differences within groups.

Compared to the above two methods, isoproterenol-induced MI, mainly cause chronic MI, general incidence of 4-8 weeks after injection, if operator can select an appropriate dosage, injection generally can ensure a high survival rate, and it does not require special equipment, which is easy to handle. While the infarcted area of myocardial necrosis caused by this method sometimes is not visible. Laboratory personnel can select the most appropriate MI modeling methods according to the purpose of their own experiments and other conditions.

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