Exercise for Cardiovascular Disease Prevention and Treatment From Molecular to Clinical, Part 1

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remodelling, allowing the development of possible therapeutic approaches [ 13 – 15 ].


In the following sections, the reader will find a brief description of the most used


animal models of MI in the context of ET adaptations.


2.1 Left Anterior Descending Coronary Artery Ligation (LAD)


LAD is one of the most used models of MI, since its repercussion on the organic


systems is similar to the observed in human beings. In fact, LAD-induced MI causes


autonomic dysfunction, impairment of baroreflex sensitivity (BrS), impairment on


cardiac functioning and morphology, exercise intolerance, increase in proinflamma-


tory cytokines (PICs), among others [ 13 , 14 , 16 – 19 ].


LAD is performed after animal anaesthesia (ketamine (80 mg/kg) and xylazine

(12  mg/kg) are commonly used as anaesthetics. After intubation, the animals are


positive-pressure ventilated with room air at 2.5  mL, 65 strokes/minute with a


pressure- cycled rodent ventilator. For induction of MI, a 2-cm left lateral thoracot-


omy is performed in the third intercostal space, and the left anterior descending


coronary artery is occluded with a nylon (6.0) suture at approximately 1 mm from


its origin below the tip of the left atrium. When experimental protocols using this


models are performed, the studies usually subject a control group to sham surgery,


where animals receive the same invasive interventions but are not subjected to myo-


cardial ischemia [ 13 , 14 , 16 – 19 ].


2.2 Ischemia-Reperfusion Model


Ischemia-reperfusion model has been used, generally, to study the effects of reper-


fusion stress on reactive oxygen species (ROS) behaviour [ 20 , 21 ].


After anaesthesia and intubation for mechanical ventilation, the rats are sub-

jected to a procedure similar to that described previously in LAD model, in which


the proximal left anterior descending artery is identified and the artery is then tran-


siently ligated (or can be tied by a slipknot) using a 6.0 nylon suture for a 30-minute


ischemic period, but without exteriorization of the heart. To allow cardiac reperfu-


sion, microsurgical scissors are used to cut the knot in the ligature (or by releasing


the slipknot), made by the 6.0 nylon suture, 30  minutes following ligation of the


artery. In sham control rats, the procedure is identical, except for the artery which is


not transiently ligated. The outflow is then briefly (1–2  s) pinched off on the


respirator to allow re-inflation of the lungs. The chest retractor is then removed and


the ribs are drawn together using a 2.0 nylon suture with an interrupted suture pat-


tern. Once the ribs are closed, the outflow of the ventilator is again briefly (1–2 s)


pinched off to ensure proper breathing. The skin is closed using 6.0 nylon sutures


with a continuous suture pattern [ 22 ].


9 Myocardial Infarction and Exercise Training: Evidence from Basic Science

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