**3.1 Ischemia**

It implies the interruption of blood flow, the supply of O2 and nutrients. The myocyte stops producing ATP from the fatty acid oxidation and switches to another metabolic pathway that is suboptimal not only because it cannot maintain a balance between nutrient supply and demand and O2 but also because of the accumulation of metabolic wastes that this route produces, and that generates an environment harmful to the subsistence of the cells and the appropriate reperfusion, favoring the phenomenon of reperfusion injury [18]. The alternative route for ATP production during ischemia is anaerobic glycolysis; its potential to produce ATP is 20 times less than aerobic glucose metabolism and even less than the route commonly used by myocyte which is the aerobic metabolism of fatty acids. The glycogen reserve as a source of anaerobic ATP is depleted in 30–60 minutes and also generates lactic acidosis, high concentration of protons at tissue level, and excess of H2O. The mechanisms of myocardial damage due to ischemia involve low production of ATP that is insufficient not only for myocyte function but also to preserve its structure and to maintain hydroelectrolytic balance by the Na-K ATPase pump, which implies an increase in Na and intracellular H2O with tissue and cellular edema, vacuolization, and cell burst [19, 20]. Inactivation of the Na-K ATPase pump leads to the activation of the Na-Ca exchange, resulting in increased intracellular calcium with hypercontraction of myocytes (contraction band necrosis) [21, 22]. The entry of Ca into the cell is one of the mechanisms by which the permeability of the transition pores of the mitochondria increases and their destruction occurs [23]. Myocardial ischemia can be either primary before applying reperfusion therapy or secondary, that is, after recanalizing the occlusion. As for primary ischemia, it can occur in a sustained or episodic manner. In some cases, episodic primary ischemia can generate a protective myocyte phenomenon known as ischemic preconditioning [24]. The mechanical factors that produce arterial occlusion and primary ischemia are plaque thrombus, and vasospasm. Secondary ischemia is always harmful and may be due to failed angioplasty, no reflow phenomenon, distal embolism, thrombotic reocclusion, post-reperfusion, vasospasm, etc. Consequently, myocardial ischemia occurs from the onset of AMI and may end with primary angioplasty, or persist (not reflow), or recur after it.

### **3.2 Mechanical forces**

The ischemic myocardium stops contracting and is distended; this situation subjects it to exceptional mechanical forces of tension, traction, and stretching. In each systole, the nonischemic myocardium, which acts in a state of compensatory hypercontractility, pulls on the edges of the ischemic myocardium. In addition, in each systole, the healthy myocardium presses the blood against the ischemic myocardium causing distension and increased wall tension [25]. These forces of stretching and traction produce direct tissue damage [26] but also by increasing the tumor necrosis factor trigger mechanisms of apoptosis [27] dependent on caspases that produce cell death in early and late stages of AMI. The strongest evidence of the

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**3.4 Reperfusion injury**

*Primary Angioplasty: From the Artery to the Myocardium*

onset of ischemia and lasts beyond reperfusion.

after the onset of ischemia and continues beyond reperfusion.

Myocardial reperfusion can itself produce more damage and cell death; this process defines the phenomenon of reperfusion injury [31–33] that could be prevented by applying additional therapies [34]. Reperfusion injury could be responsible for up to 50% of the final myocardial damage during acute myocardial infarction. The time elapsed since the onset of symptoms, diabetes, TIMI 0 flow in baseline angiography, DA involvement, and presentation with heart failure is associated with a greater chance of presenting reperfusion injury [35]. Elevation of white blood cells, greater activation (platelet size and reactivity), high levels of thromboxane

**3.3 Inflammation**

damage that mechanical forces can produce is the rupture of the ventricular wall. As they are direct forces exerted on the ischemic myocardium, it is to be assumed that the damage is related to the magnitude and frequency of exposure; therefore, the higher the heart rate and inotropism, the greater the damage produced by this mechanism. This mechanism of myocardial damage begins immediately after the

The inflammatory response during the acute ischemic event plays a decisive role in the size of the infarction and the subsequent adverse left ventricle remodeling [28]. The onset of myocardial ischemia during AMI triggers a pro-inflammatory response whose initial objective is to eliminate damaged cells and tissue from the injured area. This initial pro-inflammatory phase contributes to myocyte death and tissue damage [29, 30]. This phase is followed by a repairing anti-inflammatory stage that leads to healing. Balance alterations and the transition between the pro-inflammatory phase and the anti-inflammatory phase can increase myocardial damage during the event and contribute to an adverse left ventricle remodeling after AMI [28]. In addition, the inflammatory response as an acute phase reactant is related to the location and size of AMI. Large and anterior infarct shoots a greater extent of acute phase reactants. The initial pro-inflammatory phase includes complement cascade activation and reactive oxygen species (ROS) production [28]. The damage-associated molecular patterns (DAMPs) production that binds to receptors in membranes cell and cytosolic proteins (inflammasomes), in either, circulating or myocardium resident cells. Inflammasomes cause caspase activation (which initiate the pyroptosis phenomenon, [apoptosis, and inflammatory necrosis]) and release pro-inflammatory cytokine as such as IL-1 and IL-8 and chemokines that recruit pro-inflammatory cells (polymorphonuclear, monocytes, macrophages, T and B lymphocytes) [28]. In addition, the inflammasomes activated during AMI induce ATP loss from the injured cells to the extracellular space, K outflow, lysosomal destabilization, and ROS generation by the mitochondria [28]. The anti-inflammatory phase begins with neutrophil and dendritic cell arrival; these cells secrete antiinflammatory cytokines such as IL-10 and tissue growth factors that begin damaged tissue repair [28]. Monocytes and macrophages induced by interferon change their phenotype towards anti-inflammatory expressions [28]. Dendritic cells secrete chemotactic substances for regulatory T lymphocytes (CD4, CD25, and FOXP3) and T helper lymphocytes; these lymphocyte subtypes also secrete anti-inflammatory and reparative substances such as IL-10 and tissue growth factor and also induce the expression of anti-inflammatory macrophage phenotypes [28]. Although it is not proven, it is speculated that they could also activate pre- and post-conditioning mechanisms [28]. This myocardial damage mechanism is triggered in early stages

*DOI: http://dx.doi.org/10.5772/intechopen.91832*

damage that mechanical forces can produce is the rupture of the ventricular wall. As they are direct forces exerted on the ischemic myocardium, it is to be assumed that the damage is related to the magnitude and frequency of exposure; therefore, the higher the heart rate and inotropism, the greater the damage produced by this mechanism. This mechanism of myocardial damage begins immediately after the onset of ischemia and lasts beyond reperfusion.
