**3.4 Reperfusion injury**

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

A2 and ET1, hyperglycemia associated or not with diabetes, and C-reactive protein before reperfusion are predictors of this phenomenon [36–38]. It is possible that there is always some degree of reperfusion damage, but the patients with little time of evolution of the symptoms and those who presented previous angina seem less susceptible [39, 40]. There is a useful premise to estimate its magnitude; the greater and more intense the ischemia, the greater the reperfusion injury [35, 41–43]. In daily practice, the lack of resolution of the ST segment after achieving epicardial coronary flow is used as a marker of reperfusion failure. In patients who do not correct the ST, the mortality of AMI triples beyond achieving adequate epicardial flow [44, 45]. The most important events that occur during reperfusion and trigger mechanisms of injury are the steep increase in oxygen content in a medium with a low PH (tissue acidosis caused by ischemia). In this scenario, O2 binds to hydrogen protons generating reactive oxygen species that by themselves generate DNA, protein, and lipid damage to the membranes and consequently direct cell death [46, 47]. Besides, reactive oxygen species have pro-inflammatory effects mediated by cytokines that cause apoptosis and cellular necroptosis [48]. At the level of the mitochondria, ROS causes the opening of the transition pores of their membranes making them susceptible to irreversible damage [48]. At the endoplasmic reticulum level, the damage caused by ROS alters the dynamics of calcium, which in the context of reperfusion of an acidotic environment generates calcium entry into the sarcolemma, producing sustained hypercontraction that results in necrosis with contraction bands [47–49]. The calcium entry activates Ca-dependent proteases that degrade structural components of the cell [50]. The reperfusion injury affects not only the myocyte but also the microvasculature, where ROS not only produces direct damage to the endothelial cells causing increased permeability of the capillary wall resulting in edema but also is chemotactic for neutrophils, activates complement, and triggers pro-thrombotic phenomena [48–51]. In brief, microvascular occlusion occurs due to perivascular edema, cluster of neutrophils, and local thrombosis. Injury due to reperfusion occurs due to the arrival of saturated O2 blood to myocardial tissue that is vulnerable to metabolic changes and the local internal environment, which occurred during ischemia. Reperfusion injury is a rapid and irreversible phenomenon [52].

The phenomena of ischemia, damage due to mechanical forces, inflammation, and reperfusion injury take a variable and sometimes unpredictable preponderance at different times during the evolution of AMI (**Figure 4**).

Also, the damage caused by the different mechanisms is irreversible; therefore, any therapeutic strategy must be preventive that implies pathophysiological

**249**

*Primary Angioplasty: From the Artery to the Myocardium*

**4. Analysis of guidelines for AMI treatment**

found in the current guides are reproduced below.

ischemic pain, hypertension, or pulmonary congestion [54].

indication with level of evidence B [55–57].

**4.1 AHA-ACC guides 2013**

*4.1.1 Nitroglycerin*

*4.1.2 B blockers*

*4.1.3 Metabolic control*

intervention [58].

conditions that culminate in myocardial damage and act before the point of no

Both the AHA-ACC guidelines and the ESC guidelines for AMI treatment are strongly oriented to early and sustained reperfusion, which constitutes the most powerful resource for improving prognosis and saving lives during the event. The best way to show successful post-PCI or thrombolytic reperfusion is to verify the correction of the ST segment of the ECG performed after reperfusion therapy. Approximately 30% of patients receiving primary angioplasty in a timely manner do not correct ST elevation or initially correct it but continue to lose positive ECG vectors after apparently successful reperfusion. As we saw in the previous section, this happens because there is myocardial damage before, during, and after reperfusion [53]. However, the analysis of the guidelines shows that measures to reduce myocardial damage beyond reperfusion are poorly developed. The related items

It improves the conditions of pre- and post-load of the ventricle and could also improve collateral flow and reduce BP which would improve the imbalance between supply and demand of O2 in some patients. Based on the evidence provided by a meta-analysis that included 22 clinical trials and more than 80,000 patients, 3 or 4 deaths could be avoided per 1000 treated patients, which implies a net benefit. Nitroglycerin is a class I indication with a level of evidence C for patients with

During the first hours of AMI, the B blockers can decrease the demand for O2 by the myocardium by decreasing heart rate, blood pressure, and contractility and, additionally, by prolonging diastole, can improve ischemic myocardial perfusion, mainly of the subendocardium. As a consequence of this, B blockers can reduce the size of the AMI. Based on the clinical evidence provided by the ISIS I, MIAMI, TIMI II, and Taste I trials, the use of B blockers early, in the absence of contraindications, may offer benefits from the first day and in a sustained way avoiding around 6 deaths per 1000 patients treated. B oral blockers have class I indication level of evidence A, and in the form of intravenous administration, they have class IIa

The metabolic modulation of the insulin glucose axis by infusion of glucoseinsulin-potassium was evaluated in different trials with diverse and contradictory results that when taken together result in an intervention without net benefit compared to placebo. However, these guidelines suggest that it could be of benefit in patients with less than 12 hours of evolution, in Killip Kimball. Beyond that, the guidelines do not establish an indication with a level of evidence defined for this

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

return in the viability of the cell occurs.

**Figure 4.** *Myocardial damage mechanism, importance, and development over time.*

conditions that culminate in myocardial damage and act before the point of no return in the viability of the cell occurs.
