*4.1.1 Nitroglycerin*

*Cardiac Diseases - Novel Aspects of Cardiac Risk, Cardiorenal Pathology and Cardiac Interventions*

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

The phenomena of ischemia, damage due to mechanical forces, inflammation, and reperfusion injury take a variable and sometimes unpredictable preponderance

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

at different times during the evolution of AMI (**Figure 4**).

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

**248**

**Figure 4.**

irreversible phenomenon [52].

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