Open access peer-reviewed chapter

Primary Angioplasty: From the Artery to the Myocardium

Written By

Miguel Angel Farah, Franco Farah and Miguel Alejandro Farah

Submitted: 19 November 2019 Reviewed: 20 February 2020 Published: 04 May 2020

DOI: 10.5772/intechopen.91832

From the Edited Volume

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

Edited by David C. Gaze and Aleksandar Kibel

Chapter metrics overview

594 Chapter Downloads

View Full Metrics

Abstract

The prognosis of patients suffering from acute myocardial infarction (AMI) is related to the amount of muscle loss and ventricular function deterioration caused by the event. Primary angioplasty is the most effective reperfusion strategy. Early reperfusion limits the size of the infarction and improves the prognosis. However, the incidence of death and post-AMI heart failure remains around 20% during the first year. Factors that contribute to myocardial damage are ischemia, mechanical forces, inflammation, and reperfusion injury. All those take a variable and sometimes unpredictable preponderance at different times during the evolution of acute myocardial infarction. The damage caused by the different mechanisms is irreversible; therefore, any therapeutic strategy must be preventive. Developed treatments for continuous myocardial protection could potentially preserve the myocardium during the delay of the system and during the early evolution of the event. Developed controlled reperfusion procedures where the interventional cardiologist assumes the treatment not only of the culprit vessel but also of the myocardium could potentially decrease myocardial damage, preserve ventricular function, and improve patients’ prognosis.

Keywords

  • myocardial damage
  • acute myocardial infarction
  • ischemia
  • mechanical forces
  • inflammation
  • reperfusion injury
  • continuous myocardial protection
  • controlled reperfusion

1. Introduction

The prognosis of patients suffering from acute myocardial infarction (AMI) is directly related to the amount of muscle loss and the deterioration of ventricular function caused by the event [1, 2, 3, 4]. Consequently, the goal of treatment in the initial phase, beyond preserving life, is to limit myocardial damage. Early reperfusion of the myocardium limits the size of the infarction and improves the prognosis of patients [3, 4]. Primary angioplasty is the most effective reperfusion strategy for the treatment of acute myocardial infarction [5, 6, 7]. From the first reports of mechanical reperfusion to the present, the primary angioplasty strategy continuously improved in different aspects such as greater accessibility to the method [8, 9, 10], safer vascular accesses [11, 12], and the use of drug-eluting stents that modulate the scarring of the coronary artery wall [13, 14] to prevent restenosis of the vessel or vessels treated. In addition, the development of antithrombotic and antiplatelet drugs also contributed to improving early and late artery permeability [15, 16]. The enormous effort focused on the treatment of the coronary artery has led to the fact that the success of primary angioplasty is now greater than 95% [7]. The angiographic success rate ceased to be a problem. However, the post-AMI incidence of death and heart failure remains around 20% during the first year [17], and as mentioned earlier this correlates directly with the amount of myocardium damaged and the deterioration of ventricular function.

Advertisement

2. The following case serves to illustrate the result of AMI usual treatment at present

52-year-old male, with grade II obesity, dyslipidemia, hypertension, and smoking history and with no previous cardiovascular events, arrives at the hospital 60 minutes after the onset of symptoms. The first electrocardiogram (ECG) shows rS in V1, V2, and V3 and ST-segment elevation from V1 to V6 (Figure 1).

Figure 1.

ECG at admission.

At admission the arterial blood pressure was 145/80 mm of hg, the heart rate was 78 beats per minute, and the Killip Kimball grade was A. The patient received aspirin (250 mg), clopidogrel (600 mg), unfractionated heparin in intravenous bolus (5000 UI), and rosuvastatin (40 mg). At 80 minutes after admission, 140 minutes from the onset of symptoms, coronary angiography is performed showing single-vessel disease with thrombotic occlusion of the middle third of the anterior descending artery (ADA) and TIMI 0 flow. Primary angioplasty is performed to the middle third of the ADA with thromboaspiration and stent implantation achieving an adequate result with TIMI 3 flow, symptom relief, and absence of complications. The post-procedure ECG shows QS in V1, V2, and V3 and ST level and negative T from V1 to V6 (Figure 2).

Figure 2.

ECG postprimary angioplasty.

IECA and B blockers are started. It evolves without recurrence of symptoms; however, at 48 hours, the ECG shows QS from V1 to V5 and low R in V6 (Figure 3).

Figure 3.

ECG at 48 hours.

Note that despite early assistance, it no longer has positive vectors in V1, V2, and V3, and after the usual successful treatment and aligned with the guidelines based on current evidence, it continues to lose precordial vectors after primary angioplasty. The echocardiogram shows antero-apical dyskinesia and impaired ventricular function, with an ejection fraction of 35% measured by the Simpson method. There are several mechanisms by which the myocardium is lost in the different phases of AMI.

Advertisement

3. Etiopathogenesis of myocardial damage

The factors that contribute to myocardial damage are as follows:

Ischemia.

Mechanical forces.

Inflammation.

Reperfusion injury.

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 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.

3.3 Inflammation

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 anti-inflammatory 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 after the onset of ischemia and continues beyond reperfusion.

3.4 Reperfusion injury

Myocardial reperfusion can itself produce more damage and cell death; this process defines the phenomenon of reperfusion injury [31, 32, 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, 37, 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, 42, 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, 48, 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, 49, 50, 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).

Figure 4.

Myocardial damage mechanism, importance, and development over time.

Also, the damage caused by the different mechanisms is irreversible; therefore, any therapeutic strategy must be preventive that implies pathophysiological conditions that culminate in myocardial damage and act before the point of no return in the viability of the cell occurs.

Advertisement

4. Analysis of guidelines for AMI treatment

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 found in the current guides are reproduced below.

4.1 AHA-ACC guides 2013

4.1.1 Nitroglycerin

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].

4.1.2 B blockers

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 indication with level of evidence B [55, 56, 57].

4.1.3 Metabolic control

The metabolic modulation of the insulin glucose axis by infusion of glucose-insulin-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 intervention [58].

4.1.4 Glycemia control

During AMI, the levels of catecholamines and cortisol increase, insulin decreases, and blood glucagon increase. This leads to a notable increase in blood glucose and decreased glucose utilization by cells. Free fatty acids and their metabolites are increased that increase myocardial damage by different mechanisms (direct inhibition of glucose oxidation, increased demand for O2, direct toxicity). Insulin can reverse some of these mechanisms by inducing the production of ATP from aerobic glucose metabolism in the myocyte. Several studies mentioned in these guidelines demonstrated benefits in patients with hyperglycemia who received insulin infusion for strict glycemic control during the event. These guidelines establish that the normalization of insulin glycemia is a class I indication with a level of evidence B for patients with complicated AMI and class IIa with a level of evidence B for patients with uncomplicated AMI [59, 60, 61, 62].

4.2 ESC guides 2017

These guidelines mention, scarcely, that to reduce myocardial damage beyond reperfusion therapy, some strategies that include pharmacological and mechanical therapies have been demonstrating the potential to reduce the size of AMI by decreasing the impact of reperfusion injury in small clinical trials. But there is no large-scale clinical study that has demonstrated clinical benefit. Therefore, they make no recommendation regarding measures to limit reperfusion injury or any other therapy to reduce myocardial damage during the event, beyond reperfusion [63].

Advertisement

5. Current reperfusion adjuvant therapy status

The use of B blockers and nitrates is favorable to reduce myocardial damage caused by primary and secondary ischemia, reducing the imbalance between supply and demand of O2 and nutrients until reperfusion. Beside, these drugs are useful to optimize the conditions of pre- and post-loading of LV, decrease heart rate and blood pressure, and thus limit the damage caused by mechanical stress. A wide variety of potent platelet antiplatelets such as clopidogrel, prasugrel, or ticagrelor added to the routine use of aspirin were shown to reduce the recurrence of ischemic events after reperfusion (secondary ischemia). Although it is not clearly established by evidence from clinical trials, thromboaspiration; potent vasodilators at the microvasculature level such as adenosine and calcium blockers, among others; and the use of IIb–IIIa glycoprotein inhibitors may be effective in prevention and treatment of no-reflow. The phenomenon of no-reflow can cause ischemia (secondary ischemia) to continue beyond the recanalization of the epicardial artery. However, reperfusion inflammation and injury are not prevented or treated in daily practice.

Advertisement

6. Perspectives

The development of reperfusion therapies for AMI was shown to reduce mortality strongly. There are possibilities to optimize its use. Health teams must continue fighting to shorten the system times and detect the best strategy according to the context in which they operate. There are working groups that carry out research in basic sciences, translational research, and clinical research and are making advances in myocardial protection. Cyclosporine and colchicine are currently evaluated for their ability to reduce the damage caused by inflammation. Developed treatments for continuing myocardial protection [52], which the clinical cardiologists administer from the moment of diagnosis until the convalescence of the patient in a critical unit, could potentially preserve myocardium during the delay of the system and the early evolution of the event. Developed controlled reperfusion [52] procedures where the interventional cardiologist assumes the treatment not only of the guilty vessel but also of the myocardium could potentially decrease myocardial damage, preserve ventricular function, and improve the prognosis of patients suffering from AMI. The concept of controlled reperfusion involves deciding how to reperfuse (e.g., post-conditioning) and with what to reperfuse (e.g., administering to the ischemic myocardium, through dedicated catheters, before the opening of the artery, blood modified or enriched with drugs), preparing the myocardium for a more complete and definitive recovery.

A wide field of research appears to improve the treatment outcome of patients suffering from AMI aiming not only at arterial recanalization but also at myocardial preservation.

Advertisement

Abbreviations

AMIacute myocardial infarction
ECGelectrocardiogram
ROSreactive oxygen species
ADAanterior descending artery

References

  1. 1. Cohn JN, Ferrari R, Sharpe N, et al. Cardiac remodeling—Concepts and clinical implications: A consensus paper from an international forum on cardiac remodeling behalf of an International Forum on Cardiac Remodeling. Journal of the American College of Cardiology. 2000;35:569-582
  2. 2. Sabbah HN, Goldstein S, et al. Ventricular remodelling: Consequences and therapy. European Heart Journal. 1993;14(suppl C):24-29
  3. 3. Gibson CM et al. NRMI and current treatment patterns for ST-elevation myocardial infarction. American Heart Journal. 2004;148(5 Suppl):S29-S33
  4. 4. Keeley EC, Hillis LD, et al. Primary PCI for myocardial infarction with ST-segment elevation. The New England Journal of Medicine. 2007;356(1):47-54
  5. 5. Grines CL, Cox DA, Stone GW, et al. Coronary angioplasty with or without stent implantation for acute myocardial infarction. Stent primary angioplasty in myocardial infarction study group. The New England Journal of Medicine. 1999;341(26):1949-1956
  6. 6. Stone GW, Brodie BR, Griffin JJ, et al. Prospective, multicenter study of the safety and feasibility of primary stenting in acute myocardial infarction: In-hospital and 30-day results of the PAMI stent pilot trial. Journal of the American College of Cardiology. 1998;31(1):23-30
  7. 7. Keeley EC, Boura JA, Grines CL, et al. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: A quantitative review of 23 randomised trials. Lancet. 2003;361(9351):13-20
  8. 8. Herrin J, Miller LE, Turkmani DF, et al. National performance on door-in to door-out time among patients transferred for primary percutaneous coronary intervention. Archives of Internal Medicine. 2011;171(21):1879-1886
  9. 9. Sorensen JT, Terkelsen CJ, Norgaard BL, et al. Urban and rural implementation of pre-hospital diagnosis and direct referral for primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction. European Heart Journal. 2011;32(4):430-436
  10. 10. Wang TY, Nallamothu BK, Krumholz HM, et al. Association of door-in to door-out time with reperfusion delays and outcomes among patients transferred for primary percutaneous coronary intervention. Journal of the American Medical Association. 2011;305(24):2540-2547
  11. 11. Karrowni W, Vyas A, Giacomino B, et al. Radial versus femoral access for primary percutaneous interventions in ST-segment elevation myocardial infarction patients: A meta-analysis of randomized controlled trials. JACC: Cardiovascular Interventions. 2013;6(8):814-823
  12. 12. Vranckx P, Frigoli E, Valgimigli M, et al. Radial versus femoral access in patients with acute coronary syndromes with or without ST-segment elevation. European Heart Journal. 2017;38(14):1069-1080
  13. 13. De Luca G, Stone GW, et al. Drug-eluting vs bare-metal stents in primary angioplasty: A pooled patient-level meta-analysis of randomized trials. Archives of Internal Medicine. 2012;172(8):611-621
  14. 14. Wallace EL, Abdel-Latif A, et al. Meta-analysis of long-term outcomes for drug-eluting stents versus bare-metal stents in primary percutaneous coronary interventions for ST-segment elevation myocardial infarction. The American Journal of Cardiology. 2012;109(7):932-940
  15. 15. Braunwald E, McCabe CH, Montalescot G, Gibson CM, Antman EM, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. The New England Journal of Medicine. 2007;357(20):2001-2015
  16. 16. Wallentin L, Becker RC, Harrington RA, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. The New England Journal of Medicine. 2009;361(11):1045-1057
  17. 17. Kochar A, Christopher B, et al. Post-myocardial infarction heart failure. Journal of the American College of Cardiology. 2018;6(3):179-186
  18. 18. Piper HM, Garcia-Dorado D, Ovize M, et al. A fresh look at reperfusion injury. Cardiovascular Research. 1998;38:291-300
  19. 19. Inserte J, Garcia-Dorado D, Ruiz-Meana M, Padilla F, Barrabés JA, Pina P, et al. Effect of inhibition of Na(+)/Ca(2+) exchanger at the time of myocardial reperfusion on hypercontracture and cell death. Cardiovascular Research. 2002;55:739-748
  20. 20. Garcia-Dorado D, Theroux P, Munoz R, Alonso J, Elizaga J, Fernandez-Avilés F, et al. Favorable effects of hyperosmotic reperfusion on myocardial edema and infarct size. The American Journal of Physiology. 1992;262:H17-H22
  21. 21. Siegmund B, Zude R, Piper HM, et al. Recovery of anoxic-reoxygenated cardiomyocytes from severe calcium overload. The American Journal of Physiology. 1992;263:H1262-H1269
  22. 22. Barrabes JA, Garcia-Dorado D, Ruiz-Meana M, Piper HM, Solares J, Gonzalez MA, et al. Myocardial segment shrinkage during coronary reperfusion in situ. Relation to hypercontracture and myocardial necrosis. Pflügers Archiv. 1996;431:519-526
  23. 23. Kingma JG et al. Acute myocardial injury: A perspective on lethal reperfusion injury. Journal of Cardiovascular Pharmacology. 2017;6(5):216
  24. 24. Karila-Cohen D, Czitrom D, Brochet E, et al. Decreased no-reflow in patients with anterior myocardial infarction and pre-infarction angina. European Heart Journal. 1999;20(23):1724-1730
  25. 25. Olivetti G, Quaini F, et al. Acute myocardial infarction in humans is associated with activation of programmed myocyte cell death in the surviving portion of the heart. Journal of Molecular and Cellular Cardiology. 1996;28(9):2005-2016
  26. 26. Erlebacher JA, Weiss JL, Myron L, et al. Early dilation of the infarcted segment in acute transmural myocardial infarction: Role of infarct expansion in acute left ventricular enlargement. Journal of the American College of Cardiology. 1984;4(2):201-208
  27. 27. Teringova E, Tousek P, et al. Apoptosis in ischemic heart disease. Journal of Translational Medicine. 2017;15:87
  28. 28. Derek J. Hausenloy, et al. Inflammation following acute myocardial infarction: Multiple players, dynamic roles, and novel therapeutic opportunities. Pharmacology & Therapeutics. 2018;186:73-87
  29. 29. Zhao ZQ , Nakamura M, Wang NP, Wilcox JN, Shearer S, Ronson RS, et al. Reperfusion induces myocardial apoptotic cell death. Cardiovascular Research. 2000;45:651-660
  30. 30. Zhao ZQ , Velez DA, Wang NP, Hewan-Lowe KO, Nakamura M, Guyton RA, et al. Progressively developed myocardial apoptotic cell death during late phase of reperfusion. Apoptosis. 2001;6:279-290
  31. 31. Yellon DM, Hausenloy DJ, et al. Myocardial reperfusion injury. The New England Journal of Medicine. 2007;357(11):1121-1135
  32. 32. Hausenloy DJ, Yellon DM, et al. Targeting myocardial reperfusion injury—The search continues. The New England Journal of Medicine. 2015;373(11):1073-1075
  33. 33. Braunwald E, Kloner RA, et al. Myocardial reperfusion: A double-edged sword? The Journal of Clinical Investigation. 1985;76(5):1713-1719
  34. 34. Collet JP, Montalescot G, et al. The acute reperfusion management of STEMI in patients with impaired glucose tolerance and type 2 diabetes. Diabetes & Vascular Disease Research. 2005;2(3):136-143
  35. 35. Iwakura K, Ito H, Kawano S, et al. Predictive factors for development of the no-reflow phenomenon in patients with reperfused anterior wall acute myocardial infarction. Journal of the American College of Cardiology. 2001;38(2):472-477
  36. 36. Campo G, Valgimigli M, Gemmati D, et al. Value of platelet reactivity in predicting response to treatment and clinical outcome in patients undergoing primary coronary intervention: Insights into the STRATEGY Study. Journal of the American College of Cardiology. 2006;48(11):2178-2185
  37. 37. Niccoli G, Giubilato S, Russo E, et al. Plasma levels of thromboxane A2 on admission are associated with no-reflow after primary percutaneous coronary intervention. European Heart Journal. 2008;29(15):1843-1850
  38. 38. Niccoli G, Lanza GA, Shaw S, et al. Endothelin-1 and acute myocardial infarction: A no-reflow mediator after successful percutaneous myocardial revascularization. European Heart Journal. 2006;27(15):1793-1798
  39. 39. Karila-Cohen D, Czitrom D, Brochet E, et al. Decreased no-reflow in patients with anterior myocardial infarction and pre-infarction angina. European Heart Journal. 1999;20(23):1724-1730
  40. 40. Komamura K, Kitakaze M, Nishida K, et al. Progressive decreases in coronary vein flow during reperfusion in acute myocardial infarction: Clinical documentation of the no reflow phenomenon after successful thrombolysis. Journal of the American College of Cardiology. 1994;24(2):370-377
  41. 41. Nallamothu BK, Bradley EH, Krumholz HM, et al. Time to treatment in primary percutaneous coronary intervention. The New England Journal of Medicine. 2007;357(16):1631-1638
  42. 42. Turschner O, D’hooge J, Dommke C, et al. The sequential changes in myocardial thickness and thickening which occur during acute transmural infarction, infarct reperfusion and the resultant expression of reperfusion injury. European Heart Journal. 2004;25(9):794-803
  43. 43. Uyarel H, Cam N, Okmen E, et al. Level of Selvester QRS score is predictive of ST-segment resolution and 30-day outcomes in patients with acute myocardial infarction undergoing primary coronary intervention. The American Heart Journal. 2006;151(6):1239.e1-1239.e7
  44. 44. de Lemos JA, Braunwald E, et al. ST segment resolution as a tool for assessing the efficacy of reperfusion therapy. Journal of the American College of Cardiology. 2001;38(5):1283-1294
  45. 45. Buller CE, Fu Y, Mahaffey KW, et al. ST-segment recovery and outcome after primary percutaneous coronary intervention for ST-elevation myocardial infarction: Insights from the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial. Circulation. 2008;118(13):1335-1346
  46. 46. Zweier JL, Talukder MA, et al. The role of oxidants and free radicals in reperfusion injury. Cardiovascular Research. 2006;70(2):181-190
  47. 47. Barber AM, Maizel JV Jr, et al. Sequence EditingAligner: A multiple sequence editor and aligner. Genetic Analysis, Techniques and Applications. 1990;7(2):39-45
  48. 48. Kalogeris T, Baines CP, Krenz M, et al. Cell biology of ischemia/reperfusion injury. International Review of Cell and Molecular Biology. 2012;298:229-317
  49. 49. Hoffman JW Jr, Gilbert TB, Poston RS, et al. Myocardial reperfusion injury: Etiology, mechanisms, and therapies. The Journal of Extra-Corporeal Technology. 2004;36(4):391-411
  50. 50. Verma S, Fedak PW, Weisel RD, et al. Fundamentals of reperfusion injury for the clinical cardiologist. Circulation. 2002;105(20):2332-2336
  51. 51. Reffelmann T, Hale SL, Dow JS, et al. No-reflow phenomenon persists long-term after ischemia/reperfusion in the rat and predicts infarct expansion. Circulation. 2003;108(23):2911-2917
  52. 52. Farah A, Barbagelata A. Unmet goals in the treatment of acute myocardial infarction: Review. F1000Research. 2017;6(F1000 Faculty Rev):1243
  53. 53. Farah A. Pereira JM, Infarto agudo de miocardio: Factores relacionados con la falta de resolución del segmento ST luego de una angioplastia primaria angiograficamente exitosa. Revista de la Federación Argentina de Cardiología. 2008;37:154-158
  54. 54. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: A randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. Lancet. 1995;345:669-685
  55. 55. Yusuf S, Peto R, Lewis J, Collins R, Sleight. Beta blockade during and after myocardial infarction: An overview of the randomized trials. Progress in Cardiovascular Diseases. 1985;27:335-371
  56. 56. ISIS-1. First International Study of Infarct Survival Collaborative Group. Randomised trial of intravenous atenolol among 16 027 cases of suspected acute myocardial infarction. Lancet. 1986;2:57-66
  57. 57. The MIAMI Trial Research Group. Metoprolol in acute myocardial infarction: Patient population. The American Journal of Cardiology. 1985;56:10G-14G
  58. 58. van der Horst IC, Zijlstra F, van’t Hof AW, et al. Glucose-insulin-potassium infusion in patients treated with primary angioplasty for acute myocardial infarction: The glucose-insulin-potassium study: A randomized trial. Journal of the American College of Cardiology. 2003;42:784-791
  59. 59. Finney SJ, Zekveld C, Elia A, Evans TW. Glucose control and mortality in critically ill patients. Journal of the American Medical Association. 2003;290:2041-2047
  60. 60. Clement S, Braithwaite SS, Magee MF, et al. Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004;27:553-597
  61. 61. van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patients. The New England Journal of Medicine. 2001;345:1359-1367
  62. 62. O’Gara PT, Kushner FG, Ascheim DD, CaseyJr DE, Chung MK, de Lemos JA, et al. ACCF/AHA guideline for the management of ST-elevation myocardial infarction. Circulation. 2013;127:e362-e425
  63. 63. Ibanez B, James S, et al. 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. European Heart Journal. 2018;39:119-177

Written By

Miguel Angel Farah, Franco Farah and Miguel Alejandro Farah

Submitted: 19 November 2019 Reviewed: 20 February 2020 Published: 04 May 2020