Present day Bulgarian population marks a significant percentage (66%) mortality rate due to coronary artery disease (CAD), including myocardial infarction and its lethal mechanical complications. The most common cause of death in Bulgaria - coronary artery disease is not an exception in comparison to the same most common cause of death worldwide.
Difficult and controversial remains the enigma when exactly human civilization became aware of coronary artery disease (CAD) and its burden, which is initially still considered to be an illness of modern humans, with causes and risk factors attributed to genetics and lifestyle.
Atherosclerosis may be very ancient as reported in the Lancet in 2013 article in which whole body computed tomography scans of mummies from different parts of the world (Egypt, Peru, etc.) were conducted and presence of coronary lesions thousands of years old were examined and documented [1].
A well-known fact is that Leonardo da Vinci (1452–1519) was fascinated not only by the aortic root, as this usually is the first picture that comes to aortic surgeons’ mind, but also by coronary arteries which he is being credited to study and describe first.
The pioneer concept of coronary artery disease being responsible for the reduced blood passage/flow within the coronary arteries is credited to Friedrich Hoffmann (1660–1742) [2].
The German-American physician Adam Hammer famous for being pioneer in ether use for pain relief during labour, in the German speaking world, is also credited to be the first to diagnose, in 1876, coronary thrombosis, resulting in interruption of blood flow, as the cause of a myocardial infarction on a live patient[3].
After the development of coronary angiography in the early 1960s by Sones and Shirley at the Cleveland Clinic, Cleveland, OH., the direct identification and visualization of coronary atherosclerotic lesions both stenoses and occlusions became possible and thereafter the landmark procedure turned into irreplaceable gold standard for detecting coronary artery disease (CAD) [4].
Due to the invention, development and introduction in surgical practice, by pioneer Dr. John H. Gibbon in 1953, of the heart-lung machine, considered to be one of the biggest cornerstone inventions of the mid-20th century, the era when Dr. Walter Lillehei performed first open heart surgery cases using controlled cross-circulation, and Dr. Clarence Dennis and team of colleagues used the first pump-oxygenators seems, from the present perspective, a time of never ending enthusiasm and effort of improving concepts, discoveries, inventions and techniques but with the disadvantage of lack of proper technology and materials.
The invention and clinical widespread use of the heart-lung machine, developed by Dr. J.H.Gibbon, accepting the concept of extracorporeal circulation and principles of developing surgical techniques, marked the beginning of a new astonishing era of the modern cardiac surgery which provides vast and safe field of options in treating patients with coronary artery disease (CAD), along with the rest of the congenital and acquired cardiac pathology [5, 6, 7].
In 1964, Vasilii Ivanovich Kolesov in Leningrad, USSR (present Saint Petersburg, Russian Federation) performed the first successful myocardial revascularization surgical operation using left internal mammary artery (LIMA), as an arterial graft conduit, which was anastomosed to distal target vessel -left anterior descending (LAD) branch of the left coronary artery, whereas Rene Favaloro in 1967 at the Cleveland Clinic, Ohio, OH, was the first surgeon to perform successful coronary artery bypass grafting (CABG) with saphenous vein graft as a conduit, anastomosed to the same distal target, mentioned above [8, 9].
A landmark date in the history of Bulgarian coronary surgery is 10 October 1974. On that day two prominent pioneer cardiovascular surgeons, Yovcho Topalov and Gencho Krastinov, performed the first successful coronary artery bypass grafting (CABG) using saphenous vein conduit [10].
The most common pathological problems of most chronic diseases, cardiovascular are no exception, are energy metabolism disorders [11]. The development of atherosclerosis and coronary artery disease (CAD). as suggested by some recent studies. is accompanied and marked by energy reduction and depletion within the main energy producers and cellular metabolism regulators, such as the mitochondria [12, 13].
Cell death, inflammation and oxidative stress can directly and inevitably be a result from mitochondrial dysfunction, but in the end a modified normal cell metabolism can also be present and functioning [14]. Such pathophysiological deteriorations can also be observed in the cardiomyocite homeostasis, occurring during the period of re-perfusion injury process in various conditions such as un-/stable angina pectoris, myocardial infarction, coronary artery bypass grafting (CABG), percutaneous coronary interventions (PCI) and other.
The generation of free radicals such as superoxide anion and hydrogen peroxide causes the myocardial re-perfusion injury. A series of scavenger enzymes and antioxidants in cardiac cells remove the mentioned above free radicals [15, 16].
A variety of conditions such as ischemia duration, presence of coronary collaterals, early restoration to normal physiological (basal) pH level at the time of re-perfusion, etc., are determinants of the cellular damage and its potential reversibility [17, 18].
Despite maximal revascularization achieved, either by coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI), a substantial number of patients would still experience events of angina recurrence symptoms [19, 20, 21]. A significant part in the anti-anginal therapy in patients after surgical or interventional coronary procedures would definitely remain for the optimal drug therapy. The first line of inti-ischemic drug agents remains for beta-blockers and nitrates, whereas the second line of choice remains for medications such as: nicorandil, ivabradine, ranolazine and trimetazidine [22, 23, 24].
Trimetazidine, [1-(2,3,4-trimethoxy benzyl)piperazine dihydrochloride] (TMZ), is a metabolic anti-ischemic drug that exerts its beneficial effects without altering coronary blood flow and cardiac contractility.Its cardio-protective action is achieved by modulating heart’s metabolism through long-chain 3-ketoacyl CoA thiolase activity inhibition, which results in oxidation reduction of free fatty acids and shifting substrate utilisation from fatty acid to glucose with no affect over hemodynamics [25]. This mechanism of action represents trimetazidine as an excellent complementary drug for treatment of coronary artery disease (CAD) with its beneficial effects on coronary vasodilation and improving endothelial function [26]. An additional short and long-term advantage of trimetazidine in diabetic patients is decreasing the fasting glucose plasma levels without affecting the lipid profile [27].
Aim
The aim of our present study is to investigate and analyse trimetazidine effects on reactive oxygen species that my result from myocardial ischemic-reperfusion damage or systemic inflammatory response after surgical coronary revascularization. A number of laboratory biomarkers for myocardial damage, such as creatinine-kinase MB fraction, high-sensitivity Troponin T and malondialdehide as evidence of oxidative stress, and functional indicators were measured and evaluated in six-month follow-up period after coronary artery bypass grafting (CABG).