A Kumar, R Sivakanesan
acute myocardial infarction, endogenous antioxidants, normal lipid profile
A Kumar, R Sivakanesan. Oxidative stress and endogenous antioxidants in normolipidemic Acute Myocardial Infarction patients. The Internet Journal of Alternative Medicine. 2007 Volume 6 Number 1.
Also total cholesterol, TC: HDL-C ratio, triglycerides, LDL-cholesterol, LDL-C: HDL-C ratio and TG: HDL-C ratio were higher in AMI subjects (p<0.001) and HDL-cholesterol were lower in AMI subjects (p<0.001).
With the explosive rise in the incidence of Coronary Artery disease (CAD) it is estimated that this will be the leading cause of morbidity and mortality in the developing world by the year 2015. (1) People hailing from Indian subcontinent had a higher probability of dying due to CAD. It is a multifactorial disease and some predisposing factors are hereditary, hyperlipidemia, obesity, hypertension, environmental factors and life style variables like stress, smoking, alcohol consumption, etc. (2) Diet especially fat plays an important role the development of CAD and the risk further increases in the presence of dyslipidemia. Lipoprotein profile has been investigated extensively in recent years, which is found to be deranged in large proportion of CAD patients; especially Asians showing a mixed picture of dyslipidemia. Low density lipoprotein cholesterol (LDL) is considered as the most important risk factor of CAD. However, a significant proportion of patients have a normal lipid profile. (3) Free radicals play an important role in the pathogenesis of tissue damage in many different clinical disorders (4).Oxygen free radicals (OFR's) are produced continuously. Normally there is a balance between tissue oxidant and antioxidant activity (5). The later is achieved by the antioxidant scavenger system which includes enzymes (superoxide dismutase , catalase, glutathione peroxidase) and antioxidant vitamins (C , A, E and other carotenoids (6). Among the endogenous antioxidant system, includes albumin, uric acid, and total bilirubin. Imbalance of this reaction either due to excess free radical formation or insufficient removal by antioxidants leads to oxidative stress (7). The oxidation of LDL is believed to have a central role in atherogenesis. Subendothelial accumulation of foam cells plays a key role in the initiation of atherosclerosis. These foam cells, which may be generated by the uptake of oxidized LDL by macrophages via scavenger receptors, accumulate in fatty streaks that evolve to more complex fibro fatty or atheromatous plaques.(8) Oxidation of low-density lipoprotein particles and cytotoxic effects of lipid peroxides enhance the formation of foam cells and atherosclerotic lesion. During the formation and development of atherosclerosis, the intensity of lipid peroxidation and activity of the antioxidant defense system significantly change. Under oxidative stress not only LDL, but other serum lipids are exposed to oxidation. Literature survey reveals that the risk of heart attacks is particularly in those groups of individuals who have dyslipidemia. Now a latest trend is emerging that even in normolipidemic subjects the chances of myocardial infarction (MI) persists.
The present study was planned to evaluate the endogenous antioxidants status in MI patients with normal lipid profile. The present study was undertaken due to varied reports on these endogenous parameters and also due to lacunae of data available on normolipidemic patients with myocardial infarction.
Materials And Methods
Blood collection and biochemical methods used: 10 ml of blood was collected after overnight fasting and serum was separated. Serum was used for determination of lipid profile, serum albumin, serum uric acid, serum total bilirubin, serum malondialdehyde and conjugated dienes.
All chemicals of analytical grade were obtained from Sigma chemicals, India.
The lipid profile is shown in Table 1, Table 2 and Table 3. Total cholesterol, TC: HDL-C ratio, triglycerides, LDL-cholesterol, LDL: HDL-C ratio were higher in AMI subjects as compared to control (p<0.001). Also, significant differences were seen in HDL-C levels between AMI and controls (p<0.001). Total cholesterol, TC: HDL-C ratio, triglycerides were higher in both genders of AMI subjects as compared to control (p<0.001). Significant differences were seen in HDL-C levels between AMI and control only in female (Table-3) (p<0.001).LDL-cholesterol, LDL: HDL-C ratio were higher in male AMI subjects compared to control (Table-1) (p<0.001)
The endogenous antioxidants status and index of lipid peroxidation are shown in Table 4, Table 5 and Table 6. All the endogenous antioxidant were significantly decreased (p<0.001) in AMI patients compared to controls. Serum malondialdehyde and conjugated dienes were significantly (p<0.001) increased in AMI patients compared to controls.
Atherosclerosis is the root cause of Acute Myocardial Infarction (AMI). Contrary to earlier belief, research in the last two decades has shown that atherosclerosis is neither a degenerative disease nor inevitable due to ageing but it seems to be a chronic inflammatory condition that is converted to an acute clinical event by the induction of plaque rupture, which in turn leads to thrombosis. Hence inflammation occupies a very important central position in all phases of atherosclerosis, although inflammation must smolder for decades before resulting in a clinical event, like AMI (16). Myocardial ischemia occurs oxygen demand exceeds the oxygen supply and if this condition is not reversed, myocardial infarction precipitates. Reperfusion of the ischemic myocardium can restore oxygen supply but sudden massive increase in oxygen supply causes a burst of oxygen consumption with the consequent generation of free radicals, resulting in an imbalance of oxidative– anti-oxidative processes. The excess production of reactive oxygen species may initiate lipid peroxidation in cell membrane. These processes may result in a loss of contractile function of the heart and lead to severe myocardial cell damage, collectively termed as reperfusion injury (17). The significant decrease in endogenous antioxidant in the patients could be due to overwhelming production and accumulation of superoxide anion causing inhibition of antioxidant activity. Whatever might be the cause of the decreased endogenous antioxidants, the net result is accumulation of H2O2, one of the most damaging products of the free radical metabolism. H2O2 can readily react with superoxide anion to produce the highly toxic hydroxyl radical and HOCl. Many findings suggests that antioxidants depletion has relevant impact to the precipitation of myocardial infarction and these findings are consistent with the notion that increased levels of antioxidants are protective(18).
The present study observed significant lowering of endogenous antioxidants namely albumin, uric acid and total bilirubin and significant higher levels of malondialdehyde and conjugated dienes in patients (p<0.001). The findings of the present study is similar to the observations of the studies conducted by Dubois Rande et al (19) and Mc Murray (20) where they reported a significant rise in MDA levels (p<0.001), a lipid peroxidation product, with a concomitant decrease in antioxidants in patients of unstable angina and chronic heart failure. The present study is in concurrence with studies of Verma
To summarize, the present study shows that during reperfusion of ischemic myocardium, there is copious generation of reactive oxygen species, depletion of antioxidants system. Future research including measurement of parameters of oxidative stress and inflammatory markers should be carried out as the role of inflammatory markers like C-reactive proteins, caeruloplasmin are emerging which could be possibly be a causative factor for atherosclerosis leading to myocardial infarction.
Myocardial Infarction is a multifactorial disease which could be caused even in normolipidemic subjects. The earlier concept of maintaining lipid profile within normal and safe limits has been overruled as the present study unearths fact. The present study suggests, measuring of serum antioxidants at regular interval of time as the present study highlight the fact. Oxidative stress appears to be an etiological factor for myocardial infraction as a consequence of the free radical scavengers namely antioxidants which tends to lower in AMI patients.
Dr. Arun Kumar Assistant Professor, Department of Biochemistry Hindustan Institute of Medical Sciences and Research Sharda Hospital, Greater Noida Uttar Pradesh, India Email: email@example.com