Oxidative stress parameters in patients with slow coronary flow.

INTRODUCTION: We investigated the probable role of free-radical damage in the pathogenesis of slow coronary flow (SCF) by using oxidative stress parameters. METHODS: Sixty-four patients with angiographically proven SCF and 63 patients with normal coronary flow (NCF) pattern with similar risk profiles were enrolled in this study. We measured erythrocyte superoxide dismutase (SOD), reduced glutathione (GSH), serum malondialdehyde (MDA), catalase and myeloperoxidase (MPO) levels in all subjects. RESULTS: There were statistically significant differences in the levels of erythrocyte SOD, GSH and serum MDA between the 2 groups. Serum MDA (P = 0.003) and erythrocyte SOD levels (P = 0.0001) were increased in the SCF group. The level of erythrocyte GSH (P = 0.010) was lower in patients with SCF. There were no differences between the groups' serum catalase (P = 0.682) and MPO levels (P = 0.070). CONCLUSION: Our data showed that in patients with SCF, serum MDA and erythrocyte SOD levels were increased while erythrocyte GSH levels were decreased significantly, compared with NCF patients. These results indicate that free-radical damage may play a role in the pathogenesis of SCF.

Right coronary artery arising as a terminal extension of the circumflex artery (a rare coronary artery anomaly).

A single coronary artery is a very rare type of coronary artery anomaly that may present in various forms. A patient is presented in whom the right coronary artery coursed as the terminal branch of the left circumflex artery. This is the second case of this anomaly in the literature.

Early sign of atherosclerosis in slow coronary flow and relationship with angiotensin-converting enzyme I/D polymorphism.

Increase in carotid artery intima-media thickness (IMT) is an early sign of atherosclerosis. Slow coronary flow (SCF) is characterized by delay of opacification of coronary arteries in coronary angiography in the absence of any evident obstructive lesion, but its etiopathogenesis remains unclear. Genes that regulate the renin angiotensin system also play a role in developing cardiovascular system disorders. The presence of deletion (D) allele in angiotensin converting enzyme (ACE) gene polymorphism is associated with coronary artery disease. The aim of this study was to investigate the carotid artery IMT measurement, as an early sign of atherosclerosis, in patients with SCF and without SCF and also to assess the effect of the renin-angiotensin gene system on carotid IMT. Forty-four patients with angiographically proven SCF and 44 cases with normal coronary flow (NCF) pattern with similar risk profile were enrolled in the study. Coronary flow patterns of the cases were determined by thrombolysis in myocardial infarction (TIMI) frame count method. Intima-media thickness was measured by recording ultrasonographic images of both the left and right common carotid artery with a 12-MHz linear array transducer. ACE I/D polymorphism and Angiotensin II tip 1 receptor (AT1R) A/C gene polymorphism were determined by polymerase chain reaction (PCR) amplification. Demographic characteristics and coronary artery disease risk factors of SCF and NCF groups were similar. Mean TIMI frame count and carotid IMT (mm) were significantly higher in the SCF group than controls (45.9 +/- 12 vs 23.3 +/- 3.7, P = 0.0001; 0.75 +/- 0.08 vs 0.69 +/- 0.06, P = 0.0001, respectively). Mean TIMI frame count was positively correlated with IMT of carotid artery in correlation analysis (r = 0.45, P = 0.0001). When analyzed in regard to ACE genotype in all subjects, IMT values were statistically different (0.78 +/- 0.06 for DD genotype, 0.72 +/- 0.05 for ID genotype, and 0.64 +/- 0.06 for II genotype, P = 0.0001). This difference remained significant in subgroup analyses for each genotype. No association could be observed between the AT1R A/C(1166) polymorphism and IMT of carotid artery measurement (P > 0.05). Lack of association was still observed with analysis carried out when genotype effect was assumed to be inherited as additive (CC versus AA versus AC) or dominant (AA versus AC+CC). Increased IMT in patients with SCF shows that subclinical atherosclerosis may play role in this phenomenon. This increase was most marked in the presence of D allele of ACE genotype, which is associated with vascular hypertrophy.

Effect of homocysteine-induced oxidative stress on endothelial function in coronary slow-flow.

BACKGROUND AND OBJECTIVE: Coronary slow-flow (CSF) phenomenon is characterized by delayed opacification of vessels in a normal coronary angiogram, but its etiopathogenesis remains unclear. Plasma homocysteine (Hcy) level can severely disturb vascular endothelial function and may play a role in the pathogenesis of CSF. In our study, endothelial function in patients with CSF and their relationship with Hcy and oxidative stress parameters are investigated. METHOD: Forty-four patients with angiographically proven CSF and 44 cases with normal coronary flow pattern with similar risk profile were enrolled in the study. Coronary flow patterns of the cases are determined by Thrombolysis in Myocardial Infarction (TIMI) frame count method. Endothelium dependent flow mediated dilatation (FMD) and independent vasodilatation characteristics are evaluated by high frequency ultrasound over the brachial artery. Superoxide dismutase (SOD) and reduced glutathione (GSH) and reduction of oxidative material in the body and the end product of lipid peroxidation, malondialdehyde (MDA) are measured as oxidative stress markers in blood samples. RESULTS: Plasma Hcy level (micromol/l) of patients with CSF was found to be significantly higher than in controls (12.2 +/- 4.9 vs. 8.5 +/- 2.8, p = 0.0001). FMD was 7.87 +/- 2.0% in controls and 4.98 +/- 1.1% in patients with CSF (p = 0.0001). GSH was reduced in patients with CSF. SOD and MDA activity were found higher in patients with CSF than control subjects. Plasma Hcy level was significantly positively correlated with mean TIMI frame count and negatively correlated with FMD in correlation analysis (r = 0.58, p = 0.0001; r = -0.41, p = 0.022; respectively). CONCLUSION: The present findings allow us to conclude that patients with CSF have increased levels of Hcy and oxidative stress markers and impaired endothelial cell function.

Interaction of plasma homocysteine and thyroid hormone concentrations in the pathogenesis of the slow coronary flow phenomenon.

BACKGROUND AND OBJECTIVE: The slow coronary flow (SCF) phenomenon is an angiographic observation and a well-recognized clinical entity characterized by delayed opacification of vessels in a normal coronary angiogram due to reasons yet unclear. Thyroid hormones exert significant effects on plasma homocysteine (Hcy) levels and microvascular resistance. Recently, several investigators have consistently reported that elevation of the plasma Hcy level can severely disturb vascular endothelial function and play a role in the pathogenesis of SCF. Accordingly, we investigated the levels of plasma Hcy and thyroid hormones and their relationship in patients with SCF. METHOD: Forty-four patients with angiographically proven SCF (Group I) (mean age 55.5 +/- 10.4 years, 26 males) and 44 cases with normal coronary flow (NCF) pattern (Group II) (mean age 53.9 +/- 11 years, 22 males) with similar risk profiles were enrolled in the study. Coronary flow patterns of the cases were determined by the thrombolysis in myocardial infarction (TIMI) frame count method. The coronary TIMI frame counts were calculated separately for each coronary artery and their average was determined as the mean TIMI frame count for each subject. Serum levels of free tri-iodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH) and Hcy were measured. Patients with thyroid disease or on medications with a potential to affect thyroid functions were excluded. RESULTS: There were no statistically significant differences between the groups concerning the demographic characteristics and major cardiovascular risk factors. Mean TIMI frame counts of SCF and NCF groups were 45.9 +/- 12 and 23.3 +/- 3.7, respectively. fT4 (ng/dl) and TSH (microIU/ml) levels of the two groups were similar (p > 0.05). The level of fT3, the active metabolite of the thyroid hormone family, was dramatically reduced in the SCF group when compared to the NCF group (2.3 +/- 0.2 vs. 3.0 +/- 0.3, p = 0.0001, respectively). Plasma Hcy levels of patients with SCF were found to be significantly higher than controls (12.2 +/- 4.9 vs. 8.5 +/- 2.9, p = 0.0001, respectively). Correlation analysis showed a significant negative correlation between the plasma fT3 and Hcy levels and the mean TIMI frame counts (r = -0.31, p = 0.003 vs. r = -0.66, p = 0.0001). Moreover, there was a significant positive correlation between the plasma Hcy levels and the mean TIMI frame counts (r = 0.58, p = 0.0001). Also, fT3 was the only significant determinant of the variance of Hcy in multiple regression analysis (r = -0.30, p = 0.005). CONCLUSION: fT3 levels were decreased and plasma Hcy levels were increased significantly in patients with SCF as compared to controls. This finding suggests that thyroid hormones and/or (?) a possible disturbance in their metabolism may be responsible for the elevated levels of plasma Hcy in patients with SCF and may play a role in the pathogenesis of the SCF phenomenon.

The antiarrhythmic effect and clinical consequences of ischemic preconditioning.

Potentially hazardous short ischemic episodes increase the tolerance of myocardium to ischemia paradoxically. This condition decreases the infarct area markedly caused by a longer duration of coronary occlusion. This phenomenon is known as 'ischemic preconditioning' and its powerful cardioprotective effect has been shown in experimental and clinical studies. Ischemic preconditioning decreases cardiac mortality markedly by preventing the development of left ventricular dysfunction and ventricular and supraventricular arrhythmias after acute myocardial infarction. Ischemia-induced opening of ATP-sensitive potassium channels and synthesis of stress proteins via activation of adenosine, bradykinin and prostaglandin receptors seem to be the possible mechanisms. By understanding the underlying mechanisms of ischemic preconditioning, it may be possible to develop new pharmacologic agents that cause ischemic preconditioning with antiischemic and antiarrhythmic properties without causing myocardial ischemia.

Carotid intima-media thickness in coronary slow flow: relationship with plasma homocysteine levels.

BACKGROUND AND OBJECTIVE: Coronary slow-flow phenomenon is characterized by delayed opacification of coronary vessels in a normal coronary angiogram. Although clinical and pathological features have been previously described, the underlying pathophysiology has not been fully elucidated. Thus, it still remains to be determined whether either microvascular or epicardial diffuse atherosclerotic disease is related to slow flow. In this study, we aimed to determine the carotid artery intima-media thickness, which is a marker of atherosclerosis in patients with coronary slow flow, and its possible relationship with the total homocysteine level. METHOD: The study population consisted of 88 patients who underwent coronary angiography because of typical and quasi-typical symptoms of angina. Forty-four patients with angiographically proven coronary slow flow and 44 individuals with normal coronary flow pattern with similar risk profiles were enrolled in the study. Coronary flow patterns of the latter were determined by the thrombolysis in myocardial infarction frame count method. Intima-media thickness was measured by recording ultrasonographic images of both the left and the right common carotid artery with a 12-MHz linear array transducer. Plasma homocysteine, folate and B12 levels were measured from blood samples. RESULTS: Plasma homocysteine levels (mumol/l) and carotid intima-media thickness (mm) of patients with coronary slow flow were found to be significantly higher than that of controls (12.4+/-4.9 vs. 8.5+/-2.8, P=0.0001; 0.75+/-0.08 vs. 0.69+/-0.06, P=0.0001, respectively). The plasma folate level (ng/ml) was lower in coronary slow-flow patients than in controls (13.8+/-4.4 vs. 16.5+/-5.6, P=0.014). The plasma homocysteine level was significantly positively correlated with the mean thrombolysis in myocardial infarction frame count and intima-media thickness of the carotid artery in correlation analysis (r=0.58, P=0.0001; r=0.41, P=0.0001; respectively). CONCLUSION: Homocysteine levels and carotid intima-media thickness increased but folate levels decreased in patients with coronary slow flow. The present findings allow us to conclude that the possible disturbance in the metabolism of homocysteine in patients with coronary slow flow may have a role in the etiopathogenesis of this phenomenon by causing generalized atherosclerosis.

Cigarette smoking induced oxidative stress may impair endothelial function and coronary blood flow in angiographically normal coronary arteries.

BACKGROUND: Smoking contributes to the progression of atherosclerotic heart disease by causing endothelial dysfunction. In the present study the effect of smoking on endothelial functions and coronary flow was investigated, as well as the relationship of these factors with oxidative stress parameters, in subjects with normal coronary arteries. MATERIALS AND RESULTS: The study group comprised 87 patients with angiographically normal coronary arteries (36 smokers, 51 nonsmokers). Coronary flow patterns were determined by the Thrombolysis In Myocardial Infarction (TIMI) frame count method. Endothelial function was evaluated by high-frequency ultrasound imaging of the brachial artery. Superoxide dismutase (SOD) and reduced glutathione (GSH) and reduction of oxidative material in the body and the endproduct of lipid peroxidation, malondialdehyde (MDA), were measured as oxidative stress markers. Mean TIMI frame count was significantly higher in smokers than nonsmokers (42.2 +/- 16 vs 29.5 +/- 9.5, p = 0.0001). Endothelium-dependent flow-mediated dilatation was 6.81+/-1.95% in nonsmokers and 5.7 +/- 2.2% in smokers (p = 0.0001). The smokers had dramatically higher levels of SOD and MDA and lower levels of GSH than the nonsmoker group. CONCLUSION: Smoking induced oxidative stress deteriorates coronary blood flow by disturbing endothelial function.

Angiographic detection of the left anterior descending and the right coronary artery after fistulas into the pulmonary artery in a patient with rheumatic mitral stenosis.

Coronary artery fistula is a rare heart defect found in approximately 0.2% of the adult population undergoing coronary angiography. The diagnosis is usually made by aortography and selective coronary angiography. We report here an adult patient with rheumatic mitral stenosis and left anterior descending coronary artery and pulmonary conus branch of right coronary artery-pulmonary artery fistulas detected by coronary angiography.

Heart rate variability in patients with rheumatoid arthritis.

Heart rate variability (HRV) is a useful tool for the detection of sympathetic-parasympathetic balance in the autonomic nervous system. Autonomic nervous system involvement in patients with rheumatoid arthritis (RA) has rarely been studied and has shown conflicting results. Our purpose was to determine if HRV showed changes in patients with RA in comparison with the normal population. Short-term analysis of HRV was performed for time-domain frequency in 42 patients with RA and 44 matched controls. In this analysis, patients displayed lower standard deviation of the mean than healthy subjects ( P<0.0001). Patients tended to display higher pNN50 and root-mean-square of successive difference values than did healthy subjects, but these differences were not statistically significant (P >0.05). In frequency domain analysis, the spectral measures of HRV showed reduced high-frequency (HF) values and an higher low-frequency (LF) values; as a result, the ratio between low and high frequencies (LF/HF), representative of sympathovagal modulation, was significantly increased (P=0.001, P=0.012, and P=0.003, respectively). Our data suggest an increase in sympathetic control of the heart rate in patients with RA. This increased sympathetic activity could play a key role in the development of ventricular tachyarrhythmias in RA and may be related to the higher incidence of sudden death in this disorder.