Is there any association between GLY82 ser polymorphism of rage gene and Turkish diabetic and non diabetic patients with coronary artery disease?

This study was carried out in 52 non-diabetic, 62 diabetic patients with coronary artery disease (CAD) and 55 controls. A Gly to Ser change RAGE gene was analyzed by PCR-RFLP techniques. GlyGly genotype frequency is higher in non-diabetics versus controls (P < 0.001). GlySer frequency is higher in diabetics than controls and non-diabetics (P < 0.001). Ser allele frequency is respectively increased in the order of diabetics > Controls > non-diabetics. These results reveals none association between Gly82Ser and the development of disease in non-diabetic patients. In diabetics with Ser allele, higher prevalence of left-ventricule-hypertrophy was observed, but the significant difference between Gly82Ser and left-ventricule-hypertrophy only found in the whole patient group. As a result Ser allele has much more importance in the development of left-ventricule-hypertrophy than other cardiovascular risk factors. In this study we found the presence of Gly allele contributes to the CAD in non-diabetics and Ser allele may contribute to disease in diabetics.

Associations of -374T/A polymorphism of receptor for advanced glycation end products (RAGE) gene in Turkish diabetic and non-diabetic patients with coronary artery disease.

BACKGROUND: In this study we aimed to determine the possible risks for the development of coronary artery disease (CAD) in diabetic (DM(+)) and non-diabetic (DM(-)) patients according to the -374T/A polymorphism of the receptor for advanced glycation end products (RAGE) gene which affects the function of RAGE itself. MATERIALS AND METHODS: This study was carried out in 52 non-diabetic and 62 diabetic patients with CAD, and 55 CAD-free, healthy volunteers as controls. The A-T transversion polymorphism at position -374 in the promotor region of the RAGE gene was analyzed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) techniques. RESULTS: The -374T/A AA genotype frequency was statistically higher in the whole patient group when compared with the control group (p=0.034), and statistically higher in the DM(+) group when compared with the control group (p=0.003). Homozygosity for the -374A allele was found to be higher, but not statistically meaningful, in DM(-) patients (17.3%) when compared with the control group (13.2%). In this study, in contrast with other studies, we found possesion of the A allele to be an independent risk factor in CAD in patients with diabetes mellitus. CONCLUSION: Possesion of the -374A allele may contribute to the CAD in diabetic patients with triggering macrophages by increased levels of AGEs.

Is LOX-1 K167N polymorphism protective for coronary artery disease?

BACKGROUND: Human lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1, OLR1) has been identified as a cell surface endocytosis receptor for oxidized low-density lipoprotein (oxLDL) on vascular endothelial cells. OxLDLs are avidly ingested by macrophages, resulting in foam cell formation. OxLDLs are also involved in inducing smooth muscle cell migration, proliferation and transformation. A single nucleotide polymorphism K167N (G501C) of the LOX-1 gene results in an amino acid dimorphism (Lys/Asn) at residue 167. Replacement of this Lys residue causes reduced binding and internalization of oxLDL. The purpose of this study was to investigate the effect of the LOX-1 K167N gene polymorphism in Turkish patients with coronary artery disease (CAD). MATERIALS AND METHODS: K167N polymorphism were studied in 91 patients with CAD and 72 healthy controls by the PCR-RFLP method. RESULTS: The frequencies of the KK genotype and the K allele were higher in the CAD group than the controls (p<0.05), while the frequency of the NN genotype was higher in the control group than in the CAD group (p<0.05). It was observed that the decreased CAD risk in patients who had the N allele was reversed by male sex (OR: 0.400 -->0.481) and smoking (OR: 0.400 -->0.949). Although male sex and smoking were lower than other cardiovascular risk factors in patients with the N allele they were higher than other cardiovascular risk factors in patients with the K allele. CONCLUSION: Male sex and smoking decrease the protective effects of the N allele. The adverse effects of the K allele on the CAD risk resulting from the K167N polymorphism appear to be independent of other cardiovascular risk factors.

Median sternotomy for an unexpected complication of permanent hemodialysis catheters: "stuck catheter".

Cuffed tunneled venous access catheters are commonly used for temporary and permanent access in patients undergoing hemodialysis. These catheters play an essential role in providing permanent access in patients in whom all other access options have been exhausted. However, they are prone to several complications like catheter thrombosis, catheter fibrin sheating and infection. Herein, we report two uncommon cases of stuck hemodialysis cuffed tunneled catheters causing stenosis and thrombosis in central veins which needed to be removed by median sternotomy.

Results of adjunctive coronary endarterectomy in 548 patients.

Coronary endarterectomy is a controversial procedure that plays a particular role in the treatment of coronary artery disease. We retrospectively investigated the results for 548 patients who underwent coronary endarterectomy as an adjunctive therapy for coronary artery bypass graft surgery during the period between 1996 and 2004. We assessed short-term outcomes and identified risk factors for adverse outcomes. Mean patient age was 67.9 + 9.3 years and mean angina class was 2.7 + 0.3. The mean number of distal anastomoses was 3.8 + 1.1 patients (73.4%) had single and 151 (27.6%) multiple coronary artery endarterectomies. Of the 151 patients who underwent multiple endarterectomies, 97 (17.7%) had endarterectomies in 2 coronary arteries, 40 (7.2%) in 3 coronary arteries, 11 (2%) in 4 coronary arteries, 2 (0.36%) in 5 coronary arteries, and 1 (0.18%) in 6 coronary arteries. Postoperative mortality was 6.2% (34 patients). The predictors for early mortality were recent myocardial infarction and left ventricular dysfunction. Our results suggest that adjunctive coronary endarterectomy can be accomplished with acceptable results but with higher mortality rates than ordinary coronary artery bypass grafting. Adjunctive coronary endarterectomy should be considered as a last option for the surgical treatment of diffuse coronary disease.

The effect of NQO1 polymorphism on the inflammatory response in cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) has been associated with systemic inflammatory response syndrome (SIRS). Endothelial dysfunction related to non-laminar flow during CPB is known to play a key role in this complex pathology. Antioxidant response element (ARE) dependent NAD(P)H:quinone oxidoreductase 1 (NQO1) promoter is a regulatory element involved in the anti-inflammatory mechanism in vasculature exposed to non-laminar flow. Mutation of the NQO1 could represent a novel anti-inflammatory effect in CPB. The goal of this study was to demonstrate whether genetic variants of NQO1 affect cytokine release after CPB. Eighteen patients who underwent standard coronary artery bypass grafting (CABG) operation were included in the study. Genotyping for NQO1 was performed. Serum Interleukin-6 (IL-6) levels were measured before induction, during CPB after declamping the aorta, and 24 h after operation. Clinical data were collected respectively. Seven patients were NQO1 T carriers and 11 patients were NQO1 T non-carriers. During CPB, IL-6 concentrations were increased in NQO1 T carriers compared to T non-carriers (p = 0.038). Although ventilation times and blood loss were higher in T carriers these were not statistically significant. Patients with NQO1 T carriers showed significantly higher IL-6 levels during CPB. Non-laminar flow during CPB may diminish the transcriptional activation of the NQO1 in T carriers. Preoperative determination of this novel anti-inflammatory mechanism could be useful to improve operative outcome in CPB.

Coronary artery bypass surgery in patients with severe left ventricular dysfunction.

OBJECTIVE: The role of coronary artery bypass grafting (CABG) in patients with severe left ventricular dysfunction was evaluated. METHODS: Two hundred and twelve patients (152 men, 60 women; age 35 to 82, mean 55) with ejection fraction (EF) of less than 30% underwent CABG between January 1996 and February 2001 by a single surgeon (SA). They compromised of 12% of 1759 patients operated on in this period. EF ranged from 17% to 30% (mean 25%). Preoperatively 68% had congestive heart failure and 72% had severe angina (CCS 3 or 4). A left main lesion was found in 26% of the cases. The mean number of grafts was 3.18 per patient. The left internal mammary artery (LIMA) was used on 107 patients (50.4%). Preoperative intraaortic balloon pump (IABP) was used on 32 patients (15%). Endarterectomy was performed on 53 patients (25%). The patients were followed for up to 58 months (mean 28.7). RESULTS: Twelve patients died in hospital (5.6%). Survival was 94%, 87%, 80% and 73% at 1, 2, 3 and 4 years respectively. Among the preoperative variables survival was negatively affected by chronic renal failure, older age, congestive heart failure, elevated pulmonary artery pressure and recent myocardial infarction, by means of multivariate analysis. Preoperative IABP support improved the operative mortality significantly (P=0.002). Use of LIMA did not have any influence on survival. CONCLUSION: CABG on patients with poor left ventricular function: (1). Can be performed with an acceptable mortality. (2). Mid term results are encouraging. (3). Preoperative IABP support improves the chance of survival.

Ischemic preconditioning and nicotinamide in spinal cord protection in an experimental model of transient aortic occlusion.

OBJECTIVES: Spinal cord injury is a devastating complication after aortic surgery. The aim of the present study is to examine the effects of ischemic preconditioning (IPC) and nicotinamide containing perfusate in transient aortic occlusion in the rat. METHODS: Thirty-two male Spraque-Dawley rats under general anesthesia were randomly assigned to four groups (n=8 in each group). The infrarenal aortas were clamped for 45 min. Groups were as follows: Group 1, undergoing occlusion but receiving no treatment. Group 2, had 5 min of IPC before occlusion. Group 3, received nicotinamide (0.2 ml/l) during the transient occlusion. Group 4, received combined IPC (5 min) and nicotinamide infusion during the transient occlusion. The rats were then allowed for recovery and were tested for their neurological status. All animals were sacrificed at the end of the 48 h and spinal cords also examined histologically. Anti- poly (ADP-ribose) polymerase p85 fragment pAb was used as an immunohistochemical marker for detection of apoptosis. RESULTS: In 24 h paraplegia represented as grade 0 and 1 occurred in six animals in Group 1 and two animals in Groups 2 and 3 and one in Group 4. In 48 h six animals in Group 1 and only one animal in Groups 2 and 3 showed a paraplegia. The incidence of neurologic deficit was significantly reduced in animals who had IPC and nicotinamide infusion (P<0.05). At 48 h, combined IPC and nicotinamide showed a significant benefit compared to nicotinamide but not to the IPC alone. Histologic examination of the spinal cords revealed that a neuronal necrosis contributes to acute spinal cord degeneration after a period of aortic occlusion and both nicotinamide and IPC have protective effects against neuronal necrosis. No difference was found among the groups. CONCLUSIONS: Both IPC and nicotinamide are beneficial in protection against neurological damage in transient aortic occlusion. IPC alone as expected is significantly beneficial both at 24 and 48 h compared to controls. At 24 h combined nicotinamide and IPC show significant benefit compared to only nicotinamide, but this difference is not maintained at 48 h.

Is there a role of angiotensin-converting enzyme gene polymorphism in the failure of arteriovenous femoral shunts for hemodialysis?

In humans, thrombosis and neointimal hyperplasia are the major factors responsible for prosthetic graft occlusion. Previous studies suggest that the renin-angiotensin system is one of the key enzymes in the vascular system and has been implicated in the pathogenesis of thrombosis and neointimal hyperplasia. We conducted a case-control study to determine the frequency of the different angiotensin-converting enzyme (ACE) genotypes among the patients who had PTFE graft implantation for hemodialysis access. Between 1997 and 1999, 30 graft implantations were performed. Twelve individuals (40%) developed thrombotic complications, 8 of the 12 patients had ACE ID polymorphism, and 2 patients had DD and 2 patients had II polymorphism. The ID polymorphism was significantly more frequent in the thrombosed arteriovenous (A-V) grafts than in nonthrombosed A-V grafts (chi2 = 7.57 and p = 0.02). Overall, the frequency of the D and I alleles was 66.6 and 33.3%, respectively. In conclusion, ID polymorphism of the ACE gene plays an important role in the pathogenesis of vascular access thrombosis in subjects undergoing hemodialysis for chronic renal failure.

Aprotinin reduces the IL-8 after coronary artery bypass grafting.

The effect of aprotinin, a protease inhibitor, on myocardial interleukin-8 (IL-8) production after ischemia-reperfusion injury was investigated. Twenty patients who had elective coronary artery bypass grafting were included in this study. Patients were randomly divided into two groups (n = 10 in each). Group A patients received high dose aprotinin (20,000 IU/kg as pretreatment followed by 7500 IU/kg for 6 h) and Group B patients received normal saline as a control. Serum IL-8 levels after the termination of cardiopulmonary bypass (CPB) showed a significant improvement in aprotinin treated group compared to control group (70 +/- 42.6 vs 360.71 +/- 87.9 ng/ml) (P < 0.005). Levels were also significantly higher at post-operative 24th hour in patients who did not received aprotinin (340.16 +/- 92.10 vs 96.13 +/- 34.33 ng/ml). However at post-operative 48th hour levels were again higher in control (untreated) group, but the difference was not statistically significant (78.8 +/- 34.4 vs 42.8 +/- 9.29 ng/ml). Aprotinin prevented the IL-8 release from myocytes in ischemia-reperfusion injury. The mechanism is highly dependent on anti-protease activity of aprotinin.

The Effect Of Enalapril Maleat In Ischemia Reperfusion Injury: Possible Role of Membrane Bound Enzymes.

The present study evaluates the protective effect of enalapril maleat on myocardial ischemia-reperfusion injury. Membrane bound enzymes; Na(+)K(+)/Mg(2+) ATPase and Ca(2+)/Mg(2+) ATPase are known to regulate the membrane integrity. We hypothesized that if we could protect the cell membrane in ischemia-reperfusion period, we might have a chance to augment contractility. Thirty-two Guinea pig hearts were studied in an isolated Krebs-Henseleit solution-perfused Langendorff cardiac model. In Group 1, control hearts (n = 8) were arrested with St. Thomas Cardioplegic Solution (STHCS) alone. In Group 2 (n = 8), animals were pretreated with oral enalapril maleat (0.2mg/kg/daily) for ten days and arrested with STHCS. In Group 3, (n = 8) the hearts were arrested with enalapril maleat- (1 µmol/L) added STHCS. In Group 4 (n = 8), the hearts were again pretreated with oral enalapril maleat for ten days and then reperfused with enalapril maleat-added Krebs-Henseleit solution. Hearts were subjected to normothermic global ischemia for 90 minutes and then were reperfused at 37 degrees C. The study groups showed better recovery of left ventricular systolic function. In terms of biochemical determinations, best results were achieved at Group 4. The Na(+)K(+) ATPase and Ca(2+) ATPase levels were measured at 466.38 +/- 5.99 to 545.23 +/- 8.79, and 884.69 +/- 9.13 to 1254.34 +/- 1.56, respectively (p < 0.05). Based on these results, it can be concluded that enalapril maleat protects the membrane integrity and thus plays a role in restoring the contractility in ischemia-reperfusion injury.

The effect of captopril on membrane bound enzymes in ischemia-reperfusion injury.

There is substantial evidence that Na(+)K(+)/Mg(2+) ATPase and Ca(2+)/Mg(2+) ATPase enzymes would effect the membrane integrity. Forty guinea pig (n=10 in each group) hearts were studied in an isolated Krebs-Henseleit solution perfused Langendorff cardiac model. The first group was utilized as the control group. Group 2 hearts were arrested with captopril (200micromol/l) added St Thomas Hospital Cardioplegic Solution (STHCS). Group 3 animals were pretreated with oral captopril (0.3mg/kg/twice a day) for 10days and then arrested with STHCS. Group 4 hearts were again pretreated with oral captopril (0.3mg/kg/twice a day for 10days) arrested with STHCS and reperfused with captopril added Krebs-Henseleit solution (200micromol/l). Hearts were subjected to normothermic global ischemia for 90min and than were reperfused at 37 degrees C. When the treated groups were compared with control, best results were achived by group 4. The Na(+)K(+) and Ca(2+)/Mg(2+) ATPase levels increased from 466.38+/-5.99 to 564.13+/-7.77 and 884.69+/-9.13 to 1254.29+/-5.75 nmol Pi/mg/prot/h respectively (P<0.05). These results suggest that captopril protects the membrane integrity and thus played a role at the recovery of depressed membrane bound Na(+)K(+)/Mg(2+) ATPase and Ca(2+)/Mg(2+) ATPase activity and also in ischemia-reperfusion injury.

The protective effect of lisinopril on membrane-bound enzymes in myocardial preservation.

A number of studies have reported that oxidant stress reduces the activity of isolated Na(+)-K(+) ATPase and Ca(2+) ATPase which are known to affect the cell membrane integrity. The aim of the study is to determine whether the administration of lisinopril is able to protect the membrane-bound enzyme levels in isolated guinea pig hearts and also ascertain whether or not a relationship exists between oxygen free radicals and membrane bound Na(+)-K(+) ATPase and Ca(2+) ATPase. Forty guinea pig hearts were studied in an isolated Krebs-Henseleit solution-perfused Langendorff cardiac model. In all groups cardioplegic arrest was achieved by administering St. Thomas' Hospital cardioplegic solution (STHCS). Group 1 (control, n=10) received only STHCS. Group 2 (n=10) were arrested with lisinopril (l micromol l(-1)) added STHCS. Group 3 (n=10) were pretreated with oral lisinopril (0.2 mg kg(-1) twice a day) for 10 days and then arrested with STHCS. Group 4 were also pretreated with oral lisinopril (0.2 mg kg(-1) twice a day for 10 days), arrested with STHCS and reperfused with lisinopril added to Krebs-Henseleit solution (l micromol l(-1)). Hearts were subjected to normothermic global ischaemia for 90 min and then reperfused at 37 degrees C. Pretreatment and addition of lisinopril in the reperfusion buffer improved the levels of membrane-bound enzymes. When the treated groups were compared with control hearts, the best results were achieved in group 4. The Na(+)-K(+) and Ca(2+) ATPase levels increased from 466.38+/-5.99 to 560.12+/-18.02 and 884.69+/-9.13 to 1287.71+/-13.01 nmolPi mg(-1) protein h(-1) respectively (p<0.05). These results suggest that lisinopril protects the cell membrane integrity and lessens free radical-induced oxidant stress.

Association between angiotensin-converting enzyme gene polymorphism and coronary artery disease.

An insertion/deletion (I/D) polymorphism in the gene for angiotensin-converting enzyme (ACE) is associated with myocardial infarction and other cardiac pathology. There is evidence for a role of the renin-angiotensin system in cell growth and in the repair of damaged arterial walls, so the ACE gene is postulated to be a candidate gene affecting the important clinical problem of coronary artery disease (CAD). In view of the clinical importance of the ACE as a major marker of cardiovascular diseases, we investigated the I/D polymorphism of the ACE gene in Turkish CAD patients in comparison with control subjects to evaluate a possible association between CAD and the gene encoding ACE. Polymerase chain reaction, restriction fragment length polymorphism, and agarose gel electrophoresis techniques were used to determine the ACE genotype in 58 subjects. The frequencies of ACE D and ACE I allele among the patients with CAD were 62.26% and 37.73 % and in the control subjects were 49.3% and 50.76%, respectively. The greater frequency of deletion allele (D) was in the CAD group than in the control subjects was significant (P < 0.01).