ABSTRACT
BACKGROUND: Patients having coronary artery disease treated by coronary bypass or PCI procedure are exposed to tissue damage because of the phenomenon called reperfusion injury. Reperfusion injury can be characterized/monitored by oxidative stress parameters, inflammatory markers and by post-operative complication rate. OBJECTIVE: Beyond the obvious factors determining its severity (affected myocardial mass, ischaemic time, collateral circulation etc.) we examined the GST enzyme group's most cardio selective member, GSTP1 and its genetic polymorphism if there is any genetically determined preventive effect on the above-mentioned parameters. MATERIALS AND METHODES: We have performed randomized prospective study in the Heart Institute of Pecs with 862 patients, treated by coronary bypass or PCI procedure. Blood samples were taken a day before, one hour, one day, one week after the operation. Leucocyte count (WBC), myeloperoxidase (MPO), thiol group (SH); Superoxide dismutase (SOD), malondialdehyde (MDA), reduced Glutathione (GSH) level was checked in different periods of time as a comparison. The onset of myocardial damage and the corresponding necro enzyme level changes were registered in the perioperative period. Our patient's GSTP1 allele pair combinations (A, B, or C) were determined by real time PCR method. RESULTS: In patients with GSTP1 AA genotype we have found significance level reaching plasma concentration rise in SOD and MDA, and drop in GSH, SH. The CKMB concentration rise in the post-operative 24 hours was significantly higher in the GSTP1 AA group. CONCLUSIONS: According to our results the AA allele combination can be considered as a risk factor. GSTP1-AA allele pair has negative effect on ischemia-reperfusion tolerance of the heart. In case of cardiovascular interventions, the study of GST enzyme polymorphisms can be an independent risk stratification factor in determining the perioperative risk in the future.
Subject(s)
Coronary Artery Bypass/adverse effects , Organic Anion Transporters/genetics , Oxidative Stress/physiology , Percutaneous Coronary Intervention/adverse effects , Polymorphism, Genetic/genetics , Reperfusion Injury/blood , Reperfusion/methods , Female , Humans , Male , Middle Aged , Prospective StudiesABSTRACT
AIMS: We studied the new anti-inflammatory effects of non-specific phosphodiesterase (PDE) inhibitor pentoxifylline (PTX) on ischaemia-reperfusion injury and postconditioning of the lower extremities. We aimed to examine the oxidative stress parameters (OSP), the inflammatory response and the changes in structure of skeletal muscle after revascularization surgery. METHODS: 50 Wistar rats in five groups underwent a 60âmin infrarenal aortic cross clamping. After the ischaemia in IR+PC group ischemic postconditioning was performed, intermittent 15 seconds reperfusion, 15 seconds ischaemic periods were applied four times. The ischemic phase was followed by a 120âmin of reperfusion. In IR+PTX group the animals were treated with PTX. In IR+PC+PTX group both ischemic postconditioning and PTX treatment were performed. Blood samples and biopsy from quadriceps muscle were collected. Plasma malondialdehyde, reduced glutathione, -SH-groups, TNF-alpha, IL-6 concentrations and superoxide dismutase enzyme activity were measured. RESULTS: The levels of OSP and the inflammatory proteins were significantly higher in the IR group. PTX treatment and PC could significantly decrease the levels of OSP and inflammatory proteins. When the animals were co-treated with PTX and PC the results were even better. CONCLUSIONS: Inhibition of PDE by PTX could markedly decrease the inflammatory response and moderate the ischaemia-reperfusion damages after lower limb ischemia and reperfusion. Administration of PTX could potentiate the beneficial effects of PC.
Subject(s)
Aorta, Abdominal/pathology , Aortic Aneurysm, Abdominal/drug therapy , Ischemia/pathology , Pentoxifylline/pharmacology , Reperfusion Injury/metabolism , Animals , Male , Rats , Rats, Wistar , ReperfusionABSTRACT
Acute kidney injury (AKI) remains an independent risk factor for mortality and morbidity after vascular surgery (affecting the renal arteries) or aortic surgery (requiring suprarenal aortic clamping). These types of vascular surgery produce renal ischemia/reperfusion (I/R) injury, a common cause of AKI. The present studies aimed at monitoring the course of renal I/R injury at the cellular level and investigating the efficacy of long-term preoperative and single-shot intraoperative administration of sodium pentosan polysulfate (PPS) to protect renal tissue from acute I/R injury both in native and diabetic kidneys in rats. Western blot analyses of the proapoptotic (bax) and antiapoptotic (bcl-2) signaling pathways, as well as the extent of DNA damage (phospho-p53), were performed. Oxidative stress followed upon the termination of malondialdehyde, reduced glutathione, thiol group, and superoxide dismutase plasma levels. Inflammatory changes were measured by the determination of serum tumor necrosis factor-α and interleukin-1 levels. Morphological changes were detected by histological examinations. Our results showed that the long-term administration of PPS has an advantage in reducing I/R kidney injury in diabetic rats, while high-dose, single-shot parenteral administration of PPS prior to revascularization might be useful in nondiabetic rats.
Subject(s)
Acute Kidney Injury/prevention & control , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Inflammation Mediators/blood , Kidney/drug effects , Oxidative Stress/drug effects , Pentosan Sulfuric Polyester/pharmacology , Reperfusion Injury/prevention & control , Acute Kidney Injury/etiology , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Animals , Apoptosis Regulatory Proteins/metabolism , Biomarkers/blood , DNA Damage , Diabetes Mellitus, Experimental , Interleukin-1/blood , Kidney/metabolism , Kidney/pathology , Lipid Peroxidation/drug effects , Male , Rats, Wistar , Reperfusion Injury/etiology , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Tumor Necrosis Factor-alpha/bloodABSTRACT
AIMS: We studied the effects of the inhibition of the endogene antioxidant glutathione-S-transferase (GST) by ethacrynic acid (EA) on ischemia-reperfusion (IR) injury and postconditioning (PC) in the lower extremities. We aimed to examine the oxidative stress parameters (OSP), inflammatory response and activation of proapoptotic signaling proteins (PSP) after revascularization surgery. METHODS: Sixty Wistar rats were divided into 6 groups: control, IR, PC, EA-control, IR and administration of EA (IR/EA) and PC and administration of EA (PC/EA). The IR, PC, IR/EA and PC/EA groups underwent 60 min of infrarenal aortic cross-clamping. After that, PC was performed in the PC and PC/EA groups. In 3 of the groups, the animals were treated with EA (EA-control, IR/EA and PC/EA groups) as well. The ischemia was followed by 120 min of reperfusion. Blood samples and biopsy specimens were collected from the quadriceps muscle. Plasma malondialdehyde, reduced glutathione, thiol/sulfhydryl group levels, TNF-α and IL-6 concentrations and superoxide-dismutase enzyme activity were measured. RESULTS: The levels of the OSP and the inflammatory proteins were higher in the EA-administered groups. The ratio of phosphorylated PSP was higher in the EA-administered groups and the protective effect of PC did not develop. CONCLUSIONS: Inhibition of GST by EA augmented the IR damage. GST inhibition was associated with a different activation of the mitogen-activated protein kinases and the PSP, regulating these pathways in the process of apoptosis and PC.
Subject(s)
Ethacrynic Acid/toxicity , Glutathione Transferase/antagonists & inhibitors , Hindlimb/blood supply , Ischemic Postconditioning , Postoperative Complications/pathology , Reperfusion Injury/pathology , Acute Disease , Animals , Apoptosis/drug effects , Glutathione/blood , Glutathione Transferase/physiology , Inflammation , Interleukin-6/blood , Male , Malondialdehyde/blood , Oxidation-Reduction , Oxidative Stress/drug effects , Postoperative Complications/enzymology , Quadriceps Muscle/blood supply , Quadriceps Muscle/pathology , Rats , Rats, Wistar , Reperfusion Injury/enzymology , Signal Transduction/drug effects , Sulfhydryl Compounds/blood , Superoxide Dismutase/blood , Tumor Necrosis Factor-alpha/analysisABSTRACT
One of the rare reasons of the non malignant superior vena cava syndrome is the thrombosis of superior vena cava. Obstruction or occlusion of central veins is one of the many complications of the more and more frequently used central venous catheters and pacemaker electrodes. The authors report a case of superior vena cava thrombosis resulting in dialysis catheter insufficiency in case of a young, uraemic, female patient wit Tesio catheter and the surgical treatment of it with the use of cardiopulmonary bypass during the operation. Apropos of this case, the authors outline the causes of malignant, non-malignant and iatrogenic superior vena cava syndrome, furthermore the conservative, surgical and catheter therapy of the syndrome.