No abstract

In the present study we explored glutathione S-transferase (GST) polymorphisms in selected patients who experienced accelerated myocardial injury following open heart surgery and compared these to a control group of patients without postoperative complications. 758 Patients were enrolled from which 132 patients were selected to genotype analysis according to exclusion criteria. Patients were divided into the following groups: Group I: control patients (n = 78) without and Group II.: study patients (n = 54) with evidence of perioperative myocardial infarction. Genotyping for GSTP1 A (Ile105Ile/Ala113Ala), B (Ile105Val/Ala113Ala) and C (Ile105Val/Ala113Val) alleles was performed by using real-time-PCR. The heterozygous AC allele was nearly three times elevated (18.5 vs. 7.7 %) in the patients who suffered postoperative myocardial infarction compared to controls. Contrary, we found allele frequency of 14.1 % for homozygous BB allele in the control group whereas no such allele combination was present in the study group. These preliminary results may suggest the protective role for the B and C alleles during myocardial oxidative stress whereas the A allele may represent predisposing risk for cellular injury in patients undergoing cardiac surgery.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a widely distributed endogenous neuropeptide, also occurring in the cardiovascular system. Among others, PACAP has been suggested as a cardioprotective factor. It has been shown that PACAP inhibits cardiac fibrosis and protects cardiomyocytes against oxidative stress and in vitro ischemia/reperfusion. The aim of the present study was to investigate whether PACAP is protective in doxorubicin-induced cell death of cardiomyocytes. Cardiomyocytes were exposed to 1 µM doxorubicin for 24 h, which resulted in a marked reduction of cell viability and a parallel increase of apoptotic cells assessed by MTT test and annexin V/propidium iodide flow cytometry assay. Co-incubation with 20 nM PACAP increased cell viability and reduced the percentage of apoptotic cells. Furthermore, doxorubicin increased the activation of caspase-3 and decreased the phosphorylation of Bad, while simultaneous PACAP treatment reduced the caspase-3 activation and increased the level of phospho-Bad. In summary, our present results demonstrate that PACAP effectively protects cardiomyocytes against doxorubicin-induced apoptotic cell death.

Objective: We studied the protective effects of postconditioning (PS) in healthy and hypercholesterolemic rats after renal ischaemia-reperfusion (IR) injury. We aimed to examine cytokine expression and apoptosis in tissue damage after revascularisation (TNF-␣ levels in serum and tissue).Methods: Male Wistar rats (n = 32) were divided into four groups. The animals of normal feed groups (NF) were fed with normal rat chow and the cholesterol feed groups (CF) were fed with 1.5% cholesterol containing diet for 8 weeks. Anaesthetized rats underwent a 45-min cross-clamping in both kidney pedicles. Ischaemia was followed by 120-min reperfusion with or without PS protocol (group PS vs. IR). Postconditioning was induced by four intermittent periods of ischaemia-reperfusion of 15-s duration each. Serum cholesterol, triglyceride, urea and creatinine levels were determined. Proinflammation was characterized by the measurement of serum TNF-␣. Tissue injury in kidney was determined by formaline-fixed, paraffin-embedded tissue sections. Tissue TNF-␣ levels were determined by immunohistochemistry.Results: Significant elevation was observed in serum TNF-␣ level after IR injury in normal feed groups, which was reduced by PS. In CF group neither the elevation nor the postconditioning induced reduction were as significant as in the NF groups. In normal feed group PS caused a significant reduction in tissue TNF-␣ level which was significantly higher in CF.Conclusions: Ischaemic postconditioning proved to be an effective defense against IR in NF groups, but it was ineffective in CF groups in kidney tissue.

Increased intra-abdominal pressure during laparoscopy leads to hypoxia due to reduced blood flow. Aim of our study was to investigate whether preconditioning can reduce this negative effect of the pneumoperitoneum. Fifty female Wistar rats were used, divided into 5 groups. I: Sham operation (Sham), II: conventional pneumoperitoneum (PP), III: transvaginal pneumoperitoneum (TV), IV: preconditioning for 2.5 minutes in two cycles (Pre 2.5), V: preconditioning for 5 minutes (Pre 5). Malondialdehyde (MDA), reduced glutathione (GSH), sulfhydrylgroup (SH-) concentrations, superoxide-dismutase (SOD) and mieloperoxidase (MPO) activity, and anti-apoptotic pathway marker p-AKT level and inflammatory cytokine TNF-α were measured. SOD activity and GSH concentration were decreased in PP and TV groups comparing to Sham and preconditioning groups. MPO activity was decreased also in PP and TV groups comparing to the Sham group but in the preconditioning groups it has remained high. MDA concentration in plasma was increased in PP and TV groups comparing to Sham and preconditioning groups. There was no difference in the case of blood MDA and SH-concentrations between groups. Anti-apoptotic pathway marker p-AKT level was decreased in the TV group comparing to the sham and preconditioning groups. TNF-α level was increased in TV and preconditioning groups compared to the sham group. According to the results preconditioning can reduce negative effects of pneumoperitoneum.