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OBJECTIVES: This study aims to investigate the acute effects of thymoquinone (TQ) which has been suggested to be a cardioprotective agent, on ventricular myocytes. METHODS: Freshly isolated rat ventricular myocytes were exposed to TQ and using standard whole-cell patch-clamp technique action potential (AP), sodium current (INa), L-type calcium current (ICaL) and transient outward potassium current (Ito) were measured. RESULTS: TQ prolonged the duration of AP and decreased the peak value compared to that of control myocytes. Consistently, it inhibited INa in a concentration-dependent manner and shifted the channel kinetics to more hyperpolarized voltages. Besides, TQ not only inhibited Ito and ICaL but also significantly attenuated the isoproterenol-induced increase in ICaL. CONCLUSION: The effect of TQ on cardiomyocytes has been demonstrated for the first time. TQ changes AP morphology along with ionic currents and alleviates ß-adrenergic response in adult ventricular myocytes. These results indicate that TQ may be considered as a therapeutic agent in cases such as diabetic cardiomyopathy and cardiac hypertrophy, wherein the ß-adrenergic system is over-activated. [ABSTRACT FROM AUTHOR]

Background: The purpose of the retrospective study was to identify the impacts of different solutions on the electrocardiogram and cardiovascular changes. Moreover, the differences between these solutions were analyzed by examining their impacts on rat ventricular cardiomyocytes. Methods: Eighty renal transplant patients were evaluated retrospectively. The patients were divided into two groups: Group UW (n =40) used the University of Wisconsin solution, and Group HTK (n =40) used the Histidine-Tryptophan-Ketoglutarate solution. Electrocardiograms of the subjects were obtained three times at different periods; during the preperfusion, intraoperative kidney reperfusion, and postperfusion phase at the end of the surgery. Any Electrocardiogram or cardiovascular alterations were noted and analyzed. Adult male Wistar rats were used for in vitro experiments. Myocyte contractility, action potentials, and membrane current were recorded in enzymatically isolated ventricular myocytes. Results: Sinus bradycardia was detected in 19 patients of Group UW, while there was short-term asystole in eight patients. However, no cardiac changes were observed in Group HTK patients. In both Groups, reperfusion and postperfusion corrected QT (QTc) intervals were different from pre-perfusion QTc intervals. Group UW patients' reperfusion and postperfusion QTc's values were higher than those of the Group HTK patients. In rat myocytes, prominent asystole episodes were observed at specific concentrations of the UW solution compared to the HTK solution. The UW solution depolarized the resting membrane potential significantly and decreased the peak value of action potential, whereas the HTK solution did not elicit a significant change in those parameters. Accordingly, the UW solution elicited a significant inward current at -70 mV, while the HTK solution activated only a modest current, which may not change the membrane potential. Conclusion: Prolongation of QTc intervals was detected with reperfusion in both groups according to electrocardiography analysis. However, the QTc interval was observed to be longer in cases using the UW solution and required intervention intraoperatively. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate whether ellagic acid (EA) treatment can prevent changes in contractile function and Ca 2+ regulation of cardiomyocytes in pathologic cardiac hypertrophy. Groups were assigned as Con group; an ISO group in which the rats received isoproterenol alone (5 mg/kg/day); and an ISO + EA group in which the rats received isoproterenol and EA (20 mg/kg/day) for 4 weeks. Subsequently, fractional shortening, intracellular Ca 2+ signals, and L-type Ca 2+ currents of isolated ventricular myocytes were recorded. Protein expression levels were also determined by the Western blotting method. The survival rate was increased, and the upregulated cardiac hypertrophy markers were significantly attenuated with the EA treatment. The fractional shortening and relaxation rate of myocytes was decreased in the ISO group, whereas EA significantly improved these changes. Ventricular myocytes of the ISO + EA rats displayed lower diastolic Ca 2+ levels, higher Ca 2+ transients, shorter Ca 2+ decay, and higher L-type Ca 2+ currents than those of ISO rats. Protein expression analyses indicated that the upregulated p-PLB and p-CaMKII expressions were restored by EA treatment, suggesting improved calcium handling in the ISO + EA rat heart. Moreover, ISO rats displayed significantly increased expression of p-22 phox and p47 phox subunits of NOX2 protein. Expression of the p22 phox subunit was reduced with EA administration, while the decrease in p47 phox did not reach a significant level. The increased ROS impairs Ca 2+ homeostasis and contractile activity of cardiac myocytes, whereas chronic EA administration prevents Ca 2+ dysregulation and functional abnormalities associated with pathological cardiac hypertrophy via the diminution of oxidative stress.

Enhancement of the late Na + current (I NaL ) increases arrhythmia propensity in the heart, while suppression of the current is antiarrhythmic. GS967 is an agent considered as a selective blocker of I NaL . In the present study, effects of GS967 on I NaL and action potential (AP) morphology were studied in canine ventricular myocytes by using conventional voltage clamp, action potential voltage clamp and sharp microelectrode techniques. The effects of GS967 (1 µM) were compared to those of the class I/B antiarrhythmic compound mexiletine (40 µM). Under conventional voltage clamp conditions, I NaL was significantly suppressed by GS967 and mexiletine, causing 80.4 ± 2.2% and 59.1 ± 1.8% reduction of the densities of I NaL measured at 50 ms of depolarization, and 79.0 ± 3.1% and 63.3 ± 2.7% reduction of the corresponding current integrals, respectively. Both drugs shifted the voltage dependence of the steady-state inactivation curve of I NaL towards negative potentials. GS967 and mexiletine dissected inward I NaL profiles under AP voltage clamp conditions having densities, measured at 50% of AP duration (APD), of -0.37 ± 0.07 and -0.28 ± 0.03 A/F, and current integrals of -56.7 ± 9.1 and -46.6 ± 5.5 mC/F, respectively. Drug effects on peak Na + current (I NaP ) were assessed by recording the maximum velocity of AP upstroke (V + max ) in multicellular preparations. The offset time constant was threefold faster for GS967 than mexiletine (110 ms versus 289 ms), while the onset of the rate-dependent block was slower in the case of GS967. Effects on beat-to-beat variability of APD was studied in isolated myocytes. Beat-to-beat variability was significantly decreased by both GS967 and mexiletine (reduction of 42.1 ± 6.5% and 24.6 ± 12.8%, respectively) while their shortening effect on APD was comparable. It is concluded that the electrophysiological effects of GS967 are similar to those of mexiletine, but with somewhat faster offset kinetics of V + max block. However, since GS967 depressed V + max and I NaL at the same concentration, the current view that GS967 represents a new class of drugs that selectively block I NaL has to be questioned and it is suggested that GS967 should be classified as a class I/B antiarrhythmic agent.

Rosuvastatin is one of the most used statins to lower plasma cholesterol levels. Although previous studies have reported remarkable cardiovascular effects of rosuvastatin (RSV), the mechanisms of these effects are largely unknown. In this study, we investigated the acute effects of RSV on L-type Ca 2+ currents and contractile function of ventricular myocytes under basal conditions and during β-adrenergic stimulation. The effects of RSV were investigated in freshly isolated adult rat ventricular myocytes. L-type Ca +2 currents and myocyte contractility were recorded using patch-clamp amplifier and sarcomere length detection system. All experimental recordings were performed at 36 ± 1 °C. L-type Ca +2 currents were significantly reduced with the administration of 1 μM RSV (~ 24%) and this reduction in Ca 2+ currents was observed at almost all potential ranges applied. Suppression of L-type Ca 2+ current by RSV was prevented by adenylyl cyclase (AC) and protein kinase A (PKA) inhibitors SQ 22536 and KT5720, respectively. However, inhibition of Rho-associated kinases (ROCKs) by Y-27632 or nitric oxide synthase (NOS) by L-NAME failed to circumvent the inhibitory effect of RSV. Finally, we examined the effect of RSV during β-adrenergic receptor stimulation by isoproterenol and observed that RSV significantly suppresses the β-adrenergic responses in both L-type Ca 2+ currents and contraction parameters. In conclusion, RSV modulates the β-adrenergic signaling cascade and thereby mimics the impact of β-adrenergic receptor blockers in adult ventricular myocytes through modulation of the AC-cAMP-PKA pathway.

Background: The purpose of the retrospective study was to identify the impacts of different solutions on the electrocardiogram and cardiovascular changes. Moreover, the differences between these solutions were analyzed by examining their impacts on rat ventricular cardiomyocytes., Methods: Eighty renal transplant patients were evaluated retrospectively. The patients were divided into two groups: Group UW (n =40) used the University of Wisconsin solution, and Group HTK (n =40) used the Histidine-Tryptophan-Ketoglutarate solution. Electrocardiograms of the subjects were obtained three times at different periods; during the pre-perfusion, intraoperative kidney reperfusion, and postperfusion phase at the end of the surgery. Any Electrocardiogram or cardiovascular alterations were noted and analyzed. Adult male Wistar rats were used for in vitro experiments. Myocyte contractility, action potentials, and membrane current were recorded in enzymatically isolated ventricular myocytes., Results: Sinus bradycardia was detected in 19 patients of Group UW, while there was short-term asystole in eight patients. However, no cardiac changes were observed in Group HTK patients. In both Groups, reperfusion and postperfusion corrected QT (QTc) intervals were different from pre-perfusion QTc intervals. Group UW patients' reperfusion and postperfusion QTc's values were higher than those of the Group HTK patients. In rat myocytes, prominent asystole episodes were observed at specific concentrations of the UW solution compared to the HTK solution. The UW solution depolarized the resting membrane potential significantly and decreased the peak value of action potential, whereas the HTK solution did not elicit a significant change in those parameters. Accordingly, the UW solution elicited a significant inward current at -70 mV, while the HTK solution activated only a modest current, which may not change the membrane potential., Conclusion: Prolongation of QTc intervals was detected with reperfusion in both groups according to electrocardiography analysis. However, the QTc interval was observed to be longer in cases using the UW solution and required intervention intraoperatively. HIPPOKRATIA 2021, 25 (1):22-30., Competing Interests: Authors declare no commercial associations, contractual relations, or proprietary considerations that might pose a conflict of interest related or unrelated to the submitted manuscript. Authors have had no involvements that might raise the question of bias in work reported or in the conclusions, implications, or opinions stated., (Copyright 2021, Hippokratio General Hospital of Thessaloniki.)

Background: Celiac disease (CD), a serious autoimmune disorder that occurs in people who are genetically predisposed, is induced by dietary gluten intake and affects primarily the small intestine. Many studies have identified an increased risk of cardiovascular problems in patients with CD. Moreover, these patients are susceptible to certain liver diseases, as well as fibrosis., Objective: The aim of this study was to assess the presence of fibrosis using the De Ritis ratio, determining its effect on the electromechanical features of the left atrium and its susceptibility to atrial fibrillation (AF) in patients with CD., Methods: A total of 97 patients diagnosed with CD by antibody test and biopsy were included in this prospective study. Two groups were created from these patients, a fibrosis-prone (FP) group and a non-fibrosis-prone (NFP) group, according to the cut-off value, as defined in previously published reports, for the AST/ALT ratio. Electrocardiographic and echocardiographic examinations were performed as part of the study., Results: There were no differences in the baseline characteristics and conventional echocardiographic parameters of the defined groups. However, the patients in the FP group, as compared to those in the NFP group, had significantly increased PWD (56.68±6.48 ms vs. 37.49±6.22 ms, P<0.001). Additionally, significantly higher interatrial (60.50±13.05 ms vs. 29.40±11.55 ms, P<0.001), intra-left atrial (44.18±14.12 ms vs. 21.02±11.99 ms, P<0.001), and intra-right atrial (15.61±8.91 ms vs. 8.38±4.50 ms, P<0.001) EMD was found among the patients in the FP group compared to that of the NFP group., Conclusion: It is believed that the susceptibility to AF cited in previous studies may be related to fibrosis. Our study is the first to examine the possible effects of fibrosis on AF susceptibility in patients with CD, whereby we propose a new biomarker for prediction of AF susceptibility of these patients.

Many antineoplastic drugs are known to be carcinogenic, teratogenic and mutagenic to humans. There is thus a potential risk due to occupational exposure to cytotoxic drugs (CDs). Nurses and pharmacists are the main groups that are exposed to these drugs in the ambulatory care and hospital settings. An analytic cross sectional study was here carried out in order to evaluate the level of knowledge of nurses on the health effects and the routes of exposure to CDs, to clarify the protective measures while handling these agents and to determine the influence of this knowledge on clinical attitudes, behaviour and actual usage of safety measures. The level of knowledge of the nurses concerning antineoplastics was not satisfactory. Findings for nurses' safety behaviour and usage of recommended health safety measures showed that, notwithstanding the rules and regulations pertaining to CDs, nurses did not comply with them fully. In service training is a very effective tool to increase the level of knowledge. This study also revealed the necessity for improvement of the working environment and the availability of appropriate protective equipment.