Bakteriális lipopoliszachariddal kiváltott késői kardioprotekció az iszkémia/reperfúziós károsodással szemben = Late cardioprotection against ischemia-reperfusion injury induced by bacterial lipopolysaccharides

Hazánkban és a civilizált társadalmakban egyaránt, az iszkémiás szívbetegség az egyik leggyakoribb halálokok közé tartozik. A szivizom endogén adaptációs mechanizmusainak támogatása, illetve vizsgálata ezért nagy jelentőségű. Kísérleteink bizonyítják, hogy ez a mechanizmus emberben is hatásos védelmet jelent. Kimutattuk továbbá, hogy a farmakológiai prekondícionálás hatékonyan véd az iszkémiás károsodás ellen. A kis dózisú (0,5 mg/kg) bakteriális lipopoliszachariddal (LPS) előkezelt patkányok szíve 24 órával a kezelés után fokozottabb mértékben áll ellen az iszkémiát követő szívfunkciós károsodásnak. A 24 órás LPS előkezelés megnövelte a szívizom nitrogén-monoxid tartalmát az indukálható nitrogén oxid szintáz fokozott aktivitása révén. A LPS előkezelés hatására szignifikánsan emelkedett a szívizom szuperoxid termelése is a fokozott xantin oxidoreduktáz aktivitás miatt. A szérum nitrotirozin szintje ugyancsak emelkedett az LPS előkezelés hatására, jelezvén a NO és szuperoxid anion reakciója révén képződő peroxinitrit fokozott képződését a szervezetben. A LPS előkezelés növelte a miokardiális cGMP tartalmat is. Eredményeink szerint az oxidatív és nitrozatív stressz, valamint az NO-cGMP szignalizációs út fontos szerepet játszhat a szívizom farmakológiai prekondícionálásában. | Ischemic heart disease is one of the most frequent cause of death in the civilized societies, therefore investigation of cardioprotective mechanisms to prevent ischemic damage is essential. We have shown that this protective mechanism is effective in humans. We have also shown that pharmacological preconditioning effectively protects against ischemia/reperfuson injury. 24h pretreatment of rats with bacterial polysaccharides (LPS) has resulted in a protection against ischemia-induced deterioration of cardiac function. A 24h LPS pretreatment increased cardiac nitric oxide content via the induction of the inducible isoform of nitric oxide synthase. LPS pretreatment also increased cardiac superoxide production via an increase in the activity of xanthin oxidoreductase. LPS increased serum nitrotyrosine levels showing increased formation of peroxynitrite from NO and superoxide. In addition, LPS pretreatment increased myocardial cGMP level. Our results suggest, that both oxidative and nitrosative stress play an important role in pharmacological preconditioning of the heart

The effect of electrical stimulation of skeletal muscle on cardioprotection and on muscle-derived myokine levels in rats: A pilot study

Electrical muscle stimulation (EMS) is a widely used method in sports and rehabilitation therapies to simulate physical exercise. EMS treatment via skeletal muscle activity improves the cardiovascular functions and the overall physical condition of the patients. However, the cardioprotective effect of EMS has not been proven so far, therefore, the aim of this study was to investigate the potential cardiac conditioning effect of EMS in an animal model. Low-frequency 35-min EMS was applied to the gastrocnemius muscle of male Wistar rats for three consecutive days. Their isolated hearts were then subjected to 30 min global ischemia and 120 min reperfusion. At the end of reperfusion cardiac specific creatine kinase (CK-MB) and lactate dehydrogenase (LDH) enzyme release and myocardial infarct size were determined. Additionally, skeletal muscle-driven myokine expression and release were also assessed. Phosphorylation of cardioprotective signaling pathway members AKT, ERK1/2, and STAT3 proteins were also measured. EMS significantly attenuated cardiac LDH and CK-MB enzyme activities in the coronary effluents at the end of the ex vivo reperfusion. EMS treatment considerably altered the myokine content of the stimulated gastrocnemius muscle without altering circulating myokine levels in the serum. Additionally, phosphorylation of cardiac AKT, ERK1/2, and STAT3 was not significantly different in the two groups. Despite the lack of significant infarct size reduction, the EMS treatment seems to influence the course of cellular damage due to ischemia/reperfusion and favorably modifies skeletal muscle myokine expressions. Our results suggest that EMS may have a protective effect on the myocardium, however, further optimization is required

Effects of Cardiovascular Risk Factors on Cardiac STAT3

Nuclear, mitochondrial and cytoplasmic signal transducer and activator of transcription 3 (STAT3) regulates many cellular processes, e.g., the transcription or opening of mitochondrial permeability transition pore, and its activity depends on the phosphorylation of Tyr705 and/or Ser727 sites. In the heterogeneous network of cardiac cells, STAT3 promotes cardiac muscle differentiation, vascular element formation and extracellular matrix homeostasis. Overwhelming evidence suggests that STAT3 is beneficial for the heart, plays a role in the prevention of age-related and postpartum heart failure, protects the heart against cardiotoxic doxorubicin or ischaemia/reperfusion injury, and is involved in many cardioprotective strategies (e.g., ischaemic preconditioning, perconditioning, postconditioning, remote or pharmacological conditioning). Ischaemic heart disease is still the leading cause of death worldwide, and many cardiovascular risk factors contribute to the development of the disease. This review focuses on the effects of various cardiovascular risk factors (diabetes, aging, obesity, smoking, alcohol, depression, gender, comedications) on cardiac STAT3 under non-ischaemic baseline conditions, and in settings of ischaemia/reperfusion injury with or without cardioprotective strategies