Browsing by Subject "cardioprotection"

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  • Arola, Olli; Saraste, Antti; Laitio, Ruut; Airaksinen, Juhani; Hynninen, Marja; Bäcklund, Minna; Ylikoski, Emmi; Wennervirta, Johanna; Pietila, Mikko; Roine, Risto O.; Harjola, Veli-Pekka; Niiranen, Jussi; Korpi, Kirsi; Varpula, Marjut; Scheinin, Harry; Maze, Mervyn; Vahlberg, Tero; Laitio, Timo; Xe-HYPOTHECA Study Grp (2017)
    BACKGROUND The authors previously reported that inhaled xenon combined with hypothermia attenuates brain white matter injury in comatose survivors of out-of-hospital cardiac arrest (OHCA). OBJECTIVES A pre-defined secondary objective was to assess the effect of inhaled xenon on myocardial ischemic damage in the same study population. METHODS A total of 110 comatose patients who had experienced OHCA from a cardiac cause were randomized to receive either inhaled xenon (40% end-tidal concentration) combined with hypothermia (33 degrees C) for 24 h (n = 55; xenon group) or hypothermia treatment alone (n = 55; control group). Troponin-T levels were measured at hospital admission, and at 24 h, 48 h, and 72 h post-cardiac arrest. All available cases were analyzed for troponin-T release. RESULTS Troponin-T measurements were available from 54 xenon patients and 54 control patients. The baseline characteristics did not differ significantly between the groups. After adjustments for age, sex, study site, primary coronary percutaneous intervention (PCI), and norepinephrine dose, the mean +/- SD post-arrival incremental change of the ln-transformed troponin-T at 72 h was 0.79 +/- 1.54 in the xenon group and 1.56 +/- 1.38 in the control group (adjusted mean difference -0.66; 95% confidence interval: -1.16 to -0.16; p = 0.01). The effect of xenon on the change in the troponin-T values did not differ in patients with or without PCI or in those with a diagnosis of ST-segment elevation myocardial infarction (group by PCI or ST-segment elevation myocardial infarction interaction effect; p = 0.86 and p = 0.71, respectively). CONCLUSIONS Among comatose survivors of OHCA, in comparison with hypothermia alone, inhaled xenon combined with hypothermia suggested a less severe myocardial injury as demonstrated by the significantly reduced release of troponin-T. (C) 2017 by the American College of Cardiology Foundation.
  • Korpi, Anna (Helsingfors universitet, 2011)
    Heart failure is a complex and severe syndrome caused by different kinds of cardiovascular diseases. Pathophysiology of heart failure involves, for example, activation of sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS), insufficiently contracting left ventricle, cardiac remodeling, myocyte mishandling of Ca2+ and myocyte loss owing to apoptosis. Despite advances in the management of patients with heart failure, the mortality of patients with heart failure remains high. The use of classic inotropic agents is hampered by poor prognosis due to increase in [Ca2+]i, induction of arrhytmias and increase in the myocardial oxygen consumption. Levosimendan is an inotropic agent that has positive inotropic and anti-stunning effects mediated by the calcium sensitization of the contractile proteins and vasodilatory, anti-ischemic and cardioprotective effects mediated by opening of sarcolemmal and mitochondrial KATP channels. Levosimendan also inhibits cardiac PDE3 predominately at higher concentrations. Levosimendan is currently used only as 24-hour infusion to improve symptoms of acute decompensated heart failure. However, other promising indications have also been discovered. For example, chronic use of oral levosimendan improves survival and protects cardiovascular system in vivo. In the present study, the effects of oral levosimendan, valsartan and their combination use on survival, blood pressure and cardiac remodeling were examined in Dahl/Rapp rats on a high salt diet (8 %). Levosimendan improved the survival in Dahl/Rapp rats on a high-salt diet, although not statistically significantly when compared to control group. The drug combination prevented completely salt-induced cardiovascular mortality. The combination therapy also produced a blood pressure-dependent protection against hypertension-induced hypertrophy measured by heart weight-to-body weight ratio (HW/BW) and echocardiographic parameters. Interestingly, the combination use of levosimendan and valsartan had an additive antihypertensive effect in Dahl/Rapp rats. Levosimendan slightly improved systolic function. However, echocardiography revealed increased IVRT in Dahl/Rapp control rats when compared to control group on low salt diet (0,2 %) indicating impaired diastolic relaxation in Dahl/Rapp rats. In the present study, levosimendan, alone and in combination with valsartan, also corrected hypertension-induced diastolic dysfunction.
  • Stark, Christoffer K. -J.; Tarkia, Miikka; Kentala, Rasmus; Malmberg, Markus; Vahasilta, Tommi; Savo, Matti; Hynninen, Ville-Veikko; Helenius, Mikko; Ruohonen, Saku; Jalkanen, Juho; Taimen, Pekka; Alastalo, Tero-Pekka; Saraste, Antti; Knuuti, Juhani; Savunen, Timo; Koskenvuo, Juha (2016)
    The use of cardiopulmonary bypass (CPB) and aortic cross-clamping causes myocardial ischemia-reperfusion injury (I-RI) and can lead to reduced postoperative cardiac function. We investigated whether this injury could be attenuated by thymosin beta 4 (TB4), a peptide which has showed cardioprotective effects. Pigs received either TB4 or vehicle and underwent CPB and aortic cross-clamping for 60 min with cold intermittent blood-cardioplegia and were then followed for 30 h. Myocardial function and blood flow was studied by cardiac magnetic resonance and PET imaging. Tissue and plasma samples were analyzed to determine the amount of cardiomyocyte necrosis and apoptosis as well as pharmacokinetics of the peptide. In vitro studies were performed to assess its influence on blood coagulation and vasomotor tone. Serum levels of the peptide were increased after administration compared to control samples. TB4 did not decrease the amount of cell death. Cardiac function and global myocardial blood flow was similar between the study groups. At high doses a vasoconstrictor effect on mesentery arteries and a vasodilator effect on coronary arteries was observed and blood clot firmness was reduced when tested in the presence of an antiplatelet agent. Despite promising results in previous trials the cardioprotective effect of TB4 was not demonstrated in this model for global myocardial I-RI.