It is widely recognized that mitochondrial dysfunction is a key component of the multifactorial process of ageing. The effects of age on individual components of mitochondrial function vary across species and strains. In this study we investigated the oxygen consumption, the mitochondrial membrane potential (Δψ), the sensitivity of mitochondrial permeability transition pore (mPTP) to calcium overload, and the production of reactive oxygen species (ROS) in heart mitochondria isolated from old compared with adult healthy Sprague-Dawley rats. Respirometry studies and Δψ measurements were performed with an Oxygraph-2k equipped with a tetraphenylphosphonium electrode. ROS production and calcium retention capacity were measured spectrofluorimetrically. Our results show an important decline for all bioenergetic parameters for both complex I and complex II supported-respiration, a decreased Δψ in mitochondria energized with complex I substrates, and an increased mitochondrial ROS production in the old compared with the adult group. Mitochondrial sensitivity to Ca²⁺-induced mPTP opening was also increased in the old compared with the adult animals. Moreover, the protective effect of cyclosporine A on mPTP opening was significantly reduced in the old group. We conclude that healthy ageing is associated with a decrease in heart mitochondria function in Sprague-Dawley rats.
High-resolution respirometry of permeabilized myocardial fibers offers reliable insights concerning the integrated mitochondrial function while using small amounts of cardiac tissue. The aim of the present study was to assess the respiratory function in permeabilized fibers of human right atrial appendages harvested from patients with coronary heart disease (CHD) (n = 6) versus patients with valvular disease (n = 5) and preserved ejection fraction that underwent non-emergency cardiac surgery. Human bundle samples (1-3 mg wet weight) permeabilized with saponin were transferred into the 2 ml Oxygraph-2 k chambers to measure complex I(CI) and II (CII)-dependent respiration, respectively. The following values (expressed in pmol/s mg) were obtained for CI-dependent respiration: oxidative phosphorylation (OXPHOS), 35.65 ± 1.10 versus 42.43 ± 1.08, electron transport system (ETS), 37.87 ± 1.72 versus. 46.58 ± 1.85, and respiratory control ratio (RCR, calculated as the ratio between OXPHOS and LEAK states), 2.43 ± 0.09 versus 2.73 ± 0.068 (p < 0.05). In conclusion, in patients with CHD we showed a significant decline for the OXPHOS capacity, ETS and RCR for mitochondria energized with CI (but not with CII) substrates. These observations are suggestive for an early impairment of complex I supported respiration in ischemic heart disease, as previously demonstrated in the setting of experimental ischemia/reperfusion in several animal species.
Introduction: The COVID-19 Pandemic started in December 2019 in China and it affected millions of people, forcing them to radically change their lifestyle.Aim: Thus, the idea of starting a study that evaluates the effects of the online media transfer on the life routine of PESF-WUT students was outlined, becoming the purpose of the present paper.Material and methods: This study consisted of analyzing a developed questionnaire applied on a study group of 334 students from PESF–WUT, which evaluated 3 aspects of our students’ life: the educational aspect, physical activity and leisure time.Results: The results revealed that COVID-19 Pandemic was a major life changing factor for our students, affecting all aspects of their daily routines. The evaluation of behavior regarding physical activity revealed that this component of our students’ life is of great importance in both the educational and leisure aspects of life.Conclusion: The study revealed that face to face, interpersonal contact has a great impact for both educational performance and the psychological and social aspect, by keeping the level of motivation at high standards. Last but not least, physical activity performed even in unusual conditions, such as Pandemic lockdowns has a great influence on stress management.
Orotic acid and its salts chronically administered have been shown to significantly improve cardiac function in pathological settings associated with ischemia-reperfusion (I/R) injury. The aim of our study was to investigate the effect of magnesium orotate (Mg-Or) administration at the onset of post-ischemic reperfusion on myocardial function and infarct size (IS). Ex-vivo experiments performed on isolated perfused rat hearts were used to compare Mg-Or administration with a control group (buffer treated), ischemic post-conditioning, orotic acid treatment, and MgCl2 treatment. Mg-Or administration was also investigated in an in-vivo model of regional I/R performed in rats undergoing reversible coronary ligation. The effect of Mg-Or on mitochondrial permeability transition pore (mPTP) opening after I/R was investigated in vitro to gain mechanistic insights. Both ex-vivo and in-vivo experiments showed a beneficial effect from Mg-Or administration at the onset of reperfusion on myocardial function and IS. In-vitro assays showed that Mg-Or significantly delayed mPTP opening after I/R. Our data suggest that Mg-Or administered at the very onset of reperfusion may preserve myocardial function and reduce IS. This beneficial effect may be related to a significant reduction of mPTP opening, a usual trigger of cardiac cell death following I/R.
Monoamine oxidases (MAOs) have recently emerged as important mitochondrial sources of oxidative stress in the cardiovascular system. Generation of reactive oxygen species during the brief episodes of ischemic preconditioning (IPC) is responsible for the cardioprotection at reperfusion. The aim of this study was to assess the effects of two MAO inhibitors (clorgyline and pargyline) on the IPC-related protection in isolated rat hearts. Animals subjected to 30 min global ischemia and 120 min reperfusion were assigned to the following groups: (i) Control, no additional intervention; (ii) IPC, 3 cycles of 5 min ischemia and 5 min reperfusion before the index ischemia; (iii) IPC-clorgyline, IPC protocol bracketed for 5 min with clorgyline (50 μmol/L); (iv) IPC-pargyline, IPC protocol bracketed for 5 min with pargyline (0.5 mmol/L). The postischemic functional recovery was assessed by the left ventricular developed pressure (LVDP) and the indices of contractility (+dLVP/dt max) and relaxation (-dLVP/dt max). Infarct size (IS) was quantified by TTC staining. In both genders, IPC significantly improved functional recovery that was further enhanced in the presence of either clorgyline or pargyline. IS reduction was comparable among all the preconditioned groups, regardless of the presence of MAO inhibitors. In isolated rat hearts, acute inhibition of MAOs potentiates the IPC-induced postischemic functional recovery without interfering with the anti-necrotic protection.
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