Remote Ischemic Preconditioning of the Heart: Protective Responses in Functional and Biophysical Properties of Cardiac Mitochondria

Abstract

Remote ischemic preconditioning (RIP)-induced protection of myocardial energetics was well documented on the level of tissue, but data concerning the involvement of mitochondria were missing. We aimed at the identification of changes in membrane properties and respiratory functions induced in rat heart mitochondria by RIP. Experiments were performed on 46 male Wistar rats divided into control and RIP-treated groups of 21 animals each. Blood flow in the occluded area was recorded by MRI angiography in four animals. RIP protocol comprised of three successive 5-min occlusions each followed by 5-min reperfusions of descending branches of the right hind limb femoral artery. The efficacy of RIP was evaluated as the extent of RIP-induced protection against damage to the functions of mitochondria isolated by differential centrifugation after 30-min global ischemia followed by 40-min reperfusion of the hearts in Langendorff mode. Assessments: mitochondrial membrane fluidity with a fluorescent probe DPH, CoQ9 and CoQ10 with HPLC, mitochondrial respiration with the Oxygraph-2k (Oroboros). Results revealed that RIP was affecting the mitochondria. The immediate protection conferred by RIP involves beneficial and prognostically significant effects: a total elimination of ischemia/reperfusion-induced depression of mitochondrial membrane fluidity and a trend for better preservation of mitochondrial state 3 respiration.

Cardioprotection Induced by Remote Ischemic Preconditioning Preserves the Mitochondrial Respiratory Function in Acute Diabetic Myocardium

“…Likely an increase in membrane fluidity can actually help ease the rotary-catalysis movement and thus increase the ATP synthase activity, which is supported by finding a positive association between both characteristics (Patel and Katyare 2006). A similar effect has been observed in our previous work demonstrated the beneficial protective effect of RPC on the heart mitochondria causing an elimination of I/R-induced massive depression of mitochondrial membrane fluidity (Ferko et al 2014).…”

“…Several studies have investigated various effect of IPC in the context of the inhibition of mitochondrial respiratory chain in the presence of NADH-linked substrates (da Silva et al 2003), the increase of basal state of mitochondrial respiration (Liem et al 2008) and the improving of mitochondrial state 3 respiration during reperfusion (Crestanello et al 2002). Although the most of physiological parameters, including myocardial infarct size, were reported to be ameliorated after application of RPC (Ferko et al 2015, Zhu et al 2013, we did not observe improvement in mitochondrial respiratory function corresponding to the earlier study (Ferko et al 2014). However, data from absorption spectrophotometry suggest that RPC prevented the decrease of ATP synthase activity after ischemia-reperfusion and that this contributed to the preservation of mitochondrial function following I/R injury.…”

“…However, despite these positive findings, the actual role of mitochondrial bioenergetics in the myocardial protection conveyed by RPC and DM is still elusive. There is some evidence that the immediate protection by RPC might involve a preservation of mitochondrial state 3 respiration (Ferko et al 2014) and, at the combined intervention of RPC and DM, the preservation of mitochondrial function is associated with an increase in the mitochondrial membrane fluidity (Ferko et al 2015). Perhaps, the most prompting experimental task is to elucidate the nature of the model interaction that would result in the protective effect on the myocardiumwhether it is additive, synergistic or antagonistic.…”

The impact of sugar-sweetened beverage intake on rat cardiac function

“…Measurement of mitochondrial respiration was performed with a polarographic oxygen sensor in 2 mL glass chambers of an Oxygraph 2K (Oroboros Instruments, Innsbruck, Austria) as described before [21] . All substrates and chemicals were purchased from Sigma-Aldrich (St. Louis MO).…”

Adenosine A1receptors and mitochondria: targets of remote ischemic preconditioning

“…Because of this, mitochondria are viewed as end effectors of ischemic preconditioning (49), and the preservation of mitochondrial function after I/R is a key event that might determine the survival of cardiomyocytes (19,22,23,28). In rats, the myocardial infarct size reduction by rIPC was associated with preserved mitochondrial morphology (6,18) and retained mitochondrial membrane potential and increased mitochondrial manganese superoxide dismutase activity (5,26). Furthermore, reactive oxygen species (ROS) at high levels do play an adverse role in myocardial I/R injury but contribute to endogenous cardioprotection at lower concentrations (7).…”