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Background: Aging, as a recognized risk factor for ischemic heart disease, interferes with protective mechanisms and abolishes the optimal effectiveness of cardioprotective interventions, leading to the loss of cardioprotection following myocardial ischemia/reperfusion (I/R) injury. This study was designed to explore the possible interaction of aging with cardioprotection induced by combination therapy with coenzyme Q10 (CoQ10) and mitochondrial transplantation in myocardial I/R injury of aged rats. Methods: Male Wistar rats (n = 72, 400–450 g, 22–24 months old) were randomized into groups with/without I/R and/or CoQ10 and mitochondrial transplantation, alone or in a combinational mode. An in vivo model of myocardial I/R injury was established by left anterior descending coronary artery occlusion and re-opening. Mitochondria were isolated from donor rats and injected intramyocardially (150 µl of the mitochondrial suspension containing 2 × 105±0.3 × 105 mitochondria) at the onset of reperfusion in recipient groups. CoQ10 (20 mg/kg/day) was injected intramuscularly for 7 days before I/R operation. Lastly, myocardial function, cTn-I level, expression of autophagy-associated proteins (Beclin1, p62, and LC3-II/LC3-I), and the levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were assessed. Results: Co-application of CoQ10 and mitotherapy concomitantly improved myocardial function and decreased cTn-I level in aged reperfused hearts (P <.001). This combination therapy also modulated autophagic activity and decreased pro-inflammatory cytokines (P <.01 to P <.001). This combinational approach induced noticeable cardioprotection in comparison with monotherapies-received groups. Conclusion: We found that combination of CoQ10 and mitochondrial transplantation attenuated myocardial I/R injury in aged rats, in part by modulating autophagy and inflammatory response, hence, appears to restore aging-related loss of cardioprotection in aged patients. [ABSTRACT FROM AUTHOR]

Objective: It is widely known that myocardial damage is not immediately terminated after the elimination of epicardial occlusion in cases of myocardial infarction. In situ thrombosis during epicardial occlusion might contribute to poor myocardial perfusion after reperfusion of an occluded epicardial artery. In the current study, we sought to determine the effects of ischemia and reperfusion on microvascular thrombotic occlusion. Methods: Thirty male Wistar rats were included in the study. After the rats had been anesthetized and thoracotomized, the left coronary artery was occluded for 30 minutes in the first group, and it was occluded for 30 minutes and reperfused for an additional 20 minutes in the second group. Ten rats were used as a sham-operated control group. After completion of the study protocol, excised heart preparations were analyzed by immunohistochemistry and electron microscopy. Results: A significant difference was found between the infarction plus reperfusion group and the other 2 groups, with respect to microvascular fibrin and thrombocyte deposition in immunohistochemistry analysis. These results were confirmed by morphological examination with electron microscopy. Conclusion: In situ fibrin formation accompanies microvascular obstruction in acute myocardial infarction. Our results indicate that additional therapeutic approaches are needed in order to achieve better tissue perfusion in contemporary treatment of acute myocardial infarction after successful reopening of the infarct-related artery.

Introduction: Liver resections may be associated with high morbidity and mortality due to intraoperative bleeding. Pringle maneuver reduces this complication at the expense of ischemia-reperfusion injury. Current strategies to minimize reperfusion injury include the use of perioperative corticosteroids. Objective: To assess the use of methylprednisolone in low doses (< 500 mg) in patients submitted to major hepatic resection under Pringle maneuver in the incidence of ischemia-reperfusion injury, peri-operative morbidity, and mortality. Material and Methods: Retrospective study from the liver resections database undertaken between the years 2000-2015 in our center. One hundred and seventy-one major liver resections were done, in 62 under Pringle maneuver. Two groups were established: (A) Patients administered methylprednisolone immediately before Pringle maneuver (n = 27) and (B) those without steroid (n = 35). We assessed ischemia-reperfusion injury by measuring liver tests on days 1, 3 and 5. Results: Patients in group A had longer ischemia time (43 ± 3.3 vs. 27 ± 2.1 min, p < 0.05) than those of group B, and significantly lower elevation of serum phosphatase alkaline and bilirubin on days 1 and five post-hepatectomy. We did not observe any difference in bleeding magnitude, and there were no differences in morbidity or mortality. Conclusions: The use of low doses of methylprednisolone seems to diminish the impact of ischemia-reperfusion injury related to major hepatic resection under Pringle maneuver avoiding the adverse side effects of high dose steroid. [ABSTRACT FROM AUTHOR]

Temporary occlusion of major cerebral blood vessels occasionally becomes necessary during surgical procedures. Ascorbic acid (Vitamin C) is an important non-enzymatic scavenger of free radicals and its protective effect on the brain in permanent focal cerebral ischaemia has been proven in a primate model of focal cerebral ischaemia [16]. Additional damage caused by reperfusion of the infarcted area has been shown in the rat model [22]. This study was undertaken to study the efficacy of ascorbic acid in decreasing infarct size in ischaemic reperfused brain. Maccaca radiata monkeys in the treated group were given two grams of ascorbic acid, parentally immediately before clipping the middle cerebral artery and the control group was given placebo. Reperfusion was done after four hours. Mean infarct size in all the three brain slices in the ascorbic acid pretreated group was 7.3%±2.7 and in the placebo group 22.1±6.7 under similar conditions. The mean infarct size in the ascorbic acid pretreated group of monkeys was significantly lower when compared with the placebo group (p=0.0003). [ABSTRACT FROM AUTHOR]

Objective: The aim was to compare the infarct limiting effect of Ro 40-5967 (Ro40), a new calcium antagonist with little negative inotropic activity, with that of verapamil and with ischaemic preconditioning, a potent endogenous cardioprotective mechanism. Methods: Dogs (n = 53) of either sex were subjected to 60 min of coronary occlusion followed by 3 h of reperfusion. Drug treated dogs received either verapamil (1.0 mg·kg−1) or Ro40 (3.0 mg·kg−1) intravenously for 100 min starting 15 min prior to the occlusion. Control dogs received a saline infusion. Ischaemic preconditioning consisted of four 5 min cycles of ischaemia alternating with four 5 min cycles of reperfusion. After 3 h of reflow, hearts were excised and infarct size was measured using tripheyltetrazolium chloride macrochemistry and expressed as percent of the ischaemic area at risk (AAR). To control for variation in infarct size due to variation in collateral blood flow, infarct size among groups was compared using ANCOVA, in which infarct size and collateral blood flow, measured at 30 min of occlusion, were dependent and independent variables, respectively. Results: Transmural collateral blood flow and AAR were not significantly different between any of the groups. Mean infarct size (adjusted by ancova for slight differences in collateral blood flow among groups) in control dogs (n=13) was 25.9(SEM 3.2)% of the AAR. Both verapamil (n= 11) and Ro40 (n = 9) limited infarct size [14.2(3.2)% AAR and 16.7(2.9)% AAR, respectively; both p<0.05]. Preconditioning (n = 17) also significantly limited infarct size [8.1(1.8)%; p<0.01]. Conclusions: The new calcium antagonist, Ro 40-5967, was as effective as verapamil in limiting infarct size after 60 min of regional ischaemia followed by 3 h of reperfusion, although neither calcium antagonist was as effective as ischaemic preconditioning.Cardiovascular Research 1994;28:1526-1532 [ABSTRACT FROM PUBLISHER]

Background: Activated inflammation and oxidant stress during cerebral ischemia reperfusion injury (IRI) lead to brain damage. Astaxanthin (ASX) is a type of carotenoid with a strong antioxidant effect., Objective: The aim of this study was to investigate the role of ASX on brain IRI., Methods: A total of 42 adult male Sprague-Dawley rats were divided into 3 groups as control (n=14) group, IRI (n=14) group and IRI + ASX (n=14) group. Cerebral ischemia was instituted by occluding middle cerebral artery for 120 minutes and subsequently, reperfusion was performed for 48 hours. Oxidant parameter levels and protein degradation products were evaluated. Hippocampal and cortex cell apoptosis, neuronal cell count, neurological deficit score were evaluated., Results: In the IRI group, oxidant parameter levels and protein degradation products in the tissue were increased compared to control group. However, these values were significantly decreased in the IRI + ASX group (p<0.05). There was a significant decrease in hippocampal and cortex cell apoptosis and a significant increase in the number of neuronal cells in the IRI + ASX group compared to the IRI group alone (p<0.05). The neurological deficit score which was significantly lower in the IRI group compared to the control group was found to be significantly improved in the IRI + ASX group (p<0.05)., Conclusion: Astaxanthin protects the brain from oxidative damage and reduces neuronal deficits due to IRI injury., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Hepatic ischemia and reperfusion injury (IRI) is a major complication in liver surgery, and hepatic steatosis is a primary factor aggravating cellular injury during IRI. Both pro-inflammatory cytokines and reactive oxygen species (ROS) are key mediators of hepatic IRI. Ischemic preconditioning (IpreC), remote ischemia preconditioning (RIPC) and ischemic postconditioning (IpostC) have offered protections on hepatic IRI, but all these methods have their own shortcomings. Grape seed proanthocyanidins (GSP) has a broad spectrum of pharmacological properties against oxidative stress. Thus, GSP has potential protective effects against hepatic IRI., Methods: C57BL/6 mice suffering 30mins hepatic ischemia process were sacrificed after 1h reperfusion to build murine warm hepatic IRI model. The mice were injected GSP intraperitoneally 10, 20, 40mg/kg/day for 3 weeks as pharmacological preconditioning. Obese mice fed with high-fat diet for 24 weeks before used. Three pathways related to IRI, including ROS elimination, pro-inflammatory cytokines release and hypoxia responses were examined., Results: Our data show that GSP could significantly reduce hepatic IRI by protecting hepatocyte function and increasing the activity of ROS scavengers, as well as decreasing cytokines levels. At the same time, GSP also enhance the hypoxia tolerance response. Combined GSP and postconditioning can provided synergistic protection. In the obese mice suffering hepatic IRI group, GSP was more effective than postconditioning on protecting liver against IRI, and the combined strategy was obviously superior to the solo treatment., Conclusion: GSP could protect liver against IRI: particularly in high-fat diet induced obese mice. GSP used as pharmacological preconditioning and combined with other protocols have huge potential to be used in clinical.