Evaluating Myocardial Ischemic Preconditioning by Quantifying Post-Ischemic Mechanical and Electrical Activity Using Ex-Vivo Rat Hearts

2014 ◽  
Vol 31 (3/2014) ◽  
Keyword(s):  
Electrical Activity ◽  
Ischemic Preconditioning ◽  
Ex Vivo ◽  
Rat Hearts

scholarly journals Exercise Training Preserves Ischemic Preconditioning in Aged Rat Hearts by Restoring the Myocardial Polyamine Pool

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Weiwei Wang ◽  
Hao Zhang ◽  
Guo Xue ◽  
Li Zhang ◽  
Weihua Zhang ◽  
...  
Keyword(s):  
Exercise Training ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Polyamine Metabolism ◽  
Aged Rat ◽  
Isolated Hearts ◽  
Age Related ◽  
Rat Hearts ◽  
Myocardial Ischemia Reperfusion

Background. Ischemic preconditioning (IPC) strongly protects against myocardial ischemia reperfusion (IR) injury. However, IPC protection is ineffective in aged hearts. Exercise training reduces the incidence of age-related cardiovascular disease and upregulates the ornithine decarboxylase (ODC)/polyamine pathway. The aim of this study was to investigate whether exercise can reestablish IPC protection in aged hearts and whether IPC protection is linked to restoration of the cardiac polyamine pool.Methods. Rats aging 3 or 18 months perform treadmill exercises with or without gradient respectively for 6 weeks. Isolated hearts and isolated cardiomyocytes were exposed to an IR and IPC protocol.Results. IPC induced an increase in myocardial polyamines by regulating ODC and spermidine/spermine acetyltransferase (SSAT) in young rat hearts, but IPC did not affect polyamine metabolism in aged hearts. Exercise training inhibited the loss of preconditioning protection and restored the polyamine pool by activating ODC and inhibiting SSAT in aged hearts. An ODC inhibitor,α-difluoromethylornithine, abolished the recovery of preconditioning protection mediated by exercise. Moreover, polyamines improved age-associated mitochondrial dysfunctionin vitro.Conclusion. Exercise appears to restore preconditioning protection in aged rat hearts, possibly due to an increase in intracellular polyamines and an improvement in mitochondrial function in response to a preconditioning stimulus.

Ischemic preconditioning-mediated restoration of membrane dystrophin during reperfusion correlates with protection against contraction-induced myocardial injury

2004 ◽  
Vol 287 (1) ◽  
pp. H81-H90 ◽  
Author(s):  
Masakuni Kido ◽  
Hajime Otani ◽  
Shiori Kyoi ◽  
Tomohiko Sumida ◽  
Hiroyoshi Fujiwara ◽  
...  
Keyword(s):  
Ischemic Preconditioning ◽  
Myocardial Injury ◽  
Contractile Activity ◽  
Integral Membrane Protein ◽  
Contractile Force ◽  
Global Ischemia ◽  
Blue Dye ◽  
Perfused Heart ◽  
Complete Restoration ◽  
Rat Hearts

Dystrophin is an integral membrane protein involved in the stabilization of the sarcolemmal membrane in cardiac muscle. We hypothesized that the loss of membrane dystrophin during ischemia and reperfusion is responsible for contractile force-induced myocardial injury and that cardioprotection afforded by ischemic preconditioning (IPC) is related to the preservation of membrane dystrophin. Isolated and perfused rat hearts were subjected to 30 min of global ischemia, followed by reperfusion with or without the contractile blocker 2,3-butanedione monoxime (BDM). IPC was introduced by three cycles of 5-min ischemia and 5-min reperfusion before the global ischemia. Dystrophin was distributed exclusively in the membrane of myocytes in the normally perfused heart but was redistributed to the myofibril fraction after 30 min of ischemia and was lost from both of these compartments during reperfusion in the presence or absence of BDM. The loss of dystrophin preceded uptake of the membrane-impermeable Evans blue dye by myocytes that occurred after the withdrawal of BDM and was associated with creatine kinase release and the development of contracture. Although IPC did not alter the redistribution of membrane dystrophin induced by 30 min of ischemia, it facilitated the restoration of membrane dystrophin during reperfusion. Also, myocyte necrosis was not observed when BDM was withdrawn after complete restoration of membrane dystrophin. These results demonstrate that IPC-mediated restoration of membrane dystrophin during reperfusion correlates with protection against contractile force-induced myocardial injury and suggest that the cardioprotection conferred by IPC can be enhanced by the temporary blockade of contractile activity until restoration of membrane dystrophin during reperfusion.

scholarly journals Detecting Validated Intracellular ROS Generation with 18F-dihydroethidine-Based PET

2021 ◽  
Author(s):  
Edward C. T. Waters ◽  
Friedrich Baark ◽  
Zilin Yu ◽  
Filipa Mota ◽  
Thomas R. Eykyn ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Contractile Function ◽  
Ex Vivo ◽  
Glutathione Depletion ◽  
Ros Generation ◽  
Cardiac Contractile ◽  
Rat Hearts ◽  
Intracellular Ros ◽  
Cardiac Contractile Dysfunction

Abstract Purpose To determine the sensitivity of the 18F-radiolabelled dihydroethidine analogue ([18F]DHE) to ROS in a validated ex vivo model of tissue oxidative stress. Procedures The sensitivity of [18F]DHE to various ROS-generating systems was first established in vitro. Then, isolated rat hearts were perfused under constant flow, with contractile function monitored by intraventricular balloon. Cardiac uptake of infused [18F]DHE (50–150 kBq.min−1) was monitored by γ-detection, while ROS generation was invoked by menadione infusion (0, 10, or 50 μm), validated by parallel measures of cardiac oxidative stress. Results [18F]DHE was most sensitive to oxidation by superoxide and hydroxyl radicals. Normalised [18F]DHE uptake was significantly greater in menadione-treated hearts (1.44 ± 0.27) versus control (0.81 ± 0.07) (p < 0.05, n = 4/group), associated with concomitant cardiac contractile dysfunction, glutathione depletion, and PKG1α dimerisation. Conclusion [18F]DHE reports on ROS in a validated model of oxidative stress where perfusion (and tracer delivery) is unlikely to impact its pharmacokinetics.

scholarly journals STAT subtype specificity and ischemic preconditioning in mice: is STAT-3 enough?

2011 ◽  
Vol 300 (2) ◽  
pp. H522-H526 ◽  
Author(s):  
Michael D. Goodman ◽  
Sheryl E. Koch ◽  
Muhammad R. Afzal ◽  
Karyn L. Butler
Keyword(s):  
Ischemic Preconditioning ◽  
Ischemia Reperfusion Injury ◽  
Contractile Function ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Cardiac Performance ◽  
Subtype Specificity ◽  
Developed Pressure ◽  
Perfused Hearts

The role of other STAT subtypes in conferring ischemic tolerance is unclear. We hypothesized that in STAT-3 deletion alternative STAT subtypes would protect myocardial function against ischemia-reperfusion injury. Wild-type (WT) male C57BL/6 mice or mice with cardiomyocyte STAT-3 knockout (KO) underwent baseline echocardiography. Langendorff-perfused hearts underwent ischemic preconditioning (IPC) or no IPC before ischemia-reperfusion. Following ex vivo perfusion, hearts were analyzed for STAT-5 and -6 phosphorylation by Western blot analysis of nuclear fractions. Echocardiography and postequilibration cardiac performance revealed no differences in cardiac function between WT and KO hearts. Phosphorylated STAT-5 and -6 expression was similar in WT and KO hearts before perfusion. Contractile function in WT and KO hearts was significantly impaired following ischemia-reperfusion in the absence of IPC. In WT hearts, IPC significantly improved the recovery of the maximum first derivative of developed pressure (+dP/d tmax) compared with that in hearts without IPC. IPC more effectively improved end-reperfusion dP/d tmax in WT hearts compared with KO hearts. Preconditioned and nonpreconditioned KO hearts exhibited increased phosphorylated STAT-5 and -6 expression compared with WT hearts. The increased subtype activation did not improve the efficacy of IPC in KO hearts. In conclusion, baseline cardiac performance is preserved in hearts with cardiac-restricted STAT-3 deletion. STAT-3 deletion attenuates preconditioning and is not associated with a compensatory upregulation of STAT-5 and -6 subtypes. The activation of STAT-5 and -6 in KO hearts following ischemic challenge does not provide functional compensation for the loss of STAT-3. JAK-STAT signaling via STAT-3 is essential for effective IPC.

scholarly journals Down-regulation of Connexin43 in Early Myocardial Ischemia and Protective Effect by Ischemic Preconditioning in Rat Hearts In Vivo

2004 ◽  
Vol 45 (6) ◽  
pp. 1007-1019 ◽  
Author(s):  
Kazuhito Hatanaka ◽  
Hiroyuki Kawata ◽  
Toshihiko Toyofuku ◽  
Ken-ichi Yoshida
Keyword(s):  
Myocardial Ischemia ◽  
Protective Effect ◽  
Ischemic Preconditioning ◽  
Down Regulation ◽  
Rat Hearts

scholarly journals Difference in the Cardioprotective Mechanisms Between Ischemic Preconditioning and Pharmacological Preconditioning by Diazoxide in Rat Hearts

2004 ◽  
Vol 68 (2) ◽  
pp. 156-162 ◽  
Author(s):  
Nobuyuki Wakahara ◽  
Hideki Katoh ◽  
Yasuhiro Yaguchi ◽  
Akihiko Uehara ◽  
Hiroshi Satoh ◽  
...  
Keyword(s):  
Ischemic Preconditioning ◽  
Rat Hearts ◽  
Pharmacological Preconditioning

Circadian rhythms in myocardial metabolism and contractile function: influence of workload and oleate

2007 ◽  
Vol 293 (4) ◽  
pp. H2385-H2393 ◽  
Author(s):  
David J. Durgan ◽  
Michael W. S. Moore ◽  
Ngan P. Ha ◽  
Oluwaseun Egbejimi ◽  
Anna Fields ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Fatty Acid ◽  
Circadian Rhythms ◽  
Rat Heart ◽  
Myocardial Metabolism ◽  
Contractile Function ◽  
Ex Vivo ◽  
Light Phase ◽  
Rat Hearts ◽  
Male Wistar Rats

Multiple extracardiac stimuli, such as workload and circulating nutrients (e.g., fatty acids), known to influence myocardial metabolism and contractile function exhibit marked circadian rhythms. The aim of the present study was to investigate whether the rat heart exhibits circadian rhythms in its responsiveness to changes in workload and/or fatty acid (oleate) availability. Thus, hearts were isolated from male Wistar rats (housed during a 12:12-h light-dark cycle: lights on at 9 AM) at 9 AM, 3 PM, 9 PM, and 3 AM and perfused in the working mode ex vivo with 5 mM glucose plus either 0.4 or 0.8 mM oleate. Following 20-min perfusion at normal workload (i.e., 100 cm H2O afterload), hearts were challenged with increased workload (140 cm H2O afterload plus 1 μM epinephrine). In the presence of 0.4 mM oleate, myocardial metabolism exhibited a marked circadian rhythm, with decreased rates of glucose oxidation, increased rates of lactate release, decreased glycogenolysis capacity, and increased channeling of oleate into nonoxidative pathways during the light phase. Rat hearts also exhibited a modest circadian rhythm in responsiveness to the workload challenge when perfused in the presence of 0.4 mM oleate, with increased myocardial oxygen consumption at the dark-to-light phase transition. However, rat hearts perfused in the presence of 0.8 mM oleate exhibited a markedly blunted contractile function response to the workload challenge during the light phase. In conclusion, these studies expose marked circadian rhythmicities in myocardial oxidative and nonoxidative metabolism as well as responsiveness of the rat heart to changes in workload and fatty acid availability.

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