Pre-conditioning and postconditioning to limit ischemia–reperfusion-induced myocardial injury: What could be the next footstep?

Balakumar, Pitchai; Rohilla, Ankur; Singh, Manjeet

doi:10.1016/j.phrs.2008.05.006

Cited by 56 publications

(34 citation statements)

References 167 publications

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“…Opening of mito K ATP channels is a major event considered to mediate the cardioprotective eŠects of IPC. 77) In the present study, treatment with diazoxide (30 mM), a K ATP channel opener, also restored the cardioprotective eŠects of IPC in Hhcy rat hearts. This suggests that the closure of K ATP channels occurs as a result of Hhcy, which may be an important abnormality in the downstream signaling mechanism of IPC in Hhcy rat hearts.…”

Section: Discussionsupporting

confidence: 64%

Possible Role of JAK-2 in Attenuated Cardioprotective Effect of Ischemic Preconditioning in Hyperhomocysteinemic Rat Hearts

Singh¹,

Rohilla²,

Singh³

et al. 2009

YAKUGAKU ZASSHI

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The present study investigated the possible role of Janus kinase-2 (JAK-2) in hyperhomocysteinemia-induced attenuation of the cardioprotective eŠects of ischemic preconditioning (IPC). Rats were administered L-methionine (1.7 g/kg/day, p.o.) for 4 weeks to produce hyperhomocysteinemia. Isolated LangendorŠ's perfused normal and hyperhomocysteinemic rat hearts were subjected to global ischemia for 30 min, followed by reperfusion for 120 min. Myocardial infarct size was assessed macroscopically using triphenyltetrazolium chloride staining. Coronary eOEuent was analyzed for lactate dehydrogenase (LDH) and creatine kinase (CK) release to assess the extent of cardiac injury. The oxidative stress in the heart was assessed by measuring thiobarbituric acid-reactive substances (TBARS), superoxide anion generation and the reduced form of glutathione. Ischemia-reperfusion (I/R) induced oxidative stress by increasing TBARS, superoxide anion generation and decreasing reduced form of glutathione in normal and hyperhomocystenemic rat hearts. Moreover, I/R produced myocardial injury, which was assessed in terms of the increase in myocardial infarct size, LDH and CK release in coronary eOEuent, and decrease in coronary ‰ow rate in normal and hyperhomocysteinemic rat hearts. The hyperhomocysteinemic rat hearts showed enhanced I/R-induced myocardial injury with a high degree of oxidative stress as compared with normal rat hearts subjected to I/R. Four episodes of IPC (5 min each) aŠorded cardioprotection against I/R-induced myocardial injury in normal rat hearts as assessed in terms of improvement in coronary ‰ow rate and reduction in myocardial infarct size, levels of LDH, CK, and oxidative stress. On the other hand, IPC-mediated myocardial protection against I/R-injury was abolished in hyperhomocysteinemic rat hearts. Tyrphostin AG490 (5 mM), a selective inhibitor of JAK-2, did not aŠect the cardioprotective eŠects of IPC in normal rat hearts, but its administration markedly restored the cardioprotective potential of IPC in hyperhomocysteinemic rat hearts. Administration of diazoxide (30 mM), an ATP-sensitive potassium (K ATP ) channel opener, also restored the cardioprotective eŠects of IPC in hyperhomocysteinemic rat hearts. In conclusion, it is suggested that the high degree of oxidative stress produced in hyperhomocysteinemic rat hearts during reperfusion and consequent activation of JAK-2 and closure of K ATP channels may be responsible for abolishing the cardioprotective potential of IPC against I/Rinduced myocardial injury.

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Section: Discussionsupporting

confidence: 64%

Possible Role of JAK-2 in Attenuated Cardioprotective Effect of Ischemic Preconditioning in Hyperhomocysteinemic Rat Hearts

Singh¹,

Rohilla²,

Singh³

et al. 2009

YAKUGAKU ZASSHI

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“…Although the cardioprotection of IPoC is involved in several signaling pathways, activation of reperfusion injury salvage kinase (RISK) signaling pathway, which subsequently acts to prevent mPTP opening and further regulate the apoptosis-related pathway, is still considered as a major mechanism of IPoC [9,10]. Therefore, we infer that the abrogation of IPoC in the presence of hypercholesterolemia is involved in inactivation of RISK signaling pathway and dysregulation of apoptosis-related pathways.…”

Section: Introductionmentioning

confidence: 96%

Hypercholesterolemia abrogates the protective effect of ischemic postconditioning by induction of apoptosis and impairment of activation of reperfusion injury salvage kinase pathway

Zhang

Jia

et al. 2015

Biochemical and Biophysical Research Communications

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“…Hyperglycemia or hyper-insulinemia may be the inhibitor of such protection. 19,20) As a result, K ATP channels may be associated with cardio-vascular disease, and sulphonylureas (i.e. glibenclamide and tolbutamide) for longterm treatment of type 2 diabetes can increase the risk of cardio-vascular disease due to their effects on K ATP channels in the heart.…”

Section: Discussionmentioning

confidence: 99%

Effects of Metformin on Rosiglitazone-Induced Cardiac Hypertrophy in Mice

Lee

Yeh

Chen³

et al. 2010

Biological & Pharmaceutical Bulletin

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Thiazolidinediones (TZD) can cause adipose tissue accumulation and myocardial hypertrophy. This study aimed to determine if combined Metformin (Glucophage) and Rosiglitazone (Avandia) could reduce the risk of heart failure caused by Rosiglitazone in BALB/c mice. BALB/c mice were treated with oral Rosiglitazone/Metformin twice daily for four weeks. Metformin or Rosiglitazone alone and non-treated mice acted as double control. Myocardial hypertrophy and associated side effects of the combined therapy were determined through isolated heart and body weights. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were applied to evaluate expression of sulfonylurea receptor 2A (SUR2A) and Kir 6.2. The activities of peroxisome proliferator activated receptor a (PPARa) in the myocardium were also observed. Rosiglitazone/Metformin decreased body weight gain and food intake, and inhibited an increasing adipose ratio but did not reduce myocardial hypertrophy. Rosiglitazone increased Kir6.2/SUR2A, Kir6.2/SUR2B, and PPARa gene expression. The Rosiglitazone/Metformin combination further increased these gene expressions, especially PPARa. Metformin inhibits obesity but has no effect in reducing myocardial hypertrophy caused by Rosiglitazone. Whether Metformin can reduce side effects of TZDs in humans warrants further study.

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Pre-conditioning and postconditioning to limit ischemia–reperfusion-induced myocardial injury: What could be the next footstep?

Cited by 56 publications

References 167 publications

Possible Role of JAK-2 in Attenuated Cardioprotective Effect of Ischemic Preconditioning in Hyperhomocysteinemic Rat Hearts

Possible Role of JAK-2 in Attenuated Cardioprotective Effect of Ischemic Preconditioning in Hyperhomocysteinemic Rat Hearts

Hypercholesterolemia abrogates the protective effect of ischemic postconditioning by induction of apoptosis and impairment of activation of reperfusion injury salvage kinase pathway

Effects of Metformin on Rosiglitazone-Induced Cardiac Hypertrophy in Mice

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