Contradictory effects of short- and long-term hyperglycemias on ischemic injury of myocardium via intracellular signaling pathway

Xu, Guang; Takashi, En; Kudo, Mitsuhiro; Ishiwata, Toshiyuki; Naito, Zenya

doi:10.1016/j.yexmp.2003.08.003

Cited by 57 publications

(50 citation statements)

References 29 publications

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“…Some studies showed that hyperglycemia can increase myocardial IS and myocyte apoptosis, exaggerate LV failure, and decrease survival after MI/R by increasing inflammation and oxidative stress and abolishes ischemic preconditioning (4,13,14,20). In contrast, other studies demonstrated that hyperglycemia protected against ischemiainduced myocardial damage, decreased the myocardial IS and the number of apoptotic myocytes, and improved the recovery of heart function after MI/R (3,24). In the present study, rats were subjected to 30 min of ischemia and 4 h of reperfusion, and severe myocardium injury was observed.…”

Section: Discussionmentioning

confidence: 99%

Acute hyperglycemia exacerbates myocardial ischemia/reperfusion injury and blunts cardioprotective effect of GIK

Shan¹,

Sun²,

Ma³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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. Acute hyperglycemia exacerbates myocardial ischemia/reperfusion injury and blunts cardioprotective effect of GIK. Am J Physiol Endocrinol Metab 293: E629-E635, 2007. First published May 22, 2007; doi:10.1152/ajpendo.00221.2007.-There is a close association between hyperglycemia and increased risk of mortality after acute myocardial infarction (AMI). However, whether acute hyperglycemia exacerbates myocardial ischemia/reperfusion (MI/R) injury remains unclear. We observed the effects of acute hyperglycemia on MI/R injury and on the cardioprotective effect of glucose-insulin-potassium (GIK). Male rats were subjected to 30 min of myocardial ischemia and 6 h of reperfusion. Rats were randomly received one of the following treatments (at 4 ml ⅐ kg Ϫ1 ⅐ h Ϫ1 iv): Vehicle, GIK (GIK during reperfusion; glucose: 200g/l, insulin: 60 U/l, KCL: 60 mmol/l), HG (high glucose during ischemia; glucose:500 g/l), GIK ϩ HG (HG during I and GIK during R) or GIK ϩ wortmannin (GIK during R and wortmannin 15 min before R). Blood glucose, plasma insulin concentration and left ventricular pressure (LVP) were monitored throughout the experiments. Hyperglycemia during ischemia not only significantly increased myocardial apoptosis (23.6 Ϯ 1.7% vs. 18.8 Ϯ 1.4%, P Ͻ 0.05 vs. vehicle), increased infarct size (IS) (45.6 Ϯ 3.0% vs. 37.6 Ϯ 2.0%, P Ͻ 0.05 vs. vehicle), decreased Akt and GSK-3␤ phosphorylations (0.5 Ϯ 0.2 and 0.6 Ϯ 0.1% fold of vehicle, respectively, P Ͻ 0.05 vs. vehicle) following MI/R, but almost completely blocked the cardioprotective effect afforded by GIK, as evidenced by significantly increased apoptotic index (19.1 Ϯ 2.0 vs. 10.3 Ϯ 1.2%, P Ͻ 0.01 vs. GIK), increased myocardial IS (39.2 Ϯ 2.8 vs. 27.2 Ϯ 2.1%, P Ͻ 0.01 vs. GIK), decreased Akt phosphorylation (1.1 Ϯ 0.1 vs. 1.7 Ϯ 0.2%, P Ͻ 0.01 vs. GIK) and GSK-3␤ phosphorylation (1.4 Ϯ 0.2 vs. 2.3 Ϯ 0.2%, P Ͻ 0.05 vs. GIK). Hyperglycemia significantly exacerbates MI/R injury and blocks the cardioprotective effect afforded by GIK, which is, at least in part, due to hyperglycemia-induced decrease of myocardial Akt activation.Akt; glucose-insulin-potassium IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION (AMI), stress hyperglycemia can commonly be observed. An association between hyperglycemia and an increased risk of mortality and poor prognosis after AMI was well noted in patients with or without diabetes (1, 21). Mechanisms for the association between stress hyperglycemia and adverse outcomes after AMI in nondiabetic patients are not well understood. Additional studies showed that acute hyperglycemia in AMI patients without diabetes was independently associated with larger enzymatic infarct size and higher long-term mortality rates after AMI (22). These results suggest that poor outcomes of patients with AMI may be related to hyperglycemia. However, direct evidence to support a causative role of acute hyperglycemia in exacerbating myocardial ischemia/reperfusion (MI/R) injury is not currently available, and the underlying mechanisms remain unidentified.Glucose-insulin-potassiu...

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Section: Discussionmentioning

confidence: 99%

Acute hyperglycemia exacerbates myocardial ischemia/reperfusion injury and blunts cardioprotective effect of GIK

Shan¹,

Sun²,

Ma³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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“…Although long-term elevation of blood glucose in diabetics has been established to cause diabetic cardiomyopathy, [30][31][32] patients with diabetes mellitus were excluded from the current study. Recent studies have shown that acute hyperglycemia induced apoptosis in perfused rat hearts, 33 and activation of inflammatory cytokines and the immune system, which might cause further damage to the myocardium.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of Blood Glucose in Patients With Cardiogenic Shock

Tada

Nagao

Tanjoh

et al. 2006

Circ J

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Background Although an elevated blood glucose has prognostic value in cardiovascular disease, few data are available regarding its prognostic value for patients across the spectrum of cardiogenic shock. Method and Results A total of 81 patients with cardiogenic shock whose blood glucose and adrenaline were measured on arrival at the emergency room (ER) were enrolled in this prospective study. The primary endpoint was death from any cause in hospital. The rate of death was 12.3% (10/81), and the glucose level was lower among patients who were discharged alive than among those who died (8.7±3.7 mmol/L vs 13.8±6.7 mmol/L, p<0.001). The unadjusted rate of death increased in a stepwise fashion among patients in increasing quartiles of glucose level (p<0.05). The blood glucose level of 9.2 mmol/L had the highest combined sensitivity and specificity for the identification of death. In the multiple logistic-regression analysis for the primary outcome, the adjusted odd ratio for a glucose level of 9.2 mmol/L or more was 5.8 (95% confidence interval, 1.0-32.8, p=0.047). There was a significant positive correlation between the glucose and adrenaline levels (R=0.726, p<0.0001). Conclusion The measurement of blood glucose level on ER arrival provides predictive information for use in risk stratification across the spectrum of cardiac emergencies complicated by cardiogenic shock. (Circ J 2006; 70: 1064 -1069

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“…Indeed, experimental studies have shown that the chronic treatment of isolated cardiomyocytes with a high glucose content medium increased the rate of cell death [16] . In contrast, exposure to short periods of a high glucose medium or diabetes has been found to protect the heart against a variety of pathological insults, including ischemia, hypoxia, and calcium overload [17][18][19] . Several mechanisms have been proposed to explain the cardioprotective role of high glucose exposure, such as upregulation of antiapoptotic factor Bcl-2, inactivation of proapoptotic factor Bad, and activation of prosurvival factors [17,20] .…”

Section: Cellular Survival Factors: Cell Death and Angiogenesismentioning

confidence: 99%

Impact of conditioning hyperglycemic on myocardial infarction rats: Cardiac cell survival factors

Malfitano

Souza

Irigoyen

2014

WJC

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in diabetic animals leads to increased capillary density before myocardial infarction. Despite poor prognostic in the long-term, all these results suggest that diabetes mellitus and consequently hyperglycemia may indeed play a cardioprotective role against myocardial infarction in the short term.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Conditioned hyperglycemia; Diabetes mellitus; Myocardial infarction; Cardioprotection; Survival factors Core tip: Hyperglycemia or diabetes triggers a conditioned state that may protect the heart against ischemic injury and associated detrimental effects. These beneficial effects are present in short term diabetes and/ or moderate hyperglycemia. The increase in glucose availability, the preferred energy substrate of the heart in stress condition, is likely to be one of the main cardioprotector mechanisms of hyperglycemia. However, other cardioprotective mechanisms seem to be involved, such as the release of cellular survival factors, ions preventing overload and angiogenesis. A fuller understanding of the mechanisms underlying conditioned hyperglycemia is then critical for the development of effective therapeutic strategies against ischemic heart disease. AbstractWhile clinical data have suggested that the diabetic heart is more susceptible to ischemic heart disease (IHD), animal data have so far pointed to a lower probability of IHD. Thus, the aim of this present review is to look at these conflicting results and discuss the protective mechanisms that conditioned hyperglycemia may confer to the heart against ischemic injury. Several mechanisms have been proposed to explain the cardioprotective action of high glucose exposure, namely, upregulation of anti-apoptotic factor Bcl-2, inactivation of pro-apoptotic factor bad, and activation of pro-survival factors such as protein kinase B (Akt), vascular endothelial growth factor (VEGF), hypoxia inducible factor-1α and protein kinase C-ε. Indeed, cytosolic increase in Ca 2+ concentration, the mitochondrial permeability transition pore, plays a key role in the genesis of ischemic injury. Previous studies have shown that the diabetic heart decreased Na + /Ca 2+ and Na + /H + exchanger activity and as such it accumulates less Ca 2+ in cardiomyocyte, thus preventing cardiac injury and the associated heart dysfunctions. In addition, the expression of VEGF TOPIC HIGHLIGHTSubmit a

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Contradictory effects of short- and long-term hyperglycemias on ischemic injury of myocardium via intracellular signaling pathway

Cited by 57 publications

References 29 publications

Acute hyperglycemia exacerbates myocardial ischemia/reperfusion injury and blunts cardioprotective effect of GIK

Acute hyperglycemia exacerbates myocardial ischemia/reperfusion injury and blunts cardioprotective effect of GIK

Prognostic Value of Blood Glucose in Patients With Cardiogenic Shock

Impact of conditioning hyperglycemic on myocardial infarction rats: Cardiac cell survival factors

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