Insulin stimulates pyruvate dehydrogenase and protects human ventricular cardiomyocytes from simulated ischemia

Rao, Vivek; Merante, Frank; Weisel, Richard D.; Shirai, Toshizumi; Ikonomidis, John S.; Cohen, Gideon; Tumiati, Laura C.; Shiono, Noritsugu; Li, Ren‐Ke; Mickle, Donald A.G.; Robinson, Brian H.

doi:10.1016/s0022-5223(98)70015-7

Cited by 59 publications

(43 citation statements)

References 21 publications

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“…9 Insulin added to cardioplegic solutions in CABG patients enhances aerobic metabolism on reperfusion and improves left ventricular stroke work index. 17 Exogenous insulin also decreases oxidative stress and the inflammatory response. Low-dose infusions of insulin (2 IU/h) in obese patients significantly decreased levels of reactive oxygen species, adhesion molecules, and C-reactive protein within 2 hours.…”

Section: Discussionmentioning

confidence: 99%

Tight Glycemic Control in Diabetic Coronary Artery Bypass Graft Patients Improves Perioperative Outcomes and Decreases Recurrent Ischemic Events

et al. 2004

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Background-This study sought to determine whether tight glycemic control with a modified glucose-insulin-potassium (GIK) solution in diabetic coronary artery bypass graft (CABG) patients would improve perioperative outcomes. Methods and Results-One hundred forty-one diabetic patients undergoing CABG were prospectively randomized to tight glycemic control (serum glucose, 125 to 200 mg/dL) with GIK or standard therapy (serum glucose Ͻ250 mg/dL) using intermittent subcutaneous insulin beginning before anesthesia and continuing for 12 hours after surgery. GIK patients had lower serum glucose levels (138Ϯ4 versus 260Ϯ6 mg/dL; PϽ0.0001), a lower incidence of atrial fibrillation (16.6% versus 42%; Pϭ0.0017), and a shorter postoperative length of stay (6.5Ϯ0.1 versus 9.2Ϯ0.3 days; Pϭ0.003). GIK patients also showed a survival advantage over the initial 2 years after surgery (Pϭ0.04) and decreased episodes of recurrent ischemia (5% versus 19%; Pϭ0.01) and developed fewer recurrent wound infections (1% versus 10%, Pϭ0.03). Conclusions-Tight glycemic control with GIK in diabetic CABG patients improves perioperative outcomes, enhances survival, and decreases the incidence of ischemic events and wound complications.

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Section: Discussionmentioning

confidence: 99%

Tight Glycemic Control in Diabetic Coronary Artery Bypass Graft Patients Improves Perioperative Outcomes and Decreases Recurrent Ischemic Events

et al. 2004

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“…To verify anoxia, 2 ml of anoxic PBS was placed in a center dish within the sealed chamber and tested at the termination of each anoxic period to ensure a PO2 of 0 mmHg. Previous studies have demonstrated that this model of low-volume anoxia produced biochemical effects similar to the effects of clinical low-volume anoxia and reoxygenation (8,18,19,22,30,37,41). Heart cells reverted to anaerobic metabolism, producing lactic acidosis, a fall in ATP, and cell injury associated with the release of creatine kinase and troponin I.…”

Section: Experimental Model Of Low-volume Anoxia and Reoxygenationmentioning

confidence: 69%

“…These results suggest that cGMP-regulated K ATP channels are possibly important in L-arginine-mediated cardioprotection. Opening K ATP channels during reoxygenation after low-volume anoxia may facilitate the recovery of aerobic mitochondrial ATP production (8,18,30). Mitochondrial K ATP channel opening may improve electron transport (8).…”

Section: Effects Of L-arginine On Cellular Injury and No Production Amentioning

confidence: 99%

“…The quiescent nature of these myocytes exposed to low-volume anoxia simulates the low-flow and noncontractile conditions encountered during cardioplegic arrest. This model has been employed extensively to assess the effects of cardioplegic additives and myocardial preconditioning (8,18,19,22,30,37,41). Importantly, this model facilitates examination of pharmacological interventions independent of other cell types such as endothelial cells, neutrophils, and platelets.…”

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confidence: 99%

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l-Arginine protects human heart cells from low-volume anoxia and reoxygenation

Shiono

Rao

Weisel

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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-Arginine protects human heart cells from low-volume anoxia and reoxygenation. Am J Physiol Heart Circ Physiol 282: H805-H815, 2002; 10.1152/ajpheart.00594. 2001.-Protective effects of L-arginine were evaluated in a human ventricular heart cell model of low-volume anoxia and reoxygenation independent of alternate cell types. Cell cultures were subjected to 90 min of low-volume anoxia and 30 min of reoxygenation. L-Arginine (0-5.0 mM) was administered during the preanoxic period or the reoxygenation phase. Nitric oxide (NO) production, NO synthase (NOS) activity, cGMP levels, and cellular injury were assessed. To evaluate the effects of the L-arginine on cell signaling, the effects of the NOS antagonist N G -nitro-L-arginine methyl ester, NO donor S-nitroso-N-acetyl-penicillamine, guanylate cyclase inhibitor methylene blue, cGMP analog 8-bromocGMP, and ATP-sensitive K ϩ channel antagonist glibenclamide were examined. Our data indicate that low-volume anoxia and reoxygenation increased NOS activity and facilitated the conversion of L-arginine to NO, which provided protection against cellular injury in a dose-dependent fashion. In addition, L-arginine cardioprotection was achieved by the activation of guanylate cyclase, leading to increased cGMP levels in human heart cells. This action involves a glibenclamide-sensitive, NO-cGMP-dependent pathway. ventricular myocytes; cardiac surgery; nitric oxide DURING CARDIAC SURGERY, the heart is arrested with cardioplegia to facilitate surgical intervention and is subsequently reoxygenated after removal of the aortic cross-clamp. Cardioplegic arrest provides a unique clinical situation in which myocardial low-volume anoxia and reoxygenation can be anticipated and allows for interventions to prevent biochemical and functional derangements.Previous studies have demonstrated that nitric oxide (NO) exerts beneficial effects after low-volume anoxia and reoxygenation (1,7,11,13,26,33,45). The cardioprotective effects of L-arginine and NO were ascribed to endothelial cell preservation, decreased neutrophil activation, improved coronary blood flow, and a reduction in free-radical-mediated injury. The majority of these studies employed isolated whole heart and/or openchest models (26,33,45), and the relative contribution of individual cell types (i.e., endothelial cells, cardiomyocytes, neutrophils, and platelets) toward the beneficial effects of L-arginine could not be determined. The direct, cardioprotective effects of L-arginine on ventricular heart cells have not been previously examined.We have developed a unique model of low-volume anoxia and reoxygenation in human ventricular heart cells. The quiescent nature of these myocytes exposed to low-volume anoxia simulates the low-flow and noncontractile conditions encountered during cardioplegic arrest. This model has been employed extensively to assess the effects of cardioplegic additives and myocardial preconditioning (8,18,19,22,30,37,41). Importantly, this model facilitates examination of pharmacological interventions independen...

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“…40 Hyperglycemia associated with insulin resistance has also been demonstrated in critically ill patients with no history of diabetes. 41 …”

Section: Pathophysiology Of Hyperglycemia In Critical Illnessmentioning

confidence: 99%

Intensive Insulin Therapy in Critically Ill Patients

2002

N Engl J Med

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Insulin stimulates pyruvate dehydrogenase and protects human ventricular cardiomyocytes from simulated ischemia

Abstract: Insulin protected human ventricular cardiomyocytes from ischemia and reperfusion. This protection may be due to a stimulation of pyruvate dehydrogenase activity which resulted in improved aerobic metabolism.

Cited by 59 publications

References 21 publications

Tight Glycemic Control in Diabetic Coronary Artery Bypass Graft Patients Improves Perioperative Outcomes and Decreases Recurrent Ischemic Events

Tight Glycemic Control in Diabetic Coronary Artery Bypass Graft Patients Improves Perioperative Outcomes and Decreases Recurrent Ischemic Events

l-Arginine protects human heart cells from low-volume anoxia and reoxygenation

Intensive Insulin Therapy in Critically Ill Patients

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