Proposed Metabolic Vicious Circle in Patients With Large Myocardial Infarcts and High Plasma-Free-Fatty-Acid Concentrations

Opie, L.H.; Tansey, Michael; Kennelly, Brian M.

doi:10.1016/s0140-6736(77)90830-3

Cited by 91 publications

(32 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The plasma FFA level rises in relation to the measured size of the developing infarct. 63 Even in nondiabetic patients with ACS, blood glucose concentrations spontaneously rise, 64 but tissue glucose metabolism is impaired by insulin resistance. 65 Both high plasma FFA levels and insulin resistance are countered by provision of glucose-insulin as in GIK.…”

Section: Discussionmentioning

confidence: 99%

Glucose-Insulin-Potassium Revived

et al. 2013

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Glucose-Insulin-Potassium Revived

et al. 2013

View full text Add to dashboard Cite

“…Increased FFA levels aggravate the severity of myocardial infarction (for a review, see Van Der Vusse et al 19 ), and a close relation between peak plasma FFA levels and infarct size in patients with acute myocardial infarction has been demonstrated. 20 Additionally, high concentrations of palmitate caused apoptosis in myocardial cells. 21 Enhanced FAO in peripheral tissues and the heart by GW7647 could diminish the detrimental effect of the accumulated FFAs to the heart.…”

Section: Discussionmentioning

confidence: 99%

Activation of Peroxisome Proliferator–Activated Receptor-α Protects the Heart From Ischemia/Reperfusion Injury

et al. 2003

View full text Add to dashboard Cite

Background-Peroxisome proliferator-activated receptor-␣ (PPAR-␣) is expressed in the heart and regulates genes involved in myocardial fatty acid oxidation (FAO). The role of PPAR-␣ in acute ischemia/reperfusion myocardial injury remains unclear. Methods and Results-The coronary arteries of male mice were ligated for 30 minutes. After reperfusion for 24 hours, ischemic and infarct sizes were determined. A highly selective and potent PPAR-␣ agonist, GW7647, was administered by mouth for 2 days, and the third dose was given 1 hour before ischemia. GW7647 at 1 and 3 mg · kg Ϫ1 · d Ϫ1 reduced infarct size by 28% and 35%, respectively (PϽ0.01), and myocardial contractile dysfunction was also improved. Cardioprotection by GW7647 was completely abolished in PPAR-␣-null mice. Ischemia/reperfusion downregulated mRNA expression of cardiac PPAR-␣ and FAO enzyme genes, decreased myocardial FAO enzyme activity and in vivo cardiac fat oxidation, and increased serum levels of free fatty acids. All of these changes were reversed by GW7647. Moreover, GW7647 attenuated ischemia/reperfusion-induced release of multiple proinflammatory cytokines and inhibited neutrophil accumulation and myocardial expression of matrix metalloproteinases-9 and -2. Furthermore, GW7647 inhibited nuclear factor-B activation in the heart, accompanied by enhanced levels of inhibitor-B␣. Conclusions-Activation of PPAR-␣ protected the heart from reperfusion injury. This cardioprotection might be mediated through metabolic and antiinflammatory mechanisms. This novel effect of the PPAR-␣ agonist could provide an added benefit to patients treated with PPAR-␣ activators for dyslipidemia.

show abstract

“…The original premise for GIK therapy for AMI was not glucose control but the reduction of free fatty acids by insulin (17). Recently it has been recognized that insulin also has anti-inflammatory properties and suppresses reactive oxygen species under euglycemic conditions (18).…”

Section: Glucose Control and Mortalitymentioning

confidence: 99%

The Hyperglycemia: Intensive Insulin Infusion In Infarction (HI-5) Study

2006

View full text Add to dashboard Cite

OBJECTIVE—There is conflicting evidence regarding the benefit of intravenous insulin therapy on mortality following acute myocardial infarction (AMI). The goal of the current study was to determine whether improved glycemic control, achieved through an insulin/dextrose infusion with a variable rate of insulin, reduces mortality among hyperglycemic patients with AMI. RESEARCH DESIGN AND METHODS—Subjects suffering AMI with either known diabetes or without diabetes but blood glucose level (BGL) ≥7.8 mmol/l were randomized to receive insulin/dextrose infusion therapy for at least 24 h to maintain a BGL <10 mmol/l or conventional therapy. RESULTS—A total of 240 subjects were recruited. Insulin/dextrose infusion did not reduce mortality at the inpatient stage (4.8 vs. conventional 3.5%, P = 0.75), 3 months (7.1 vs 4.4%, P = 0.42), or 6 months (7.9 vs. 6.1%, P = 0.62). There was, however, a lower incidence of cardiac failure (12.7 vs. 22.8%, P = 0.04) and reinfarction within 3 months (2.4 vs. 6.1%, P = 0.05). When analyzed by mean BGL achieved during the first 24 h, mortality was lower among subjects with a mean BGL ≤8 mmol/l, compared with subjects with a mean BGL >8 mmol/l (2 vs. 11% at 6 months, P = 0.02). CONCLUSIONS—We did not find a reduction in mortality among patients who received insulin/dextrose infusion therapy. However, it remains possible that tight glycemic control with insulin therapy following AMI improves outcomes.

show abstract

Proposed Metabolic Vicious Circle in Patients With Large Myocardial Infarcts and High Plasma-Free-Fatty-Acid Concentrations

Cited by 91 publications

References 23 publications

Glucose-Insulin-Potassium Revived

Glucose-Insulin-Potassium Revived

Activation of Peroxisome Proliferator–Activated Receptor-α Protects the Heart From Ischemia/Reperfusion Injury

The Hyperglycemia: Intensive Insulin Infusion In Infarction (HI-5) Study

Contact Info

Product

Resources

About