Acute Hyperglycemia-Induced Injury in Myocardial Infarction

Abstract

Acute hyperglycemia is a transient increase in plasma glucose level (PGL) frequently observed in patients with ST-elevation myocardial infarction (STEMI). The aim of this review is to clarify the molecular mechanisms whereby acute hyperglycemia impacts coronary flow and myocardial perfusion in patients with acute myocardial infarction (AMI) and to discuss the consequent clinical and prognostic implications. We conducted a comprehensive literature review on the molecular causes of myocardial damage driven by acute hyperglycemia in the context of AMI. The negative impact of high PGL on admission recognizes a multifactorial etiology involving endothelial function, oxidative stress, production of leukocyte adhesion molecules, platelet aggregation, and activation of the coagulation cascade. The current evidence suggests that all these pathophysiological mechanisms compromise myocardial perfusion as a whole and not only in the culprit coronary artery. Acute hyperglycemia on admission, regardless of whether or not in the context of a diabetes mellitus history, could be, thus, identified as a predictor of worse myocardial reperfusion and poorer prognosis in patients with AMI. In order to reduce hyperglycemia-related complications, it seems rational to pursue in these patients an adequate and quick control of PGL, despite the best pharmacological treatment for acute hyperglycemia still remaining a matter of debate.

Keywords: coagulation; coronary flow; diabetes mellitus; endothelium; inflammation.

Figure 1

Effects of PKC activation induced by hyperglycemia. Activation of PKC inhibits eNOS expression and increases ET-1 activity, resulting in increased permeability of endothelium coupled with an improved expression of the permeability-enhancing factor VEGF in smooth muscle cells. PKC also contributes to increased microvascular matrix protein production through the expression of TGF-β and overexpression of the fibrinolytic inhibitor PAI-1. ENOS, endothelial nitric oxide synthetase; ET-1, endothelin-1; NAD(P)H, nicotinamide adenine dinucleotide phosphate; NFkB, nuclear factor kappa-light-chain-enhancer of activated B cells; PAI-1, plasminogen activator inhibitor-1; PKC, protein kinase C; TGF, transforming growth factor; VEGF, vascular endothelial growth factor.

Figure 2

Mechanism of hyperglycemia-induced injury in myocardial infarction. ADMA, asymmetric dimethylarginine; AGE, advanced glycation end-products; CRP, C-reactive protein; DAG, diacylglycerol; eNOS, endothelial nitric oxide synthase; FVII, coagulation factor VII; GP, glycoprotein; ICAM, intercellular adhesion molecule; IL, interleukin; MRC, mitochondrial respiratory chain; NO, nitric oxide; PAI, plasminogen activator inhibitor; PKC, protein kinase C; PTL, platelet; TNF, tumor necrosis factor; tPA, tissue plasminogen activator; TXA, thromboxane-A.

Figure 3

Elevated cTFC in patients with acute hyperglycemia (A). Coronary angiogram (CA) at the 25th cine frame (utilizing 30 fps acquisition), revealing contrast opacification only up to the proximal segment of LAD and CX. (B) CA at the 50th cine frame. (C) CA at the 75th cine frame. (D) CA at the 100th cine frame cTFC, showing full opacification of left coronary artery (normal value ≤ 25 frames).