HYPOXIA-INDUCIBLE FACTOR (HIF)-1 is a redox-responsive transcription factor that regulates the expression of numerous genes under physiological and pathological conditions (19). HIF-1 has been implicated in the regulation of angiogenesis, cell survival and proliferation, cell motility and adhesion, glucose metabolism, vascular tone, and pH regulation (19). Unstable under normoxic conditions, th...

The March issue of Shock continues to provide the latest update in clinical and basic science topics that will interest our readers. The issue begins with two excellent reviews that cover very timely topics for the treatment of shock. The first review by Roberts et al. (1) covers a topic that has been of interest for yearsVnitric oxide. It is clear that nitric oxide is involved in the pathophys...

MYOCARDIAL INFARCTION (MI) is a leading cause of death and disability globally that typically results from the abrupt occlusion of an epicardial coronary artery (9). As a result, cardiomyocytes distal to the occlusion are subject to oxygen and nutrient deprivation, which triggers mitochondrial electron transport chain (ETC) inhibition, reactive oxygen species (ROS) generation, and necrotic deat...

MYOCARDIAL ATP-SENSITIVE POTASSIUM (KATP) channels appear to play central roles in the adaptation of the heart to both physiological and pathological metabolic stress (1, 3, 5, 7, 8, 14, 16, 21). In the heart, KATP channels are thought to act as metabolic sensors that respond (by opening) when cytosolic [ATP] falls and cellular energy status is diminished (1, 4, 13, 14). There are two types of ...

MYOCARDIAL ISCHEMIA related to infarction is a disease of multiple pathways with variable outcomes. Both ischemia and reperfusion contribute to cell and tissue damage after cardiac infarction. Myocardial ischemia-reperfusion initiates maldistribution of ions and various signaling mechanisms, leading to oxidative injury and inflammatory responses that include liberation of cytokines (16) and fre...

MYOCARDIAL ADAPTATION TO ISCHEMIA occurs through the activation of several tyrosine kinases (3). Phosphorylation of tyrosine kinases has been shown to be linked with the activation of both phospholipase C and phospholipase D, leading to the activation of multiple kinases including PKC and mitogen-activated protein (MAP) kinases. The MAP kinases play an essential role in mediating intracellular ...

N,N,N ,N -Tetrakis(2-pyridylmethyl)-ethylenediamine (TPEN), a transition-metal chelator, was recently found to protect against myocardial ischemia-reperfusion injury. The goals of this study were to investigate the in vivo antiarrhythmic and antifibrillatory potential of TPEN in rats and guinea pigs and to study the in vitro effects of TPEN on calcium homeostasis in cultured newborn rat cardiac...

Epidemiological studies strongly suggest an inverse correlation between plasma high-density lipoprotein (HDL) concentration and the risk of ischemic heart disease.1,2 Experimental evidence also exists to indicate cardioprotective effects of HDL.3 However, the mechanism for protective effect of HDL against ischemic heart disease is not completely understood. Although the widely accepted mechanis...

ISCHEMIA OCCURS when arterial blood flow is insufficient to meet the metabolic demands of the target tissue, resulting in a series of coordinated molecular, cellular, tissue-specific, and systemic events that cause tissue damage. Paradoxically, reperfusion that occurs following ischemia can exacerbate tissue injury and necrosis. The detrimental effects of reperfusion injury were first observed ...

In the 1970s, during the peak of eicosanoid research, platelets were generally considered to play a major role in mediating the cell and tissue injury known to occur in cerebral ischemia/stroke, myocardial ischemia/infarction, and traumatic injury to other organs or regions. Foremost among the platelet-derived humoral mediators of this type of tissue injury were the prostaglandins (eg, PGF2a), ...