Myocardial protection against ischemia-reperfusion injury: novel approaches in maintaining homeostatic stability in blood.
Homeostatic vascular response to complement activation in cardiac surgery patients requiring cardiopulmonary bypass results in mechanisms leading to ischemia-reperfusion injury and myocardial cell death. Various pro-inflammatory cytokines, released by the inflamed tissue, play an essential role in the activation of the complement system and co-localize with activated complement proteins within the circulating blood and the myocardium. Throughout the past decade, much effort has thus been spent on deciphering the molecular signaling pathways mediating this pathophysiology. Basic and clinical investigations into many of the diverse aspects of cardiovascular drugs discovery employ varied approaches aimed at determining physiologic and pathophysiological efficiency of candidate agents for therapeutic utility. Identification of novel molecules regulating homeostatic dysfunction has offered the basis, with ultimate hope of identifying agents capable of exerting salutary influence upon cardiac and vascular tissue. This review will provide detailed synopses on recent insights into the ischemia-reperfusion signaling and associated myocardial injury. In addition, we will consider current and emerging novel approaches in attenuating cardiopulmonary bypass mediated injury with ultimate goal to prevent or delay the onset of post pump modulated heart failure and sudden deaths in such patients. Careful examination of the literature on recent patented and non-patented publications has identified several agents shown to be effective and specific in modulating and abrogating ischemia-reperfusion injury with some suggestions of potential clinical use.
Elahi
Maqsood M
MM
Department of Cardiothoracic Surgery, Faculty of Medicine and Surgery, PIC, Lahore, Pakistan.
Matata
Bashir M
BM
D000818:Animals; D003167:Complement Activation; D006152:Cyclic GMP / Q000502:physiology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006321:Heart / Q000187:drug effects*; D006706:Homeostasis; D006801:Humans; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D015398:Signal Transduction
D043562:Receptors, G-Protein-Coupled; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D017869:Cyclic GMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D006152:Cyclic GMP