Dynamic changes in matrix metalloprotienase activity within the human myocardial interstitium during myocardial arrest and reperfusion.
نویسندگان
چکیده
BACKGROUND Past studies have clearly established that matrix metalloproteinases (MMPs) contribute to adverse myocardial remodeling with ischemia and reperfusion. However, these studies measured MMP levels in extracted samples, and therefore whether and to what degree actual changes in interstitial MMP activity occur within the human myocardium in the context of ischemia/reperfusion remained unknown. METHODS AND RESULTS The present study directly quantified MMP interstitial activity within the myocardium of patients (n=14) undergoing elective cardiac surgery during steady-state conditions, as well as during and following an obligatory period of myocardial arrest and reperfusion achieved by cardiopulmonary bypass. Interstitial MMP activity was continuously monitored using a validated MMP fluorogenic substrate, a microdialysis system placed within the myocardium, and in-line fluorescent detection system. MMP activity, as measured by fluorescent emission, reached a stable steady state level by 10 minutes after deployment of the microdialysis system. During initiation of cardiopulmonary bypass, MMP activity increased by 20% from baseline values (P<0.05), and then rapidly fell with cardiac arrest and longer periods of cardiopulmonary bypass. However, with restoration of myocardial blood flow and separation from cardiopulmonary bypass, MMP interstitial activity increased by over 30% from baseline (P<0.05). CONCLUSIONS The present study directly demonstrated that MMP proteolytic activity exists within the human myocardial interstitium and is a dynamic process under conditions such as myocardial arrest and reperfusion.
منابع مشابه
Effect of losartan on NOX2 transcription following acute myocardial ischemia-reperfusion
Introduction: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-2 (Nox2) is one of the predominant sources of ROS production during myocardial ischemia-reperfusion and can be induced by angiotensin II. The evidence suggests that pharmacological blockers of renin-angiotensin system can exert direct tissue effects independent of their ability to regulate blood pressure. The mechanism...
متن کاملThe Effect of Verapamil Administred before the Reperfusion Insult in Isolated Preconditioned Rat Heart on the Microsomal ATPase and Mitochondrial Enzyme Activities
Background: Calcium overload and free radical mediated damage in the mitochondria is the most important pathological changes associated with myocardial ischemic-reperfusion injury. The verapamil post-treatment has been previously reported to prevent reperfusion-induced myocardial injury but functional recovery may be delayed due to the drug's inherent direct myocardial depression effect. In the...
متن کاملExploring the role of dimethylarginine dimethylaminohydrolase-mediated reduction in tissue asymmetrical dimethylarginine levels in cardio-protective mechanism of ischaemic postconditioning in rats
Objective(s): Reperfusion of ischaemic myocardium results in reduced nitric oxide (NO) biosynthesis by endothelial nitric oxide synthase (eNOS) leading to endothelial dysfunction and subsequent tissue damage. Impaired NO biosynthesis may be partly due to increased levels of asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of eNOS. As dimethylarginine dimet...
متن کاملMyocardial and interstitial matrix metalloproteinase activity after acute myocardial infarction in pigs.
A structural event during the evolution of a myocardial infarction (MI) is left ventricular (LV) remodeling. The mechanisms that contribute to early changes in LV myocardial remodeling in the post-MI period remain poorly understood. Matrix metalloproteinases (MMPs) contribute to tissue remodeling in several disease states. Whether and to what degree MMP activation occurs within the myocardial i...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Circulation
دوره 118 14 Suppl شماره
صفحات -
تاریخ انتشار 2008