Preload induces troponin I degradation independently of myocardial ischemia.
نویسندگان
چکیده
BACKGROUND Although global ischemia induces troponin I (TnI) degradation, regional ischemia does not. We hypothesized that this disparity is related to preload-induced proteolysis, which varies as a function of the amount of myocardium at risk of ischemia. METHODS AND RESULTS Isolated rat hearts were buffer-perfused at controlled levels of preload. Increasing preload to 25 mm Hg in the absence of ischemia produced pronounced TnI degradation (27 kDa versus 31 kDa bands: 16.4 +/- 3.6% versus 4.7 +/- 1.9% in immediately excised controls, P<0.05). TnI degradation could be blocked by preventing the activation of endogenous calpains with 25 micromol/L calpeptin (4.3 +/- 0.6%). This improved function, with left ventricular systolic pressure increasing from 103 +/- 4 mm Hg to 137 +/- 7 mm Hg (P<0.05). Eliminating elevations in preload after global ischemia-induced stunning also prevented TnI degradation. CONCLUSIONS Calpain-mediated TnI proteolysis can be dissociated from stunning and arises from elevations in preload rather than ischemia. This raises the possibility that ongoing preload-induced TnI degradation could impair myocardial function long-term.
منابع مشابه
Long-term biventricular support with the heartware implantable continuous flow pump.
1. Cooper LT, Jr. Myocarditis. N Engl J Med 2009;360:1526-38. 2. Kadota S, Takeuchi Y, Izuhara M, et al. The importance of serial cardiac troponin measurement for evaluating the response to immunosuppressive therapy for myocarditis. J Cardiol 2008;52:154-8. 3. Giannoni A, Giovannini S, Clerico A. Measurement of circulating concentrations of cardiac troponin I and T in healthy subjects: a tool f...
متن کاملTroponin I degradation and covalent complex formation accompanies myocardial ischemia/reperfusion injury.
Selective troponin I (TnI) modification has been demonstrated to be in part responsible for the contractile dysfunction observed with myocardial ischemia/reperfusion injury. We have isolated and characterized modified TnI products in isolated rat hearts after 0, 15, or 60 minutes of ischemia followed by 45 minutes of reperfusion using affinity chromatography with cardiac troponin C (TnC) and an...
متن کاملLack of effect of plasma of myocardial preconditioned, ischemic and ischemic-reperfused rats of myocardium on differentiation of mesenchymal stem cells into cardiomyocytes
Introduction: Numerous studies have shown that enriched plasma protects myocardial cells against ischemia. The aim of this study was to evaluate the effect of rat enriched plasma by preconditioning, ischemia, and reperfusion on the differentiation of bone marrow mesenchymal stem cells (BMMSC) into cardiomyocytes. Methods: In this experimental and laboratory study, BMMSCs were extracted from th...
متن کاملIntracellular action of matrix metalloproteinase-2 accounts for acute myocardial ischemia and reperfusion injury.
BACKGROUND Matrix metalloproteinases are best recognized for their ability to degrade the extracellular matrix in both physiological and pathological conditions. However, recent findings indicate that some of them are also involved in mediating acute processes such as platelet aggregation and vascular tone. The acute contractile defect of the heart after ischemia-reperfusion may involve the pro...
متن کاملValues of troponin T and myoglobin predictive of non-cardiac ischemia in rats
Objective(s):Biochemical markers are important for the timely diagnosis and follow-up of ischemic events. Most of the markers have been previously studied in the context of cardiac ischemia. However, research on markers of non-cardiac events has been insufficient. Therefore, we investigated the relationship between troponin and myoglobin which are commonly used markers of cardiac ischemia, in n...
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 103 16 شماره
صفحات -
تاریخ انتشار 2001