SummaryBackground: No-reflow phenomenon is observed in approximately one-third of patients after percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI), and is associated with poor functional and clinical outcomes. On the other hand, the formation of free radicals in vasculature exerts deleterious effects on coronary microcirculation.Hypothesis: We hypothesized that redox state in coronary circulation may play a crucial role in no-reflow phenomenon in AMI.Methods: Consecutive 26 patients with first AMI who underwent primary PCI < 24 h after onset were enrolled. Before PCI, blood samples were obtained from coronary sinus to measure plasma or serum antioxidative vitamins (vitamin C, vitamin E, and beta-carotene) and antioxidative enzymes (extracellular glutathione peroxidase [GPX], superoxide dismutase, and catalase). After PCI, the corrected Thrombolysis In Myocardial Infarction (TIMI) frame count (CTFC) was measured in the target vessel. Patients with TIMI ≤ 2 flow despite an optimal PCI result were designated as no-reflow group (Group NR, n = 6) and the others as reflow group (Group R, n = 20).Results: Levels of vitamin C, vitamin E, and GPX before PCI were significantly lower in Group NR than in Group R.
itric oxide (NO) is an important regulator of cardiac function. 1,2 In patients with congestive heart failure (CHF) the concentrations of NO and tumor necrosis factor-increase in proportion to the severity of heart failure. 3,4 Previous studies have shown that inhibition of cardiac NO synthase (NOS) augments the positive inotropic response to -adrenergic receptor stimulation in human heart failure, suggesting that increased activity of myocardial NOS and NO attenuates -adrenergic responsiveness. [5][6][7] In patients with severe CHF, the increase in intracellular cyclic AMP and myocardial contractility in response toadrenergic receptor stimulation is reduced, 5 which reflects cardiac desensitization to -receptor agonists, 8 partly modulated by the increased production of NO in the myocardium. 5 Previous studies have shown that forskolin produces beneficial cardiac effects by directly stimulating adenylyl cyclase in the failed human heart, especially in those with a relative insensitivity to -adrenergic receptor stimulation. 9 Colforsin daropate (NKH477; 6-(3-dimethyl-aminopropionyl) forskolin hydrochloride) is a new water-soluble forskolin derivative, which experimental studies have shown to be able to generate positive inotropic and vasodilatory actions. 10,11 Furthermore, we previously reported that NKH477 might be a superior alternative to dobutamine for mechanical energy transduction in patients with left ventricular (LV) systolic dysfunction. 12 It remains to be clarified how NO modulates -adrenergic post-receptor signaling, such as adenylyl cyclase stimulation in the failing human heart. The objective of this study was to address the role of NO by evaluating the effects of cardiac NOS inhibition on LV hemodynamics and mechanoenergetics in response to adenylyl cyclase stimulation with colforsin daropate in patients with idiopathic cardiomyopathy (IDC).
Methods
Study SubjectsWe examined 13 patients (10 men, 3 women, mean age 56±13 years) who were undergoing diagnostic cardiac catheterization for the evaluation of heart failure on their first admission to hospital. All patients showed normal sinus rhythm and were diagnosed as IDC by the absence of coronary artery disease or other known causes of dilated cardiomyopathy. The patients were in New York Heart Association functional class II (n=8) or class III (n=5) with a LV ejection fraction (LVEF) of less than 40%. None of Background Increased nitric oxide (NO) in the failing heart attenuates the myocardial contractile response to -adrenergic receptor stimulation. However, the physiological effects of NO on the -adrenergic post-receptor signaling system are unknown. The objective of the present study was to examine the effects of cardiac NO synthase (NOS) inhibition on left ventricular (LV) hemodynamics and mechanoenergetics in response to adenylyl cyclase stimulation in human heart failure.
Methods and ResultsThe study group comprised 13 patients with heart failure because of idiopathic cardiomyopathy (IDC). Emax was examined as an index of LV contractility, LV...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.