Myocardial fibrosis blunts nitric oxide synthase-related preload reserve in human dilated cardiomyopathy.
نویسندگان
چکیده
The purpose of the study was to investigate interactions between myocardial nitric oxide synthase (NOS) and myocardial fibrosis, both of which determine left ventricular (LV) preload reserve in patients with nonischemic dilated cardiomyopathy (DCM). In previous animal experiments, chronic inhibition of NOS induced myocardial fibrosis and limited LV preload reserve. Twenty-eight DCM patients underwent LV catheterization, balloon caval occlusions (BCO; n = 8), intracoronary substance P infusion (n = 8), and procurement of LV endomyocardial biopsies for determinations of collagen volume fraction (CVF), of gene expression of NOS2, NOS3, heme oxygenase (HO)-1, and TNF-alpha, and of NOS2 protein. CVF was unrelated to the intensity of NOS2, NOS3, HO-1, or TNF-alpha gene expression or of NOS2 protein expression. Preload recruitable LV stroke work (PR-LVSW) correlated directly with NOS2 gene expression (P = 0.001) and inversely with CVF (P = 0.04). High CVF (>10%) reduced baseline LVSW and PR-LVSW at each level of NOS2 gene expression. In DCM, myocardial fibrosis is unrelated to the intensity of myocardial gene expression of NOS, antioxidative enzymes (HO-1), or cytokines (TNF-alpha) and blunts NOS2-related recruitment of LV preload reserve.
منابع مشابه
Endomyocardial nitric oxide synthase and left ventricular preload reserve in dilated cardiomyopathy.
BACKGROUND Patients with heart failure have modified myocardial expression of nitric oxide synthase (NOS), as is evident from induction of calcium-insensitive NOS isoforms. The functional significance of this modified NOS gene expression for left ventricular (LV) contractile performance was investigated in patients with dilated nonischemic cardiomyopathy. METHODS AND RESULTS In patients with ...
متن کاملNitric oxide: the missing lusitrope in failing myocardium.
During the last decade, the effects of nitric oxide (NO) on contractile function of failing myocardium elicited a lot of interest and research activity. Because of initial reports of NO acutely reducing the extent and velocity of shortening of isolated cardiomyocytes, especially following b-adrenergic stimulation, and because of increased activity of inducible nitric oxide synthase (NOS2) in hu...
متن کاملDiastolic Left Ventricular Dysfunction A Clinical Appraisal
Objective: In dilated cardiomyopathy and in athlete’s heart, progressive LV dilatation is accompanied by rightward displacement of thediastolic LV pressure–volume relation. In dilated cardiomyopathy, an increase in diastolic LV stiffness can limit this rightwarddisplacement thereby decreasing LV systolic performance. Because nitric oxide (NO) reduces diastolic LV stiffness, the present ...
متن کاملEndomyocardial nitric oxide synthase and the hemodynamic phenotypes of human dilated cardiomyopathy and of athlete's heart.
OBJECTIVE In dilated cardiomyopathy and in athlete's heart, progressive LV dilatation is accompanied by rightward displacement of the diastolic LV pressure-volume relation. In dilated cardiomyopathy, an increase in diastolic LV stiffness can limit this rightward displacement thereby decreasing LV systolic performance. Because nitric oxide (NO) reduces diastolic LV stiffness, the present study r...
متن کاملEvaluation of myocardial blood flow reserve in patients with chronic congestive heart failure due to idiopathic dilated cardiomyopathy.
This study demonstrates a significant impairment in coronary blood flow reserve in most patients with idiopathic dilated cardiomyopathy despite normal epicardial coronary arteries. This change may prevent appropriate increases in coronary blood flow and thus lead to myocardial ischemia and progression of disease. An association between decreased response to adenosine and acetylcholine supports ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- American journal of physiology. Heart and circulatory physiology
دوره 284 1 شماره
صفحات -
تاریخ انتشار 2003