ABSTRACT
Although nitric oxide synthase (NOS)3 is implicated as an important modulator of left ventricular (LV) remodeling, its role in the cardiac response to chronic pressure overload is controversial. We examined whether selective restoration of NOS3 to the hearts of NOS3-deficient mice would modulate the LV remodeling response to transverse aortic constriction (TAC). LV structure and function were compared at baseline and after TAC in NOS3-deficient (NOS3(-/-)) mice and NOS3(-/-) mice carrying a transgene directing NOS3 expression specifically in cardiomyocytes (NOS3(-/-TG) mice). At baseline, echocardiographic assessment of LV dimensions and function, invasive hemodynamic measurements, LV mass, and myocyte width did not differ between the two genotypes. Four weeks after TAC, echocardiographic and hemodynamic indexes of LV systolic function indicated that contractile performance was better preserved in NOS3(-/-TG) mice than in NOS3(-/-) mice. Echocardiographic LV wall thickness and cardiomyocyte width were greater in NOS3(-/-) mice than in NOS3(-/-TG) mice. TAC-induced cardiac fibrosis did not differ between these genotypes. TAC increased cardiac superoxide generation in NOS3(-/-TG) but not NOS3(-/-) mice. The ratio of NOS3 dimers to monomers did not differ before and after TAC in NOS3(-/-TG) mice. Restoration of NOS3 to the heart of NOS3-deficient mice attenuates LV hypertrophy and dysfunction after TAC, suggesting that NOS3 protects against the adverse LV remodeling induced by prolonged pressure overload.
Subject(s)
Hypertension/physiopathology , Hypertrophy, Left Ventricular/physiopathology , Myocytes, Cardiac/enzymology , Nitric Oxide Synthase Type II/metabolism , Ventricular Dysfunction, Left/physiopathology , Ventricular Remodeling/physiology , Animals , Cells, Cultured , Mice , Mice, Transgenic , Nitric Oxide Synthase Type IIIABSTRACT
We report a case of a patient who was admitted to our hospital complaining of angina pectoris. On auscultation, a systolic ejection murmur was heard at the right upper sternal border. Transthoracic echocardiography displayed regional wall motion abnormalities and detected a mobile mass in the left ventricular outflow tract, causing mild obstruction during systole. The mass appeared as an unilocular cystic tumor. Coronary angiography showed a significant lesion in the left anterior descending artery. Surgical treatment was indicated for coronary artery disease and for the unpredictable behaviour of the neoplasm. The mass was identified as arising from the top of the anterior papillary muscle. Histopathological examination revealed that the tumor was a cavernous hemangioma. Cardiac hemangiomas are rare, benign vascular tumors of the heart. This is an unusual case of left ventricular hemangioma incidentally discovered, which raised an interesting differential diagnosis.
Subject(s)
Heart Neoplasms/complications , Heart Neoplasms/diagnostic imaging , Hemangioma, Cavernous/complications , Hemangioma, Cavernous/diagnostic imaging , Ventricular Outflow Obstruction/diagnostic imaging , Ventricular Outflow Obstruction/etiology , Aged , Humans , Male , UltrasonographyABSTRACT
AIMS: Currently available non-invasive imaging methods frequently fail to detect alterations in left ventricular (LV) function despite histological evidence of injury. Tissue Doppler imaging (TDI) can detect subtle LV dysfunction. The aim of this study was to investigate whether TDI indices can predict LV systolic dysfunction and mortality following exposure to doxorubicin (DOX) in mice. METHODS AND RESULTS: TDI-derived peak endocardial systolic velocity (V(ENDO)) and strain rate (SR), as well as M-mode and two-dimensional indices of LV systolic function, were measured serially in mice after receiving DOX as a single dose (20 mg/kg). Haemodynamic measurements were obtained invasively before and at 1, 2, 4, and 5 days after the single DOX dose. Cardiac apoptosis was measured before and at 1 day after DOX. V(ENDO) and SR decreased after 1 and 2 days, respectively, whereas changes in fractional shortening (FS) and LV ejection fraction (LVEF) were not detected before 5 days. The reduction in both V(ENDO) and SR correlated with the decrease in dP/dt(MAX), and the change in V(ENDO) correlated with the early increase in cardiac cell apoptosis. In a subsequent experiment, DOX was administered at 4 mg/kg/week for 5 weeks, and LV function was followed serially for 16 weeks. In this chronic experiment, TDI indices decreased before FS and LVEF, correlated with late LV dysfunction, and predicted DOX-induced mortality. CONCLUSION: In a murine model of DOX-induced cardiac injury, TDI detects LV dysfunction prior to alterations in conventional echocardiographic indices and predicts mortality. This study suggests that TDI may be a reliable tool to detect early subtle changes in DOX-induced cardiac dysfunction.
