Isoproterenol-induced Cardiotoxicity in Sprague-Dawley Rats: Correlation of Reversible and Irreversible Myocardial Injury with Release of Cardiac Troponin T and Roles of iNOS in Myocardial Injury

Abstract

The present study was undertaken to characterize myocardial lesions in the rat induced by low doses of isoproterenol (Iso) and to correlate lesion severity with release of cardiac troponin T (cTnT) and changes in myocyte iNOS expression. Two types of cardiac injury patterns were observed. A Type I response, noted 3 or 6 hours postdosing with 8, 16, 32, or 64 mug/kg Iso, included potential reversible myocardial alterations associated with slight increases in serum cTnT (< 0.3 ng/mL) and a slight reduction in myocyte cTnT immunoreactivity. The second type of response noted 3, 6, 12, 24 or 48 hours postdosing with 125, 250, or 500 mug/kg Iso consisted of irreversible myocyte alterations, together with significant increases in serum cTnT (3-14 ng/mL) and a marked reduction of cTnT immunoreactivity. By 48 hours the hearts of rats dosed with 125-500 mug/kg Iso had developed interstitial fibrosis, and serum cTnT had declined to near control levels (0.06-0.18 ng/mL). Increases in iNOS immunoreactivity correlated with the lesion severity. These findings suggest that low doses of Iso exert complex effects on the myocardium and that the generation of NO through increased expression of iNOS could be an important factor in the pathogenesis of myocyte injury.

Deficiency of iNOS Does Not Prevent Isoproterenol-induced Cardiac Hypertrophy in Mice

“…The level of mRNA for vascular endothelial growth factor and iNOS are increased in hypertrophied heart induced by abdominal aortic banding (Ji et al, 2008). Administration of isoproterenol increases iNOS immunoreactivity in the heart of Sprague Dawley rats (Zhang et al, 2008). Consistent with these previous results, the present study showed that chronic infusion of isoporterenol increased the protein level of iNOS in the left ventricle.…”

Revision of the Troponin T Release Mechanism from Damaged Human Myocardium

“…First, serum cTnT and cTnI concentrations return to baseline levels faster, often within 24 h, after diffuse infarctions that occur in the presence of unrestricted blood flow such as after an isoproterenol injection (22)(23)(24). After isoproterenol-induced AMI in rats, necrotic myocytes are diffusely distributed in the heart and exposed to an unrestricted plasma flow, resulting in fast extraction and clearance of cTnT and cTnI, compared with a classical thrombotic AMI when the damage is focal and there is only a limited plasma flow.…”

Ischemic Cardiomyopathy Following Seizure Induction by Domoic Acid

“…Interspersed with this presentation of coagulation necrosis and cardiomyocyte vacuolization, evidence of catecholamine toxicity seen as hypercontraction band necrosis, was also noted. 51 As the duration of time since original seizure induction progressed, the distribution of myocardial necrosis became more extensive around the subendocardial region. By day 14, cardiac tissue morphology was characterized by dead phagocytosed tissue and dense interstitial and perivascular connective tissue.…”