Myocardial ischemia increased MAPK activities, which were followed by enhancement of AP-1 and NF-kB DNA binding activity in areas of myocardial infarction in rats. These signal transduction mechanisms may contribute to the myocardial ischemia and injury associated with myocardial infarction by causing an increased expression of TGF-beta-1 mRNA, collagen I and III in the area.
Pirfenidone (5-methyl-1-phenyl-2-[ 1 H]-pyridone) is an effective drug for idiopathic interstitial pneumonia that can prevent and reverse tissue fibrosis in several organs. Therefore, we investigated whether pirfenidone has a potential role in preventing angiotensin II (Ang II)-induced cardiac hypertrophy. A cardiac hypertrophic mouse model was created using an Ang II infusion (200 ng kg À1 min À1 ) in wild-type mice for 2 weeks. Mice were divided into the following three groups: a saline-infused (control) group, an Ang II infusion (vehicle) group and an Ang II infusion+pirfenidone-treated (PFD) group, which received pirfenidone (300 mg kg À1 per day) by gastric gavage during the Ang II infusion. At 2 weeks, we assessed hemodynamics and cardiac function and investigated tissue fibrosis of the myocardium histologically and genetically. Blood pressure in the vehicle group was significantly increased compared to the control group. Although blood pressure was not different between the vehicle and PFD groups, heart weight was significantly decreased in the PFD group. Echocardiography revealed that left ventricular hypertrophy was significantly increased in the vehicle group vs. the control group. Interestingly, pirfenidone significantly inhibited this effect. Continuous infusion of Ang II increased the perivascular and interstitial tissue fibrosis, and pirfenidone inhibited these fibrotic changes. Pirfenidone also inhibited Ang II-induced hypertrophy. In the vehicle group, the mRNA expressions of atrial natriuretic peptide, brain natriuretic peptide and transforming growth factor-b1 were increased, which was significantly inhibited by pirfenidone. Furthermore, the expression of mineralocorticoid receptors was attenuated by pirfenidone. These results indicate that pirfenidone might be effective as an antifibrotic drug in the treatment of cardiac hypertrophy induced by hypertension.
Background: Myocardial fractional flow reserve (FFR) is useful in the evaluation of coronary lesion ischemia. However, the impact of lesion length on FFR has not been adequately assessed. Hypothesis: We hypothesized that lesion length would influence functional significance in intermediate coronary lesions. Methods: FFR measurements were assessed in 136 patients (163 lesions) with stable angina who had >40% stenotic coronary lesion by quantitative coronary angiography (QCA). One hundred sixty-three lesions were classified as intermediate (40%-70% stenosis; n=107; group I) or significant (≥70%; n=56; group S) by QCA. We assessed the relationships between lesion length, coronary stenosis, and FFR in these 163 lesions. Results: Regression analysis revealed an inverse correlation between the percentage of diameter stenosis (%DS) and FFR in group S (r = −0.83, P < 0.0001). In group I, no significant correlation was found between %DS and FFR (r = −0.06, P = 0.55), whereas lesion length was significantly inversely correlated with FFR (r = −0.79, P < 0.0001). Receiver operating characteristic curve analysis demonstrated that the best cutoff value for predicting an FFR value <0.80 was a lesion length >16.1 mm in group I (sensitivity, 86%; specificity, 94%). Conclusions: These study findings suggest that lesion length has a physiologically significant impact on intermediate-grade coronary lesions.
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