Inhibition of collagen synthesis with prolyl 4-hydroxylase inhibitor improves left ventricular function and alters the pattern of left ventricular dilatation after myocardial infarction.

Background- Left ventricular (LV) remodeling after myocardial infarction (MI) is associated with fibrosis, dilatation, and dysfunction. We postulated that prevention of fibrosis after MI with a prolyl 4-hydroxylase inhibitor (P4HI) would preserve LV function and attenuate LV enlargement. Methods and Results- Adult female rats (200 to 250 g) had experimental MI and were then randomized to treatment with P4HI (MI-FG041, n=29) or vehicle (MI-control, n=29) 48 hours after MI for 4 weeks in 2 phases. Echocardiograms were performed weekly with a 15-MHz linear transducer, and at 4 weeks, collagen isoform determinations and in vivo hemodynamics were performed. At randomization, the infarct size and LV function and size were similar in MI-FG041 and MI-control but significantly different from shams (n=9). At week 4, the LV function in MI-FG041 was significantly better than in MI-controls (fractional shortening 21% versus 16%, P=0.01; fractional area change 30% versus 19%, P=0.002; ejection fraction 35% versus 23%, P=0.001). In the FG041 group, LV area in systole was less (P<0.05), the dP/dt(max) after isoproterenol was higher (P<0.05), and types I and III collagen in noninfarcted LV were less than in MI-control. The hydroxyproline/proline ratio was increased by 64% in MI-control and reduced to the sham value in MI-FG041 rats. In the scar tissue, it was reduced by 24% in MI-FG041. Conclusions- This study demonstrates that prevention of interstitial fibrosis with a P4H inhibitor alters the pattern of LV enlargement and produces partial recovery of LV function after MI.

Is the technically limited echocardiographic study an endangered species? endocardial border definition with native tissue harmonic imaging and Optison contrast: a review of 200 cases.

OBJECTIVE: Our goal was to determine whether contrast adds diagnostic value to both fundamental and native tissue harmonic imaging (NTHI) for endocardial border definition. METHODS: Two hundred consecutive patients who underwent stress echocardiography imaging were studied in either fundamental (n = 52) or NTHI mode (n = 148) with an Acuson Sequoia echocardiographic system. Contrast agent (Optison) was administered (0.5 to 1 mL) for enhancement of endocardial borders. Two- and 4-chamber views were analyzed before and after administration of contrast at peak stress for grading of 5 endocardial border segments. Scores from 0 to 5 were assigned to each study for all the images both before and after contrast (0 = 0 segments completely visualized; 5 = 5 segments completely visualized). RESULTS: The use of Optison contrast significantly enhanced border definition when imaging was performed in either fundamental or NTHI mode. Addition of contrast resulted in better endocardial border definition in fundamental mode (4.1 + or - 1.0 versus 2.3 + or - 1.3, P <.001). However, in NTHI mode, the presence of contrast resulted in enhanced definition of endocardial border compared with its absence (4.8 + or - 0.5 versus 3.3 + or - 1.1, P <.001). The combination of NTHI and contrast resulted in more visualization of endocardium when compared with the combination of fundamental imaging and contrast (4.8 + or - 0.5 versus 4.1 + or - 1.0, P <.001). In addition, interobserver agreement for border detection increased from 83% in fundamental mode without contrast to 95% with the use of NTHI with Optison (P <.001). CONCLUSION: As defined in 200 cases, the combination of NTHI with Optison contrast results in nearly complete and consistent endocardial border definition.