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Background: Heart failure (HF) remains a chronic condition needing added treatment options. Natriuretic peptides (NP) have been effective in ameliorating acute HF symptoms and reducing pathologic cardiac remodeling when infused short-term (<72h) or applied intermittently for longer. However, longer-term effects of continuous dosing are less explored.
Methods: To evaluate such effects of a NP after myocardial infarction (MI; LAD ligation), we used osmotic mini-pumps to continuously infuse brain natriuretic peptide (BNP) into 1 of 3 groups of rats: (1) MI-only (n= 15); (2) MI+ BNP infusion 6-8 ug/kg/d for 8 wks (n= 16); and (3) Sham-surgery group (n= 10). At 8 wks, echocardiography and hemodynamic measures were run, serum collected, and myocytes isolated from LV non-infarcted area and dimensions determined by Coulter Channelyzer and microscopy.
Results: In MI+BNP group, serum BNP levels were elevated (Sham 3.1(.6), MI 2.9(.6), BNP 4.0(1.0) ng/ml, mean(SD); BNP vs Sham, P=.014; vs MI, P=.005) and body wt and heart rate were unchanged (P>0.5). As reported previously, MI led to myocyte lengthening only and BNP had no effect on this remodeling pattern. There were no changes between the MI+BNP and MI-only groups in various hemodynamic parameters (end systolic pressure minus Pmin (ESP-Pmin), MI 113(7), BNP 103(16) mm Hg, P=.16); and maximum systolic pressure change rate (dPmax); MI 7332(1250), BNP 7391(1136) mm Hg/sec, P=.89). There were unexpected increases in heart wt (MI 912(42), BNP 998(84) mg, P=.006) and HW/body wt ratio (MI 3.66(.14), BNP 3.90(.36) mg/g, P=.05) at necropsy. Echocardiographs revealed BNP-associated fractional shortening impaired vs MI-alone (18(4) vs 23(4)%, P<.001) and increased systolic LV diameter (7.7(.9) vs 6.8(.4) mm, P=.003). Due to collagenase digestion for isolated myocytes, comprehensive histological analysis of whole heart remodeling was not feasible.
Conclusions: In contrast to BNP given briefly or intermittently, continuous long-term BNP treatment post-MI interfered or exacerbated restorative cardiac remodeling and was associated with further impairment of LV function. Results suggest that chronic BNP does not lead to improved remodeling of myocyte shape after MI and may lead to worsening LV function.
Moderated Poster Contributions
Heart Failure and Cardiomyopathies Moderated Poster Theater, Poster Hall, Hall C
Friday, March 17, 2017, 4:00 p.m.-4:10 p.m.
Session Title: Hormones and Heart Failure
Abstract Category: 12. Heart Failure and Cardiomyopathies: Basic
Presentation Number: 1177M-05
- 2017 American College of Cardiology Foundation