Combination Angiotensin Converting Enzyme and Direct Renin Inhibition in Heart Failure following Experimental Myocardial Infarction. Issue 2 (4th July 2011)

• Record Type: Journal Article
• Authors: Connelly, K.A.; Advani, A.; Advani, S.; Zhang, Y.; Thai, K.; Thomas, S.; Krum, H.; Kelly, D.J.; Gilbert, R.E.
• Is Part Of: Cardiovascular therapeutics. Volume 31:Issue 2(2013:Apr.)
• Page Start: 84
• Page End: 91
• Publication Date: 2011-07-04
• Subjects: Cardiovascular pharmacology -- Periodicals; Cardiovascular agents -- Periodicals; Cardiovascular system -- Diseases -- Chemotherapy -- Periodicals; Cardiovascular Agents -- Periodicals; Cardiovascular Diseases -- drug therapy -- Periodicals; Agents cardiovasculaires -- Périodiques; Appareil cardiovasculaire -- Maladies -- Chimiothérapie -- Périodiques; 616.1005
• DOI: 10.1111/j.1755-5922.2011.00292.x
• Languages: English
• ISSNs: 1755-5914

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>SUMMARY</title> <p> <bold>Aims:</bold> Diminishing the activity of the renin–angiotensin system (RAS) plays a pivotal role in the treatment of heart failure. In addition to angiotensin converting enzyme (ACE) inhibitors and angiotensin‐receptor blockers, direct renin inhibition has emerged as a potential adjunctive treatment to conventional RAS blockade. We sought to determine the effectiveness of this strategy after myocardial infarction (MI) in the setting of preexisting hypertension, a common premorbid condition in patients with ischemic heart disease.</p> <p> <bold>Methods and Results:</bold> Ten‐week‐old female heterozygous hypertensive (mRen‐2)27 transgenic rats (Ren‐2), were randomized to one of five groups (n = 8 per group); sham, MI, MI + aliskiren, MI + lisinopril and MI + combination lisinopril and aliskiren. Cardiac function was assessed by echocardiography and <italic>in vivo</italic> cardiac catheterization. Untreated MI animals developed heart failure with hypotension, dilation, reduced ejection fraction (EF), and raised left ventricular end‐diastolic pressure (LVEDP). Treatment with single agent treatment had only modest effect on cardiac function though combination therapy was associated with significant improvements in EF and LVEDP when compared to untreated MI animals (<italic>P</italic> < 0.05). Histologic analysis demonstrated increase extracellular matrix deposition and cardiomyocyte hypertrophy in the noninfarct region of all MI groups when compared with sham operated animals (<italic>P</italic> < 0.05) that was reduced by ACE inhibitor monotherapy and combination treatment but not by aliskiren alone.</p> <p> <bold>Conclusion:</bold> In a hypertensive rat model that underwent experimental MI, EF, and LVEDP, key functional indices of heart failure, were improved by treatment with combination ACE and direct renin inhibition when compared with either agent used alone.</p> </abstract>