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J Thorac Cardiovasc Surg 2001;121:750-761
© 2001 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

Left ventricular aneurysm repair in rats: Structural, functional, and molecular consequences

Genichi Sakaguchi, MDa, Richard L. Young, PhDa, Masashi Komeda, MD,PhD b * , Kazou Yamanaka, MDb, Brian F. Buxton, MB, MS, FRACSb, William J. Louis, MD, FRACPa

From the Departments of Clinical Pharmacology and Therapeuticsa and Cardiac Surgery,b Austin and Repatriation Medical Centre, Heidelberg,Victoria, Australia.

G.S. is the recipient of a grant from the Suntory Institute for Bioorganic Research (Japan). During the course of these studies R.L.Y. was the recipient of a National Health and Medical Research Council of Australia Dora Lush Biomedical Postgraduate Scholarship. This study was supported by grants from the Sir Edward Dunlop Medical Research Foundation and the Austin Hospital Medical Research Foundation.

Received for publication Feb 7, 2000. Revisions received Oct 4, 2000. Accepted for publication Oct 20, 2000. Address for reprints: Richard L. Young, PhD, Department of Clinical Pharmacology and Therapeutics, Austin and Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia (E-mail: richardy{at}ariel.ucs.unimelb.edu.au).

Abstract

Objectives: This study examined the effects of aneurysm repair in a rat model of myocardial infarction on functional indices and on the spatiotemporal distribution of cardiac contractile protein and natriuretic peptide messenger RNA.
Methods: In a rat infarct model, expanded left ventricular aneurysms were plicated 4 weeks after infarction. At 30 weeks, transverse heart sections were taken at 4 levels (apex [level 1] through base [level 4]) and assessed by in situ hybridization histochemistry to determine regional messenger RNA levels of pre-pro-atrial natriuretic peptide, cardiac {alpha}-actin, skeletal {alpha}-actin, myosin light chain-2v, and ß-myosin heavy chain.
Results: Rats with plicated left ventricular aneurysms had reduced left ventricular endocardial circumference (19%, P < .005), lower heart weight ratio (31%, P < .05), left ventricular end-diastolic pressures (51%, P < .05), and increased ±dP/dt (34%-38%, P < .05). Cardiac messenger RNA levels of pre-pro-atrial natriuretic peptide were reduced in the septum (levels 2 and 3), and skeletal {alpha}-actin levels were reduced in the septum and left ventricular free wall of plicated rats (level 3). ß-Myosin heavy chain levels were markedly reduced in peri-infarct regions of the left ventricular free wall, septum, and right ventricle in plicated rats at level 4, whereas myosin light chain-2v levels were reduced at levels 2 and 4 in the left ventricular free wall and at level 4 in the right ventricle.
Conclusions: Plication of left ventricular aneurysm after infarction in the rat significantly reduced cardiac hypertrophy, improved cardiac function, and reduced the upregulation of pre-pro-atrial natriuretic peptide and both fetal and adult contractile protein isoforms associated with cardiac hypertrophy.




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