Abstract | OBJECTIVE: METHODS: Lewis rats underwent ligation of the left anterior descending coronary artery and direct injection of adenovirus encoding leukemia inhibitory factor (n = 10) or null transgene as control (n = 10) into the myocardium bordering the ischemic area. A sham operation group (n = 10) underwent thoracotomy without ligation. After 6 weeks, the following parameters were evaluated: cardiac function with a pressure-volume conductance catheter, left ventricular geometry and architecture by histologic methods; myocardial fibrosis by Masson trichrome staining, apoptosis by terminal deoxynucleotidal transferase-mediated deoxyuridine triphosphate nick-end labeling assay, and cardiomyocyte size by immunofluorescence. RESULTS: Rats with overexpression of leukemia inhibitory factor had more preserved myocardium and less fibrosis in both the infarct and its border zone. The border zone in leukemia inhibitory factor-treated animals contained fewer apoptotic nuclei (1.6% +/- 0.1% vs 3.3% +/- 0.2%, P < .05) than that in control animals and demonstrated cardiomyocytes with larger cross-sectional areas (910 +/- 60 microm 2 vs 480 +/- 30 microm 2 , P < .05). Leukemia inhibitory factor-treated animals had increased left ventricular wall thickness (2.1 +/- 0.1 mm vs 1.8 +/- 0.1 mm, P < .05) and less dilation of the left ventricular cavity (237 +/- 22 microL vs 301 +/- 16 microL, P < .05). They also had improved cardiac function, as measured by maximum change in pressure over time (3950 +/- 360 mm Hg/s vs 2750 +/- 230 mm Hg/s, P < .05) and the slopes of the maximum change in pressure over time-end-diastolic volume relationship (68 +/- 5 mm Hg/[s . microL] vs 46 +/- 6 mm Hg/[s . microL], P < .05) and the preload recruitable stroke work relationship (89 +/- 10 mm Hg vs 44 +/- 4 mm Hg, P < .05). CONCLUSIONS:
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Authors | Mark F Berry, Timothy J Pirolli, Vasant Jayasankar, Kevin J Morine, Mireille A Moise, Omar Fisher, Timothy J Gardner, Paul H Patterson, Y Joseph Woo |
Journal | The Journal of thoracic and cardiovascular surgery
(J Thorac Cardiovasc Surg)
Vol. 128
Issue 6
Pg. 866-75
(Dec 2004)
ISSN: 0022-5223 [Print] United States |
PMID | 15573071
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Interleukin-6
- Leukemia Inhibitory Factor
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Topics |
- Adenoviridae
(genetics)
- Animals
- Gene Expression
- Gene Transfer Techniques
- Heart Rupture, Post-Infarction
(metabolism, pathology, therapy)
- Heart Ventricles
(pathology)
- In Situ Nick-End Labeling
- Interleukin-6
(metabolism)
- Leukemia Inhibitory Factor
- Male
- Myocardium
(metabolism)
- Myocytes, Cardiac
(metabolism)
- Rats
- Ventricular Pressure
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