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INCREASED COLLAGEN CONTENT REDUCES THE RISK OF POST -INFARCT CARDIAC
RUPTURE IN MICE THAT OVEREXPRESS BETA 2‑-ADRENERGIC
RECEPTORS IN THE HEART. XM. Gao*, RJ. Dilley, E. Percy, M.
Follerton, E. Woodcock and XJ. Du. Baker Medical Institute, Melbourne,
Australia. Left ventricular (LV) rupture is a fatal complication after acute
myocardial infarction (MI). Transgenic (TG) mice overexpressing
B2‑-adrenergic receptor (AR) in the heat have enhance
LV contractility, which may raise the incidence of rupture after
MI. TG and wild type (WT) mice underwent
surgery to induce LV MI. Haemodynamics
were measured by a LV catheter. Deaths
occurred during 24 h~7 days post MI were analyzed. Infarct size (IS, % LV) was measured digitally and collagen
content in LV was determined by both sirius red staining and hydroxyproline
assay. IS in TG and WT mice was not
different. 32 mice died within 24 h~7
days due to acute heart failure (HF) or rupture, post .MI mortality was
30.5%. 13 WT but only 1 TG mice died of
rupture during 3-~5 days after MI and all ruptures were located at LV free
wall. At day 7, haemodynamics remained
significantly higher in TG mice with MI.
In the infarcted zone, TG mice had a smaller area of coagulative
necrosis (5.4±0.9% vs. 12±2.1%, P<0.01) and a higher collagen content
(sirius red staining) than WT mice (15.7±1.6% vs. 10.3±1.8%, P<0.05). TG mice without MI also had a higher
concentration of hydroxyproline in the LV than WT mice at age of 4 (2.1±0.1 vs.
1.2±0.2:g/mg) and 10 months (2.9±0.2 vs. 1.7±0.1:g/mg. both P<0.01). Conclusion: TG mice overexpressing $2 .AR have a lower risk of
cardiac rupture during the acute phase after MI despite a higher LV
contractility. The mechanisms are most
likely due to a higher collagen content in the LV and a facilitated repair
process after MI. Our results
demonstrate the importance of collagen in maintaining tensile strength of the
infarcted LV. Death
within 24 h~7 days Rupture Total Acute
HF Rupture %
total death TG
(n=39) 23.1%
(9) 20.5%
(8) 2.5%
(1) 11.1%
(1/9) WT
(n=66) 34.8%
(23) 15.2%
(10) 19.7%*
(13) 56.5%*
(13/23) *P<0.05 vs. TG. |
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