Lower risk of postinfarct rupture in mouse heart overexpressing beta 2-adrenergic receptors: importance of collagen content.

Abstract

This paper addresses whether the enhanced left ventricular (LV) contractility and heart rate, seen in transgenic mice overexpressing beta -adrenergic receptor in the heart, might raise the incidence of LV rupture after myocardial infarct. Transgenic and wild-type mice underwent left coronary artery occlusion. Postinfarct deaths that occurred 1-7 days after surgery were analyzed. Hemodynamics, morphologic parameters, and collagen content in the LV were determined. A significantly lower incidence of LV rupture was observed in transgenic than in wild-type mice 3-5 days after myocardial infarct (2.5 versus 19.7%, p < 0.05), despite a similar infarct size between the two groups and better hemodynamic function in transgenic mouse hearts. Morphologic analysis showed a more severe infarct expansion in wild-type versus transgenic mice or in mice dying of rupture versus those that died of acute heart failure. Collagen content was higher in the LV of sham-operated transgenic than wild-type mice (p < 0.01) with both type I and type III collagen elevated. Such difference in collagen content between transgenic and wild-type mice was maintained in noninfarcted and infarcted LV. In conclusion, transgenic mice overexpressing beta -adrenergic receptor had a lower risk of cardiac rupture during the acute phase after infarction despite the markedly enhanced LV contractility and heart rate. As a hyperdynamic function due to beta-adrenergic activation would likely increase the risk of cardiac rupture and infarct expansion, the lack of rupture in this transgenic mouse model suggests that the interstitial collagen level is a more important factor than functional status in the pathogenesis of rupture and infarct expansion.

• Authors: Xiao-Ming Gao, Rodney J Dilley, Chrishan S Samuel, Elodie Percy, Meryl J Fullerton, Anthony M Dart, Xiao-Jun Du
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 40 Issue 4 Pg. 632-40 (Oct 2002) ISSN: 0160-2446 [Print] United States
• PMID: 12352327 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Adrenergic, beta-2
• Collagen

Topics

• Animals
• Collagen (genetics, metabolism)
• Female
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Myocardial Infarction (genetics, metabolism, pathology)
• Myocardium (metabolism, pathology)
• Receptors, Adrenergic, beta-2 (biosynthesis, genetics)
• Risk
• Ventricular Dysfunction, Left (genetics, metabolism, pathology)