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A new method to denude the endothelium without damage to media: structural, functional, and biomechanical validation

Department of Biomedical Engineering, University of California, Irvine, California 92697

Submitted 10 September 2003 ; accepted in final form 5 January 2004

The intimial thickening that occurs in human and animal atherogenesis can be induced by mechanical injury to the endothelium. The objective of the present study was to develop a new method to induce arterial endothelial injury without damage to the media for future investigations of mechanisms of intimal thickening and atherogenesis. A specifically designed catheter was inserted into the common femoral artery of Wistar rats (n = 9) through an arteriotomic mouth. After application of Tyrode solution containing 0.14 M KCl on the surface of the vessel, the vessel contracted onto the catheter. The catheter was then moved back and forth to scrape away the endothelium. The left common femoral artery of the same rat was subjected to the standard balloon injury model. The two models were evaluated structurally, functionally, and biomechanically. Structurally, we verified that both techniques remove the endothelium, but the balloon method damages the media. Functionally, we examined the contractile response of the artery to [K⁺] and norepinephrine 2 days after the denudation. We found that the right femoral artery underwent contraction in response to [K⁺], whereas the left artery did not. Furthermore, neither artery responded to norepinephrine. Biomechanically, we measured the pressure-diameter relationship and the zero-stress state of the vessel and computed the stress-strain relation. The circumferential stretch ratios at 120 mmHg were 1.38 ± 0.08 for the control, 1.41 ± 0.08 (P > 0.05) for the new method, and 1.56 ± 0.09 for the balloon injury (P < 0.05). The opening angles at the zero-stress state were 113 ± 21° for the control, 102 ± 18° for the new method (P > 0.05), and 8 ± 13° for the balloon injury (P < 0.001). In conclusion, the new method removes the endothelium while maintaining the structure, contractile function, and biomechanical properties of the vessel.

injury; zero-stress state; balloon injury; endothelin

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