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Title: THE CORONARY ARTERY HISTOPATHOLOGIC RESPONSE TO ANGIOPLASTY BALLOON INJURY IN A SWINE MODEL IS GENDER- AND HORMONAL-DEPENDENT

Author
item WRAY-CAHEN, DIANE - FDA, CDRH
item PRITCHARD, WILLIAM - FDA, CDRH
item HILBERT, STEPHEN - FDA, CDRH
item Elsasser, Theodore
item KARANIAN, JOHN - FDA, CDRH

Submitted to: Endocrine Society Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 4/17/2003
Publication Date: 6/19/2003
Citation: Wray-Cahen, D., Pritchard, W.F., Hilbert, S.L., Elsasser, T.H., Karanian, J.W. 2003. The coronary artery histopathologic response to angioplasty balloon injury in a swine model is gender- and hormonal-dependent [abstract]. Annual Endocrine Society Meeting. p. 164.

Interpretive Summary:

Technical Abstract: The effects of gender and exogenous estrogen on the histopathologic response of the left anterior descending coronary artery (LAD) to angioplasty balloon over-inflation were examined in this study. In addition, we sought to develop an animal model to predict adequately the effects of cardiovascular interventional devices on vascular response in men and women to balloon angioplasty. Vascular responses in four gender groups of sexually mature domestic swine (123±1.6 kg) were compared: intact males (M; n=9), intact females (F; n=5), castrate males (Mx; n=7), and ovariectomized females (Fx; n=12). Exogenous estrogen (100 mg/kg, b-estradiol 17-cypionate) was administered daily via i.m. injection to ovariectomized females and was included as a fifth treatment group (Ex; n=7). Balloon over-inflation (21±1%) of the LAD was performed in all treatment groups and animals were allowed to recover from surgery. Animals received aspirin (1300 mg/d) for three days following the procedure. Thirty days (28-32d) after angioplasty balloon procedure, general anesthesia was induced, all animals were thoracotomized, and LADs harvested for histological preparation. Vessel diameter across all treatments was positively correlated to animal body weight (P<0.01). The balloon injury generally disrupted the internal elastic lamina and induced neointimal hyperplasia (NH) consisting primarily of loosely organized smooth muscle cells interposed in fibrotic extracellular matrix. A marked NH was noted in M. The proliferation index (PI), the ratio of neointima area/media area, was greater in M than F (0.36±0.06 vs. 0.07±0.02, respectively; P<0.01) and ovariectomy increased the PI to 0.33±0.07 (Fx vs. F; P<0.05). Castration did not significantly reduce the PI (Mx, 0.23±0.05). Estrogen administration tended to reduce the PI in ovariectomized animals (0.16±0.05; Fx vs. Ex, P<0.1), but did not obtain PI values observed in the F group. Similar gender differences were observed in intimal area, with the largest difference between M and F (0.85±0.23 vs. 0.11±0.06 mm2, respectively; P<0.05). NH was dependent on both gender and hormonal state; greater in M than in F and ovariectomy removed the observed female gender advantage. These data suggest that gender and hormonal factors play a role in the vascular tissue response to interventional devices and should be considered in the development of interventional strategies to limit adverse responses.