Effects of Hypertension and Propranolol upon Aneurysm Expansion in the Anidjar/Dobrin Aneurysm Modela

Abstract

Propranolol has been suggested to slow aortic aneurysm (AAA) expansion by a mechanism independent of simple blood pressure (BP) reduction. To investigate this hypothesis, we designed a series of experiments to examine the effects of hypertension and propranolol upon AAA expansion. Using an established animal model, we induced AAA in normotensive and genetically hypertensive rats by perfusion of the isolated infrarenal aorta with elastase for two hours. Systolic tail BP was monitored with a plethysmograph. AAA size was measured directly with a micrometer on postoperative days 7 and 14. All data are expressed as the mean +/- standard deviation (SD). BP (mmHg) was significantly higher in hypertensive rats: 164 +/- 15 versus 119 +/- 7 (p < 0.001). AAA were also significantly larger in hypertensive rats with a mean expansion rate (mm/day) nearly twice that of normotensive animals: 0.13 +/- 0.09 versus 0.07 +/- 0.03. In a second series of animals, propranolol treatment was compared to placebo. In those animals, hypertensive propranolol-treated rats had significantly smaller AAA than placebo-treated controls (p < 0.05). There was no difference in normotensive animals but these rats had an unexplained paradoxical rise in BP with treatment. In this model, hypertension increases the expansion rate of AAA. Propranolol reduced the size of AAA in hypertensive animals, at least in part because of a decrease in BP. Other possible mechanisms of propranolol's action may be operative and require further study.

The Effect of Immunosuppression on Aortic Dilatation in a Rat Aneurysm Model

“…17 Other investigators have reported that aortic dilatation can be attenuated by a variety of compounds. [15][16][17][18][19][21][22][23][24] In these reports elastin fibers were also preserved as in the animals studied by Dobrin et al…”

“…Since this experimental model exhibits several similarities to human abdominal aortic aneurysms, 14 a variety of laboratories have used it to investigate the pathogenesis and prevention of aneurysm growth. 10,12,13,[15][16][17][18][19][21][22][23][24] In this study, we used a modification of the model that we recently described. 25 An inflammatory response is a critical step in this model.…”

“…[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] These inflammatory cells include neutrophils, monocyte-macrophages, and lymphocytes. 11,13,14,17,18 The interactions of these cells with one another modify their functions at the sites of inflammation.…”

“…8 An elastase-induced rat aneurysm model is commonly used to investigate the pathogenesis and prevention of abdominal aortic aneurysms. [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] In this model, inflammatory cell infiltration of the aortic wall occurs in temporal relation to an increase in the aortic diameter. 9,11,13,14 Inflammatory cell infiltration is considered to be a critical step in the development of aortic aneurysms in these rats.…”

The time course of elastin fiber degeneration in a rat aneurysm model

“…Previous investigators have reported that aortic dilatation is attenuated by various compounds in this aneurysm model, [3][4][5][8][9][10][11]13 and that elastin fibers are well preserved under these conditions. [3][4][5][9][10][11]13 These investigators have interpreted these findings as follows: there is very little damage to the elastin fibers immediately after elastase infusion; endogenous proteinases produced either by infiltrating cells or resident mesenchymal cells cause degeneration of the elastin fibers; and the exogenously infused elastase is essential for the induction of endogeneous proteinases rather than the degeneration of elastin fibers directly.…”