Effects of hypertension and propranolol upon aneurysm expansion in the Anidjar/Dobrin aneurysm model.

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.

Enhanced revascularisation after angiogenic stimulation in a rabbit model of bilateral limb ischaemia.

OBJECTIVE: We previously demonstrated stimulation of collateral vessel formation in a rabbit model of unilateral limb ischaemia after administration of endothelial cell growth factor (ECGF). To distinguish clearly the effects of ischaemia alone from those of ischaemia combined with angiogenic stimulation in the same animal, a model of bilateral hindlimb ischaemia was used to evaluate further the angiogenic effect of ECGF. DESIGN: Ischaemia was produced in both hindlimbs of 11 rabbits by femoral artery excision. Beginning 10 days later, ECGF (8 mg in 3 ml of saline) was injected in one hindlimb while 3 ml of saline alone was injected in the other every other day for a total of five doses. OUTCOME MEASURES: Calf systolic blood pressure was measured in both limbs on postoperative days, 10, 30, and 50. On day 50, collateral formation was quantitated angiographically, and muscle samples were obtained for quantitation of capillary density and histologic studies. RESULTS: The mean calf systolic blood pressure in the both hindlimbs was similar on day 10 (36.9 +/- 2.3 versus 38.1 +/- 2.9 mmHg) but was significantly higher in the ECGF-treated limb on day 30 (68.9 +/- 3.1 versus 45.0 +/- 2.9 mmHg) and day 50 (83.0 +/- 3.0 versus 57.0 +/- 1.7; p < 0.0001 for both comparisons). On day 50, collateral vessels were significantly more numerous in the ECGF-treated limb (17.2 +/- 1.6 versus 11.0 +/- 0.8; p < 0.0006), as were capillaries (225.9 +/- 11.4 versus 159.6 +/- 12.9 per mm2; p < 0.002). CONCLUSION: Local administration of ECGF enhanced collateral development leading to significantly improved perfusion in the treated as compared with the untreated limb in the same animal. Exogenous administration of an angiogenic mitogen can upregulate the normal collateral response to ischaemia and may be useful in treating severe limb ischaemia.

Pulmonary embolism in pediatric trauma patients.

Recent articles in the literature on adults have recommended prophylaxis for pulmonary embolism (PE) in selected trauma patients; however, to date no information is available regarding pediatric patients. We decided to investigate whether the incidence of PE in pediatric trauma patients is as high as that reported in adults, and identify those children who might be at high risk and benefit from prophylactic treatment. Utilizing the data from the National Pediatric Trauma Registry (NPTR), records were reviewed of all pediatric trauma patients (age < 19 years) admitted to the participating institutions between December 1987 and February 1993. Patients with documented PE were identified as well as those having associated risk factors as identified in adult trauma patients (deep venous thrombosis, extremity injury, spinal cord injury, and head injury). A total of 28,692 pediatric trauma patients were reviewed from the NPTR. The mean age was 9 years and the mean Injury Severity Score for the group was 11. Two thousand one children (7%) had serious head injuries (Glasgow Coma Scale score < 8), over 5700 (20%) had an isolated extremity injury, 290 had an identified spinal cord injury (108 with associated paralysis), and deep venous thrombosis was identified in 6 patients. Pulmonary embolism occurred in only two of the children in this series. Both patients with PE had spinal cord injuries with associated paraplegia, significant pulmonary injury, and high ISSs (25 and 27). The overall incidence of PE in the group was 0.000069%, and for those children with paralysis from spinal cord injury 1.85%.(ABSTRACT TRUNCATED AT 250 WORDS)

Expansion of aortic aneurysms is reduced by propranolol in a hypertensive rat model.

PURPOSE: It has been suggested that propranolol has unique effects that slow aneurysm expansion by remodeling the structural proteins of the aorta. These effects are believed to be independent of blood pressure reduction, a hypothesis we tested in this investigation with a rat model of abdominal aortic aneurysm (AAA). METHODS: With an established model, AAA were induced in normotensive Wistar-Kyoto (WKY) rats and genetically hypertensive Wistar-Kyoto (WKHT) rats by perfusing an isolated segment of the infrarenal aorta with elastase. A propranolol dose-response was studied for each strain: (1) saline solution controls (n = 18); (2) propranolol, 10 mg/kg subcutaneously (n = 18); (3) propranolol, 30 mg/kg (n = 14). Systolic blood pressure was determined by tail plethysmography before operation and on day 14, as well as by direct recording at surgery and on day 14. Rats were killed at 14 days, and aneurysm diameter was measured. RESULTS: The initial tail BP was 129 +/- 22 mm Hg in WKY animals and 158 +/- 21 mm Hg in WKHT animals (p < 0.0001). Tail BP and intraaortic systolic, diastolic, and mean blood pressure (BP) were not significantly decreased by propranolol treatment in either strain of rats. However, BP tended to rise in WKY rats, whereas it fell slightly in WKHT rats. Initial aortic size in all animals was 1.06 +/- 0.12. The final aortic size in untreated, hypertensive rats was more than twice that of untreated normotensive controls: 1: WKHT, 3.0 +/- 0.73 mm, 1: WKY, 6.9 +/- 3.5 mm (p < 0.01). After treatment with both doses of propranolol, hypertensive aneurysms were significantly smaller than the untreated WKHT group (p < 0.05) and not significantly different from aneurysms in all groups of normotensive animals: 2: WKY, 3.1 +/- 1.13 mm, 2: WKHT, 4.0 +/- 1.81 mm; 3: WKY, 4.1 +/- 0.41 mm, 3: WKHT, 2.9 +/- 1.24 mm. There was no significant difference in aortic size between the three normotensive WKY groups. CONCLUSIONS: Hypertension increases the size of aortic aneurysms in this experimental model. Propranolol significantly reduces the size of experimental AAA in hypertensive animals independently of the dose and by a mechanism that may be unrelated to simple BP reduction.

Abdominal aortic aneurysm expansion rate: effect of size and beta-adrenergic blockade.

PURPOSE: The purpose of this study was to investigate the hypothesis that abdominal aortic aneurysm (AAA) expansion may be slowed by beta-adrenergic antagonists. METHODS: One hundred twenty-one patients with infrarenal AAA were monitored with serial aortic ultrasound examinations. Eighty-three patients received no beta-blockers (group I), and 38 patients received beta-blockers (group II). Values are expressed as mean +/- SD. RESULTS: The mean follow-up was 43 +/- 29 months with 5.5 +/- 3.4 ultrasound examinations per patient. The expansion rate among all AAA was 0.38 +/- 0.44 cm/yr. Large aneurysms (> or = 5 cm) expanded significantly faster than small aneurysms (p = 0.02) in patients not treated with beta-blockers. Among patients with large AAA, those receiving beta-blockers had a significantly reduced mean expansion rate; 0.36 +/- 0.20 versus 0.68 +/- 0.64 cm/yr, (p < 0.05). Although rupture rates were lower in group I (5%) versus group II (13%), this difference was not statistically significant. Thirty-four patients in a poor-risk category with AAA were monitored greater than 5 cm in diameter. Ten of these AAA ruptured. The mean expansion rate was significantly greater in those patients with ruptured AAA versus those patients with AAA that did not rupture; 0.82 +/- 0.74 versus 0.42 +/- 0.41 cm/yr (p = 0.04). CONCLUSIONS: In patients not undergoing beta-blocker therapy, large AAA expand at a significantly greater rate than smaller AAA. Large aneurysms that rupture show more rapid expansion than those AAA that do not rupture. We have demonstrated a significantly reduced rate of expansion of large AAA in patients receiving beta-blockade.

Hypertension accelerates the growth of experimental aortic aneurysms.

Hypertension has long been suspected to increase the growth rate of abdominal aortic aneurysms (AAA), but there is little experimental evidence to support this hypothesis. Using an established model, aneurysms were induced in normotensive Wistar-Kyoto (WKY) rats and in a unique strain of genetically hypertensive Wistar-Kyoto (WKHT) rats by perfusing an isolated segment of the infrarenal aorta with elastase (n = 14, each group). Aortic diameter was measured with a micrometer and systolic blood pressure (sBP) determined by tail plethysmography. Rats were killed at 7 or 14 days, aneurysm diameter was measured, and aneurysms were examined histologically. Systolic blood pressure was significantly higher in WKHT rats (164 +/- 15 mm Hg) compared to WKY animals (119 +/- 7 mm Hg, P < 0.001). Initial aortic size was 1.10 +/- 0.02 mm in the two groups. Aneurysms in the hypertensive animals were significantly larger at Day 7 (WKY, 2.31 +/- 0.09 mm; WKHT, 2.54 +/- 0.22 mm; P = 0.02) and Day 14 (WKY, 2.36 +/- 0.25; WKHT, 3.45 +/- 0.89; P = 0.001). Overall, the mean AAA growth rate of the WKYHT group was nearly twice that of the WKY group: 0.13 +/- 0.09 mm/day vs 0.07 +/- 0.03 mm/day, (P = 0.004). Growth rates were also positively correlated with sBP (r = 0.82, P < 0.0001). Both groups showed elastic lamellar disruption and inflammatory cell infiltration within the wall of the aorta. As demonstrated in this experimental model, hypertension does indeed increase the rate of growth of AAA.