A complex role for the progesterone receptor in the response to vascular injury.

Clinical studies of hormone replacement therapy to prevent cardiovascular diseases have heightened interest in the cardiovascular effects of progestins. However, the role of the progesterone receptor (PR) in vascular biology has not been studied in vivo. We studied ovariectomized female PR knockout (PRKO) mice and their wild-type (WT) littermates using the mouse carotid artery injury model. Placebo-treated PRKO mice showed significantly greater vascular medial hypertrophy and vascular smooth muscle cell (VSMC) proliferation in response to vascular injury than did WT mice. Progesterone had no significant effect in the PRKO mice, but worsened the response to injury in WT mice. VSMCs cultured from PRKO mouse aortae were markedly hyperproliferative, and their growth was not affected by progesterone. In contrast to the in vivo findings, progesterone inhibited proliferation of WT-derived VSMCs. Furthermore, reintroduction of PR into PRKO-derived VSMCs using adenoviral methods restored progesterone-mediated inhibition of proliferation to these cells. This effect was reversed by the PR antagonist, RU 486. Thus, the effects of PR and progesterone differ markedly between cultured VSMCs and intact blood vessels. These data demonstrate a direct role for the PR in regulating the response to vascular injury and VSMC proliferation.

Immunologic effects of acute hyperglycemia in nondiabetic rats.

BACKGROUND: This study was designed to determine the consequences of acute hyperglycemia on the immune function of peripheral neutrophils, peritoneal macrophages, and alveolar macrophages in nondiabetic rats. METHODS: The animals were randomly divided into nonsurgical (normal) and surgical groups. The postoperative rats were further divided into normoglycemic (control) and hyperglycemic (glucose) groups. The hyperglycemic condition was maintained by constant infusion of glucose to raise plasma glucose concentration to 300 mg/dL for 3 hours. The immune cells were then harvested to determine their phagocytic and oxidative capacities via flow cytometry. RESULTS: The results showed that hyperglycemia significantly decreased the respiratory burst of alveolar macrophages (p < .05). In contrast, hyperglycemia enhanced phagocytosis in these cells (p < .002). There was a significant activation of the respiratory burst in peripheral neutrophils by surgery (p < .002), but no effect of hyperglycemia. CONCLUSIONS: We conclude that hyperglycemia itself can influence immune function in some phagocytic cells, which may be an important factor in postsurgical infection.

The carotid artery as alternative access for endoluminal aortic aneurysm repair.

Endograft treatment of aortic aneurysms has become a common procedure in many centers. However, not all patients are candidates for this new technology, because of their vascular anatomy and device limitations. One common problem is iliofemoral occlusive disease, which when present, even in a moderate degree, may preclude introduction of the large-diameter delivery devices currently in use. We present a case of a high-risk male patient with a thoracic aortic aneurysm and severe occlusive disease of the iliac arteries. An alternative approach for device delivery through the carotid artery was used and the procedure was successful with no neurologic complications. We recommend this technique for highly selected patients with an aneurysm who can undergo tube endograft repair without feasible access through the iliac or femoral arteries.

Factors predicting prolonged length of stay after carotid endarterectomy.

BACKGROUND: Over the last several years, implementation of critical pathways in patients undergoing carotid endarterectomy has decreased postoperative length of stay significantly. Discharge the day after surgery has become commonplace in many centers, including our own. Unfortunately, managed care may interpret this refinement as a standard of care and limit reimbursement or even disallow admissions extending beyond 1 day. We therefore examined our carotid registry to identify risk factors associated with postoperative length of stay exceeding 1 day. METHODS: We retrospectively reviewed all patients undergoing carotid endarterectomy at our academic center from May 1996 through April 1999. Combined procedures and patients undergoing subsequent noncarotid-related procedures on those admissions were excluded. The charts were inspected for atherosclerosis risk factors, including sex and age, specific attending surgeon, side of the surgery, use of intravenous vasoactive drugs, actual preoperative blood pressure, and presence of neurologic symptoms or postoperative complications. Multiple regression analysis was performed on all collected variables. Statistical significance was inferred for P less than.05. RESULTS: A total of 188 patients met the study criteria and had complete, retrievable medical records. A mean postoperative length of stay of 1.65 +/- 0.08 days and a mean total length of stay of 2.17 +/- 0.14 days were observed. Fifty-seven percent of patients went home the day after surgery. There was a 1.6% stroke-mortality rate. Significant predictors of a prolonged stay, listed in order of decreasing importance on the basis of their calculated contribution to prolonging the postoperative length of stay, are as follows (P value; beta coefficient): postoperative complications (<.0001; 1.03), age > 79 years (.008; 0.547), diabetes mellitus (.011; 0.407), female sex (.007; 0.398), and intravenous vasodilator requirement (. 035; 0.382). Other atherosclerosis risk factors, prior neurologic symptoms, the postoperative use of vasopressors, and reoperative surgery did not contribute to extended length of stay. CONCLUSIONS: Discharge on the first postoperative day is feasible in many, but not all, patients undergoing carotid endarterectomy. Our data help define subsets of patients at risk for prolonged postoperative stay. Targeting these subsets for preoperative medical and social interventions may allow safe early discharge more frequently.

Estrogen inhibits the vascular injury response in estrogen receptor beta-deficient female mice.

The protective effects of estrogen in the cardiovascular system result from both systemic effects and direct actions of the hormone on the vasculature. Two estrogen receptors have been identified, ERalpha and ERbeta. We demonstrated previously that estrogen inhibits the response to vascular injury in both wild-type and ERalpha-deficient mice, and that ERbeta is expressed in the blood vessels of each, suggesting a role for ERbeta in the vascular protective effects of estrogen. In the present study, we examined the effect of estrogen administration on mouse carotid arterial injury in ERbeta-deficient mice. Surprisingly, in ovariectomized female wild-type and ERbeta knockout mice, 17beta-estradiol markedly and equally inhibited the increase in vascular medial area and the proliferation of vascular smooth muscle cells after vascular injury. These data demonstrate that ERbeta is not required for estrogen-mediated inhibition of the response to vascular injury, and suggest that either of the two known estrogen receptors is sufficient to protect against vascular injury, or that another unidentified estrogen receptor mediates the vascular protective effects of estrogen.