A nonpeptide mimic of bradykinin blunts the development of hypertension in young spontaneously hypertensive rats.
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We tested whether FR190997, a nonpeptide B(2) agonist, prevented the development of hypertension in young spontaneously hypertensive rats (SHR), which secrete less kallikrein into the urine than do Wistar-Kyoto rats. An intra-arterial (IA) injection of FR190997 (0.3 to 30 nmol/kg) caused dose-dependent hypotension in conscious Sprague-Dawley rats. Although the maximum hypotensive potency of FR190997 equaled that of bradykinin, its action lasted approximately 10 times as long. Hoe140 (100 nmol/kg IA) significantly blocked the hypotensive response induced by FR190997 (10 nmol/kg). Atropine (100 nmol/kg IA) did not affect this response. A selective infusion of FR190997 into the renal artery induced natriuresis and diuresis in anesthetized rabbits. A continuous infusion (2 nmol. 10 mL(-1). h(-1) per rat) of FR190997 into the abdominal aorta of young SHR (6 weeks old, n=6) for 6 days significantly (P<0.05) reduced mean blood pressure to 114+/-6 (day 2) and 110+/-6 (day 5) mm Hg, from 149+/-7 and 162+/-6 mm Hg, respectively, in vehicle-infused rats (n=6). At 8 days after continuous infusion (day 14), mean blood pressure (148+/-5 mm Hg) in FR190997-infused rats remained significantly (P<0. 05) lower than that in vehicle-infused rats (190+/-6 mm Hg), almost the peak value. The mesenteric artery isolated from FR190997-treated rats (day 14) had lower contractile sensitivity to norepinephrine than that from vehicle-treated rats. These results suggested that the continuous infusion of a nonpeptide B(2) agonist may prevent hypertension if performed in the critical phase. (+info)
Vascular hyporesponsiveness in simulated microgravity: role of nitric oxide-dependent mechanisms.
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Simulated microgravity depresses the ability of arteries to constrict to norepinephrine (NE). In the present study the role of nitric oxide-dependent mechanisms on the vascular hyporesponsiveness to NE was investigated in peripheral arteries of the rat after 20 days of hindlimb unweighting (HU). Blood vessels from control rats and rats subjected to HU (HU rats) were cut into 3-mm rings and mounted in tissue baths for the measurement of isometric contraction. Mechanical removal of the endothelium from carotid artery rings, but not from aorta or femoral artery rings, of HU rats restored the contractile response to NE toward control. A 10-fold increase in sensitivity to ACh was observed in phenylephrine-precontracted carotid artery rings from HU rats. In the presence of the nitric oxide synthase (NOS) substrate L-arginine, the inducible NOS inhibitor aminoguanidine (AG) restored the contractile responses to NE to control levels in the femoral, but not carotid, artery rings from HU rats. In vivo blood pressure measurements revealed that the peak blood pressure increase to NE was significantly greater in the control than in the HU rats, but that to AG was less than one-half in control compared with HU rats. These results indicate that the endothelial vasodilator mechanisms may be upregulated in the carotid artery, whereas the inducible NOS expression/activity may be increased in the femoral artery from HU rats. These HU-mediated changes could produce a sustained elevation of vascular nitric oxide levels that, in turn, could contribute to the vascular hyporesponsiveness to NE. (+info)
Hospital cost of endovascular versus open repair of abdominal aortic aneurysms: a multicenter study.
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BACKGROUND: Technology-driven innovation in medicine is frequently associated with higher costs than conventional therapy. A significantly higher cost for endovascular ($21,250, n = 190) versus open abdominal aortic aneurysm (AAA) repair ($12,342, n = 60) was suggested by a direct cost analysis of patients in a multicenter trial. Estimated inpatient costs (not charges) incurred nationwide by hospitals for endovascular and open repair of AAA were studied to validate these observed trends. METHODS: A retrospective analysis of 131 patients undergoing endovascular AAA repair was compared with 49 patients undergoing open repair as part of a Food and Drug Administration phase II prospective multicenter clinical investigation (AneuRx-Medtronic). A model to estimate costs was constructed using important clinical descriptors of these patients. These clinical characteristics where then matched with those from 22, 460 patients undergoing AAA repair obtained from a large national database (Medicare Provider Analysis and Review). Estimated hospital cost was then assigned to each study patient according to the national average of the total hospital costs for the respective matched patients in Medicare Provider Analysis and Review. RESULTS: Total inpatient hospital costs of endovascular repair were significantly higher than that of open repair ($19,985 +/- 7396 versus $12,546 +/- 5944, respectively, P =.0001). Endograft device cost ($10,400) accounted for 52% of the total cost of endovascular repair. The 1999 mean blended Medicare reimbursement for AAA repair was $18,989. CONCLUSION: In this early development stage, hospital cost for endovascular AAA repair is significantly greater than open repair when device cost greatly exceeds $5000. Although incremental reductions in cost of endovascular repair may be anticipated if use of diagnostic studies, operating time, and length of stay decrease, device cost has the single greatest impact on the expense of endovascular AAA repair. At current device pricing, mean blended Medicare reimbursement does not cover the cost of endovascular AAA repair. (+info)
The reduction of the allogenic transfusion requirement in aortic surgery with a hemoglobin-based solution.
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OBJECTIVE: Because of allogenic red blood cell (RBC) availability and infection problems, novel alternatives, including hemoglobin-based oxygen-carrying solutions (HBOC), are being explored to minimize the perioperative requirement of RBC transfusions. This study evaluated HBOC-201, a room-temperature stable, polymerized, bovine-HBOC, as a substitute for allogenic RBC transfusion in patients undergoing elective infrarenal aortic operations. METHODS: In a single blind, multicenter trial, 72 patients were prospectively randomized two-to-one to HBOC (n = 48) or allogenic RBC (n = 24) at the time of the first transfusion decision, either during or after elective infrarenal aortic reconstruction. Patients randomized to the HBOC group received 60 g of HBOC for the initial transfusion and had the option to receive three more doses (30 g each) within 96 hours. In this group, any further blood requirement was met with allogenic RBCs. Patients randomized to the allogenic RBC group received only standard RBC transfusions. The efficacy analysis was a means of assessing the ability of HBOC to eliminate the requirement for any allogenic RBC transfusions from the time of randomization through 28 days. Safety was evaluated by means of standard clinical trial methods. RESULTS: The two treatment groups were comparable for all baseline characteristics. Although all patients in the allogenic RBC group required at least one allogenic RBC transfusion, 13 of 48 patients (27%; 95% CI, 15% to 42%) in the HBOC group did not require any allogenic RBC transfusions. The only significant changes documented were a 15% increase in mean arterial pressure and a three-fold peak increase in serum urea nitrogen concentration after HBOC. The complications were similar in both groups, with no allergic reactions. There were two perioperative deaths (8%) in the allogenic RBC group and three perioperative deaths (6%) in the HBOC group (P = 1.0). CONCLUSION: HBOC significantly eliminated the need for any allogenic RBC transfusion in 27% of patients undergoing infrarenal aortic reconstruction, but did not reduce the median allogenic RBC requirement. HBOC transfusion was well tolerated and did not influence morbidity or mortality rates. (+info)
Local infusion of heparin reduces anastomotic neointimal hyperplasia in aortoiliac expanded polytetrafluoroethylene bypass grafts in baboons.
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PURPOSE: Recently, we designed and characterized a novel expanded polytetrafluoroethylene (ePTFE)-based local drug delivery approach that selectively concentrates infused pharmacologic agents specifically within those blood layers adjacent to the graft wall and at downstream anastomotic sites. In this study, we locally administrated standard heparin therapy and evaluated its effects on neointimal hyperplasia formation in a baboon model of aortoiliac bypass graft placement. METHODS: Six adult male baboons underwent bilateral aortoiliac bypass grafting with ringed ePTFE (4 mm internal diameter x 5 cm length). In each animal, the distal anastomosis of one graft was continuously infused with heparin (50 U/h) and the distal anastomosis of the contralateral graft was infused with saline solution at the same rate (2.5 microL/h), with osmotic pumps implanted for 4 weeks. Platelet counts and activated partial thromboplastin time measurements were performed weekly. The specimens were harvested at 4 weeks and were subjected to morphometric analysis. Cell proliferation was assessed with bromodeoxyuridine immunostaining. RESULTS: All the harvested grafts were patent except for one control graft. There were no significant differences in platelet counts or activated partial thromboplastin time measurements taken before and during heparin infusion. As expected, there were no significant differences in graft neointimal hyperplasia and cell proliferation at the proximal anastomoses between the heparin-infused and control grafts. In contrast, at the treated distal anastomoses, heparin infusion significantly reduced the graft neointimal area by 65% and the cell proliferation index by 47% as compared with the untreated control distal anastomoses. CONCLUSION: These results show that local infusion of heparin significantly reduces distal anastomotic neointimal hyperplasia and cell proliferation without measurable systemic anticoagulation or other side effects. Thus, this approach may represent an attractive strategy for prolonging ePTFE bypass graft patency. (+info)
Lateral zone of cell-cell adhesion as the major fluid shear stress-related signal transduction site.
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It has been proposed previously that actin filaments and cell adhesion sites are involved in mechanosignal transduction. In this study, we present certain morphological evidence that supports this hypothesis. The 3D disposition of actin filaments and phosphotyrosine-containing proteins in endothelial cells in situ was analyzed by using confocal microscopy and image reconstruction techniques. Surgical coarctations were made in guinea pig aortas, and the same 3D studies were conducted on such areas 1 week later. Stress fibers (SFs) were present at both basal and apical regions of endothelial cells regardless of coarctation, and several phosphotyrosine-containing proteins were associated with SF ends. Apical SFs had one end attached to the apical cell membrane and the other attached to either the basal membrane or the lateral cell border. Within the coarctation area, the actin filament-containing and vinculin-containing structures became prominent, especially at the apical and the lateral regions. Substantially higher levels of anti-phosphotyrosine and anti-Src staining were detected in the constricted area, particularly at the cell-cell apposition, whereas the anti-focal adhesion kinase, anti-CT10-related kinase, anti-platelet endothelial cell adhesion molecule-l, anti-vinculin, and phalloidin staining intensities increased only slightly after coarctation. We propose that apical SFs directly transmit the mechanical force of flow from the cell apex to the lateral and/or basal SF anchoring sites and that the SF ends associated with signaling molecules are sites of signal transduction. Our results support the idea that the cell apposition area is the major fluid shear stress-dependent mechanosignal transduction site in endothelial cells. (+info)
Endovascular healing is inadequate for fixation of Dacron stent-grafts in human aortoiliac vessels.
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BACKGROUND: migration and kinking of stent-grafts can occur late after endovascular aneurysm repair. It is unknown if endovascular grafts incorporate enough to be permanently anchored. In this report, healing of aortic stent-grafts was assessed in humans. PATIENTS AND METHODS: we retrieved 23 Dacron stent-grafts from patients treated for an aortic aneurysm since 1993. Twelve stent-grafts were explanted at late conversion to open repair and 11 at autopsy. The deaths were unrelated to graft fixation. The median age of the patients was 74 years (IQR 55-84 years) and the grafts were explanted 9 months (1-31 months) after insertion. Microscopic slides were prepared by conventional techniques or by cutting and grinding arterial specimens embedded in plastic with the stent-grafts in situ. RESULTS: the stent-grafts detached readily from the native arteries at surgery or autopsy, except when the stents had hooks or barbs which engaged the vessel wall. A space filled with poorly organised blood components persisted between the graft and the aortic wall 2.5 years after implantation. No firm incorporation of the grafts was observed proximally in the aneurysm neck or distally in the iliac segment. A friable neo-intimal layer covered parts of the luminal aspect of the grafts. CONCLUSIONS: endovascular healing provides poor fixation of Dacron stent-grafts in humans. At present, fixation relies on the mechanical properties of the stent-grafts. (+info)
Abdominal aortic laparoscopic surgery: retroperitoneal or transperitoneal approach?
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OBJECTIVE: to define the respective advantages and pitfalls of the trans- or retroperitoneal approaches in laparoscopic abdominal aortic reconstruction (LAOR). DESIGN: prospective study. MATERIAL: ten patients (8 males; average age 58) underwent an aortouni- (n=2) or bifemoral bypass (n=8) to treat aortoiliac occlusive disease (n=8) or an aortic aneurysm (n=2). METHODS: a retroperitoneal approach (the "apron" technique) was used in the first 5 cases (Group I) and a transperitoneal approach in the last 5 cases (Group II). RESULTS: no early or late death occurred, and all bypasses remain patent after a mean follow-up of 5.7 months. Mean surgical and clamping times are similar in both groups (370 and 126 min in Group I; 324 and 137 min in Group II). One intraoperative conversion to open surgery and two postoperative surgical complications occurred in Group I. Four minilaparotomies of 8-10 cm were necessary in Group II. Two patients were discharged on postoperative day 6 in Group I and five in Group II. CONCLUSION: this preliminary study shows the feasibility of LAOR through both approaches. In Group II, a better exposure of the right aortic wall and of the right iliac axis was noted and division of the inferior mesenteric artery was not always necessary. (+info)