Alterations in wall tension and shear stress modulate tyrosine kinase signaling and wall remodeling in experimental vein grafts

AbstractPurpose: Hemodynamic alterations have been implicated as major stimuli for the development of intimal hyperplasia in vein grafts that are implanted in the arterial circulation. Tyrosine kinase is known to mediate cell signaling. However, its role with in vivo mechanotransduction is not yet well defined. We used a novel bioprosthetic collagen tube to provide an external support to vein grafts and examined the subsequent changes in hemodynamics, tyrosine kinase signaling, wall remodeling, and vasomotor function. Methods: Carotid interposition bypass grafting was performed with the reversed jugular vein in New Zealand white rabbits. In the experimental group (n = 15), after the completion of the proximal anastomosis, the vein was passed through a 4-mm collagen tube and the distal anastomosis was performed. The tube support was fashioned to completely cover the vein grafts. The control animals (n = 14) had no tube support. After surgery, the blood pressure and flow rate were measured and the wall tension and shear stress were calculated in the vein grafts on day 3 or day 28 (n = 5 per group). Tyrosine phosphorylation was assessed with the Western blot test in vein grafts at day 3 (n = 4 per group). The intimal and medial dimensions of the vein grafts were assessed with videomorphometry on day 28 (n = 5 per group). The cumulative dose response curves of the vein grafts to contractile and relaxant agonists were determined in isometric tension studies on day 28 (n = 5 per group). Results: The use of tube support reduced wall tension 1.7-fold (P < .01) and increased shear stress 4.8-fold (P < .001) without altering the flow rate or blood pressure. The tyrosine kinase activity was reduced 15-fold (P < .001) in the tube-supported vein grafts. The intimal thickness was reduced by 45% in the tube-supported vein grafts as compared with the control grafts (46 ± 2 mm vs 84 ± 5 mm, respectively; P < .0001), and the media thickness was reduced by 20% (63 ± 8 mm vs 79 ± 4 mm, respectively; P < .05). Isometric tension studies showed preservation of contractile function and modulation of endothelial-dependent dysfunctional relaxation in tube-supported vein grafts. Conclusion: These results show that reduced wall tension and increased shear stress with an external tube support can effectively modulate the signaling, functional, and hyperplastic responses in vein grafts. We conclude that this simple strategy deserves further study and clinical consideration. (J Vasc Surg 1999;29:334-44.

Cerebral monitoring with transcranial Doppler ultrasonography improves neurologic outcome during repairs of acute type A aortic dissection

ObjectiveNeurologic complications after repair of acute type A aortic dissection remain significant. The use of power M-mode transcranial Doppler monitoring to verify cerebral blood flow during these repairs might decrease cerebral ischemia by correcting malperfusion. The purpose of this study was to analyze the use of power M-mode transcranial Doppler monitoring during repairs of acute type A dissection with regard to neurologic outcome.MethodsWe performed a prospective study of patients undergoing repairs of acute type A aortic dissection. Repairs included profound hypothermic circulatory arrest and retrograde cerebral perfusion. Patients in whom transcranial Doppler monitoring was used to monitor cerebral blood flow and modify operative technique during repair (study group) were compared with those without monitoring and modification (control group).ResultsBetween September 2001 and October 2003, we repaired 56 cases of acute type A dissection. Power M-mode transcranial Doppler monitoring was used in 50% (28/56) of cases. Power M-mode transcranial Doppler monitoring altered operative cannulation and guided retrograde cerebral perfusion flow in 28.5% (8/28) and 78.6% (22/28) of cases, respectively. Two patients presented with preoperative stroke, one in each group. One operative death occurred in each group. In-hospital mortality and the occurrence of new stroke were not significantly different between the 2 groups. Temporary neurologic dysfunction occurred less often in the study group (14.8% [4/27] vs 51.8% [14/27], P = .008).ConclusionsIdentification of cerebral malperfusion requires cerebral monitoring. By ensuring cerebral blood flow by using power M-mode transcranial Doppler monitoring and correcting cerebral malperfusion by modifying operative technique, neurologic outcome was improved during repairs of acute type A aortic dissection

Glomerular filtration rate is superior to serum creatinine for prediction of mortality after thoracoabdominal aortic surgery

BackgroundClinically evident renal disease (dialysis, history of renal insufficiency, or serum creatinine >2.0 mg/dL) is a known risk factor for mortality after thoracoabdominal aortic aneurysm repair. We extended this concept to the questions of whether subclinical renal disease is also a risk factor and how best to identify subclinical disease. We hypothesized that the glomerular filtration rate (GFR) would be a more sensitive determinant of renal function than serum creatinine alone.MethodsBetween 1991 and 2004, we repaired 1106 thoracoabdominal aortic aneurysms and descending thoracic aortic aneurysms. The median age was 67 years. There were 400 (36%) women and 706 (64%) men. We estimated GFR by using the Cockcroft-Gault equation. We divided baseline serum creatinine and baseline GFR into quartiles and estimated the association of the quartiles with 30-day postoperative mortality by χ2 testing. We further subdivided the population into patients with and without clinically evident renal disease and repeated the analysis in the patients without clinically apparent disease (n = 869).ResultsClinically apparent renal disease was highly associated with 30-day mortality (odds ratio, 3.2; P < .0001). In all patients, serum creatinine quartile and GFR quartile were also both highly significantly associated with 30-day mortality (P < .0001). In patients without clinically apparent renal disease, both creatinine and GFR predicted additional mortality, but GFR was a much stronger predictor (P < .02 for creatinine vs <.0001 for GFR). In these patients, mortality ranged from 5% in the best GFR quartile to 27% in the worst. Taken as continuous variables in logistic regression equations, serum creatinine had no discrimination in patients without clinical disease (P = .73), whereas GFR remained strong (P <.0001).ConclusionsPreoperative renal function is an important determinant of early mortality even in patients without clinically evident disease. Estimated GFR is a much more powerful determinant of mortality risk than serum creatinine alone

Local treatment with recombinant tissue factor pathway inhibitor reduces the development of intimal hyperplasia in experimental vein grafts

AbstractBackground: Tissue factor (TF)–initiated thrombin generation has been implicated in the development of intimal hyperplasia after arterial injury. An increase in intimal TF expression has been shown to precede the development of intimal hyperplasia in vein grafts. This study examines the effects of local treatment with recombinant human tissue factor pathway inhibitor (rTFPI) in experimental vein grafts. Methods: Thirty-six male New Zealand white rabbits underwent bypass grafting of the carotid artery by use of the reversed ipsilateral jugular vein and were divided into four groups. Twenty animals had ex vivo incubation with rTFPI treatment (50 μg · mL–1; n = 10) or placebo vehicle (control; n = 10). Sixteen animals received both ex vivo incubation and in vivo gel treatment with rTFPI (50 μg · mL–1; n = 8) or without rTFPI (gel-control; n = 8). After operation, vein grafts were harvested at 3 days for immunohistochemical and Western analyses and at 28 days for histomorphologic study. Results: Western analysis demonstrated a 6.2-fold reduction in the expression of TF protein with rTFPI treatment in comparison to without rTFPI treatment. CD-18 leukocyte staining was diminished, whereas Tie-2 endothelial staining was increased in all rTFPI-treated vein grafts, compared with control and gel-control vein grafts. Intimal thickness was reduced by 21% with ex vivo rTFPI treatment compared with placebo (69 ± 4 versus 87 ± 5 μm; P <.05) and by 30% with the addition of rTFPI in vivo compared with gel-control (60 ± 4 versus 86 ± 5 μm; P <.01). Conclusion: Local administration of rTFPI exerts early beneficial effects and limits the development of intimal hyperplasia in vein grafts. Therefore blocking TF-mediated pathway may offer new therapeutic options to reduce vein graft failure. (J Vasc Surg 2001;33:400-7.