David G. Neschis

Bone Formation in Carotid Plaques A Clinicopathological Study

Background and Purpose— Bone formation and dystrophic calcification are present in carotid endarterectomy plaques. The clinical significance of these findings is unknown. The purpose of this study was to determine whether bone formation and extensive dystrophic calcification are associated with stable plaques and protective against ischemic vascular events. Methods— Carotid endarterectomy plaques were collected from 142 patients (94 men) with carotid stenosis. The specimens were evaluated for lamellar bone formation, dystrophic calcifications, inflammatory infiltrates, neovascularization, and histological type or grade of plaque according to a standard AHA grading system. Immunohistochemical staining was performed to identify vascular endothelial cells in neovascularization (factor VIII) and lymphocytes. Clinical data, including history of cerebrovascular and cardiovascular events, were recorded at the time of surgery. Results— Patients with calcification of carotid plaques had fewer symptoms of stroke and transient ischemic attack (P =0.042) than those without calcification. Stroke and transient ischemic attack occurred less frequently in patients with plaques with large calcific granules (P =0.021). Of the patients, 13% had lamellar bone formation, which directly correlated with the presence of sheetlike calcifications (P =0.0001) and inversely correlated with ulcerated lesions (P =0.048). The presence of bone also correlated with diabetes (P <0.01) and coronary artery disease (P <0.01). Of the 20 patients with bone, 6 had a history of stoke and transient ischemic attack (P =0.5). Conclusions— The results indicate that bone formation tends to occur in heavily calcified carotid lesions devoid of ulceration and hemorrhage. Patients with extensive calcification of the carotid plaques are less likely to have symptomatic disease.

Antisense basic fibroblast growth factor gene transfer reduces neointimal thickening after arterial injury

PURPOSE To determine whether synthesis of endogenous basic fibroblast growth factor (bFGF) after arterial injury is critical to the intimal thickening response, intraluminal adenoviral gene transfer of an antisense bFGF (Ad.ASbFGF) transgene was used to inhibit the subsequent synthesis of bFGF protein after injury. METHODS Sprague-Dawley rats underwent balloon catheter carotid artery injury and in vivo gene transfer. Isolated segments of rat common carotid artery were infected with an adenoviral vector encoding an antisense bFGF transcript at concentrations of 2 x 10(9), 1 x 10(10), or 1 x 10(11) pfu/ml. Control rats were treated with either a control adenovirus encoding the beta-galactosidase gene, (Ad.lacZ), at 1 x 10(10), or 1 x 10(11) pfu/ml, or phosphate-buffered saline solution (vehicle). Two weeks after injury the rats were killed and perfusion-fixed. Cross-sectional areas of the carotid arterial intima and media were measured by planimetry, and the intima/media ratio (I/M) was calculated for each vessel. RESULTS The mean I/M for each Ad.ASbFGF group and controls were compared and the significance assessed by analysis of variance. At two weeks after injury, the highest dose of Ad.ASbFGF, 1 x 10(11) pfu/ml, resulted in a near total inhibition of thickening (I/M = 0.14 +/- 0.04, mean +/- SEM) when compared with phosphate-buffered saline solution alone (I/M = 0.99 +/- 0.07), or Ad.lacZ 1 x 10(10) pfu/ml (I/M = 1.01 +/- 0.10) control treatments (p < 0.01). A tenfold lower dose of Ad.ASbFGF, 1 x 10(10) pfu/ml, also caused significant reduction in intimal thickening (I/M = 0.39 +/- 0.07, p < 0.01). Treatment with 2 x 10(9) pfu/ml Ad.ASbFGF did not significantly limit intimal thickening (I/M = 0.72 +/- 0.12). CONCLUSIONS Inhibition of bFGF synthesis in vivo using an antisense RNA strategy significantly inhibits intimal thickening after arterial balloon injury. This study suggests that continued bFGF synthesis contributes to intimal thickening after arterial injury, and that antisense bFGF may represent an effective strategy in limiting restenosis after angioplasty.

Management of pancreaticoduodenal artery aneurysms presenting as catastrophic intraabdominal bleeding

BACKGROUND Pancreaticoduodenal artery aneurysms (PDAs) are rare, accounting for only 2% of all visceral artery aneurysms. The majority of reported cases of patients with PDA have presented subsequent to rupture. Presentation without rupture also has been reported and is often associated with abdominal discomfort or diagnosed incidentally on radiologic studies. PDA rupture is associated with a high mortality rate, with fatal bleeding into the retroperitoneal space, intraperitoneal cavity, or gastrointestinal tract. METHODS This article reports two cases of ruptured PDA, both presenting as catastrophic intraabdominal bleeding and both treated successfully at celiotomy. In addition, the literature concerning PDA is reviewed. RESULTS Only 11 cases of PDA associated with sudden, severe abdominal pain and shock have been described. The mortality rate in these 11 cases was 36%, with half the patients not reaching the operating room alive. Successful management includes rapid resuscitation and control of the bleeding site with minimal pancreatic dissection, angiography for confirmation of vascular control and anatomic localization, and further definitive treatment if obliteration is incomplete. CONCLUSIONS The aneurysm should be obliterated whenever possible to avoid both rebleeding and local complications related to mass effect such as pancreatic duct obstruction or erosion of the mass into neighboring structures. With appropriate and expeditious treatment, these gravely ill patients can be managed effectively and good outcomes obtained.

Endograft repair of traumatic aortic injury-a technique in evolution: a single institution's experience.

Objective:We evaluated a large single center experience of endograft repair of blunt traumatic injury of the thoracic aorta. Summary Background Data:Traumatic aortic transection is a devastating injury with high morbidity and mortality. Endograft repair of these injuries has reduced the rates of death and paraplegia seen with open surgical treatment in the past. However, endograft repair has been associated with a higher incidence of device related failure. Methods:The records of 43 consecutive cases of endograft treatment of traumatic aortic injury from December 2004 to November 2008 were reviewed. Patient demographics, procedure details, and outcomes were recorded. Aortic morphology was analyzed for predictors of device failure. Results:Forty-three patients (32 men) with a mean age of 44 years (range: 17–88) were treated. Primary technical success was 86%. Six proximal endoleaks (14.3%) occurred. Two were repaired with a more proximal cuff, but 3 required explantation and open repair (7%). Mortality in this series was 11.6%, but no death was aorta related. No patient having endograft treatment suffered postoperative paraplegia. Early device failure is associated with sharp angulation of the aorta and shortened distance between the left subclavian artery and the site of injury. Follow-up ranged from 1 to 38 months (mean: 7.4 months). There were no late device failures or complications. Conclusions:Endovascular repair of blunt traumatic aortic injury can be performed with a low morbidity and mortality. Anatomic patterns in the aortic arch appear to be predictive of early device failure. Midterm durability is excellent, but reliable follow-up remains challenging in this group of patients.

Thermal Preconditioning Before Rat Arterial Balloon Injury Limitation of Injury and Sustained Reduction of Intimal Thickening

Heat shock proteins (HSPs) are a family of highly conserved proteins, essential to cell survival, that are induced during times of physiological stress. These proteins, when induced, can provide tolerance to subsequent injury. Several studies have documented that HSPs play an important role in the response of vascular cells to injury or stress. Whether the vasculature itself can be effectively preconditioned before arterial injury is unknown. Vascular HSP induction by whole-body hyperthermia (WBH) was evaluated with regard to its effects on the vascular response to balloon injury. WBH treatment of Sprague-Dawley rats (colonic temperatures of 41 to 42 degrees C for 15 minutes) resulted in maximal arterial HSP expression within 8 to 12 hours. Rats (male, 300 g, n=59) were randomly assigned to undergo either WBH or no treatment 8 hours before standard carotid balloon injury. At 14 (n=26) and 90 (n=21) days after balloon injury, histomorphometric analysis revealed a significant limitation of intimal accumulation in preconditioned arteries as compared to controls (intimal/medial area ratios+/-SEM: 14 days, 0.57+/-0.07 versus 0.86+/-0.08, P=0.01; 90 days, 0.78+/-0.12 versus 1.19+/-0.14, P<0.05). The medial cell proliferation index at 4 days (n=12) was significantly reduced in the treated group as well (3.6+/-0.9% versus 7.2+/-1.3%, P<0.05). Conversely, the mean total cell number in the media of heated arteries was higher (393+/-20 versus 328+/-17, P<0.05). Vascular preconditioning with brief WBH induces a heat shock response in the arterial wall that is associated with a significant and sustained reduction in intimal accumulation. This effect appears to be due in part to preservation of medial cell integrity and limitation of the proliferative response. These results suggest that thermal preconditioning of vascular tissue may be an effective strategy to improve long-term results after revascularization procedures.

Endovascular Embolization of a Giant Renal Artery Aneurysm With Preservation of Renal Parenchyma

Renal artery aneurysm is a rare condition that has an unclear etiology. Although some patients present with symptoms of hypertension, pain, hematuria, or rupture, the majority are asymptomatic. Traditional surgical repair of renal artery aneurysms is often complex and may require ex vivo repair and reimplantation of the kidney if branch vessels are involved. Very large aneurysms made require nephrectomy. More recently, reports have described endovascular approaches to renal artery aneurysms, including coil embolization and stent graft coverage. This report describes successful endovascular treatment of a 10-cm renal artery aneurysm with preservation of renal mass.

Stent grafting for a distal thoracic aortic injury.

Aortic injury following blunt trauma can be potentially devastating, particularly when it occurs in multiply injured patients. This injury normally occurs just distal to the left subclavian artery. Recently, stent grafting has become a mainstay in therapy. Although technical challenges certainly exist in stent grafting aortic injuries in this location, the ability to avoid all complications associated with traditional open repair make stent grafting extremely attractive. We present a case on a 41-year-old man who sustained an aortic injury just proximal to the celiac axis. We used stent grafting to treat this injury with a very favorable result.

Late-Term Complication of Endograft Repair for Aortoenteric Fistula

Aortoenteric fistula is a devastating complication of aortic aneurysm repair. Traditional repair carries a high risk of mortality and significant morbidity. While endograft repair can be effective at mitigating the immediate life-threatening bleed, the temptation to consider endograft repair as definitive treatment should be resisted. We present a case of a 72 year old male who developed an aortoenteric fistula four years following surgical repair of a ruptured aortic aneurysm. Four years thereafter the patient developed infection of the graft and required extra-anatomic bypass and excision of the infected graft. Endograft repair of aortoenteric fistula is associated with persistent infection and should be viewed as a temporizing measure. Here we present the case and review the literature regarding the treatment and outcome of this condition.

Combined endovascular and surgical repair of a large traumatic pseudoaneurysm of the thigh. A case report

Thigh pseudoaneurysms are rare compared to pseudoaneurysms of the groin, and usually result from direct injury to an arterial branch. Direct open repair can be associated with a large volume blood loss. The authors describe a combined endovascular and surgical approach to a large, traumatic, pseudoaneurysm of the thigh. The patient was a 49-year-old man with a history of left femur fracture treated by open reduction and internal fixation, who presented with a painfully swollen left thigh. Duplex ultrasound and computed tomography (CT) scan suggested a large (7.7 x 5.0 x 6.3 cm) pseudoaneurysm that appeared to be associated with a branch of the deep femoral artery. In the operating room, angiography was used to identify and selectively access the feeding artery. This artery was then successfully coil embolized, allowing surgical decompression of the thigh with minimal effort and blood loss. Endovascular and surgical therapy were complementary in successfully treating a large traumatic pseudoaneurysm of the thigh.

Low dose heparin therapy: In vitro verification of antithrombotic effect

Low dose heparin therapy has been used routinely for prophylaxis of deep venous thrombosis, yet in vitro data regarding its antithrombotic effects are sparse. The effects of heparin on venous thrombus formation were studied in an in vitro perfusion system. Fresh blood collected from human volunteers was treated with varying heparin doses and perfused at a shear rate of 100 sec-1 over everted, injured porcine vein segments, simulating conditions in the venous circulation. Platelet and fibrin deposition were measured by use of indium 111 and iodine 125 radiolabels, respectively. The effects of heparin on the intrinsic coagulation cascade were monitored by the activated clotting time. Increasing doses of heparin resulted in significant reductions in fibrin and platelet deposition (ANOVA F = 2.67 and 3.17, respectively, p less than 0.05). At a dose of only 0.19 USP units/ml blood, equivalent to a 1000 unit bolus of heparin in a 70 kg man, a noticeable reduction in both fibrin and platelet deposition was observed without an increase in the activated clotting time. These data confirm the antithrombotic effects of heparin at low dose ranges and may explain the clinically observed phenomenon of deep venous prophylaxis without an appreciable alteration in the conventional coagulation assays.