Stuart I. Myers

Creation of a neo-aortoiliac system from lower extremity deep and superficial veins

OBJECTIVE This study evaluated the morbidity, mortality, and intermediate term follow-up of patients undergoing replacement of their aortoiliac-femoral systems with lower extremity deep and superficial veins. SUMMARY BACKGROUND DATA The most commonly used treatment for aortic prosthetic infection is ectopic bypass and removal of the prosthesis. The overall mortality rate with this approach is approximately 20%, with an amputation rate of 10% to 14%. Other limitations include thrombosis of the ectopic bypass leading to limb loss, reinfection of the ectopic bypass, and aortic stump blowout. Dissatisfaction with this approach has led the authors to develop the following. METHODS A neo-aortoiliac system (NAIS) was fashioned from lower extremity deep veins (DV), greater saphenous veins (GSV), or both in patients with infected aortobifemoral prosthesis (n = 17) and other complex aortic problems (n = 3). Removal of infected prosthetic material, harvest of vein, and creation of NAIS was performed as a single-staged procedure. RESULTS The in-hospital mortality and amputation rates were 10% each. The mean (+/- standard deviation [SD]) operative time was 6.5 +/- 1.8 hours and the blood transfusion requirement was 4 +/- 3 units. Four patients experienced postoperative gastrointestinal complications with peritonitis and sepsis; NAIS vein graft resisted infection and remained intact. The mean follow-up time was 22.5 +/- 16 months. NAISs constructed from GSVs were prone to the development of focal stenoses requiring intervention or diffuse neointimal hyperplasia leading to occlusion. In contrast, all NAISs from larger caliber DVs have remained widely patent. The failure rate of GSV NAISs was 64%, compared to 0% for DV NAISs (p = 0.006). Despite the high failure rate in patients with GSV NAISs, none has required amputation. In patients who had DVs harvested for NAIS reconstruction, limb edema and other signs of venous hypertension have been minimal. CONCLUSION NAIS reconstruction from lower extremity veins is a successful option in patients with extensive aortic prosthetic infection and other complex aortic problems.

THE CORONARY RISK OF UNSUSPECTED RENAL ARTERY STENOSIS

PURPOSE This study was designed to determine the prevalence of unsuspected renal artery stenoses (RAS) in patients undergoing arteriography for evaluation of aneurysmal or occlusive vascular disease and whether symptomatic coronary artery disease (CAD) is more prevalent among patients with unsuspected RAS. METHODS We reviewed the arteriograms and medical records of 346 consecutive patients with aortic aneurysms or occlusive disease in whom RAS was unsuspected on clinical grounds. RESULTS Aortography revealed unsuspected RAS (50% or greater diameter loss) in 98 patients (28%). Patients with RAS had a higher prevalence of mild, controlled hypertension (p < 0.001) and mild renal insufficiency (p < 0.001), but in no case was arteriography obtained to diagnose renovascular hypertension or ischemic nephropathy. Fifty-seven patients (58%) with unsuspected RAS had clinically overt CAD (documented myocardial infarction, positive coronary catheterization, previous coronary revascularization, ischemic electrocardiography changes, or angina pectoris), compared with 96 patients (39%) without RAS (p = 0.002). The correlation between the prevalence of CAD and RAS severity was highly significant (p < 0.001), and the relative odds ratio of CAD was highest for RAS measuring 75% or greater. Stepwise logistic regression analysis demonstrated three variables to be significantly and independently associated with CAD: 75% or greater RAS (p = 0.001), aortic aneurysm disease (p = 0.01), and hypertension (p = 0.001). RAS measuring 75% or greater diameter loss was associated with the highest estimated odds ratio: patients with this degree of RAS had a fourfold increase in the prevalence of clinically overt CAD. We also evaluated the relationship between RAS, mesenteric artery stenosis, and CAD; although RAS was more frequent among patients with mesenteric artery stenoses, mesenteric artery stenoses were not associated with CAD. CONCLUSIONS Unsuspected RAS is common among patients with peripheral vascular disease and should be considered an independent marker for CAD.

Intestinal reperfusion up-regulates inducible nitric oxide synthase activity within the lung*

BACKGROUND This study examines the hypothesis that pulmonary inducible nitric oxide synthase (iNOS) activity is up-regulated during intestinal reperfusion and that inhibition of NO generation exacerbates pulmonary microvascular dysfunction. METHODS Sprague-Dawley rats underwent intestinal ischemia and reperfusion (IIR) or sham operation (SHAM). Pulmonary iNOS activity was measured by quantitating the conversion of L-arginine (L-Arg) to L-citrulline. Another set of animals undergoing IIR or SHAM received an inhibitor of NOS (NG-nitro-L-arginine methylester; L-NAME; 20 mg/kg intravenously), substrate for NO generation (L-Arg; 300 mg/kg intravenously), or vehicle (normal saline solution; 3 ml). Pulmonary microvascular dysfunction was then quantitated by measuring the extravasation of Evans blue dye (EBD) into the lung. RESULTS Inducible NOS activity was six times greater in the lungs of animals sustaining IIR when compared with SHAM (p = 0.0005). The concentration of EBD within the lungs of animals sustaining IIR was 30% greater than SHAM (p < 0.05). Inhibiting NOS with L-NAME significantly increased pulmonary EBD concentration of both IIR and SHAM groups when compared with normal saline solution-treated animals (p < 0.0001). Treatment with L-Arg prevented this IIR-induced increase in pulmonary dye extravasation. CONCLUSIONS These data suggest that pulmonary iNOS activity is up-regulated in animals sustaining IIR and that this may serve as a compensatory protective response to remote organ injury.

Hepatic hypoperfusion after intestinal reperfusion

BACKGROUND Intestinal ischemia-reperfusion injury (IIR) induces hepatic and pulmonary dysfunction and thus has been used as a model of multiple organ failure syndrome. This study examines the hypothesis that hepatic blood flow is markedly reduced in this injury model. METHODS Sprague-Dawley rats underwent 120 minutes of intestinal ischemia and 60 minutes of reperfusion (IIR). Hepatic blood flow was measured with radiolabeled microspheres and Doppler flow probes. Hepatic dysfunction was quantitated by measuring bile flow and serum alanine aminotransferase and hepatic tissue adenosine triphosphate levels. Sham-operated animals served as controls. RESULTS Intestinal ischemia reduced portal flow by 66% when compared with sham-operated animals (p = 0.0001) but had no effect on hepatic arterial flow. In contrast, reperfusion reduced hepatic artery flow by 80% when compared with controls (p = 0.002) with most of this change occurring within 5 minutes of reperfusion. IIR induced a 63% reduction in bile flow (p < 0.05), a fivefold rise in serum alanine aminotransferase level (p < 0.0002), and a 33% reduction in hepatic adenosine triphosphate level (p < 0.05). CONCLUSIONS These data suggest that IIR induces profound hepatic hypoperfusion, which is temporally related to acute hepatic dysfunction. This observation suggests that hepatic ischemia may contribute to IIR-induced liver injury.

Role of physical examination in detection of abdominal aortic aneurysms

BACKGROUND Early detection of asymptomatic abdominal aortic aneurysms (AAAs) has been advocated to decrease the high mortality rate of ruptured AAAs. The purpose of this study was to document how AAAs were detected, whether AAAs not detected on physical examination (PE) were palpable, and what factors precluded detection by PE. METHODS Two hundred forty-three patients undergoing elective infrarenal AAA repair at a Veterans Affairs, county, or university hospital during a 10-year period were analyzed retrospectively. The method of initial detection of the AAA, size of the AAA at initial detection and before repair, and whether the AAA was palpable on preoperative PE were recorded, and the body mass index [BMI; weight in kg/(height in meters)2] was calculated. Obese patients were defined with BMI of greater than 85th percentile. RESULTS Only 93 (38%) patients had their AAAs initially detected by PE; the remainder (62%) were found incidentally on radiologic examinations performed for other indications. Patients with AAAs detected by PE had lower BMIs (PE, 23.7 +/- 3.6 kg/m2; incidental, 26.0 +/- 4.6 kg/m2, p < 0.001), but there was no difference in AAA size (PE, 5.8 +/- 1.6 cm; incidental, 5.5 +/- 1.9 cm, not significant). Forty-three percent of patients with AAAs detected on radiologic examination had palpable AAAs and should have been detected on PE. Overall, 55 (23%) AAAs were not palpable on preoperative PE, even when the diagnosis was known. Obese patients had only 15% of AAAs detected by PE, and only 33% were palpable. CONCLUSIONS AAAs are underdiagnosed by PE, especially in obese persons. More widespread abdominal examination to detect a widened aortic pulse would improve detection of AAAs.

Detection of unsuspected renal artery stenoses in patients with abdominal aortic aneurysms: Refined indications for preoperative aortography

Renal artery stenoses (RASs) that are unsuspected on clinical grounds are common in patients with peripheral vascular disease. These lesions may be missed in patients with abdominal aortic aneurysms (AAAs) who undergo arteriography based on selective clinical indications alone. We reviewed 98 consecutive patients with AAAs to determine how often selective arteriography would fail to diagnose unsuspected RAS. The location and degree of RASs were noted on preoperative arteriograms, which were routinely obtained in all patients considered for AAA repair during the study period. Medical records were studied to determine the presence of selective clinical indications for preoperative arteriography (moderate to severe hypertension or renal insufficiency). Twenty-four patients had a significant (≥50% diameter loss) RAS, and 10 patients had a severe (≥75% diameter loss) RAS or renal artery occlusion. Patients with significant RAS had a higher incidence of hypertension (p=0.035) and renal insufficiency (p=0.018). All 10 patients with severe RASs required at least two antihypertensive medications to control their hypertension compared with 22 of 88 patients who did not have a severe RAS (p<0.001). Forty-three patients had an indication for arteriography according to selection criteria (renal insufficiency, moderate or severe hypertension, or both). No severe RASs were found in patients who did not meet the selection criteria for arteriography. Using arteriography based on the presence of hypertension requiring two or more medications for control will detect the vast majority of severe, unsuspected RASs in AAA patients.

Intestinal reperfusion-induced pulmonary edema is related to increased pulmonary inducible nitric oxide synthase activity

BACKGROUND This study examines the hypothesis that specific inhibition of the inducible isoform of nitric oxide synthase (iNOS) will attenuate intestinal reperfusion-induced pulmonary microvascular dysfunction. METHODS Sprague-Dawley rats underwent intestinal ischemia-reperfusion (IR) or sham operation (SHAM). Before injury, the animals received a selective inhibitor of iNOS (S-methylisothiourea sulfate, SMT: L-N6-[1-iminoethyl] lysine L-NIL), a nonselective inhibitor of NOS (NG-nitro-L-arginine methylester, L-NAME) or vehicle (0.9% saline). IR-induced changes in pulmonary microvascular permeability were assessed by quantitating the extravasation of Evans blue dye (EBD)-bound protein into the lung. Pulmonary iNOS activity and content were assessed by radiochemical analysis and Western blot, respectively. RESULTS There was 60% more EBD within the lungs of animals sustaining IR when compared with controls (P < .05). Pretreatment with SMT or L-NIL totally prevented the increase in EBD extravasation associated with IR. In contrast, pretreatment with L-NAME resulted in a 10% increase in dye extravasation in those animals sustaining IR when compared with similarly injured animals receiving saline (P > .05). There was significantly greater iNOS activity and enzyme content within the lungs of animals sustaining IR compared with controls. CONCLUSIONS These data are consistent with the hypothesis that the release of nanomolar quantities of nitric oxide generated by iNOS contributes to IR-induced pulmonary microvascular dysfunction.

Cocaine-induced alterations in prostaglandin production in rabbit aorta

To determine if alterations in endothelial prostaglandin production occur after long-term cocaine use, 26 New Zealand White rabbits were randomized to a low fat diet with (n = 12) or without (n = 14) daily intravenous cocaine (2 mg/kg body weight). Rabbits were killed at 6 or 12 weeks. Segments of aorta were examined in blinded manner for histologic changes. Additional slices were incubated in oxygenated Krebs buffer and release of 6-keto-prostaglandin F1 alpha, thromboxane B2 and prostaglandin E2 was assayed by radioimmunoassay. Minimal intimal histologic changes were seen in the aorta of three cocaine-treated rabbits. At 12 weeks 6-keto-prostaglandin F1 alpha was increased in the cocaine group (p = 0.063) as compared with levels in the control group. When rabbits killed at 6 and 12 weeks were considered together, increases in thromboxane B2 (p = 0.044) and a trend to increased prostaglandin E2 (p = 0.083) were seen in the cocaine group. The ratio of thromboxane B2 to 6-keto-prostaglandin F1 alpha was increased in the cocaine group compared with that in the control group (p less than 0.02). These data suggest that an increase in prostaglandin production occurs in the vascular endothelium of rabbits ingesting cocaine before gross histologic changes are evident. In addition, thromboxane B2 increases disproportionately with respect to 6-keto-prostaglandin F1 alpha, suggesting that a milieu for thrombosis may exist in users of cocaine.

Is routine CT scanning necessary in the preoperative evaluation of patients undergoing carotid endarterectomy

To evaluate the usefulness of CT scanning before carotid endarterectomy, a prospective study was performed on 469 consecutive patients considered for carotid endarterectomy during a 5-year period. All patients underwent carotid duplex scanning and CT scanning before carotid arteriography. Two hundred thirty-seven patients (51%) had transient ischemic attacks, 109 (23%) had a prior stroke, and 122 (26%) were asymptomatic. Results of the CT scan were abnormal in 68 (62%) of the 109 patients with stroke. Fifty-one of the 360 patients (14%) without a clinical history of stroke had an abnormal CT scan outcome. Of patients with a stroke documented by CT scanning, 27 had lacunar infarcts, and 92 had cortical infarcts; these findings did not change surgical management in any patient. CT scanning did not reveal any unsuspected infarcts or tumors. Two hundred thirty carotid endarterectomies were performed on 206 patients. Forty-seven patients (23%) in the operative group had abnormal CT scan findings, but the scan did not influence operative decisions or timing in any case. Seventy-two patients (27%) in the nonoperative group had abnormal CT scan results, but CT scan findings did not exclude any patient from arteriography or surgery. Three perioperative strokes (1.3%) occurred. CT scan findings did not correlate with postoperative neurologic complications. Cost of CT scanning was one-half million dollars in our study alone. Routine CT scanning is unnecessary before carotid endarterectomy and is not cost-effective.

The natural history of patients with claudication with toe pressures of 40 mm Hg or less

PURPOSE This study was performed to determine the natural history of patients with symptoms of claudication and systolic toe pressures (TP) of 40 mm Hg or less. METHODS We followed the clinical course of 56 men with stable claudication and TP of 40 mm Hg or less. All TP measurements were performed on at least two occasions 6 months apart. Primary end points included development of rest pain, tissue loss, or gangrene. The clinical course of 56 case controls with TP greater than 40 mm Hg matched for age, sex, and race was used for comparison. RESULTS During a mean (+/- SD) follow-up time of 31 +/- 4 months, 37 (66%) patients with TP of 40 mm Hg or less remained stable, and 19 (34%) had ulceration (n = 10), rest pain (n = 6), or gangrene (n = 3). Nine (24%) of the 37 stable patients had gradual improvement of TP values greater than 40 mm Hg. Among the 19 patients whose conditions deteriorated, eight (42%) patients underwent successful bypasses, and five (26%) patients required amputations. Two patients who had rest pain had spontaneous resolution, and three patients who had ulcerations healed without intervention. In contrast, five (9%) of the case controls with TP greater than 40 mm Hg had rest pain (n = 2) or gangrene (n = 3) (p = 0.003). Among patients with TP of 40 mm Hg or less, there were no statistically significant differences between the stable patients and patients with deteriorating conditions in age, ankle-brachial indexes, or risk factors (including diabetes mellitus). However, diabetes conferred a higher probability of clinical deterioration (p = 0.005, Kaplan-Meier). CONCLUSIONS In patients with symptoms of intermittent claudication, TP of 40 mm Hg or less portends clinical deterioration. Patients with diabetes in this group have a significantly higher risk of development of critical ischemia. Close scrutiny is warranted.