Timothy R.S. Harward

Visceral ischemia-reperfusion injury promotes tumor necrosis factor (TNF) and interleukin-1 (IL-1) dependent organ injury in the mouse

Acute visceral ischemia and subsequent reperfusion injury, which accompanies the surgical repair of a thoracoabdominal aorta aneurysm, is associated with high rates of morbidity and mortality. The purpose of the present study was to determine whether endogenous tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) production contributes to organ dysfunction in animals subjected to visceral ischemia secondary to 30 min of supraceliac aortic occlusion. C57BL6/j mice were treated with either a TNF binding protein (TNF-bp-10 mg/kg) or an anti-IL-1 receptor type 1 antibody (150 μg) 2 h prior to 30 min of supraceliac aortic occlusion. An additional group of mice received 30 min of infrarenal aortic occlusion to determine the contribution of lower torso ischemia-reperfusion injury to the changes seen following supraceliac aortic occlusion. Visceral organ ischemia for 30 min produced by supraceliac aortic occlusion followed by 2 h of reperfusion produced measurable TNF-α in 38% of untreated mice, but TNF-α was undetectable in both sham-operated mice and following infrarenal aortic occlusion. After 2 h of reperfusion, lung myeloperoxidase levels were significantly elevated in the mice experiencing visceral ischemia-reperfusion compared with either a sham operation or infrarenal ischemia-reperfusion (11.6 ± 1.3 U/g vs. 3.4 ± .2 U/g and 3.7 ± 1.0 U/g, respectively, p < .05). Pretreatment with TNF-bp and anti-IL-1 antibody decreased lung neutrophil recruitment (7.2 ± 1.2 U/g and 4.6 ± 1.1 U/g) and capillary membrane permeability changes in mice following visceral ischemia-reperfusion. The present study demonstrates that brief (30 min) clinically relevant visceral ischemia produces TNF-α and IL-1 dependent lung injury.

Attenuation of skeletal muscle ischemia/reperfusion injury by inhibition of tumor necrosis factor

PURPOSE Tumor necrosis factor alpha (TNF-alpha) has been shown to play a role in pulmonary injury after lower-extremity ischemia/reperfusion (I/R). However, its role in direct skeletal muscle injury is poorly understood. The hypothesis that endogenous TNF production contributes to skeletal muscle injury after hindlimb I/R in rats was tested. METHODS Juvenile male Sprague-Dawley rats underwent 4 hours of bilateral hindlimb ischemia and 4 hours of reperfusion (IR) or sham operation (SHAM). A subset was treated with a soluble TNF receptor I construct (STNFRI, 10 mg/kg) 1 hour before ischemia (PRE) or at reperfusion (POST). Direct skeletal muscle injury (SMII) and muscle endothelial capillary permeability (MPI) were quantified by means of Tc99 pyrophosphate and I125 albumin uptake. Pulmonary neutrophil infiltration and hepatocellular injury were assessed by means of myeloperoxidase content (MPO) and aspartate aminotransferase (AST) concentrations, respectively. Serum TNF bioactivity was measured with the WEHI bioassay. RESULTS Hindlimb I/R (IR vs SHAM) resulted in a significant (P <.05) increase in the SMII (0.52 +/- 0.06 vs 0.07 +/- 0.01) and MPI (0.35 +/-.04 vs 0.06 +/- 0.01). Pretreatment with STNFRI (PRE vs IR) significantly ameliorated both SMII (0.30 +/- 0.05 vs 0.52 +/- 0.06) and MPI (0.23 +/- 0.02 vs 0.35 +/- 0.04), whereas treatment at reperfusion (POST vs IR) had no effect. Hindlimb I/R (IR vs SHAM) resulted in both significant pulmonary neutrophil infiltration (MPO 16.4 +/- 1.06 U/g vs 11.3 +/- 1.4 U/g) and hepatocellular injury (AST 286 +/- 45 U/mL vs 108 +/- 30 U/mL), but neither was inhibited by pretreatment with STNFRI before ischemia. Detectable levels of TNF were measured during ischemia in a significantly higher percentage of the IR group compared with SHAM (9 of 12 vs 3 of 12), and the maximal TNF values were also significantly greater (51.1 +/- 12.6 pg/mL vs 5.5 +/- 2.9 pg/mL). No TNF was detected in any treatment group during reperfusion nor after administration of the STNFRI. CONCLUSION Acute hindlimb IR initiates a systemic TNF response during the ischemic period that is partly responsible for the associated skeletal muscle injury.

Detection of celiac axis and superior mesenteric artery occlusive disease with use of abdominal duplex scanning

PURPOSE Detection of mesenteric arterial insufficiency is clinically difficult, and diagnosis frequently requires arteriography. Advances in duplex scanning make this an ideal technique to noninvasively screen patients for chronic mesenteric arterial occlusive disease. However, the accuracy of mesenteric duplex scanning compared with arteriography remains unclear. This study will clearly define the accuracy of abdominal duplex scanning for detection of mesenteric arterial insufficiency. METHODS The mesenteric duplex scans of 38 patients obtained over a 4-year period were reviewed and compared with lateral aortograms to clarify this issue. Optimal peak systolic frequency (PSF) for predicting less than 50% or 50% or greater stenoses of the superior mesenteric artery (SMA) and celiac axis (CA) were determined from receiver-operating characteristic curves. RESULTS In the SMA a PSF of 4.5 kHz was 96% sensitive (24/25), 92% specific (12/13), and 95% accurate (36/38) at predicting stenoses less than 50% or 50% or greater. For arteries with stenoses 50% to 99%, regression analysis demonstrated excellent linear correlation between percent stenosis and PSF (r = 0.89). In the CA a PSF of 4.0 kHz had a sensitivity of 100% (30/30), a specificity of 88% (7/8), and an accuracy of 97% (37/38). Again, for arteries with stenoses 50% to 99%, an excellent linear correlation existed between PSF and percent stenosis (r = 0.86). All total arterial occlusions (14) were correctly identified. In all, mesenteric arterial duplex scanning was 96% accurate for predicting SMA and CA stenoses/occlusions. CONCLUSIONS Abdominal duplex scanning is a noninvasive technique that accurately detects total occlusions and objectively quantitates SMA and CA arterial stenoses.

The use of arm vein conduits during infrageniculate arterial bypass

To further examine the use of arm vein for bypass to the popliteal or infrapopliteal arteries, we retrospectively reviewed 43 patients undergoing infrageniculate arterial bypass by use of an arm vein as a conduit. Nine grafts were done to the below-knee popliteal artery and 34 to the infrapopliteal arteries. Six grafts were done by use of a single segment of an arm vein, whereas 37 grafts were composites of either multiple segments of arm vein (n = 19) or segments of saphenous and arm vein (n = 18). Mean follow-up time was 15 1/2 months. Initial (30-day) graft patency and limb salvage were 95%. Primary graft patency by life-table analysis was 67% at 1 year and 49% at 3 years. Follow-up examination detected graft stenosis before occlusion in six patients (all of whom were given anticoagulant medication) and three failing grafts were salvaged. This increased overall 3-year secondary graft patency to 64% and 3-year secondary patency for infrapopliteal bypasses to 66%. Eleven of 12 graft occlusions resulted in major amputations (eight were above the knee, and three were below the knee) so that limb salvage paralleled secondary graft patency (63% at 3 years). Thus arm veins provide an excellent alternative venous conduit for infrageniculate arterial bypass, even when composite venous grafts must be used.

Natural history of asymptomatic ulcerative plaques of the carotid bifurcation

In 79 patients with 91 asymptomatic ulcerating lesions of the carotid bifurcation who were followed an average of 54 months, there were two strokes, one of which was preceded by a warning transient ischemic attack. These data suggest that asymptomatic type A and type B carotid ulcerating lesions do not carry a significant early risk of stroke and do not warrant prophylactic carotid endarterectomy. However, the effect of antiplatelet drugs and anticoagulation in enhancing the development of subintimal hemorrhagic lesions remains uncertain. Further data with serial follow-up, preferably by noninvasive means, will be necessary to define the evolution of asymptomatic ulcerating carotid plaques and eventually permit identification of those lesions that have significant stroke potential.

Current status of duplex Doppler ultrasound in the examination of the abdominal vasculature

Duplex Doppler ultrasound has come to play a central role in the diagnosis of a broad spectrum of vascular diseases such as carotid artery occlusive disease and deep vein thrombosis. The role of duplex Doppler in the evaluation of intra-abdominal vascular disease remains unclear. This article summarizes the current status of duplex scanning in the investigation of the mesenteric arteries, the renal arteries, and the portal venous system. The examination is technically demanding, operator-dependent, time-consuming, and frequently unsatisfactory due to bowel gas, obesity, complex anatomy, or postoperative alterations in the normal anatomic patterns. Its advantages reside primarily in the absence of toxicity and in the generation of physiologic as well as anatomic information. In centers with the proper instrumentation and a skilled technician, duplex examination can be useful in the diagnosis and management of abdominal vascular disease and avoids the inherent dangers of contrast angiography.

Impact of angioscopy on infrainguinal graft patency

To investigate the impact of angioscopy on infrainguinal graft patency, 50 consecutive cases with angioscopy as an adjuvant to infrainguinal arterial bypass performed during a 12-month period were reviewed (group I). For comparison, 42 similar cases of infrainguinal arterial reconstruction performed during the 12 months prior to introduction of routine intraoperative angioscopy were also reviewed (group II). Patients were followed up for 12 months and graft patency was determined at 1, 3, 6, and 12 months. An abnormality was identified in 13 (26%) group I patients (10, angioscopy alone; 1, arteriography alone; 2, both). Defects were anastomotic abnormalities (n = 7), vein sclerosis (n = 3), retained valve cusp (n = 2), and proximal artery stenosis (n = 1). A similar percentage, but different types of defects, were seen in group II; 11 patients (26%) had an abnormality (anastomotic abnormality [n = 3], vein sclerosis [n = 4], retained valve cusp [n = 1], and arterial outflow stenoses [n = 3]). All significant defects were surgically explored and corrected. Graft patency rates in group I and II at 1, 3, 6, and 12 months were 100% and 85% (P < 0.005), 94% and 80% (P < 0.05), 87% and 74% (P = non-significant [NS]), and 86.1% and 73.7% (P = NS), respectively. Intraoperative angioscopy detects anastomotic and vein graft defects not always seen on arteriography; the repair of these defects significantly improves early infrainguinal bypass graft patency rates.

Selection of patients for renal artery repair using captopril testing

BACKGROUND Prediction of improvement following surgical or radiologic intervention in patients thought to have renovascular hypertension (RVH) is often unreliable. Use of the angiotensin-converting enzyme inhibitor captopril in conjunction with measurement of peripheral renin levels or radioisotope renograms is thought to detect patients with functionally significant renal artery stenosis. However, it is unclear whether these tests can identify patients whose hypertension will significantly improve after renal artery repair. PATIENTS AND METHODS The records of 52 consecutive hypertensive patients undergoing captopril studies followed by renal artery repair were reviewed. All patients had either renal artery stenosis > 75% or renal artery occlusion. Preprocedure evaluation included a captopril challenge test (measurement of peripheral renin levels after captopril ingestion) (n = 12) or a captopril renogram (determination of renal blood flow and glomerular filtration rate before and after captopril administration) (n = 40). Either renal artery bypass/nephrectomy (n = 41) or balloon angioplasty (n = 11) was done in all patients (18 bilateral/34 unilateral). No periprocedural deaths occurred. All surgically placed bypass grafts were shown to be patent by contrast or carbon dioxide arteriography before hospital discharge. RESULTS Preprocedure captopril tests were positive (suggestive of RVH) in 39 patients (75%) and negative in 13 (25%). All patients with positive captopril tests had improvement in their RVH after intervention (17 cured, 22 improved) while 8 of 13 patients with negative captopril tests had no improvement in blood pressure control. Four of five false-negative tests were associated with a unilateral total renal artery occlusion, making detection of a postcaptopril effect impossible. If these 4 patients are excluded from analysis, preprocedure captopril testing was 98% accurate in predicting postprocedure outcome. CONCLUSIONS Preprocedure captopril testing permits extremely accurate selection of patients with renal artery stenosis who will benefit from renal artery repair.

The demise of primary profundaplasty

Although the importance of the profunda femoris artery in maintenance of lower extremity integrity was recognized in the earliest days of modern vascular surgery, disappointment with the performance of primary profundaplasty has emerged fully only in recent years. During the 10 year period from 1977 to 1987, only 17 patients were subjected to this procedure at Northwestern Memorial Hospital. The nine men and eight women averaged 65.6 years in age and exhibited the usual precursors of arterial insufficiency: a history of smoking in 12 patients (71 percent), clinical coronary artery disease in 8 patients (47 percent), hypertension in 7 patients, diabetes mellitus in 6 patients, hyperlipidemia in 2 patients, and uremia in 1 patient. Four patients exhibited hemodynamic improvement after profundaplasty (ankle-brachial index increase of greater than 0.15). Four required amputation postoperatively, and a fifth exhibited hemodynamic failure 9 months postoperatively and required amputation. Two patients required subsequent femoral-to-peroneal bypass to improve distal arterial perfusion. One patient died after the procedure, for a 5.9 percent mortality rate. Thus, the fact that profundaplasty has proved disappointing in the treatment of severe arterial insufficiency deserves emphasis at this time.

Posterior communicating artery visualization in predicting results of carotid endarterectomy for vertebrobasilar insufficiency

Retrospectively, 51 patients who related two or more signs or symptoms of vertebrobasilar insufficiency and possessed concomitant carotid arterial disease were identified. The patient population was separated into two groups based on the presence or absence of an angiographically visualized posterior communicating artery during selective carotid artery injection. All patients had undergone unilateral or staged bilateral carotid endarterectomy. Comparison of postoperative clinical outcome with intracerebral angiographic findings exhibited statistically significant improvement in favor of those patients with at least one visualized posterior communicating artery. There was a greater likelihood of severe vertebral artery stenosis in those patients whose symptoms were not relieved by carotid endarterectomy.