Michael P. Lilly

Collagen types and matrix protein content in human abdominal aortic aneurysms

Deficiencies of total collagen, type III collagen, and elastin have been proposed to explain aneurysm formation. Infrarenal aortas were collected from 19 patients (age 70 +/- 7 years) undergoing operative repair of abdominal aortic aneurysms (diameter 7 +/- 2 cm) and from 13 autopsies (age 63 +/- 17 years) of patients without aneurysm disease (controls). Wall thickness and collagen and elastin concentration were determined in full-thickness aorta. Collagen types I and III were measured after digestion with cyanogen bromide, which solubilized nearly 90% of total collagen for typing. Cyanogen bromide peptides were separated by sequential carboxymethylcellulose and agarose chromatography and quantified by peak area measurement with computerized image analysis. Histologic examination revealed prominent inflammatory cell infiltration and deficient, fragmented elastin in the aneurysms. Aortic wall thickness was similar in aneurysms and in control specimens. In the aneurysms, collagen was increased (37% +/- 16% vs 24% +/- 5%; p less than 0.05) and elastin was decreased (1% +/- 1% vs 12% +/- 7%; p less than 0.001), expressed as a percentage of delipidized, decalcified dry weight. Collagen type I accounted for 74% +/- 4% of aneurysm and 73% +/- 4% of control collagen solubilized for typing, and collagen type III accounted for 26% +/- 4% of aneurysm and 27% +/- 4% of control collagen solubilized for typing. Neither patients with a family history of aneurysms nor those without a history of aneurysms had collagen type III deficiency. Atherosclerotic abdominal aortic aneurysms are associated with an inflammatory process and may result from elastin degradation and not a deficiency of type III collagen.

Regression of proximal deep venous thrombosis is associated with fibrinolytic enhancement

PURPOSE Recanalization after acute lower limb deep venous thrombosis (DVT) is well documented, but the precise mechanism and timing of these events has not been well characterized. Regression of DVT has been presumed to result from activation of the endogenous fibrinolytic system. This study was performed to compare measurements of the enzymatic components of the intrinsic fibrinolytic system (tissue plasminogen activator [tPA], plasminogen activator inhibitor [PAI-1]) with the observed morphologic changes in thrombosed venous segments using venous duplex ultrasound scanning (VDUS) at intervals after diagnosis of acute DVT. METHODS Nineteen patients with acute DVT underwent serial VDUS to assess regression of thrombus at intervals of 1 to 2 weeks, 3 to 6 weeks, 8 to 12 weeks, and 24 to 36 weeks. The extent of thrombus in each limb was quantitated at each interval by VDUS of the residual thrombus present in each of five major axial venous segments: the common femoral, superficial femoral, profunda femoris, popliteal, and tibial veins. Thrombus scores for the group at each interval were compared with baseline scores at diagnosis to calculate the percent residual thrombus. Endogenous fibrinolytic activity was determined at the same intervals by serologic assay of the biologic activities of tPA and its inhibitor PAI-1. RESULTS Thrombus regression was evident by VDUS at 1 to 2 weeks and progressed such that only 26% of residual thrombus remained at 24 to 36 weeks. Complete resolution of thrombus occurred in 10 of 18 patients (56%) who completed the 9-month study. Baseline mean tPA activity was 0.60 +/- 0.07 IU/ml and increased to 1.31 +/- 0.26 IU/ml at 1 to 2 weeks (p = 0.014). tPA activity remained significantly elevated through the 8 to 12 week interval and returned to baseline at 24 to 36 weeks. PAI-1 activity was elevated relative to an age-matched population at baseline (23.1 +/- 1.8 AU/ml) but remained unchanged throughout the study period. Progression of thrombus was observed in three patients (15.8%). Patients who experienced propagation of thrombus did not have the increased tPA activity that appeared to mark activation of intrinsic fibrinolysis. CONCLUSIONS Regression of acute DVT begins early and continues for at least 9 months. It is accompanied by significant enhancement of the endogenous fibrinolysis, which appears to be primarily mediated by increased tPA activity. Patients who have thrombus propagation in spite of standard antithrombotic therapy may have failure of activation of endogenous fibrinolysis.

Selection of the approach to the distal internal carotid artery from the second cervical vertebra to the base of the skull

Although several approaches for exposure of distal internal carotid artery lesions have been reported, the precise anatomic levels for which each of these maneuvers are most appropriate have not been well described. Since these techniques may require preoperative preparation, it is useful to determine in advance how much exposure will be needed and to select the most suitable and effective technique. We used anatomic dissection in 12 human cadaver specimens (24 carotid bifurcations) to define the limits of distal internal carotid artery exposure by several commonly advocated methods. The standard anterior approach along the sternocleidomastoid muscle allowed exposure of the internal carotid artery to the level of the upper one third of the second cervical vertebra. The upper limit of this exposure was extended to the middle of the first cervical vertebra by division of the posterior belly of the digastric muscle. Anterior subluxation of the mandible increased the distal exposure of the internal carotid artery to the superior border of the first cervical vertebra. Styloidectomy in combination with the preceding maneuvers extended the exposure an additional 0.5 cm cephalad. Lateral mandibulotomy did not significantly extend exposure beyond that obtained with mandibular subluxation and styloidectomy. Exposure of the internal carotid artery in the 1 cm immediately below the base of the skull required a posterior approach with mastoidectomy.

Venous hemodynamics during impulse foot pumping

PURPOSE This study was designed to measure the effect of intermittent pneumatic compression of the plantar venous plexus on popliteal vein (PV) and common femoral vein (CFV) velocities measured by duplex ultrasound scanning. METHODS Thirty lower limbs in 15 healthy volunteers had venous duplex scanning measurement of PV and CFV velocities before and during foot pumping with an arteriovenous impulse foot pump system. Venous velocities were measured at two pump pressure settings (100 mm Hg, 200 mm Hg) and during two pump impulse durations (short = 1 second, normal = 3 seconds). All limbs were examined with the subjects in the supine position, and then measurements were repeated with subjects in the 15-degree reverse Trendelenburg position. The mean maximum venous velocity (MVV) produced by foot pumping was compared with resting venous velocity at each anatomic location and for each technologic variable. RESULTS Impulse foot pumping produced a statistically significant increase in MVV in both the PV and the CFV compared with resting velocities. This significant increase was observed for both pressure settings and both impulse durations, and no differences produced by these two individual variables could be detected. The increase in MVV produced by foot pumping was similar for limbs in the supine position and those examined in the reverse Trendelenburg position. The percentage increase in MVV produced by foot pumping was significantly higher in the PV than in the CFV. CONCLUSIONS Intermittent pneumatic compression of the plantar venous plexus produces measurable increases in venous outflow from the lower limbs of normal subjects. This study seems to justify further evaluation of the effectiveness of this technique for mechanical deep venous thrombosis prophylaxis in selected high-risk patient groups.

Prevalence of Arteriovenous Fistulas in Incident Hemodialysis Patients: Correlation With Patient Factors That May Be Associated With Maturation Failure

BACKGROUND Lok et al previously reported a risk equation for arteriovenous fistula (AVF) maturation failure. It is unclear whether this model or a more comprehensive model correlates with incident AVF use in the US hemodialysis population. STUDY DESIGN Cross-sectional study. SETTING & PARTICIPANTS 195,756 adult patients initiating outpatient hemodialysis therapy in the United States between July 1, 2005, and December 31, 2009, with 6 months or more prior nephrology care. PREDICTOR Patient characteristics (age, peripheral vascular disease, coronary artery disease, and race) populating the AVF maturation failure risk equation and other demographic and clinical variables from the Centers for Medicare & Medicaid Services (CMS) Medical Evidence Report (CMS 2728). OUTCOMES & MEASUREMENTS AVF use at first outpatient dialysis treatment as recorded on the CMS 2728. RESULTS Using the risk categories defined by Lok et al, AVF use varied from 19.0% (very high risk) to 25.6% (low risk). In a model using only these risk categories, logistic regression showed lower ORs for moderate-, 0.90 (95% CI, 0.88-0.93); high-, 0.80 (95% CI, 0.78-0.83); and very high-risk patients, 0.68 (95% CI, 0.63-0.73) compared with low risk. In the expanded model, odds were lower for women, blacks, Hispanics, age older than 85 years, diabetes, peripheral vascular disease, congestive heart failure, other cardiac disease, and underweight. Odds were higher for hypertension, overweight, obesity, 12 months or more nephrologist care, most insurance types, and each successive year after 2005. Despite associations, the C statistic for the expanded model was 0.64. LIMITATIONS This analysis is limited by lack of access creation history before dialysis therapy initiation and minimal external validation of CMS 2728 data. CONCLUSIONS Clinical risk factors identified by Lok and expanded in this analysis have limited ability to predict incident AVF use. Even patients judged at highest risk can have successful AVF construction and initiate dialysis therapy through a functioning AVF.

Duplex ultrasound insertion of inferior vena cava filters in multitrauma patients

BACKGROUND Techniques for placement of inferior vena cava (IVC) filters have undergone continued evolution from open surgical exposure of the venous insertion site to percutaneous insertion in most cases today. However, the required transport either to an operating room or interventional suite can be complex and potentially hazardous for the multiply injured trauma patient who may require ventilator support, controlled intravenous infusions, or skeletal immobilization. Increased experience with color-flow duplex scanning for routine IVC imaging and portability of ultrasound equipment have suggested the usefulness of duplex-guided IVC filter insertion (DGFI) in critically ill trauma and intensive care unit (ICU) patients. METHODS A total of 25 multitrauma/ICU patients were considered for DGIF. Screening color-flow duplex scans were performed on all patients, and obesity or bowel gas prevented ultrasound imaging in 2 cases, leaving 23 patients suitable for DGFI. In each case, the IVC was imaged in the transverse and longitudinal planes. The right renal artery was identified as it passed posterior to the IVC and was used as a landmark of the infrarenal segment of the IVC. All procedures were performed at the bedside in a monitored ICU setting using percutaneous placement of titanium Greenfield filters. Duplex scanning after insertion was used to document proper placement, and circumferential engagement of the filter struts in the IVC wall. An abdominal radiograph was also obtained in each case to confirm proper filter location. Duplex ultrasound imaging was repeated within 1 week of insertion to assess IVC and insertion site patency. RESULTS DGFI was successful in all cases. The filter was deployed at a suprarenal level in one case, as was recognized at the time of postprocedural scanning. Three patients died as a result of their injuries but there were no pulmonary embolism deaths. Repeat duplex scanning was obtained in 17 patients, and revealed no case of IVC or insertion site thrombosis. CONCLUSIONS Vena caval interruption can be safely performed under ultrasound guidance in a monitored, ICU environment. In selected multiply injured trauma patients, this will reduce the risk, complexity and cost of transport for these critically ill patients. DGFI also reduces procedural costs compared with an operating room or interventional suite, and eliminates intravenous contrast exposure. Preprocedural scanning is essential to identify patients suitable for DGFI, and careful attention must be paid to the known ultrasonographic anatomical landmarks.

Fenoldopam Infusion Associated with Preserving Renal Function After Aortic Cross-Clamping for Aneurysm Repair

Background: Cross-clamping of the descending aorta during operative repairs causes sudden, significant reductions in renal function that may persist well beyond arterial clamp release. Commonly used agents, such as dopamine and mannitol, have not consistently affected renal outcome in these high-risk patients. Fenoldopam mesylate is a novel, highly selective dopamine type-I agonist that preferentially dilates the renal and splanchnic vasculature, but has not been investigated in patients undergoing prolonged aortic clamping for whom adverse renal outcomes should be more likely. Methods and Results: Twenty-two adult patients without significant pre-existing renal dysfunction and presenting for elective repairs of abdominal aortic aneurysms were studied. Fenoldopain mesylate was infused after obtaining baseline values ranging from 0.1 to 1.0 pg/kg/min for the first 24 hours postoperatively to maintain mean arterial pressure ±25% baseline. Serial renal function indices, including creatinine clearance and electrolyte fractional excretions, were measured at baseline, at aortic clamping and unclamping, and post-clamp release, and were estimated through hospital discharge. Creatinine clearance fell during abdominal exploration and clamping, reaching a nadir with clamp removal. Partial recovery occurred by 2 hours after clamp removal, and returned to baseline values by postoperative day 1 and thereafter. Fractional excretions rose rapidly throughout the operative phase. Total fenoldopam dose was directly related to the baseline creatinine clearance; after clamp removal, creatinine clearance was directly related to the mean arterial pressure at the lowest dose of fenoldopam, and inversely related to the mean arterial pressure at clamp release. Conclusions: In elderly patients with severe vascular disease undergoing aneurysmal repairs, the use of a fenoldopam infusion in this open-label, uncontrolled trial was associated with a relatively rapid return of renal function to baseline values, despite profound decreases during aortic cross-clamping. Further studies will be necessary to investigate how fenoldopam infusions compare with traditional therapies.

Can intrarenal duplex waveform analysis predict successful renal artery revascularizaion

PURPOSE No currently available noninvasive test can preoperatively predict a successful outcome to renal revascularization. Resistance measurements from the renal parenchyma obtained with duplex sonography reflect the magnitude of intraparenchymal disease, and patients with extensive intrarenal disease may respond less favorably to revascularization. To address this question, we reviewed our (primarily) operative experience in patients undergoing renal artery revascularization, and compared the blood pressure (BP) and renal function response with resistance measurements obtained from the kidney both before and after revascularization. METHODS During a 56-month period, 31 consecutive renal artery revascularizations (25 surgical and 6 percutaneous angioplasties) were performed in 23 patients (21 atherosclerotic, 2 fibromuscular dysplasia). Duplex sonography was performed in each patient before and after revascularization, and parenchymal diastolic/systolic (d/s) ratios were calculated. BP and renal function response to intervention were compared with measurements of intrarenal flow patterns before and after revascularization. RESULTS Mean parenchymal peak systolic velocity was significantly higher after repair in all patients (pre-repair: 19.5 +/- 1.3, postrepair: 27.2 +/- 1.7; P < .0001). Despite this, there were no statistical differences between preoperative and postoperative parenchymal d/s ratios. A favorable (cured or improved) BP response was seen in 81% (17 of 21) of revascularizations performed for hypertension. Among these successes, parenchymal d/s ratios were in the normal range (ie, > or = 0.30) both before and after repair (mean prerepair: 0.34 +/- 0.03, mean postrepair: 0.31 +/- 0.03; not significant). In 4 patients in which BP failed to improve after intervention, the d/s ratio was abnormal before surgery (< 0.3), and remained so after revascularization (mean preoperative d/s ratio: 0.18 +/- 0.04, mean postoperative d/s ratio: 0.11 +/- 0.04; P = .003). Mean preoperative parenchymal d/s ratios were significantly higher in all patients with a successful BP response when compared with failures (P = .048). Similarly, among patients with single artery repairs, mean preoperative d/s ratios approached significance in successes vs. failures (success: 0.40 +/- 0.03, failure: 0.21 +/- 0.03; P = .054). A decrease in serum creatinine greater than or equal to 20% was seen in 8 of 18 patients (44%) with ischemic nephropathy. These patients also had normal d/s ratios preoperatively (mean 0.39 +/- 0.04), whereas the 10 patients who failed to improve had significantly lower ratios (mean 0.24 +/- 0.03; P = .041). Kidney length did not correlate with d/s ratio. CONCLUSION Although we do not believe that duplex sonographic measurement of intrarenal flow patterns alone is an accurate means of assessing main renal artery occlusive disease, the resistive indices seem to reflect the magnitude of intraparenchymal disease, and thus may provide important prognostic information for patients undergoing surgical revascularization. Our data suggest that a preoperative d/s ratio below 0.3 correlates with clinical failure relative to BP and renal function responses.

Saline resuscitation after fixed-volume hemorrhage : role of resuscitation volume and rate of infusion

The authors have reported previously that small-volume resuscitation (1.8 χ bled volume) with 0.9% NaCl restores blood volume and attenuates hormonal responses after large hemorrhage without correction of arterial hypotension. The authors studied the role of rate of infusion in this observation in chronically prepared dogs (aortic flow probe, right atrial pressure and volume, and arterial catheters) after 30% hemorrhage (24.1 ± 0.4 mL/kg). After 30 minutes, subjects were observed either without treatment (no resuscitation) or with infusion of 43 mL/kg 0.9% NaCl over 3 hours by one of three protocols: (1) impulse infusion over 10 minutes, (2) variable rate infusion, bolus with tapering infusion, or (3) constant rate infusion. Significant improvement in cardiac output and in blood volume and significant decreases of vasopressin and arterial catecholamines were observed in all fluid-treated groups. This benefit was relatively independent of rate of infusion, although impulse infusion produced greater early improvement, which dissipated with time, and constant rate infusion produced better late results. In none of the fluid-treated groups were these improvements reflected in improved mean arterial pressure compared with the no resuscitation group. The authors conclude that small-volume, slow-rate saline infusion produces physiologic benefits that cannot be assessed by easily measured clinical parameters. Thus, early resuscitation after trauma could aid patients even if arterial pressure is unchanged. This benefit might be even greater in patients with uncontrolled bleeding because arterial pressure, and hence bleeding, may not be increased by resuscitation of this type. A reassessment of the value of prehospital fluid resuscitation in the injured patient is warranted.

Defective fibrinolysis occurs after infrainguinal reconstruction

PURPOSE Early thrombosis of infrainguinal bypass grafts may occur as a result of hypercoagulable states. Major surgical procedures are known to induce a procoagulant state that is manifested in part by reduced endogenous fibrinolytic activity or fibrinolytic shutdown. This study was performed to assess the timing and biologic mechanism of fibrinolytic shutdown after infrainguinal bypass procedures by direct assay of the serologic markers of in vivo fibrinolytic activity. METHODS Twenty patients underwent infrainguinal bypass procedures under epidural anesthesia. Endogenous fibrinolytic activity was assessed by measurement of tissue plasminogen activator (tPA) and its naturally occurring inhibitor, plasminogen activator inhibitor (PAI-1). The tPA and PAI-1 antigen (total protein) levels were determined using enzyme-linked immunosorbent assays, and measurements of in vivo biologic activity were performed using an amidolytic method. Measurements of tPA and PAI-1 were made before surgery, after surgery, and on postoperative days 1, 2, 7, and 30. RESULTS The mean preoperative PAI-1 activity was 20.6 +/- 1.4 arbitrary units (AU)/ml, which was higher than that of an age-matched population without severe atherosclerosis. PAI-1 activity rose significantly after surgery (29.6 +/- 2.2 AU/ml; p = 0.002) and remained elevated through the second day after surgery. Preoperative tPA activity level was 2.04 +/- 0.59 IU/ml and fell to 0.79 +/- 0.23 IU/ml (p = 0.046) immediately after the bypass procedure. All serologic indicators of fibrinolytic shutdown returned to baseline levels by 72 hours after surgery. No early graft thrombosis or other atherothrombotic complications occurred in these study patients. CONCLUSIONS Defective endogenous fibrinolytic activity occurs in the early postoperative period after infrainguinal bypass grafting procedures. Diminished endogenous fibrinolytic activity in these patients appears to be mediated by a combination of reduced tPA activity and significantly increased PAI-1 activity. No practical method is available to directly treat postoperative fibrinolytic shutdown, but postoperative antithrombotic therapy may be useful during this period to prevent early graft occlusion related to a relative hypercoagulable state.