Static and dynamic vascular impact of large artery irradiation.

PURPOSE: To evaluate functional post-radiotherapy arterial change in a select patient population. METHODS AND MATERIALS: Thirty-five seminoma patients were identified in the Radiation Oncology departmental records at Indiana University Medical Center. In this group the ipsilateral pelvis is treated with the contralateral pelvis available for evaluation as a matched control. Additionally, this group is generally young and unlikely to have pre-existing vascular disease, and shows excellent radiocurability with historically standard radiotherapy. Nineteen patients volunteered for a noninvasive vascular evaluation which included: Doppler ultrasound, segmental leg pressures, pulse volume recordings, and post-exercise testing. Average age at treatment was 36 (range 14-68) with an average follow-up of 8.8 years (range 1-20) with five patients now over 15 years post-treatment. The majority of the patients received 2500-2600 cGy. RESULTS: Three of 19 patients had abnormal vascular evaluations. Of these, two had bilateral abnormalities not felt to be solely associated with irradiation. The remaining patient showed both resting and post-exercise ipsilateral vascular abnormalities. Irradiation was the only identifiable etiologic agent for this patient's vascular abnormality. CONCLUSION: Subclinical vascular change attributable to low dose radiotherapy was identified in one of 19 patients (5%). Considering the radiocurability of seminoma patients this incidence is acceptable. In light of this slight, yet documented, arterial abnormality occurring with low dose radiotherapy, we recommend additional study of high dose radiotherapy patients to determine the incidence and morbidity of radiation-induced arteriopathy in this group.

Hemodynamic effects of varied graft diameters in the venous system.

Both in vivo and mathematical models of venous hypertension were used to evaluate the hemodynamic effects of 4, 6, 8, and 10 mm diameter cross-femoral venous bypass grafts (CFBs). Eighteen grafts (length 138 +/- 3.4 mm) were tested in paired sequential fashion (four grafts, 4 and 8 mm; five grafts, 6 and 10 mm) in nine greyhounds (femoral vein diameter, 7.7 +/- 0.09 mm). Bilateral hindlimb venous pressures and flows were measured before and after unilateral iliofemoral venous ligation, 30 minutes after CFB insertion, and for 5 minutes after venous flow augmentation induced by stimulated muscle contraction. CFBs of all sizes were equally effective at relieving the occlusive venous hypertension at rest. Muscle contraction elevated venous pressure in all ligated hindlimbs (p less than 0.0001); however, the pressure returned to baseline by 3 minutes in dogs with 6, 8, and 10 mm grafts but remained elevated (p less than 0.05) with the 4 mm grafts even after 5 minutes. Peak graft flow (first 90 seconds after contraction) was significantly greater through the 8 mm grafts than through the 4 mm grafts (p less than 0.01), although no difference was noted in flow rates between 6 and 10 mm grafts. The pressure gradient across the graft as predicted by the mathematic model for 6 to 10 mm conduits was less than 5 mm Hg for flows up to 1000 ml/min, although the pressure gradient of the 4 mm graft exceeded 5 mm Hg at 200 ml/min and approached 30 mm Hg at 1000 ml/min. Therefore, data from both canine and mathematical models agreed that, at rates approximating human resting flow (1000 ml/min), no adverse short-term hemodynamic consequences result from CFB conduits of 6 to 10 mm diameter.

Long-term follow-up of the Palmaz stent for iliac occlusive disease.

BACKGROUND: Thirty-eight limbs with iliac occlusive disease were treated with Palmaz stents from 1987 through 1991. METHODS: Indications for stent utilization included dissection induced by percutaneous transluminal balloon angioplasty (PTA) (10), restenosis after PTA (nine), post-PTA residual stenosis (nine), multiple stenoses or occlusion (five), and unfavorable location (five). RESULTS: The ankle/brachial pressure index increased from 0.53 +/- 0.27 to 0.8 +/- 0.26 after stent deployment. The intraluminal pressure gradient decreased from 31.9 +/- 16.3 to 0.9 +/- 2.2 mm Hg after stent deployment. Complications included pseudoaneurysm (one), arteriovenous fistula (one), iliac perforation (one), groin hematoma (two), and occlusion (two). Follow-up arteriogram showed stenosis proximal or distal (n = 4) or within the stents (n = 4). These were treated with PTA or stents. Two patients required an aortobifemoral graft. Nine patients have died. Life table analysis showed a 1-, 3-, and 5-year primary and secondary cumulative patency of 87% +/- 5.9%, 74% +/- 8.2%, and 63% +/- 10% and 91% +/- 5.1%, 91% +/- 5.6%, and 86% +/- 7.6%, respectively. CONCLUSIONS: Palmaz stents, often required to salvage a PTA failure, appear to maintain overall patency at a high level. However, intimal hyperplasia and the progression of atherosclerotic disease may result in a need for additional procedures to obtain this favorable outcome.

Venous hemodynamics in a chronic venous valvular insufficiency model.

To develop a large-animal model of chronic venous valve incompetence, 13 greyhound dogs underwent unilateral hindlimb venous valve lysis with a valve cutter apparatus pulled retrograde through the iliac, femoral, and lateral saphenous veins. Bilateral venous pressures in the lateral saphenous vein were recorded before valve lysis, immediately after valve lysis, and at intervals from 1 to 14 weeks after valve lysis, with the dogs in the supine position and elevated 80 degrees semierect, as well as after stimulated hindlimb muscle contraction to empty the hindlimb veins. Passive venous filling time with elevation and 90% venous refilling time after muscle contraction were calculated. From immediately after through 14 weeks after valve lysis, a shortened venous filling time and 90% venous refilling time as well as an elevated poststimulation venous pressure were noted. This valve lysis method successfully produced a hemodynamically verified model of venous valvular insufficiency.

Clinical implications of combined hypogastric and profunda femoral artery occlusion.

From 1983 to 1990, nine patients with combined hypogastric (HA) and profunda femoral arterial (PFA) occlusive disease presented with five nonhealing hip disarticulations, three nonhealing above-the-knee amputations, perineal necrosis in six patients, buttock necrosis in four patients, visceral ischemia in two patients, and lumbosacral spinal ischemia in one patient. Obviously some patients had more than one regional complication. Five patients died from complications of HA/PFA ischemia. Survivors included two patients who required a hemipelvectomy, one patient who required an axillary-to-hypogastric artery bypass graft for stump salvage, and one patient who survived despite lumbosacral paralysis and complete cystectomy. The 56% mortality and 100% morbidity emphasize the critical significance of combined hypogastric/profunda femoral artery circulatory compromise. Efforts should be made to preserve or re-establish the HA and/or PFA circulation whenever possible. A hemipelvectomy may be required to allow the wounds to finally heal. Furthermore, the certainty of an above-the-knee amputation healing is not present in these patients; therefore, a hemodynamic assessment of the healing potential of an above-the-knee amputation is required.

An experience with upper-extremity vascular trauma.

In this 6-year study of 101 limbs requiring surgical intervention for upper-extremity vascular trauma, most patients were male, young, and injured by penetrating objects. Injured vessels included 13 axillary/subclavian, 23 brachial, 40 radial, and 25 ulnar arteries. Concomitant injuries included nerve injury in 50 cases, tendon laceration in 29, and bony fracture in 11. Arterial repair was accomplished by primary repair in 54 limbs, vein graft in 26 limbs, and vein patch in 3 limbs. Seventeen arterial injuries were ligated. Ancillary procedures included 30 nerve or 27 tendon repairs. The limb salvage rate was 99%. No functional deficits were noted in those cases with only a vascular injury. In 64% and 25% of patients with nerve or musculoskeletal injury, respectively, the arm was functionally impaired. Prompt diagnosis and surgical intervention eliminate vascular injury as a factor in upper-extremity limb loss or disability. Functional deficits are the result of nerve or orthopedic injuries.

Prospective comparison of noninvasive techniques for amputation level selection.

This study prospectively compared the following tests for their accuracy in amputation level selection: transcutaneous oxygen, transcutaneous carbon dioxide, transcutaneous oxygen-to-transcutaneous carbon dioxide, foot-to-chest transcutaneous oxygen, intradermal xenon-133, ankle-brachial index, and absolute popliteal artery Doppler systolic pressure. All metabolic parameters had a high degree of statistical accuracy in predicting amputation healing whereas none of the other tests had statistical reliability. Amputation site healing was not affected by the presence of diabetes mellitus nor were the test results for any of the metabolic parameters.

Cerebral vascular reactivity assessed with acetazolamide single photon emission computer tomography scans before and after carotid endarterectomy.

BACKGROUND AND METHODS: In 64 patients, cerebral perfusion and vascular reactivity were assessed before and after carotid endarterectomy (CEA) using acetazolamide (ACZ)-enhanced single photon emission computer tomography (SPECT). Twenty-five patients were asymptomatic, whereas the remainder were symptomatic. Sixty-one patients had a > or = 70% ipsilateral internal carotid artery stenosis. RESULTS: Fifty SPECT scans revealed decreased vascular reactivity. Twenty-three showed infarcts. Fourteen patients had normal studies. Twenty of the SPECT scans of asymptomatic patients demonstrated poor vascular reactivity. After CEA, 39 patients had improved ipsilateral vasoreactivity. In 12 patients, contralateral improvement was also found. CONCLUSION: ACZ-enhanced SPECT scans, by assessing cerebral perfusion and vascular reactivity, may help to identify patients at risk of stroke should perfusion further diminish. Postoperative studies confirm improvement in vascular reactivity. ACZ-enhanced SPECT scans may provide objective evidence for the selection of patients with a high-grade asymptomatic carotid stenosis for CEA.

Acute mesenteric venous thrombosis. Revisited in a time of diagnostic clarity.

Historically, mesenteric venous thrombosis (MVT) has been found during laparotomy or at autopsy. Improvements in computed tomography (CT) and ultrasound (U/S) may identify patients earlier in their clinical course. How has this altered the treatment strategy of the authors? This 10-year retrospective study of acute MVT consisted of 12 men and three women (average age 43). Presenting signs and symptoms were nonspecific in 10/15 patients resulting in multiple diagnostic tests. All CT scans (10) and angiograms (4) revealed mesenteric clot. U/S exams detected clot in 6/9 patients. The remaining five patients exhibited clinical signs requiring operations rather than diagnostic studies. The only consistent laboratory abnormality was an elevated white blood cell count in 12/15 patients. Management of MVT varied. Five patients, heparinized once the diagnosis was made, did not experience dysfunction from MVT. Ten patients were not initially treated with heparin and were divided into three groups. Three patients received neither heparin nor surgery and have had no sequelae. MVT contributed to the death of two patients. The remaining five patients were diagnosed in the operating room following bowel resection. Two of these patients received postoperative heparin and had a favorable outcome. Two of the three patients not heparinized after surgery suffered additional bowel infarction. MVT can present as nonspecific abdominal pain, but also as peritonitis requiring operation. CT and U/S can identify patients with early MVT. It appears that heparin has both a primary therapeutic role in early disease and a postoperative adjunctive role in advanced disease. With such care, these patients can expect an acceptable prognosis (86% survival).

Vascular injuries during pancreatobiliary surgery.

Fourteen cases of vascular injury during pancreatobiliary surgery have been treated at our institution. The patients' mean age was 49 years, and nine were males. Six operations were performed for chronic pancreatitis, six for cancer, and two for an inflammatory process. Operations included 11 pancreatic resections and one laparoscopic cholecystectomy, one sphincteroplasty, and one pseudocyst drainage. Vessels injured included the portal vein (7), superior mesenteric vein (6), superior mesenteric artery (3), hepatic arteries (4), splenic vein (3). Six patients experienced more than one vascular injury. In all but one case, the injury was recognized and repaired during the initial operation. Primary repair was possible in seven cases. Six cases utilized autogenous tissue for repair. The one unrecognized injury was a right hepatic artery ligation, and a delayed repair was not possible. Follow-up demonstrated two occlusions, one following a portal vein repair without clinical sequela and a superior mesenteric artery repair which resulted in a small bowel stricture. The one unrecognized hepatic artery injury resulted in necrosis of the proximal common hepatic duct. Vascular injury following pancreatobiliary injury tends to occur in the presence of pancreatitis or cancer with its associated dense adhesions and inflammatory process. The variable anatomy of this area contributes to vascular injuries. Immediate recognition of the injury and repair appears to yield excellent results.

Arteriovenous fistulas as adjuncts to venous bypass grafts.

A canine model of occlusive hindlimb venous hypertension was used to determine which of two different, clinically applicable, adjunctive arteriovenous fistulas (AVFs), sequential or peripheral, would augment flow in autogenous cross-femoral venous bypass grafts (CFBs) with the least alteration of hindlimb hemodynamics. Unilateral venous hypertension was produced by iliofemoral venous ligation in three groups of five dogs: group I, venous ligation only (controls); group II, venous ligation followed by CFB with a sequential AVF; and group III, venous ligation with CFB and peripheral AVF. Bilateral hindlimb venous and arterial pressures and flows, and graft flows, were measured preoperatively and for 4 h postoperatively. Insertion of a CFB eliminated the venous hypertension in all 10 bypass dogs. Graft flow was augmented by addition of the sequential AVF (to 1167 +/- 309 mL/min from 92 +/- 12.3 mL/min: p less than .0001). However, this was accompanied, both in the limb ipsilateral to the AVF and in the contralateral limb, by the return of significant venous hypertension (p less than .001) and significant reduction (even reversal) of femoral vein flow caudad to the CFB (p less than .005). In contrast, adding the peripheral AVF augmented graft flow (to 200 +/- 62 mL/min from 65 +/- 43.7 mL/min; p less than .0001), but did not elevate venous pressure or impair venous flow in either hindlimb. The data from this short-term canine model suggest that a peripheral adjunctive AVF may effectively augment CFB graft flow without the potential for detrimental effects on venous hemodynamics characteristic of the sequential AVF.

Details of a canine venous insufficiency model.

Continued study of a chronic deep venous insufficiency (CDVI) model allows optimal comparison with the human condition. This study evaluates the model's long-term stability, its lack of observed clinical effect, and a simulated exercise study as a physiologic estimate of normal hindlimb walking. The time to maximal ankle venous pressure after standing (VFT), and to 90% of the venous refilling time after electrical stimulation, quadripedal, or hindlimb walking (VRT90), and the minimal pressure after exercise (AVP) were measured up to 10 months after CDVI model creation. The animals' intravenous resting pressure was obtained after standing stationary on all four limbs. Analysis of variance was used to determine statistical significance where indicated. VFT, AVP, and VRT90 measurements demonstrated values consistent with CDVI in animals studied up to 10 months after model creation and were statistically different from control limb values (p < or = .002, n = 8). Animals studied during quadripedal walking showed no difference in resting pressure, AVP, and VRT90 between model and control limbs (n = 5). There was no statistical difference in AVP or VRT90 measured under conditions of stimulated exercise or bipedal walking; and both conditions produced hemodynamic changes consistent with CDVI (n = 5). This animal model is a reliable long-term CDVI hemodynamic model. The normal venous hemodynamics recorded during quadripedic walking may explain the lack of clinical sequelae observed in this model. Lastly, the method of simulated exercise used in this study is a reliable test that reflects physiologic measurements obtained during bipedal walking.

Successful treatment of an iatrogenic infrarenal aortic dissection with serial Wallstents.

We report a patient who presented with acute lower extremity ischemia 13 days following removal of an intraaortic balloon pump. Dissection of the infrarenal aorta, extending into the left iliac artery, was found at operation. The patient's recent myocardial infarction, prolonged ischemia with compartment syndrome, otherwise normal aortoiliac and infrainguinal arteries and the necessity for suprarenal aortic clamping for surgical repair, were all factors in the decision for endovascular repair of the dissection. Infrarenal aortic and left iliac Wallstents, placed intraoperatively, successfully occluded the false lumen of the dissection. The patient was discharged after an uncomplicated recovery and is asymptomatic with palpable pedal pulses and triphasic pedal Doppler waveforms 1 year following the procedure.

Long-term results after inferior vena caval resection during retroperitoneal lymphadenectomy for metastatic germ cell cancer.

PURPOSE: The long-term sequelae of inferior vena caval (IVC) resection during retroperitoneal lymph node dissection for metastatic nonseminomatous germ cell testis tumor (NSGCT) were assessed. METHODS: Between December 1973 and September 1996, 2126 of our patients underwent RPLND for retroperitoneal nodal metastases from NSGCT; 955 had bulky disease (stages B2, B3, or C) after cytoreduction chemotherapy. Of this latter group, 65 patients (6.8%) required infrarenal IVC resection during tumor excision for cure. Our protocol does not include IVC reconstruction in such cases. Indications for IVC resection included tumor encasement or encroachment, postchemotherapy desmoplastic compression, or thrombus with tumor or clot in which cavotomy and thrombectomy cannot be performed. RESULTS: Twenty-four of the 65 patients (postoperative follow-up period range, 11 months to 16 years; median, 89 months) were alive and able to be examined or interviewed by written and/or phone survey to assess the long-term morbidity of their IVC resection. Based on the 1994 American Venous Forum International Consensus Committee reporting standards, the clinical classifications of these 24 patients were C0A (4), C3S (4), C4A (2), C4S (13), and C6A (1). Long-term disability was mild or absent in 75% of these patients. CONCLUSION: Only 1 (4.2%) of the patients surveyed had chronic venous sequelae that would fulfill the accepted criteria for subsequent elective IVC reconstruction. Despite recent reports of IVC reconstruction demonstrating relatively good patency rates and low morbidity, the addition of such a complex, time-consuming procedure to extensive retroperitoneal lymph node dissection for metastatic NSGCT involving IVC resection is generally not necessary.

Elevated cutaneous leukocyte concentration in a rodent model of acute venous hypertension.

BACKGROUND: The pathophysiologic mechanism of the skin pathology in chronic venous insufficiency is venous hypertension (VHTN). Microvascular dysfunction involving leukocytes has recently been proposed as the primary mediator of tissue damage from VHTN. We developed a rodent model allowing the investigation of the effects of acute VHTN on tissue leukocyte concentration. MATERIALS AND METHODS: Under general anesthesia, adult male rats underwent transperitoneal isolation of the inferior vena cava and the common iliac veins and arteries. Bilateral thigh incisions allowed isolation of the common femoral veins and superficial epigastric veins (SEV: distal branch of the femoral vein in the thigh). Pressure in the SEV and flow in the iliac artery were measured before (T-Pre), immediately after (T-0), and for 135 min (T-1) after ligation of the cava, iliac, and femoral veins. Sham rats were identical except no venous ligation was performed. After the T-1 pressures were obtained, the distal hindlimb and forelimb skin was harvested and processed to measure myeloperoxidase (MPO) activity, an index of the number of tissue leukocytes. To evaluate the effect of arterial flow reduction known to occur with acute venous ligation, the above measurements were made in an Aortic group of rats in which the aorta was manually stenosed. RESULTS: This venous ligation technique resulted in a significant (P < 0.05) and sustained rise in venous pressure (T-Pre, 9.91 +/- 0.94 and T-1, 26.22 +/- 2.15). Hypertensive rats had significantly elevated hindlimb MPO activity (4.77 +/- 0.36) vs forelimb (0.60 +/- 0.39), Sham (hindlimb, 0.77 +/- 0.41; forelimb, 0.10 +/- 0.05), and Aortic (hindlimb, 0.96 +/- 0.38; forelimb, 0.58 +/- 0.11) controls. CONCLUSIONS: Acute VHTN was successfully created by venous ligation in this newly developed rat model. VHTN, but not arterial flow reduction, was associated with significantly elevated hindlimb skin MPO activity, suggesting that leukocytes may indeed be mediators of skin pathology in VHTN. This model will allow further investigation into the mechanisms of microvascular dysfunction in VHTN.

Increased hindlimb leukocyte concentration in a chronic rodent model of venous hypertension.

BACKGROUND: The pathophysiologic mechanism for tissue damage in chronic venous insufficiency (CVI) is venous hypertension (VH), the primary mediator behind leukocyte trapping in tissues. We developed a new rodent model of chronic hindlimb VH to allow testing of the microvascular dysfunction that occurs in clinical CVI. MATERIALS AND METHODS: Hindlimb VH was created in adult rats ( approximately 350 g, male, Wistar) by ligation of the inferior vena cava, bilateral common iliac veins, and bilateral common femoral veins. In a sham group, a loose tie was placed around the same vessels. One week later, pressure catheters were placed in the right common carotid artery, right internal jugular vein (forelimb), and right superficial epigastric vein (hindlimb). Measurements were taken 15 min later, to allow for stabilization. Bilateral forelimb and hindlimb skin specimens were harvested. The myeloperoxidase (MPO) assay, an indicator of tissue leukocyte trapping, was performed using a well-described, standard technique. RESULTS: In the chronic rats (n = 8), the hindlimb pressures (12.6 +/- 3.2 mm Hg) were significantly elevated (P < 0.05) when compared to forelimb pressures (1.75 +/- 0.71) and to chronic sham rat (n = 6) hindlimb (3.3 +/- 1.2) pressures. There was a significant (P < 0.05) elevation of MPO activity in hindlimbs of the chronic group (32.9 +/- 13.9 units) when compared to forelimbs (17 +/- 11.3) and sham hindlimbs (18 +/- 10.2). CONCLUSIONS: In our chronic model, as in clinical studies and previous acute investigations, we have demonstrated, using an MPO assay, an increase in the amount of cutaneous leukocytes in the hindlimbs with chronic VH but not in experimental forelimbs or sham hindlimbs or forelimbs.

Canine model for surgical correction of chronic venous hypertension.

A chronic model of venous hypertension was created by iliofemoral venous ligation in the left hindlimb of eight greyhounds (right limb control). Prior to ligation, immediately postligation (T0), and at 2, 4, 6, and 15 weeks postligation (T2-T15), bilateral hindlimb venous pressures were measured at rest. At T2-T15, exercise pressures were measured for 5 min after hindlimb muscle contraction induced under sedation by tetanic (20 sec, 50 Hz, 8 mA) stimulus (S30-S300 sec). Resting and exercise pressures were significantly higher in the ligated hindlimb at all time intervals (resting, P less than 0.001 at T0, T2, T4, T6, and P less than 0.025 at T15; exercise, P less than 0.001 for S30-S300 at T2-T15). In five of the animals at 15 weeks, a cross-femoral venous bypass (CFB) with adjacent adjuvant arteriovenous fistula (AVF) was constructed using autologous external jugular vein. Venous pressures were measured at 2 and 6 weeks post-CFB both at rest and after tetanic muscle stimulation. At 2 weeks, venous pressure in the ligated limb was significantly higher than that in control only after exercise (P less than 0.025 at S30-S120; P less than 0.05 at S150-S180; NS at S240-S300). At 6 weeks, venous pressures were not significantly different at rest or with exercise. All five grafts were patent at 6 weeks. Three of five dogs then successfully underwent ligation of the AVF. At 2 weeks post-AVF ligation there was no difference in resting or exercise venous pressure in the ligated limb compared to control. At 6 weeks post-AVF ligation only two dogs remained for monitoring and in these there was no trend toward venous hypertension in the ligated hindlimb. Graft patency was maintained despite AVF ligation.

Hemodynamics of revascularization for iliofemoral venous occlusion: a short-term canine model.

A short-term canine model of lower extremity venous hypertension was created to study the hemodynamics of crossfemoral venous bypass grafts (CFB). Specifically, the hemodynamic effects of bypass conduit diameter and adjunctive arteriovenous fistulas (AVFs) were investigated. Unilateral hind limb venous hypertension was produced by iliofemoral venous ligation in six groups of five greyhounds each. Group I had venous ligation alone. CFBs were constructed in the remaining five groups: group II, 3 mm bypass conduit alone; group III, 3 mm bypass plus sequential AVF; group IV, 3 mm bypass plus caudad AVF; group V, 3 mm bypass plus cephalad AVF; group VI, 6 mm bypass conduit alone. Venous hypertension was significantly reduced by CFB (group II, p less than 0.025; group VI, p less than 0.001); increasing the diameter of the bypass conduit from 3 to 6 mm produced significantly greater graft flow (p less than 0.05), while completely relieving venous hypertension. Addition of adjunctive AVFs significantly augmented graft flow (p less than 0.001) but tended to aggravate ipsilateral venous hypertension (group III, p less than 0.01; group IV increase, NSS; group V, p less than 0.001). During the 4 hours of pressure monitoring, venous hypertension diminished significantly (p less than 0.05) with the sequential AVF but not with the other AVF. We conclude that (1) AVFs may be required for adequate graft flow if a small-diameter (3 mm) bypass conduit is used to relieve venous hypertension; (2) adjunctive AVFs aggravate venous hypertension; (3) sequential AVFs seem to be the most hemodynamically efficacious; (4) AVFs may not be necessary if a large, isodiametric (6 mm) conduit is used.

Improvement of flow through arterial stenoses by drag reducing agents.

The potential of drag reducing polymers (DRP) to selectively improve blood flow through clinically significant arterial stenoses was investigated. An artificial stenosis of the left common iliac artery in dogs decreased left femoral artery pressure by 25%. High-molecular-weight polyacrylamide (PA) or polyethylene oxide (PEO) were infused at a slow constant rate while we measured left and right common iliac artery blood flows and left and right femoral artery and vein pressures. As DRP were infused, left iliac artery flow (QL) increased early and then decreased to baseline values as flow began to increase in the right iliac artery. The peak increase in QL was 24 +/- 9% for PA and 46 +/- 19% for PEO and occurred before right iliac artery flow (QR) increased. As additional polymer was infused, QR increased to a maximum of 41 +/- 12 and 131 +/- 40% with PA and PEO, respectively. Femoral artery pressures and hindlimb resistances tended to decrease in both limbs but the only significant differences occurred in the right (nonstenosed) side when QR was elevated. This study provides the first evidence that low concentrations of DRP might be capable of improving blood flow through stenotic blood vessels without altering flow in normal vessels. Although DRP might represent a new class of compounds that could be utilized in the treatment of cardiovascular diseases, the degree of variation in individual responses is a concern, the exact mechanism of action is unclear, and information on pharmacodynamics is lacking.