Pharmacomechanical thrombolysis for phlegmasia cerulea dolens.

Phlegmasia cerulea dolens (PCD) is limb-threatening. Traditional treatments are very morbid. We examine the efficacy of percutaneous treatment of PCD. Between May 2005 and September 2008, we treated 21 limbs in 20 patients with lower extremity PCD who were candidates for thrombolysis. Diagnosis was by clinical examination and duplex ultrasound. Catheter access to the deep venous system was obtained through a popliteal vein. Therapy used pulse spray thrombolysis with tissue plasminogen activator (tPA). Infusion catheters and adjunctive percutaneous techniques were used as indicated. Postoperatively, patients were treated with systemic anticoagulation, compression hose, and interval follow-up. Limbs were graded according to the CEAP classification. Twenty patients (13 male) were treated with a mean age of 55.8 years. Nine patients had hypercoagulable states, four May Thurner syndrome, three a history of cancer, one postcolon resection, one acute myocardial infarction, and one postfemoral vein puncture. All patients had resolution of PCD without the need for open surgery. The initial tPA dose was 19.5 mg with pulse spray thrombolysis. Infusion catheters were required in 18 patients and used for 16.1 hours (range, 8 to 36 hours) until complete thrombolysis. Venous angioplasty was necessary in 14 patients with nine of these requiring venous stents. One patient required above-knee amputation despite successful treatment of her PCD. Mean follow-up was 10.7 months (range, 1 to 39 months). All patients demonstrated no or minimal residual thrombus and intact valvular function and a mean clinical CEAP score of 2.4. Percutaneous treatment of PCD produced excellent results with minimal morbidity.

Saphenous vein graft aneurysm with graft-enteric fistula after renal artery bypass.

A 65-year-old female presented with upper gastrointestinal hemorrhage thirty years following an aorta-to-right renal artery bypass constructed with saphenous vein. Upper endoscopy demonstrated a duodenal ulcer, and a CAT scan demonstrated aneurysmal degeneration of her renal artery bypass with duodenal impingement. Laparotomy demonstrated erosion of the aneurysm through the posterior wall of the duodenum; extra-anatomic renovascular reconstruction and primary duodenal repair was performed. Although aneurysmal degeneration of intraabdominal saphenous vein grafts is well described and rupture likewise reported, this report represents the first description of an intraabdominal autogenous vein graft aneurysm presenting with gastrointestinal erosion and fistula.

Loss of renal function and microvascular blood flow after suprarenal aortic clamping and reperfusion (SPACR) above the superior mesenteric artery is greatly augmented compared with SPACR above the renal arteries.

OBJECTIVE: Renal insufficiency continues to be a complication that can affect patients after treatment for suprarenal aneurysms and renal artery occlusive disease. To our knowledge, no data are available showing that suprarenal aortic clamping and reperfusion (SRACR) above the renal arteries (renal-SRACR) preserves renal function compared with SRACR above the superior mesenteric artery (SMA-SRACR). This study examined the hypothesis that SMA-SRACR-induced downregulation of renal blood flow and function is more severe than renal-SRACR owing to the addition of systemic oxygen-derived free radical (ODFR) release. METHODS: Male Sprague-Dawley rats (about 350 g) were anesthetized and microdialysis probes or laser Doppler fibers were inserted into the renal cortex (depth of 2 mm) and into the renal medulla (depth of 4 mm). Laser Doppler blood flow was continuously monitored, and the microdialysis probes were connected to a syringe pump and perfused in vivo at 3 microL/min with lactated Ringer's solution. RESULTS: SMA-SRACR and Renal-SRACR decreased medullary and cortical blood flow and nitric oxide (NO) synthesis. SMA-SRACR downregulated cortical inducible NO synthase, whereas renal-SRACR did not. The cortex and medulla responded to the decreased blood flow and NO synthesis by increasing in prostaglandin E2 synthesis, which was due to increased cyclooxygenase-2 content. Superoxide dismutase restored SMA-SRACR (but not renal-SRACR) cortical and medullary NO synthesis, suggesting that ODFRs generated during mesenteric ischemia-reperfusion were one of the systemic mechanisms contributing to decreased renal NO synthesis in the SMA-SRACR model. The 90% decrease in creatinine clearance after SMA-SRACR was greater than the 60% decrease after renal-SRACR. CONCLUSIONS: These data show that NO is important in maintaining renal cortical and medullary blood flow and NO synthesis after renal and SMA-SRACR. These data also suggest that in addition to the renal ischemia-reperfusion caused by both models, SMA SRACR induces mesenteric ischemia-reperfusion, resulting in the generation of ODFRs, which contribute to decreased renal cortical and medullary NO synthesis. Maintaining splanchnic blood flow or attempting to keep SRACR below the SMA level may be helpful in developing strategies to minimize the renal injury after SRACR.

Preliminary results of subintimal angioplasty for limb salvage in lower extremities with severe chronic ischemia and limb-threatening ischemia.

OBJECTIVE: This study examined the hypothesis that superficial femoral artery (SFA) subintimal angioplasty (SI-PTA) can maintain limb salvage with minimal complications in patients with symptomatic occlusive arterial disease. METHODS: From March 1, 2004, until April 28, 2006, 78 patients with rest pain (62.2%), gangrene (25.6%), or severe progressive claudication (12.2%) were treated consecutively with 82 SFA SI-PTAs (4 bilateral). The mean age was 59 +/- 1.2 years, and 21 (27%) of the patients were female. All patients were treated in the operating room under local anesthesia by using fluoroscopic guidance, and the percentage SFA that was occluded was measured during the diagnostic portion of the procedure. Selective stent placement was performed after successful recanalization of the occluded arterial segments. Patients were treated with chronic aspirin and clopidogrel bisulfate for 3 months and followed up at 30 days and then every 3 months with physical examination and arterial duplex scan. RESULTS: Of the 82 SFA SI-PTA attempts, 76 (92%) were initially successful, with an increase in the ankle-brachial index from 0.46 +/- 0.02 to 0.88 +/- 0.01 (P < .001). Five of the six patients with a failed SFA SI-PTA were female, two of the six had had previous bypass attempts, and one of the six had had a previous SFA SI-PTA attempt by another physician. Forty-nine (64%) of the 76 initially successful SFA SI-PTAs required placement of a stent, and 43 (56.5%) of the successful 76 SFA SI-PTAs required additional PTA of 1 or more arterial segments. The group treated with a successful SFA SI-PTA had 42.5% +/- 3.5% SFA occlusion, compared with 82% +/- 10% (P < .05) in the group with a failed attempt at SFA SI-PTA. Two of the six patients with initial SI-PTA failure underwent leg amputation within 30 days, three were treated with successful leg bypass surgery, and one was lost to follow-up. Of the 76 successful SFA SI-PTAs, 5 (6.5%) failed within 90 days, and the patients were treated successfully with leg bypass surgery. Of the 71 limbs with patent SI-PTAs at 90 days, 68 have remained patent with a mean follow-up 10.4 +/- 0.7 months (range, 2-24 months). Three of the 71 SFA SI-PTAs failed between 4 and 7 months (mean, 5 +/- 0.7 months): 1 patient was treated with successful bypass surgery, 1 patient is currently considering further intervention, and 1 patient was treated with amputation. Ten (14%) of the 71 successful SFA SI-PTAs required limited PTA for asymptomatic restenosis, as identified by the arterial duplex scan (7.4 +/- 1.4 months; range, 2-16 months). There were no perioperative deaths, and three patients have died during follow-up with patent SFA SI-PTAs (9.3 +/- 1.4 months). CONCLUSIONS: These data suggest that SFA SI-PTA can be successfully used for limb salvage with minimal morbidity and mortality in a group of patients with severe lower extremity occlusive vascular disease.

Iodinated contrast induced renal vasoconstriction is due in part to the downregulation of renal cortical and medullary nitric oxide synthesis.

OBJECTIVES: The loss of renal function continues to be a frequent complication of the iodinated contrast agents used to perform diagnostic angiography and endovascular procedures. This study examined the hypothesis that contrast-induced renal injury is partly due to a decrease in cortical and medullary microvascular blood flow after the downregulation of endogenous renal cortical and medullary nitric oxide (NO) synthesis. METHODS: Anesthetized male Sprague-Dawley rats (300 g) had microdialysis probes or laser Doppler fibers inserted into the renal cortex to a depth of 2 mm and into the renal medulla to a depth of 4 mm. Laser Doppler blood flow was continuously monitored, and the microdialysis probes were connected to a syringe pump and perfused in vivo at 3 muL/min with lactated Ringer's solution. Dialysate fluid was collected at time zero (basal) and 60 minutes after infusion of either saline or Conray 400 (6 mL/kg). Both groups were treated with saline carrier, N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME, 30 mg/kg), L-arginine (400 mg/kg), or superoxide dismutase (10,000 U/kg), an oxygen-derived free radical scavenger. Dialysate was analyzed for total NO and eicosanoid synthesis. The renal cortex and medulla were analyzed for inducible NO synthase (iNOS), cyclooxygenase-2 (COX2), prostacyclin synthase, and prostaglandin E(2) (PGE(2)) synthase content by Western blot analysis. RESULTS: Conray caused a marked decrease in cortical and medullary blood flow with a concomitant decrease in endogenous cortical NO, PGE(2), and medullary NO synthesis. The addition of L-NAME to the Conray further decreased cortical and medullary blood flow and NO synthesis, which were restored toward control by L-arginine. Neither L-NAME nor L-arginine (added to the Conray) altered cortical or medullary eicosanoids release. Medullary PGE(2) synthesis decreased when superoxide dismutase was added to the Conray treatment, suggesting that oxygen-derived free radicals had a protective role in maintaining endogenous medullary PGE(2) synthesis after Conray treatment. Conray did not significantly alter iNOS, COX-2, prostacyclin synthase, or PGE(2) synthase content. CONCLUSIONS: These findings suggest that the downregulation of renal cortical and medullary NO synthesis contributes to the contrast-induced loss of renal cortical and medullary microvascular blood flow. Preservation of normal levels of renal cortical and medullary NO synthesis may help prevent or lessen contrast-induced renal vasoconstriction and lessen contrast-induced renal injury found after diagnostic and therapeutic endovascular procedures.

Oxygen-radical regulation of renal blood flow following suprarenal aortic clamping.

OBJECTIVE: Renal insufficiency continues to be complication that can affect patients after treatment for suprarenal aneurysms and renal artery occlusive disease. One proposed mechanism of renal injury after suprarenal aortic clamping (above the superior mesenteric artery) and reperfusion (SMA-SRACR) is the loss of microvascular renal blood flow with subsequent loss of renal function. This study examines the hypothesis that the loss of medullary and cortical microvascular blood flow following SMA-SRACR is due to oxygen-derived free radical down-regulation of endogenous medullary and cortical nitric oxide synthesis. METHODS: Anesthetized male Sprague-Dawley rats (about 350 g) either had microdialysis probes or laser Doppler fibers inserted into the renal cortex (depth of 2 mm) and into the renal medulla (depth of 4 mm). Laser Doppler blood flow was continuously monitored. The microdialysis probes were connected to a syringe pump and perfused in vivo at 3 microL/min with lactated Ringer's solution. The animals were subjected to SMA-SRACR (or sham) for 30 minutes, followed by 60 minutes of reperfusion. Laser Doppler blood flow after the 30 minutes of SMA-SRACR followed by 60 minutes of reperfusion was compared with the time zero (basal) and with the corresponding sham group and reported as percent change compared with the time zero baseline. The microdialysis fluid was collected at time zero (basal) and compared with the dialysis fluid collected after 30 minutes of SMA-SRACR followed by 60 minutes of reperfusion as well as the corresponding sham group. The microdialysis dialysate was analyzed for total nitric oxide (microM) and prostaglandin E2 (PGE2), 6-keto-PGF(1alpha) (PGI2 metabolite), and thromboxane B2 synthesis. The data are reported as percent change compared with the baseline time zero. The laser Doppler blood flow and microdialysis groups were treated with either saline carrier, N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME) (30 mg/kg, nitric oxide synthesis inhibitor), L-arginine (400 mg/kg, nitric oxide precursor), superoxide dismutase (SOD, 10,000 U/kg, oxygen-derived free radical scavenger), L-NAME + SOD, or L-arginine + SOD. SOD was given 30 minutes before the reperfusion, and the other drugs were given 15 minutes before reperfusion. The renal cortex and medulla were separated and analyzed for inducible nitric oxide synthase (iNOS), cyclooxygenase-2, prostacyclin synthase, and PGE2 synthase content by Western blot. RESULTS: Superior mesenteric artery-SRACR caused a marked decrease in medullary and cortical blood flow with a concomitant decrease in endogenous medullary and cortical nitric oxide synthesis. These changes were further accentuated by L-NAME treatment but restored toward sham levels by L-arginine treatment after SMA-SRACR. The kidney appeared to compensate for these changes by increasing cortical and medullary PGE2 synthesis and release. SOD treatment restored renal cortical and medullary nitric oxide synthesis and blood flow in the ischemia-reperfusion group and in the ischemia-reperfusion group treated with L-NAME. CONCLUSIONS: These data show that nitric oxide is important in maintaining renal cortical and medullary blood flow and nitric oxide synthesis. These data also support the hypothesis that the loss of medullary and cortical microvascular blood flow following SRACR is due in part to oxygen-derived free radical downregulation of endogenous medullary and cortical nitric oxide synthesis.

Suprarenal aortic clamping and reperfusion decreases medullary and cortical blood flow by decreased endogenous renal nitric oxide and PGE2 synthesis.

OBJECTIVE: This study examined the hypothesis that clamping the aorta above the superior mesenteric artery (SMA) followed by suprarenal aortic clamping and reperfusion (SRACR) decreases microvascular blood flow by loss of endogenous medullary and cortical nitric oxide (NO) and prostaglandin (PG) E(2) synthesis. STUDY DESIGN: Anesthetized male Sprague-Dawley rats (350 g) had either microdialysis probes or laser Doppler fibers inserted into the renal cortex to a depth of 2 mm and into the renal medulla at 4 mm. Laser Doppler blood flow was continuously monitored (data reported as percentage of change compared to basal), and the microdialysis probes were connected to a syringe pump and perfused in vivo at 3 microL/min with lactated Ringer solution. Dialysate fluid was collected at basal time zero, following 30 minutes of suprarenal aortic clamping (ischemia) followed by 60 minutes of reperfusion and compared to a sham operation. Both groups were treated with saline carrier, indomethacin (INDO) (10 mg/kg, a cyclooxygenase [COX] inhibitor), N(G)-nitro-L-arginine methyl ester (L-NAME) (20 mg/kg, a NO synthase [NOS] inhibitor), or L-arginine (200 mg/kg, an NO precursor). Dialysate was analyzed for total NO (muM) and PGE(2) (pg/mL) synthesis. The renal cortex and medulla were analyzed for inducible NOS (iNOS) and COX-2 content by Western blot. All data are reported as mean +/- SEM, N > 5 and analyzed by analysis of variance. RESULTS: SRACR caused a marked decrease in medullary and cortical blood flow with a concomitant decrease in endogenous medullary and cortical NO synthesis. Treatment with L-NAME further decreased blood flow and NO synthesis in the medulla and cortex. L-Arginine restored medullary and cortical NO synthesis and blood flow in the cortex but not the medulla. SRACR did not alter renal medullary or cortical PGE(2); however, addition of INDO, COX inhibitor, caused a concomitant decrease in medullary and cortical PGE(2) synthesis and blood flow. CONCLUSIONS: NO is an important endogenous renal vasodilator that, when maintained can help preserve cortical blood flow following SRACR. These data also suggest that avoidance of COX-2 inhibitors can help maintain endogenous renal cortical and medullary PGE(2) synthesis and thus contribute to maintaining normal blood flow. CLINICAL RELEVANCE: This study is the first to combine in vivo physiologic assays to simultaneously identify clinically relevant intrarenal vasodilators (cortical and medullary) that are required to maintain microvascular blood flow. Identification of endogenous renal cortical and medullary vasodilators responsible for maintaining renal microvascular blood flow will allow development of treatment strategies to preserve these vasodilators following SRACR. Successful preservation of endogenous intrarenal vasodilators will help maintain renal microvascular blood flow and renal function in the treatment of complex aortic pathology that requires SRACR.

Cholecystokinin (CCK) down regulates PGE2 and PGI2 release in inflamed Guinea pig gallbladder smooth muscle cell cultures.

This study examines the hypothesis that cholecystitis down-regulates Guinea pig gallbladder (GPGB) smooth muscle cholecystokinin (CCK)-stimulated prostaglandin (PG) release. Guinea pig gallbladder from Control and 48 h bile duct ligated (BDL) animals were placed in cell culture and grown to confluence. The cultures underwent Western Blot analysis for smooth muscle cell content of COX-1, COX-2, Prostacyclin Synthase (PS), or were incubated with CCK at 10(-8)M or 10(-6)M with and without indomethacin for 1h and analyzed for release of 6-keto-PGF1alpha, PGE2 and TxB2 by EIA. BDL increased Guinea pig gallbladder cell culture basal PGE2 and PGI2 release which was in part due to increased COX-2 content. CCK incubation down-regulated BDL Guinea pig gallbladder cell culture release of 6-keto-PGF1alpha and PGE2 and down-regulated COX-2 content but did not alter the Control group. The decrease in CCK-mediated BDL cell Guinea pig gallbladder release may be an endogenous mechanism to limit physiologic derangements induced by increased endogenous gallbladder PG synthesis during early acute cholecystitis.

Complete regression of an intramural hematoma of the aorta after distal reperfusion.

A 58-year-old man with hypertension, severe abdominal pain, and pulseless extremities was diagnosed with an isolated abdominal intramural hematoma (IMH). The IMH extended from the distal descending thoracic aorta to just proximal to the renal arteries. beta-Blockade treatment resolved the abdominal pain but induced progressive oliguria; decreasing beta-blockade treatment increased urine output but caused return of abdominal pain. An axillobifemoral bypass allowed distal perfusion and retrograde visceral artery perfusion while maintaining normal blood pressure. The abdominal pain resolved, urine output increased, and the patient was discharged on day 7. Six months later the patient required an emergent thrombectomy of the axillobifemoral graft and normal antegrade aortic flow was found. A computed tomography scan showed resolution of the IMH.

Physicochemical properties of perfluorochemical liquids influence ventilatory requirements, pulmonary mechanics, and microvascular permeability during partial liquid ventilation following intestinal ischemia/reperfusion injury.

OBJECTIVE: To test the hypothesis that the physicochemical properties of perfluorochemical liquid used in partial liquid ventilation can influence ventilatory requirements, pulmonary mechanics, microvascular permeability, and vasoactive mediator release in the abnormal lung. DESIGN: Prospective, controlled animal study. SETTING: Research laboratory in a university setting. SUBJECTS Male Sprague-Dawley rats: sham and intestinal ischemia/reperfusion injury. INTERVENTIONS: Treatment with perfluorochemical partial liquid ventilation (PLV: PP-5 or H-130) or conventional mechanical ventilation (CMV) over 60 mins of superior mesenteric artery occlusion and 60 mins of reperfusion. MEASUREMENTS AND MAIN RESULTS: Gas exchange, ventilatory requirements, and pulmonary mechanics were measured in vivo. Subsequently, pulmonary vascular resistance, microvascular permeability, and thromboxane were measured by using the isolated perfused lung preparation. PLV with PP-5 required significantly (p <.05) higher positive end-expiratory pressure resulting in increased mean airway pressures and pulmonary vascular resistance in both sham and intestinal ischemia/reperfusion injured animals compared with those treated with CMV or PLV H-130. PLV PP-5 also resulted in significantly (p <.05) lower respiratory compliance and greater microvascular permeability compared with sham animals. Following intestinal ischemia/reperfusion injury, PLV H-130 treated animals had significantly higher (p <.05) respiratory compliance than those treated with PLV PP-5 and a significantly lower (p <.05) intestinal ischemia/reperfusion-mediated increase in microvascular permeability than those treated with CMV or PLV PP-5. Thromboxane levels were significantly higher (p <.01) in injured animals treated with CMV or PLV PP-5 compared with comparably treated shams, were significantly lower (p <.01) in both PLV groups than CMV, and were further attenuated (p <.01) by PLV H-130 compared with PLV PP-5 animals. CONCLUSION: We conclude that PLV with perfluorochemical liquids attenuates pulmonary sequelae resulting from remote organ injury and that the extent of lung protection depends on the physicochemical properties of the perfluorochemical liquids.