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1.
Dis Colon Rectum ; 45(2): 165-70, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11852327

ABSTRACT

PURPOSE: The aim of this study was to determine the optimal management of patients with colorectal cancer and abdominal aortic aneurysm in the elective situation. METHODS: All patients with a history of colorectal cancer and abdominal aortic aneurysm between 1986 and July 2000 were identified, and charts of those with concomitant disease were reviewed. RESULTS: A total of 435 patients with available charts were reviewed. Eighty-three patients with concomitant abdominal aortic aneurysm and colorectal cancer were identified. In 64 patients the colorectal cancer was treated first, and 44 of these patients had an abdominal aortic aneurysm less than 5 cm in diameter (average = 3.8 cm). No abdominal aortic aneurysm ruptured in the postoperative period. Median delay to colorectal cancer surgery from diagnosis was four days. Twenty patients with abdominal aortic aneurysm of 5 cm or greater (average = 5.4 cm) were treated for colorectal cancer first. In two of these patients (with abdominal aortic aneurysms sized 5 and 6.4 cm), the abdominal aortic aneurysm ruptured in the early postoperative period. Median delay to colorectal cancer resection was eight days. Twelve patients had both abdominal aortic aneurysm and colorectal cancer treated at the same time. The average size of the abdominal aortic aneurysm was 6.4 cm. Median delay from colorectal cancer diagnosis to resection was 15 days. No documented cases of graft infection occurred in this group; median follow-up was 3.2 years. Seven patients underwent abdominal aortic aneurysm repair before resection of colorectal cancer; in two patients, colorectal cancer was found at the time of resection. The average size of abdominal aortic aneurysm was 6 cm and median delay to treatment of colorectal cancer was 122 days, a statistically significant longer delay than in the other two groups (P < 0.0001). CONCLUSION: In patients with colorectal cancer and abdominal aortic aneurysm of 5 cm or more, treatment of colorectal cancer first may result in life-threatening rupture, whereas treatment of abdominal aortic aneurysm first may significantly delay treatment of colorectal cancer. Concomitant treatment seems to be a safe alternative. If anatomically suitable, the abdominal aortic aneurysm may be considered for endovascular repair followed by a staged colon resection. The presence of an abdominal aortic aneurysm less than 5 cm does not affect colorectal cancer treatment.


Subject(s)
Aortic Aneurysm, Abdominal/complications , Colorectal Neoplasms/complications , Aged , Aortic Aneurysm, Abdominal/epidemiology , Aortic Aneurysm, Abdominal/surgery , Aortic Rupture/surgery , Case-Control Studies , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/surgery , Female , Follow-Up Studies , Humans , Male , Time Factors
2.
J Vasc Surg ; 34(5): 785-91, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11700476

ABSTRACT

PURPOSE: Primary chylous disorders (PCDs) are rare. Rupture of dilated lymph vessels (lymphangiectasia) may result in chylous ascites, chylothorax, or leakage of chyle through chylocutanous fistulas in the lower limbs or genitalia. Chyle may reflux through incompetent lymphatics, causing lymphedema. To assess the efficacy of surgical treatment, we reviewed our experience. METHODS: The clinical data of 35 patients with PCDs treated between January 1, 1976, and August 31, 2000, were reviewed retrospectively. RESULTS: Fifteen men and 20 women (mean age, 29 years; range, 1 day-81 years) presented with PCDs. Sixteen (46%) patients had chylous ascites, and 19 (54%) had chylothorax (20 patients), and of these, 10 (29%) had both. In 16 patients, reflux of chyle into the pelvic or lower limb lymphatics caused lymphedema (14, 88%) or lymphatic leak through cutaneous fistulae (11, 69%). Presenting symptoms included lower-limb edema (19, 54%), dyspnea (17, 49%), scrotal or labial edema (15, 43%), or abdominal distention (13, 37%). Primary lymphangiectasia presented alone in 23 patients (66%), and it was associated with clinical syndromes or additional pathologic findings in 12 (yellow nail syndrome in 4, lymphangiomyomatosis in 3, unknown in 3, Prasad syndrome (hypogammaglobulinemia, lymphadenopathy, and pulmonary insufficiency) in 1, and thoracic duct cyst in 1). Twenty-one (60%) patients underwent 26 surgical procedures. Preoperative imaging included computed tomography scan in 15 patients, magnetic resonance imaging in 3, lymphoscintigraphy in 12, and lymphangiography in 14. Fifteen patients underwent 18 procedures for chylous ascites or pelvic reflux. Ten (56%) procedures were resection of retroperitoneal/mesenteric lymphatics with or without sclerotherapy of lymphatics, 4 (22%) were lymphovenous anastomoses or grafts, 3 (17%) were peritoneovenous shunts, and 1 (6%) patient had a hysterectomy. Six patients underwent eight procedures for chylothorax, including thoracotomy with decortication and pleurodesis (4 procedures), thoracoscopic decortication (1 patient), ligation of thoracic duct (2 procedures), and resection of thoracic duct cyst (1 patient). Postoperative mean follow-up was 54 months (range, 0.3-276). Early complications included wound infections in 3 patients, elevated liver enzymes in 1, and peritoneovenous shunt occlusion with innominate vein occlusion in 1. All patients improved initially, but four (19%) had recurrence of symptoms at a mean of 25 months (range, 1-43). Three patients had postoperative lymphoscintigraphy confirming improved lymphatic transport and diminished reflux. One patient died 12 years postoperatively, from causes unrelated to PCD. CONCLUSIONS: More than half of the patients with PCDs require surgical treatment, and surgery should be considered in patients with significant symptoms of PCD. Lymphangiography is recommended to determine anatomy and the site of the lymphatic leak, especially if lymphovenous grafting is planned. All patients had initial benefit postoperatively and two thirds of patients demonstrated durable clinical improvement after surgical treatment.


Subject(s)
Chylothorax/surgery , Chylous Ascites/surgery , Adult , Chylothorax/diagnosis , Chylous Ascites/diagnosis , Female , Follow-Up Studies , Humans , Lymphangiectasis/diagnosis , Lymphangiectasis/surgery , Lymphography , Lymphoscintigraphy , Magnetic Resonance Imaging , Male , Time Factors , Tomography, X-Ray Computed
3.
J Vasc Surg ; 34(5): 900-8, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11700493

ABSTRACT

OBJECTIVE: Infected aortic aneurysms are rare, difficult to treat, and associated with significant morbidity. The purpose of this study was to review the management and results of patients with infected aortic aneurysms and identify clinical variables associated with poor outcome. METHODS: The clinical data and early and late outcomes of 43 patients treated for infected aortic aneurysms during a 25-year period (1976-2000) were reviewed. Variables were correlated with risk of aneurysm-related death and vascular complications, defined as organ or limb ischemia, graft infection or occlusion, and anastomotic or recurrent aneurysm. RESULTS: Infected aneurysms were infrarenal in only 40% of cases. Seventy percent of patients were immunocompromised hosts. Ninety-three percent had symptoms, and 53% had ruptured aneurysms. Surgical treatment was in situ aortic grafting (35) and extra-anatomic bypass (6). Operative mortality was 21% (9/42). Early vascular complications included ischemic colitis (3), anastomotic disruption (1), peripheral embolism (1), paraplegia (1), and monoparesis (1). Late vascular complications included graft infection (2), recurrent aneurysm (2), limb ischemia (1), and limb occlusion (1). Mean follow-up was 4.3 years. Cumulative survival rates at 1 year and 5 years were 82% and 50%, respectively, significantly lower than survival rates for the general population (96% and 81%) and for the noninfected aortic aneurysm cohort (91% and 69%) at same intervals. Rate of survival free of late graft-related complications was 90% at 1 year and 5 years, similar to that reported for patients who had repair of noninfected abdominal aortic aneurysms (97% and 92%). Variables associated with increased risk of aneurysm-related death included extensive periaortic infection, female sex, Staphylococcus aureus infection, aneurysm rupture, and suprarenal aneurysm location (P <.05). For risk of vascular complications, extensive periaortic infection, female sex, leukocytosis, and hemodynamic instability were positively associated (P <.05). CONCLUSION: Infected aortic aneurysms have an aggressive presentation and a complicated early outcome. However, late outcome is surprisingly favorable, with no aneurysm-related deaths and a low graft-related complication rate, similar to standard aneurysm repair. In situ aortic grafting is a safe and durable option in most patients.


Subject(s)
Aneurysm, Infected/surgery , Aortic Aneurysm, Abdominal/surgery , Aortic Aneurysm, Thoracic/surgery , Aged , Aneurysm, Infected/diagnosis , Aneurysm, Infected/mortality , Aortic Aneurysm, Abdominal/diagnosis , Aortic Aneurysm, Abdominal/mortality , Aortic Aneurysm, Thoracic/diagnosis , Aortic Aneurysm, Thoracic/mortality , Blood Vessel Prosthesis Implantation , Female , Follow-Up Studies , Humans , Male , Risk Factors , Time Factors
4.
J Vasc Surg ; 34(1): 41-6, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11436073

ABSTRACT

OBJECTIVE: Rupture of abdominal aortic aneurysms (AAAs) remains lethal. In a report of patients treated in the 1980s, we recommended aggressive management. Our continued experience prompted us to reevaluate this policy. METHODS: We reviewed clinical variables affecting outcome, morbidity, mortality, and trends in mortality of all patients managed at our institution with ruptured AAAs between January 2, 1980, and November 30, 1998. RESULTS: The study group included 413 consecutive patients, 339 men and 74 women. The mean age was 74.3 years (range, 49-96); 116 (28%) patients were older than 80 years. AAA was diagnosed before rupture in 119 (29%) patients. Eighty (19%) patients had preoperative cardiac arrest. Twenty-nine (7%) patients died before operation; 65 (17%) died during the operation. The surgical mortality rate (30-day) was 37%; the overall mortality rate was 45% and was higher in women (68%) than in men (40%) (P <.001). Advanced age, APACHE (Acute Physiology and Chronic Health Evaluation) II score, initial hematocrit, and preoperative cardiac arrest were associated multivariately with 30-day mortality rates by means of stepwise logistic regression (P <.05). Twelve (23%) of 53 patients with cardiac arrest survived the operation. Logistic regression, adjusted for age, sex, and APACHE II score, demonstrated a decrease in overall and 30-day mortality rates (P <.001) over 18 years. The mean overall mortality rate was 51% from 1980 to 1984 and 42% from 1994 to 1998. CONCLUSIONS: The mortality rate of ruptured AAAs remains excessive, despite improvement over 18 years. Patients older than 80 years with shock or cardiac arrest have the highest mortality rate and should be evaluated for possible endovascular treatment. Because the diagnosis of AAA was unknown in more than 70% of patients, screening of the high-risk population and elective repair are recommended.


Subject(s)
Aortic Aneurysm, Abdominal/mortality , Aortic Aneurysm, Abdominal/surgery , Aortic Rupture/mortality , Aortic Rupture/surgery , APACHE , Aged , Aged, 80 and over , Female , Humans , Logistic Models , Male , Middle Aged , Retrospective Studies
5.
J Invest Surg ; 14(6): 321-30, 2001.
Article in English | MEDLINE | ID: mdl-11905500

ABSTRACT

Autogenous veins are the materials of choice for arterial reconstruction. In the absence of autogenous material, prosthetic materials are used. However, vascular prostheses of less than 0.4 cm in diameter have low long-term patency. This study was designed to determine if cells would infiltrate an engineered xenogeneic biomaterial used as a small diameter arterial graft in dogs and, if so, to determine the phenotype of the infiltrating cells. Nine acellular xenogeneic grafts (0.4 cm in diameter, 5 cm long), composed of porcine collagen derived from the submucosa of the small intestine and type I bovine collagen, were implanted as end to-end interposition grafts in femoral arteries of five male mongrel dogs (total of nine grafts). All dogs received daily aspirin (325 mg). Patency of implanted grafts was monitored weekly by Duplex ultrasonography. After 9 weeks, or earlier in case of blood flow reduction by at least 75%, grafts were explanted and prepared for light or electron microscopy to evaluate cellularization. Eight of nine grafts remained patent up to 9 weeks. At explant, diameters were 0.31 +/- 0.02 cm at the midgraft, and 0.14 +/- 0.01 and 0.19 +/- 0.01 cm at the proximal and distal anastomoses. At explant, cells of mesenchymal origin (endothelial cells, smooth muscle cells, myofibroblasts) were embedded in the extracellular matrix of the graft scaffold. Minimal evidence of cellular inflammatory reaction and no aneurysmal dilatation or thrombus formation was detected. Variable degrees of hyperplasia were present at proximal and distal anastomoses. This preliminary study demonstrates that a collagen-based xenogeneic biomaterial provides a scaffold for cellularization when used for arterial reconstruction in dogs.


Subject(s)
Blood Vessel Prosthesis , Collagen , Femoral Artery/surgery , Animals , Biocompatible Materials , Cattle , Dogs , Male , Swine
6.
J Vasc Surg ; 32(5): 840-7, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11054214

ABSTRACT

PURPOSE: Klippel-Trénaunay syndrome (KTS) is a complex congenital anomaly, characterized by varicosities and venous malformations (VMs) of one or more limbs, port-wine stains, and soft tissue and bone hypertrophy. Venous drainage is frequently abnormal because of embryonic veins, agenesis, hypoplasia, valvular incompetence, or aneurysms of deep veins. We previously reported on the surgical management of KTS. In this article, we update our experience. METHODS: Twenty patients with KTS underwent surgical treatment for VMs between July 1, 1987, and January 1, 2000. This group represented 6.9% of 290 patients with KTS who were seen at our institution during this 12.5-year study period. Surgical indications, venous anatomy (determined with duplex scan, contrast phlebography, magnetic resonance imaging or magnetic resonance phlebography), operative procedures, and complications were reviewed, and outcomes were recorded. RESULTS: Twelve male and eight female patients (mean age, 23.4 years; range, 7.7-40.6 years) underwent 30 vascular surgical procedures in 21 lower limbs. All 20 patients (100%) had varicose veins or VMs, 13 (65%) had port-wine stains, and 18 (90%) had limb hypertrophy. Pain was the most common complaint, which was present in 16 patients (80%), followed by swelling in 15 (75%), bleeding in 8 (40%), and superficial thrombophlebitis and cellulitis in 3 (15%). Imaging confirmed patent deep veins in 18 patients, hypoplastic femoral vein in 1, and entrapped popliteal veins bilaterally in 1. Four patients (20%) had large persistent sciatic veins (PSVs). The CEAP clinical classification was C-3 for 17 patients (85%), C-4 for 1 patient (5%), and C-6 for 2 patients (10%). Stripping of large lateral veins, avulsion, and excision of varicosities or VMs were performed on all limbs. Three patients required staged resections. The release of entrapped popliteal veins was performed in both limbs of one patient; another underwent a popliteal-saphenous bypass graft. One patient underwent excision of a PSV. Open and endoscopic perforator vein ligation was performed in one patient each. Two patients (12%) had hematomas that required evacuation. No patients had caval filter placement; none had postoperative deep venous thrombosis or pulmonary embolus. The mean follow-up was 63.6 months (range, 0-138 months). All patients reported initial improvement, but some varicosities recurred in 10 patients (50%), an ulcer did not heal in one, and a new ulcer developed in one, 8 years after surgery. Three patients underwent reoperation for recurrent varicosities. Follow-up CEAP scores were C-2 in 10 patients (50%), C-3 in 6 patients (30%), C-4 and C-5 in 1 patient each (5%), and C-6 in 2 patients (10%). Clinical scores improved from 4.3 +/- 2.2 to 3.1 +/- 2.3. (P =.03). CONCLUSIONS: The management of patients with KTS continues to be primarily nonoperative, but those patients with patent deep veins can be considered for excision of symptomatic varicose veins and VMs. Although the recurrence rate is high, clinical improvement is significant, and reoperations can be performed if needed. Occasionally, deep vein reconstruction, excision of PSVs, or subfascial endoscopic perforator surgery is indicated. Because KTS is rare, patients should receive multidisciplinary care in qualified vascular centers.


Subject(s)
Klippel-Trenaunay-Weber Syndrome/surgery , Vascular Surgical Procedures/methods , Veins/abnormalities , Veins/surgery , Adolescent , Adult , Child , Female , Follow-Up Studies , Humans , Klippel-Trenaunay-Weber Syndrome/diagnostic imaging , Magnetic Resonance Angiography , Male , Phlebography , Tomography, X-Ray Computed , Treatment Outcome
7.
J Surg Res ; 93(1): 70-4, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10945945

ABSTRACT

BACKGROUND: The thoracoscopic approach to the aorta has the advantages of easy aortic dissection, excellent inflow, improved exposure in the thorax without insufflation, and ability to employ both laparoscopic and traditional instruments. Our aim was to develop a thoracoscopic technique for descending thoracic aorta-to-femoral artery bypass (TAFB) in the pig that results in acceptable short-term survival and graft patency. MATERIALS AND METHODS: Thoracoscopic TAFB was performed in 11 pigs. Using two-lung ventilation, the animals were placed in a 45 degrees left lateral semidecubitus position. A fan lung retractor, two dissecting ports, intercostal artery loops, and camera were placed through five 10- to 20-mm thoracoscopic incisions. After aortic dissection, an 8-mm graft was passed through a retroperitoneal tunnel. Rumel tourniquets were used for aortic occlusion after placement of a shunt. End-to-side endoscopic anastomosis was completed with knots tied extracorporeally. The left femoral anastomosis was completed under direct vision. Duplex ultrasound of the graft was done on postoperative days 1, 3, and 7. RESULTS: Thoracoscopic TAFB was completed in all animals. Mean aortic anastomosis time was 57 min (range, 34-145); and mean cross-clamp time, 74 min (range, 53-155). Mean operative time was 310 min; the first six operations lasted longer than the last five (338 min vs 276 min, P < 0.04). Average blood loss was 611 ml (range, 250-1300). Two animals died due to anesthetic complications. One (11%) of the nine surviving pigs died on day 2 due to bleeding. Complications were paraplegia in one (11%) and graft thrombosis in another (11%). CONCLUSIONS: Videoendoscopic TAFB can be completed in pigs with acceptable short-term patency and survival. Further experience in thoracoscopic techniques can make TAFB a feasible and low-risk option for selected patients with aortoiliac occlusive disease.


Subject(s)
Aorta, Thoracic/surgery , Femoral Artery/surgery , Thoracoscopy , Anastomosis, Surgical , Animals , Postoperative Complications , Swine
8.
Int Angiol ; 19(1): 75-8, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10853690

ABSTRACT

The management of a free-floating thrombus in the femoropopliteal or iliocaval veins is controversial. Such patients may have an increased risk of pulmonary embolism. The differential diagnosis of intraluminal venous malignancy or septic thrombosis must also be considered, especially in immunocompromised patients. This report reviews the management of a 56-year-old woman with bronchopulmonary aspergillosis who was found to have a free-floating thrombus in the femoral vein. Appropriate preoperative evaluation, emphasizing non-invasive studies and duplex exam, are discussed. In addition, the differential diagnosis, surgical options and perioperative care are considered. This patients represents a complex case of venous thrombosis in an immunocompromised patient and, therefore, the optimal care to minimize complications, such as pulmonary embolism, and prevent recurrence or post-thrombotic changes, is necessary.


Subject(s)
Aspergillosis/complications , Femoral Vein , Lung Diseases, Fungal/complications , Venous Thrombosis/etiology , Anticoagulants/therapeutic use , Aspergillosis/diagnostic imaging , Diagnosis, Differential , Female , Femoral Vein/diagnostic imaging , Femoral Vein/surgery , Humans , Lung Diseases, Fungal/diagnostic imaging , Middle Aged , Secondary Prevention , Thrombectomy , Tomography, X-Ray Computed , Ultrasonography, Doppler, Duplex , Venous Thrombosis/diagnosis , Venous Thrombosis/therapy
9.
J Vasc Surg ; 25(2): 398-404, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9052575

ABSTRACT

PURPOSE: The role of complex venous reconstructions (CVRs) in patients with major trauma remains a controversial topic. This study evaluates the patency and clinical outcome of CVRs in a major urban trauma center. METHODS: Between 1979 and 1994 the records of 92 patients with 100 injuries to the iliac, femoral, and popliteal venous system were reviewed. The incidence of edema, pulmonary embolism, and limb loss was documented in 75 men and 17 women (mean age of 27 years, range 14 to 59 years). The 30-day patencies were assessed in all patients with either impedance plethysmography (n = 16), venography (n = 40), or duplex scan (n = 36). Long-term patencies were assessed in 14 patients monitored for 0.5 to 9 years (mean 3.2 years). RESULTS: Mechanisms of injury consisted of 58 gunshot wounds, 23 stab wounds, 6 shotgun wounds, and 5 blunt injuries. There were 112 associated injuries, 41 of which were concomitant arterial injuries. Forty-five of the 100 venous injuries were repaired with CVRs and included 6 (13%) spiral vein grafts, 8 (18%) panel vein grafts, 8 (18%) reversed saphenous vein interposition grafts, 8 (18%) end-to-end repairs, and 15 (33%) vein patch repairs. Thirty-day patency rates for these repairs were 50%, 50%, 75%, 88%, and 87%, respectively, and an overall patency rate of 73% was observed. The remaining 55 injuries were treated with ligation (n = 27) or lateral venorrhaphy (n = 28). The cumulative 30-day patency rate for all venous repairs was 81% (59 of 73). Fourteen patients, nine of whom had CVRs, were available for long-term follow-up. In this group CVRs demonstrated a 100% patency. One patient with a spiral vein graft repair of the common femoral vein had severe reflux causing intermittent edema and mild lipodermatosclerosis. No pulmonary emboli, limb loss, or deaths were identified in patients undergoing CVRs. CONCLUSION: Patients with CVRs had a 30-day patency rate of 73%. Of this group panel and spiral vein grafts were less successful, exhibiting only a 50% 30-day patency rate, whereas end-to-end and vein patch repairs were successful in 88% and 87% of cases, respectively. Our overall evaluation suggests that use of CVRs results in successful venous repair; however, the postoperative patency of interposition panel and spiral grafts suggests selective use of these techniques.


Subject(s)
Femoral Vein/injuries , Iliac Vein/injuries , Popliteal Vein/injuries , Adolescent , Adult , Female , Femoral Vein/surgery , Follow-Up Studies , Humans , Iliac Vein/surgery , Ligation , Male , Middle Aged , Popliteal Vein/surgery , Treatment Outcome , Vascular Patency , Vascular Surgical Procedures/methods , Veins/transplantation , Wounds and Injuries/surgery
10.
Microvasc Res ; 52(3): 210-20, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8954863

ABSTRACT

Increased microvascular permeability is a hallmark of ischemia-reperfusion (I/R) injury. We hypothesized that platelet-activating factor (PAF) and nitric oxide (NO) are involved in the extrvasation of macromolecules in I/R injury. To block endogenous PAF, we used a PAF-receptor antagonist (WEB 2086; 2 mg/kg, i.v). To inhibit endogenous nitric oxide, we employed L-NG-monomethyl arginine (10(-5) M L-NMMA), a NO synthase inhibitor. We assessed microvascular permeability to FITC-dextran 150 by measuring changes in integrated optical intensity (delta IOI) using computer-assisted image analysis in the hamster cheek pouch. We examined one area of ischemia and one control area in each pouch. Ischemia was induced for 2 hr and was followed by 1 hr of reperfusion. Six groups were investigated. Group 1 (n = 5) had no pharmacologic intervention; Group 2 (n = 5) received WEB 2086 15 min before reperfusion; Group 3 (n = 5) received WEB 2086 at reperfusion; Group 4 (n = 5), WEB 2086 was infused 15 min after the onset of reperfusion. Group 5 (n = 3) received topical L-NMMA (30 min prior to reperfusion and continuously for the remainder of the experiment). Group 6 (n = 3) received both L-NMMA (as in Group 5) and WEB 2086 (administered 15 min after reperfusion). In Group 1, I/R increased the mean (+/- SEM) delta IOI value from 61.5 +/- 11.1 to 127.2 +/- 26.1. WEB 2086 inhibited the increase in delta IOI at each time point. Similarly, the groups given L-NMMA alone and L-NMMA + WEB 2086 showed no difference between ischemic and control groups. Our data demonstrate that (1) PAF and nitric oxide are involved in the permeability changes associated with the microvascular dysfunction of ischemia-reperfusion injury; (2) inhibitors of PAF and nitric oxide synthase are effective in attenuating macromolecular extravasation when given during ischemia or after initiation of reperfusion.


Subject(s)
Microcirculation/physiopathology , Nitric Oxide/physiology , Platelet Activating Factor/physiology , Reperfusion Injury/physiopathology , Animals , Capillary Permeability , Cheek/blood supply , Cheek/pathology , Cricetinae , Male , Mesocricetus , Reperfusion Injury/pathology
11.
J Vasc Surg ; 22(6): 661-9; discussion 669-70, 1995 Dec.
Article in English | MEDLINE | ID: mdl-8523600

ABSTRACT

PURPOSE: Changes in microvascular permeability play a critical role in the inflammatory sequence of tissue injury leading to leakage of proteins and subsequent edema. Primed responses induced by topical applications of platelet-activating factor (PAF) and histamine greatly increase microvascular permeability and mimic inflammation. We assessed the role of nitric oxide (NO) by use of 1-NG-monomethyl arginine (1-NMMA, a NO synthase inhibitor), on the primed microvascular permeability. We also explored the role of mast cells and a leukocyte adhesion complex by use of cromolyn sodium and 1B6 (a monoclonal antibody), respectively. METHODS: Forty anesthetized hamsters were separated into five groups: group 1 (n = 5) received no intervention; group 2 (n = 5) received topical 10(-9) mol/L PAF and 10(-6) mol/L histamine at a 5-minute interval; group 3 (n = 5 at each dose) received PAF/histamine and 1-NMMA (at 10(-5) mol/L or 10(-6) mol/L); group 4 (n = 5 at each dose) received cromolyn sodium plus PAF/histamine; group 5 (n = 5) received 1B6 plus PAF/histamine. We examined the cheek pouch with intravital videomicroscopy under fluorescent epiillumination. We quantified microvascular permeability to fluorescein isothiocyanate-dextran 150 with computer-assisted images analysis on the basis of integrated optical intensity (IOI) measurements. RESULTS: The mean (+/- SEM) IOI of the control group was 8.7 +/- 5.2, whereas the group primed with PAF and histamine was 62.4 +/- 10.8. The 1-NMMA (10(-5) mol/L and 10(-6) mol/L) abolished the changes in microvascular permeability (p < 0.05) yielding IOI values of 8.0 +/- 1.6 and 10.9 +/- 2.8, respectively. Cromolyn sodium and 1B6 did not significantly attenuate the primed response to PAF and histamine. CONCLUSION: Inhibition of NO synthase attenuates primed macromolecular extravasation in vivo. Our results indicate that NO is involved in the primed reaction of PAF and histamine, causing increases in microvascular permeability. Our study suggests a role for NO in the microcirculatory changes observed in ischemia-reperfusion injury and shock.


Subject(s)
Capillary Permeability/physiology , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide/physiology , Animals , Arginine/analogs & derivatives , Arginine/pharmacology , Capillary Permeability/drug effects , Cheek , Cricetinae , Cromolyn Sodium/pharmacology , Dextrans , Enzyme Inhibitors/pharmacology , Fluorescein-5-isothiocyanate/analogs & derivatives , Histamine/pharmacology , Inflammation/physiopathology , Macrophage-1 Antigen/physiology , Male , Mast Cells/physiology , Mesocricetus , Microcirculation/drug effects , Microcirculation/physiology , Microscopy, Video , Platelet Activating Factor/pharmacology , omega-N-Methylarginine
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