Ischemic tolerance in skeletal muscle: role of nitric oxide.

We tested the hypothesis that ischemic preconditioning (PC) of skeletal muscle provided tolerance to a subsequent ischemic event 24 h later, and that such protection was due to nitric oxide (NO). Male Wistar rats, anesthetized with halothane, were randomly assigned to groups: ischemic (no PC; n = 11), PC (n = 11), PC + N-nitro-L-arginine methyl ester (L-NAME; 100 micromol/l; n = 5), PC + N-nitro-D-arginine methyl ester (100 micromol/l; n= 4), PC + aminoguanidine (AMG; 100 micromol/l; n = 4), ischemic + L-NAME (n= 4), or ischemic + AMG (n = 4). PC consisted of 5x 10 min of ischemia and reperfusion, and, 24 h later, 2 h of ischemia were induced by a tourniquet applied to the limb. With the use of intravital microscopy, the number of perfused capillaries (Npc) in the extensor digitorum longus (EDL) muscle was measured over a 90-min reperfusion period. The ratio of ethidium bromide- to bisbenzimide-labeled nuclei was used to estimate tissue injury. PC preserved Npc (23.6 +/- 2.5) following 2 h of ischemia compared with sham muscles (11.5 +/- 5.1), significantly elevating inducible NO synthase (iNOS) activity (81% increase), but did not afford protection to the parenchyma. L-NAME and AMG prevented ischemia-reperfusion-induced reduction in Npc in muscles without PC. However, after 90 min of reperfusion, L-NAME (Npc = 15.0 +/- 1.7), but not AMG (Npc = 22.8 +/- 3.1), significantly reduced the microvascular protection afforded by PC. We conclude that PC of the EDL muscle resulted, 24 h later, in protection to microvascular perfusion only, and that such protection was due to NO from sources other than iNOS.

Clinical results of deep venous valvular repair for chronic venous insufficiency.

OBJECTIVE: To evaluate the results of venous valvular repair in the treatment of 16 cases of chronic venous insufficiency (CVI). DESIGN: A retrospective analysis of 16 venous valve repair operations (15 patients) with a minimum follow-up of 2 years. SETTING: A 650-bed university-affiliated teaching hospital. PATIENTS: Fifteen consecutive referred patients who had CVI had deep vein valve surgery. All cases were refractory to prolonged conservative care and removal of incompetent superficial and perforating veins. Investigation included ascending and descending venography, air plethysmography (APG) and colour flow duplex scanning (CFDS). All patients had class 4, 5 or 6 CVI and all demonstrated deep venous reflux from the groin to below the knee on descending venography. INTERVENTIONS: Superficial femoral vein valvuloplasty (12 operations) and venous valve transfer from the axillary vein to the above-knee popliteal vein (4 operations). MAIN OUTCOME MEASURES: Healing of ulcers, relief of edema and improvement in symptoms were clinical criteria of success. An attempt was made to correlate preoperative and postoperative APG, CFDS and descending venography. RESULTS: Ninety-two percent of the valvuloplasty patients and 75% of the valve transfer patients were clinically improved. In this series no statistical association existed between preoperative and postoperative changes noted on APG. CONCLUSION: This series suggests that deep vein valvular reconstruction for CVI refractory to conservative management and superficial surgery offers a good chance of clinical improvement.

The use of arm vein as an alternative conduit for lower-extremity bypass.

A 4-year retrospective review of all cases utilizing arm vein for lower-extremity bypass was undertaken. Thirty-six cases were reviewed. The patients had portions of the basilic or cephalic arm veins, or both, harvested and used as a bypass for limb salvage. Composite grafts using a portion of arm vein were excluded. Information on demographics, risk factors, vascular surgical history, presenting signs and symptoms, surgical complications, patient comfort (arm vs. leg pain), and patency rates was studied. We found that all patients were initially seen with claudication or rest pain, that 22% had gangrenous changes, that there was a male dominance (75%), and that all had previous coronary artery bypass grafts or lower-extremity bypass. Limb salvage rate was 85% at 4 years. Primary patency rate was 71% at 4 years. We conclude that arm vein is a useful and durable conduit for bypass. Patient acceptance and comfort is high.

Intestinal mucosal permeability to 51Cr-ethylenediaminetetraacetic acid is increased after bilateral lower extremity ischemia-reperfusion in the rat.

BACKGROUND: Despite successful revascularization of ischemic extremities, multiorgan dysfunction syndrome develops in some patients. Mechanisms responsible for this are not known; however, the gastrointestinal tract has been implicated as a possible mediator. Our objective was to demonstrate increased intestinal mucosal permeability after bilateral hindlimb ischemia-reperfusion (I-R) in a rodent model. METHODS: Sixteen male Wistar rats were randomized either to 4 hours of bilateral hindlimb tourniquet ischemia and 24 hours of reperfusion (n = 8) or control groups (n = 8). The animals received 10 MuCi 51Cr-ethylenediaminetetraacetic acid (EDTA) by gavage, and excretion was measured in urine collected every 8 hours in 16 animals and every 4 hours in 8 animals. Arterial blood pressure was monitored continuously. Intravenous normal saline solution (3 ml/hr) with fentanyl (2 microgram/100 gm/hr) was continuously administered. Immediately before death complete blood count and levels of arterial lactate, creatinine, and urea were obtained. Mesenteric lymph nodes were harvested from the ileocecal region and cultured. Distal small bowel and proximal colon were preserved for histologic analysis. An additional 11 rats, six experimental and five control, were evaluated for mesenteric lymph node cultures only. RESULTS: Urinary excretion of 51Cr-EDTA was significantly greater in the I-R group between 0 and 8 hours (p < 0.02) and 8 to 16 hours (p < 0.0002) of reperfusion. This increase occurred as early as 4 to 8 hours of reperfusion (p < 0.0001). Urine volume in the I-R group was significantly reduced during 0 to 4 hours of reperfusion (p < 0.002). Hemoglobin and lactate level were significantly different in the I-R group. Leukocyte and platelet counts, levels of creatinine and urea, and colony counts from mesenteric lymph nodes were similar in I-R and control groups. Blinded histologic analysis of bowel segments did not reveal morphologic differences. CONCLUSIONS: Bilateral hindlimb I-R produces remote intestinal mucosal injury shown by significantly increased permeability to 51Cr-EDTA. Such increased mucosal permeability may be important in the development of multiorgan dysfunction syndrome in patients who sustain lower extremity I-R injury.

Thoracic outlet syndrome: fact or fancy? A review of 409 consecutive patients who underwent operation.

OBJECTIVES: From an analysis of patients operated on by a single surgeon between 1973 and 1994 for thoracic outlet syndrome (TOS), to determine what findings are helpful in substantiating this diagnosis and what are the results of decompressive thoracic outlet surgery in the management of TOS. DESIGN: A chart review with emphasis on signs, symptoms and results. A preoperative questionnaire was presented to all patients operated on since 1989. Postoperative follow-up was by interview or telephone. SETTING: A 560-bed university-affiliated tertiary-care teaching hospital. PATIENTS: There were 409 adults; 83% were women and the average age was 36 years. In 95% of patients physiotherapy had been unsuccessful. Patients presented with neurologic type (368 [(90%]), arterial impingement (29 [7%]) and venous obstructive symptoms (12 [3%]). The series included 44 patients with bilateral symptoms and 26 patients with cervical ribs. Some form of litigation or compensation was associated with 177 patients. INTERVENTIONS: Transaxillary first rib resection in 380 (93%) patients and supraclavicular thoracic outlet decompression in 29 (7%). In 244 patients there was a follow-up of at least 2 years. These patients constituted the follow-up group. RESULTS: Preoperatively, in the 368 patients who had neurologic TOS, 99% displayed supraclavicular brachial plexus tenderness and 98% exacerbation of symptoms with arms in the abduction external rotated position. There were eight complications of surgical intervention (1.9%). In the follow-up group, there were no deaths, no subclavian/axillary artery or vein damage and no brachial plexus injury. Seventy-eight percent of the patients with neurologic TOS in this group improved postoperatively; 21% had complete relief, 32% had good relief and 25% had fair relief. Twenty-two percent showed no improvement. CONCLUSIONS: Signs and symptoms helpful in making the diagnosis of neurologic TOS are supraclavicular tenderness on palpation and exacerbation of symptoms with the arms in the abducted external rotated position. The surgical procedures are safe. Patients with TOS refractory to medical management can benefit from thoracic outlet decompression.

Leukocyte activity and tissue injury following ischemia-reperfusion in skeletal muscle.

Few studies have correlated the occurrence of leukocytes with the time course of ischemia-reperfusion (I-R)-induced tissue injury in skeletal muscle. The goal of this study was to test the hypothesis that leukocytes were responsible for not only the onset, but progression of parenchymal cell injury within skeletal muscle following no-flow ischemia. Thirteen male Wistar rats (150-250 g) were randomly allocated to either a control (no I-R; n = 3), I-R (n = 5), or a leukopenic I-R group (n = 5). Under halothane anesthesia, the extensor digitorum longus muscle was prepared for intravital microscopy to allow video recording of microvascular perfusion and leukocyte flow behavior following 3 hr no-flow ischemia of the hindlimb. Tissue injury was assessed as the ratio of ethidium bromide (impermeant dye)-labeled nuclei to bisbenzimide (permeant dye)-labeled nuclei (E/B). During reperfusion, the I-R group showed a progressive decline in the number of perfused capillaries (N(C)) (from 19.37 +/- 0.04 to 3.34 +/- 1.18), while leukopenic and control rats were not significantly different. In the I-R group, the number of rolling leukocytes increased from 4.05 +/- 1.93 to 14.77 +/- 1.33 at the onset of reperfusion and remained stable throughout the reperfusion period. The number of stuck leukocytes, in the I-R group, progressively increased from 1.41 +/- 0.01 prior to ischemia to 4.66 +/- 0.01 at the onset of reperfusion to 11.96 +/- 0.01 after 90 min. The index of tissue injury (EIB) increased asymptotically from 0.60 +/- 0.02 to 0.95 +/- 0.01 after 90 min of reperfusion in the I-R group, while leukopenia significantly reduced both the magnitude of tissue injury (i.e., 35% reduction from untreated I-R group) and the onset of such injury. In spite of the benefit afforded by leukopenia, evidence of tissue injury persisted (20% above control baseline level). We conclude that although leukocytes were responsible for the onset of parenchymal injury in skeletal muscle following 3 hr no-flow ischemia they are not the sole mediators of such injury.

Dysphagia lusoria: extrathoracic surgical management.

OBJECTIVE: To report a case of dysphagia lusoria managed by an extrathoracic approach. DESIGN: Case report and literature review. SETTING: A university hospital. PATIENT: A 39-year-old man, who presented with weight loss and dysphagia. Aortography and computed tomography revealed an aberrant subclavian artery compressing the esophagus against the aortic arch. INTERVENTION: The right subclavian artery was divided at its origin and reimplanted onto the right carotid artery. The operation was performed through a right supraclavicular incision without opening the chest. RESULTS: There was no operative morbidity. Six months postoperatively the patient was asymptomatic and had gained weight. There was no radiologic evidence of esophageal compression. CONCLUSIONS: Based on the results of our case of dysphagia lusoria and the reports of others that have started to appear in the literature, consideration should be given to repairing a symptomatic, nonaneurysmal aberrant right subclavian artery through an extrathoracic approach.

Measurement of tissue viability using intravital microscopy and fluorescent nuclear dyes.

Intravital microscopy used with fluorescent vital stains provides the opportunity to measure the temporal and spatial extent of tissue injury following disease processes. However, this assumes that prolonged exposure to such dyes does not alter microvascular perfusion or cellular viability. To test this hypothesis, the extensor digitorum longus (EDL) muscle in 24 male Wistar rats, anesthetized with sodium pentobarbital (Somnotal, 65 mg/kg, ip), were prepared for microscopy. The EDL was either bathed continuously (n = 6) in Krebs solution containing bisbenzimide (5 micrograms/ml; labels nuclei of all cells) and ethidium bromide (5 micrograms/ml; labels nuclei of injured cells) or had dyes topically applied 1 hr (n = 4) and 4 hr (n = 4) following dissection of the muscle. Noxious stimuli (i.e., hypoxia:FiO2 of 8-10% (n = 3), 95% ethanol (n = 3), and 2 hr ischemia followed by 90 min reperfusion (n = 4) were used to test the ability of ethidium bromide, when used in conjunction with intravital microscopy, to differentiate injured tissue. Video recordings at the surface of the EDL muscle were made every 30 min for 5 hr from which the number of perfused capillaries was counted (NCper). The numbers of bisbenzimide- and ethidium bromide-labeled nuclei were counted at the surface of the muscle and at two to three additional locations within the muscle (to a maximum depth of approximately 120-160 microns). The average NCper (19.05 +/- 1.7) remained constant over 5 hr, while the number of nuclei stained by bisbenzimide increased linearly with time from an initial value of 1218 +/- 125.(ABSTRACT TRUNCATED AT 250 WORDS)

Skeletal muscle injury induced by ischemia-reperfusion.

OBJECTIVE: To study the temporal progression of injury in skeletal muscle after ischemia-reperfusion insult by means of intravital videomicroscopy and nuclear fluorescent dyes. DESIGN: A controlled study in an animal model. SETTING: A vascular research laboratory at a university-affiliated hospital. SUBJECTS: Eight male Wistar rats, for each of which the extensor digitorum longus muscle of the hind limb was exposed and prepared. INTERVENTIONS: Two hours of complete no-flow ischemia followed by 90 minutes of reperfusion in five of the rats; the other three rats acted as controls and underwent the same surgical procedure but not ischemia. During the reperfusion period the fluorescent vital dyes bisbenzimide, which permeates all cells, and ethidium bromide, which permeates cells with damaged membranes, were applied. Recordings to videotape were made with the intravital microscope very 15 minutes during the reperfusion period. MAIN OUTCOME MEASURES: The number of perfused capillaries crossing three straight lines on the video monitor were counted as a measure of microvascular dysfunction. An index of tissue injury was calculated as the ratio of the number of nuclei stained by ethidium bromide to the number stained by bisbenzimide (E/B). The number of stuck and rolling leukocytes and the velocity of the rolling leukocytes were determined in postcapillary venules. RESULTS: The mean number of perfused capillaries (and standard error of the mean) fell from 20.71 (1.64)/mm before ischemia to 11.69 (1.18)/mm during reperfusion in the experimental group but remained constant in the control group. In the experimental group E/B progressed from 0.43 (0.05) at the onset of reperfusion to 0.87 (0.03) at the end of reperfusion, the number of rolling leukocytes increased from a preischemia mean of 4.00 (1.90) to 14.80 (1.30)/1000 microns2, and the number of stuck leukocytes increased from 1.42 (0.20) to 9.20 (0.70)/1000 microns2. The velocity of the rolling leukocytes did not differ between the control and the experimental groups. CONCLUSIONS: Although microvascular perfusion decreased quickly to a constant level after 2 hours of noflow ischemia plus reperfusion, a progressive increase in tissue injury occurred, which may correlate with the number of stuck leukocytes.

Intraoperative thrombolytic therapy as a treatment of small vessel thrombosis: an experimental study.

OBJECTIVE: This paper studies the effect of three doses of Streptokinase infused intra-operatively into an animal model of small vessel thrombosis. EXPERIMENTAL DESIGN: This is a controlled trial of intraoperative infusion of thrombolytic agent into a thrombosed arterial segment compared to no infusion into the contralateral limb. EXPERIMENTAL SUBJECTS: 19 New Zealand White rabbits were stratified into 3 groups. INTERVENTIONS: Thrombosis was achieved by infusing a mixture of topical thrombin and autologous blood into individual iliac arteries of the New Zealand white rabbit. A randomly selected hind limb had an infusion of one of three doses of streptokinase (A = 2,500u; B = 5,000u; C = 10,000u) in saline over 20 minute period. Preinfusion and post infusion angiography was performed. MEASUREMENTS: Angiograms were ranked by a radiologist blinded to the side of infusion and clotting parameters were assessed. RESULTS: All limbs at all doses of streptokinase infusion (SK) showed significant clot lysis when compared to the non-infused limb(C). The percentage of improved segments is as follows: iliac: SK = 100%, C = 79%; femoral SK = 79%, C = 32%; tibial SK = 52%, C = 5%. Although there was an elevation in clotting time and a reduction in fibrinogen, levels remained within normal limits. CONCLUSIONS: Streptokinase infused directly into thrombus in arteries even in low doses significantly enhances thrombolysis of vessels which are too small to be cleared by mechanical means. No significant systemic complications were encountered.

Peripheral aneurysms.

Aneurysms of the peripheral arteries usually involve the femoral or popliteal regions. Although not as common as abdominal aortic aneurysms, they carry a significant morbidity if left untreated. Rupture is a rare complication, but embolization or thrombosis may frequently threaten the viability of the limb. Elective repair of peripheral aneurysms will prevent complications of these lesions. This paper outlines the history, diagnosis, and treatment of peripheral aneurysms with emphasis on nursing care.

Myocardial and circulatory performance during the ischemic phase of superior mesenteric artery occlusion.

OBJECTIVE: To investigate myocardial and circulatory parameters during the acute ischemic phase of mesenteric artery occlusion. DESIGN: A prospective, randomized, control trial. SUBJECTS: Twelve, adult, mongrel dogs. INTERVENTIONS: In seven dogs the superior mesenteric artery was occluded with two silk ligatures (experimental group). In five dogs the ligatures were not tied (control group). Measurements were made during 7 hours of occlusion. MAIN OUTCOME MEASURES: Myocardial performance and circulatory performance. RESULTS: There were significant (p < 0.05) reductions in arterial blood pressure, mean pulmonary artery pressure, diastolic pulmonary artery pressure and cardiac index in dogs exposed to intestinal ischemia compared with the control dogs. No differences were identified in ventricular performance, stroke volume index or peripheral vascular resistance index. CONCLUSIONS: Early cardiac and central circulatory changes in massive intestinal ischemia are due to intravascular hypovolemia. Sepsis and myocardial depressant factors were not found to be a cause of death.

The management of chronic venous disease.

Chronic venous disease represents a spectrum of problems ranging from the merely cosmetic to disabling venous ulcers. Chronic venous insufficiency can result in disfigurement, disability, and a financial burden on the patient and society. Delivery of optimal care of patients with venous disease requires a thorough understanding of this complex system and of current methods of diagnosis and treatment. Successful outcome of treatment depends on appropriate patient selection, meticulous surgery, outstanding nursing care, and patient education.

State of the art of venous investigation and treatment.

OBJECTIVE: To discuss current investigative and treatment modalities in all venous problems, ranging from telangiectasia to chronic venous insufficiency. DATA SOURCES: A thorough review of current literature plus the author's personal experience and ideas. DATA SYNTHESIS: Clinical interest and research into venous disease is increasing. Despite advanced investigative technology, the definitive management of chronic venous insufficiency remains controversial. Deep valvular reconstruction is now possible; however, indications for this type of procedure are rare. CONCLUSION: The renewed interest in venous disease will likely lead to specific treatments for all aspects of venous disease, especially for chronic venous insufficiency.

Arteritis due to Salmonella with aneurysm formation: two cases.

Although arterial infection due to Salmonella is rare, it remains one of the most common causes of primary mycotic aneurysms. The presentation is one of sepsis, cultures positive for Salmonella and rapid expansion or rupture of the aneurysm. The authors' experience at Victoria Hospital, London, Ont., includes two cases of aneurysms infected with Salmonella--one aneurysm of the aorta and the other of the common femoral artery. Both patients were treated by excision of the aneurysm, extra-anatomic reconstruction in an area remote from the infected field and long-term administration of appropriate antibiotics. One patient was alive and well 36 months after resection. The other died of multiple organ failure 10 days after resection. From a review of the English and French literature since 1948, 64 cases of abdominal aortic aneurysms infected with Salmonella were found; half of the patients survived the perioperative period. The diagnosis of mycotic aneurysm must be considered in any patient with an aneurysm and culture specimens positive for Salmonella. The authors favour wide débridement of the infected aneurysm with extra-anatomic reconstruction. This view is supported by a review of the literature. The appropriate antibiotic therapy is bactericidal rather than bacteriostatic.