L-Arginine treatment decreased superoxide generation by cNOS while increasing NO accumulation, leading to protection from constriction (microvessel area, 17.77+/-0.95 versus 11.66+/-2.21 microm2 untreated, P<.0005) and reduction of edema after reperfusion (interfiber area, 16.56+/-2.13% versus 27.68+/-7.70% untreated, P<.005).

Background-Peroxynitrite generated from nitric oxide (NO) and superoxide (O 2 Ϫ ) contributes to ischemia/reperfusion (I/R) injury. Feedback inhibition of endothelial NO synthase by NO may inhibit O 2 Ϫ production generated also by endothelial NO synthase at diminished local L-arginine concentrations accompanying I/R. Methods and Results-During hindlimb I/R (2.5 hours/2 hours), in vivo NO was monitored continuously (porphyrinic sensor), and high-energy phosphates, reduced and oxidized glutathione (chromatography), and I/R injury were measured intermittently. Rabbits receiving human serum albumin (HSA) (controls) were compared with those receiving S-nitroso human serum albumin (S-NO-HSA) beginning 30 minutes before reperfusion for 1 hour or 30 minutes before ischemia for 3.5 hours (0.1 mol · kg Ϫ1 · h Ϫ1 ). The onset of ischemia led to a rapid increase of NO from its basal level (50Ϯ12 nmol/L) to 120Ϯ20 and 220Ϯ15 nmol/L in the control and S-NO-HSA-treated groups, respectively. In control animals, NO dropped below basal levels at the end of ischemia and to undetectable levels (Ͻ1 nmol/L) during reperfusion. In S-NO-HSA-treated animals, maximal NO levels never decreased below basal concentration and on reperfusion were 100Ϯ15 nmol/L (S-NO-HSA preischemia group, 175Ϯ15 nmol/L). NO supplementation by S-NO-HSA led to partial and in the preischemia group to total preservation of high-energy phosphates and glutathione status in reperfused muscle (eg, preischemia groups: ATP, 30.23Ϯ5.02 mol/g versus control, 15.75Ϯ4.33 mol/g, PϽ0.0005; % oxidized glutathione, 4.49Ϯ1.87% versus control, 22.84Ϯ6.39%, PϽ0.0001). S-NO-HSA treatment in all groups led to protection from vasoconstriction and reduced edema formation after reperfusion (eg, preischemia groups: interfiber area, 12.94Ϯ1.36% versus control, 27.83Ϯ1.95%, PϽ0.00001). Conclusions-Long

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Background/Aim: Local blood flow failure (no-reflow phenomenon) during ischemia/reperfusion (I/R) injury may be mediated by interstitial edema formation (passive vasoconstriction) and/or microvascular spasm (active vasoconstriction). The development of the no-reflow phenomenon in the rabbit hind limb I/R model and the influence of treatment with L-arginine and/or antioxidative vitamins were investigated. Methods: Untreated rabbits were compared with those treated with L-arginine (4 mg/kg/min) or antioxidative vitamins (0.4 ml/kg) alone or in combination during hind limb I/R (2.5/2 h). Interstitial edema formation and microvessel diameter alterations were measured morphometrically. Capillary blood perfusion was measured continuously with laser Doppler flowmetry. Results: I/R injury was expressed by interstitial edema formation (interstitial space increase by 80%), microvascular constriction (microvessel cross-sectional area decrease by 30%), and development of no-reflow phenomenon (blood flow reduction by 60%). Treatment with antioxidative vitamins alone or L-arginine alone reduced interstitial edema by 22 and 31%, consequently, while combined L-arginine/antioxidative vitamin treatment showed a more pronounced edema reduction by 40%. Treatment with only antioxidative vitamins failed to influence the development of no-reflow, although interstitial edema formation was reduced. L-Arginine treatment alone or in combination with antioxidative vitamins prevented microvascular constriction and preserved blood flow after reperfusion without development of no-reflow despite still apparent interstitial edema. Conclusions: Affections of active vasomotility and not merely passive changes of external pressure (i.e., interstitial edema formation) should be considered important in the development of microvascular constriction during ‘no-reflow’ phenomenon.

Summary: Background: Any surgical manoeuvre that involves cessation of blood supply to an organ with subsequent re‐establishment of blood flow can result in ischaemia/reperfusion (I/R) injury. The consequences of such injury are local and remote tissue destruction. 
Methods: I/R is characterized by ‘no reflow phenomenon’ and interstitial oedema formation. Changes in the production of nitric oxide (NO) and superoxide play an important role in the development of I/R. Overproduction of reactive oxygen‐derived free radicals (OFR) leads to a consumption and depletion of endogenous scavenging antioxidants. 
Results: Direct NO measurements showed a production of large concentrations of NO from cNOS at the beginning of ischaemia. Intracellular influx of Ca2+ after onset of ischaemia activates cNOS, leading to local depletion of L‐arginine and subsequently to disarrangement of cNOS, which produces superoxide instead of NO. Microvascular constriction during ‘no reflow’ reflects deficiency in vasodilator NO due to its consumption by vasoconstrictor oxygen free radicals. Stimulated production of thromboxane A2 and endothelin release may also promote ‘no reflow’. 
Conclusions: At least two major strategies are viable for preventing I/R injury: (a) treatment with L‐arginine and their analogues, or BH4, thus preventing L‐arginine and H4B deficient conditions, so that cNOS will not produce excessive O2–; (b) scavenging O2– already produced by cNOS and other potential sources of O2– by using large concentrations of free radical scavengers. Further research on oxidant/antioxidant biochemistry and its clinical application is needed.

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During the period 1991-1994, 99 patients (all males, median age 35 years) with combat-related injuries of major limb arteries were managed. Mechanism: mine fragments (40%), high-velocity projectiles (35%), and shotgun pellets (25%). Patients were admitted 1 hour to 16 hours (median 8 hours) after injury; 39% were in severe hemorrhagic shock. Arterial injury was diagnosed by clinical findings. Preoperative angiography was usually not necessary. Of 99 injured patients, 50 (51%) showed signs of distal ischemia and required arterial reconstruction. No primary amputation was performed. Reconstruction was always necessary in cases of injury of axillary or popliteal arteries, but not of superficial femoral or brachial arteries. Ligation of injured single forearm or crural arteries was well tolerated. End-to-end anastomosis by reconstruction was possible only in 38% of cases. In 56% of patients, autologous venous bypass was performed. Uncontrolled wound infection developed in 22% of cases, leading to a secondary hemorrhage compelling arterial ligature (8%), and thrombosis (6%). The secondary amputation rate after arterial reconstruction was 10%. Injury of major vessels was associated with limb bone fractures, nerve damage, or major vein injuries in 68% of cases, frequently on the forearm, the popliteal region, and the crural region. When limb ischemia was present, vascular reconstruction had priority over orthopedic immobilization. Arterial injury was almost always associated with the venous damage in the forearm, the popliteal region, and the crural region. Injured veins of the upper limb were ligated; venous repair was more often indicated in lower limb injury (52%). The method of choice was lateral suture/patch. Gunshot damage to peripheral nerves was rarely treated with primary repair.

Background— Although transfemoral endovascular aneurysm management (TEAM) of infrarenal abdominal aortic aneurysms (AAA) is widely performed, open graft replacement is still considered the standard of care. The aim of this study was to investigate whether clear indications for TEAM can be established in patients with significant comorbidities without investigating differences in relative procedure efficacy or durability. Methods and Results— A propensity score–based analysis of 454 consecutive patients treated electively for AAA from January 1995 through December 2000 was performed. Of those 454 patients, 248 received open surgery and 206 received TEAM. In-hospital mortality rates (MRs) were compared. After adjusting for propensity scores, a Cox proportional hazard model (COX) was employed to test the influence of the respective treatment on postoperative 900-day survival estimates (SEs). Several potential preoperative risk factors were used as covariates. The MR of all patients was 3.7%. Explorative analysis demonstrated that patients treated by TEAM presented with significantly more risk factors. In American Society of Anesthesiologists class IV patients, a significant difference in MR was detected (4.7% for TEAM versus 19.2% for open surgery; P <0.02). After adjusting for the propensity to receive TEAM or open surgery, a regression analysis of survival based on COX revealed predictive influences of impaired kidney ( P <0.047) or pulmonary function ( P <0.001), increased age ( P <0.05), and selection of treatment modality ( P <0.002) on SE. Conclusions— TEAM represents a less invasive procedure for AAA therapy in patients with significant preoperative risk factors. Especially in geriatric patients with multiple morbidities, TEAM offers a method of therapy with acceptable MRs and SEs, making active treatment possible in otherwise incurable patients.