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Background Augmented renal clearance (ARC; i.e., creatinine clearance [CLCr] ≥ 130 mL/min) has an incidence of 14%-80% in critically ill patients and has been associated with therapy failures for renally cleared drugs. However, the clinical implications of ARC are poorly defined. We hypothesize that modifiable risk factors that contribute to ARC can be identified in severely injured trauma patients and that these risk factors influence clinical outcome. Methods In 207 trauma intensive care unit patients, 24-h CLCr was correlated with clinical estimates of glomerular filtration rate (by Cockroft-Gault, modification of diet in renal disease, or chronic kidney disease epidemiology), and clinical outcomes (infection, venous thromboembolism [VTE], length of stay, and mortality). Results The population was 45 ± 20 y, 68% male, 77% blunt injury with injury severity score of 24 (17-30). Admission serum creatinine was 1.02 ± 0.35 mg/dL, CLCr was 154 ± 77 mL/min, VTE incidence was 15%, ARC incidence was 57%, and mortality was 11%. Clinical estimates of glomerular filtration rate by Cockroft-Gault, modification of diet in renal disease, chronic kidney disease epidemiology underestimated actual CLCr by 20%, 22%, or 15% (all P Conclusions ARC occurs in more than half of all high-risk trauma intensive care unit patients and is underestimated by standard clinical equations. ARC was not associated with increased incidence of VTE or infection but rather is associated with younger healthier males and reduced mortality. ARC seems to be a beneficial compensatory response to trauma.

Pediatric pelvic fractures are rare. The contribution of pelvic fracture pattern, risk factors for associated injuries, and mortality are poorly defined in this population.Patients aged 0-17 with pelvic fractures at a level I trauma center over a 20-y period were reviewed. Fracture patterns were classified according to the Young-Burgess classification when applicable. Fractures were analyzed for location, pubic symphysis or sacroiliac widening, and contrast extravasation.There were 163 pelvic fractures in 8758 admissions (incidence 2%). The most common associated injures were extremity fractures (60%, n = 98), abdominal solid organ (55%, n = 89), and chest (48%, n = 78), with the majority (61%, n = 99) sustaining injuries to multiple organs. Unstable fractures were associated with injures to the thorax (70% versus 40%), heart (15% versus 2%), and spleen (40% versus 18%), all P 0.05. Nonpelvic operative interventions were required in 45% (n = 73) and were more common in unstable fractures (36% versus 19%), contrast extravasation (63% versus 26%), sacroiliac widening (36% versus 20%), and sacral fractures (39% versus 13%), all P 0.05. Mortality was 13% and higher in males versus females (18% versus 5%), contrast extravasation (50% versus 3%), or sacroiliac/pubic symphysis widening (13% versus 2%) (all P 0.05). Male gender (OR 6.03), brain injury (OR 6.18), spine injury (OR 5.06), and cardiac injury (OR 35.0) were independently associated with mortality (all P 0.05).Pediatric pelvic fractures are rare but critical injuries associated with significant morbidity and need for interventions. Increasing fracture severity corresponds to injuries to other body systems and increased mortality.

The objective of this study was to re-evaluate and simplify the Greenfield risk assessment profile (RAP) for venous thromboembolism (VTE) in trauma using information readily available at the bedside.Retrospective review of 1233 consecutive admissions to the trauma intensive care unit from August 2011-January 2015. Univariate analyses were performed to determine which RAP risk factors were significant contributors to VTE. Multivariable logistic regression was used to develop models for risk stratification. All results were considered statistically significant at P ≤ 0.05.The study population was as follows: age 44 ± 19, 75% male, 72% blunt, injury severity score 21 ± 13, RAP score 9 ± 5, and 8% mortality. Groups were separated into +VTE (n = 104) and -VTE (n = 1129). They were similar in age, gender, mechanism, and mortality, but injury severity and RAP scores were higher in the +VTE group (all P 0.0001). The +VTE group had more transfusions and longer time to prophylaxis (all P 0.05). Receiving four or more transfusions in the first 24 h (odds ratio [OR], 2.60; 95% confidence interval [CI], 1.64-4.13), Glasgow coma score8 for4 h (OR, 2.13; 95% CI, 1.28-3.54), pelvic fracture (OR, 2.26; 95% CI, 1.44-3.57), age 40-59 y (OR, 1.70; 95% CI, 1.10-2.63), and2-h operation (OR, 1.80; 95% CI, 1.14-2.85) predicted VTE with an area under the receiver operator curve of 0.729, which was comparable with 0.740 for the RAP score alone.VTE risk in trauma can be easily assessed using only five risk factors, which are all readily available at the bedside (transfusion, Glasgow coma scale, pelvic fracture, prolonged operation, and age). This simplified model provides similar predictive ability to the more complicated RAP score. Prospective validation of a simplified risk assessment score is warranted.

A massive transfusion protocol (MTP) presents a logistical challenge for most blood banks and trauma centers. We compare the ratio of packed red blood cells (PRBC) and plasma transfused over serial time points in those requiring MTP (10-30 U PRBC/24 h) to those requiring "super" MTP (S-MTP;30 U PRBC/24 h) and test the hypothesis that changes in allocation of blood products with use of readily transfusable liquid plasma (LP) improves the ratio of PRBC and plasma during S-MTP.All transfused trauma patients (n = 1305) from January 01, 2009-April, 03, 2015 were reviewed. PRBC:plasma ratio was compared for MTP (n = 277) and S-MTP (n = 61) patients, before and after the availability of LP at our institution. Data are reported as mean ± standard deviation or median (interquartile range).Age was 41 ± 19 y, 52% blunt mechanism, injury severity score 32 ± 16, and 46.3% mortality. In 24 h, requirements were 17 (14) U PRBC and 10 (11) U plasma, with a PRBC:plasma of 1.6 (0.8). Within the first hour, PRBC:plasma for S-MTP versus MTP was 2.1:1 versus 1.7:1 (P = 0.017). With LP, S-MTP patients received significantly lower PRBC:plasma at the first hour (P0.001). Before institutional changes, PRBC:plasma positively correlated with PRBC transfused at hour 1 (r = 0.410, R(2) = 0.168, P0.001); after institutional changes and the advent of LP, there was no correlation (r = 0.177, R(2) = 0.031, P = 0.219).Within the first hour of transfusion, units of PRBC transfused positively correlated with PRBC:plasma, and patients receiving S-MTP had higher PRBC:plasma than those receiving MTP. Changes in our institution's MTP protocol to include LP improved the early PRBC:plasma transfused in patients requiring S-MTP.

Obesity negatively affects outcomes after trauma and surgery; results after burns are more limited and controversial. The purpose of this study was to determine the effect of obesity on clinical and economic outcomes after thermal injury.The National Inpatient Sample was queried for adults from 2005-2009 with International Classification of Diseases-9 codes for burn injury. Demographics and clinical outcomes of obese and nonobese cohorts were compared. Univariate and multivariate analysis using logistic regression models were performed. Data are expressed as median (interquartile range) or mean ± standard deviation and compared at P 0.05.In 14,602 patients, 3.3% were obese (body mass index ≥30 kg/m(2)). The rate of obesity increased significantly by year (P0.001). Univariate analysis revealed significant differences between obese and nonobese patients in incidence of wound infection (7.2% versus 5.0%), urinary tract infection (7.2% versus 4.6%), deep vein thrombosis in total body surface area (TBSA) ≥10% (3.1% versus 1.1%), pulmonary embolism in TBSA ≥10% (2.3% versus 0.6%), length of stay [6 d (8) versus 5 d (9)], and hospital costs ($10,122.12 [$18,074.72] versus $7892.07 [$17,191.96]) (all P 0.05). Death occurred less frequently in the obese group (1.9% versus 4%, P = 0.021). Significant predictors of grouped adverse events (urinary tract infection, wound infection, deep vein thrombosis, and pulmonary embolism) on multivariate analysis include obesity, TBSA ≥20%, age, and black race (all P ≤ 0.05).Obesity is an independent predictor of adverse events after burn injury; however, obesity is associated with decreased mortality. Our findings highlight the potential clinical and economic impact of the obesity epidemic on burn patients nationwide.

Coagulation changes in pediatric trauma patients are not well defined. To fill this gap, we tested the hypothesis that trauma evokes a hypercoagulable response.A prospective observational study was conducted in hospitalized patients (age 8months to 14years) admitted for trauma or elective surgery. Informed consent was obtained from the parents and informed assent was obtained in patients 7years of age or older. Coagulation changes were evaluated on fresh whole blood using thromboelastography (TEG) and on stored plasma using assays for special clotting factors.Forty three patients (22 trauma, median injury severity score =9; and 21 uninjured controls) were evaluated. For trauma vs control, prothrombin time (PT) was higher by about 10% (p0.001), but activated partial thromboplastin time was not altered. TEG clotting time (R;p=0.005) and fibrin cross-linking were markedly accelerated (K time, alpha angle; p0.001) relative to the control patients. d-Dimer, Prothrombin Fragment 1+2, and Plasminogen Activator Inhibitor-1 were all elevated, whereas Protein S activity was reduced (all p0.01). Importantly, a large fraction of TEG values and clotting factor assays in the pediatric control group were outside the published reference ranges for adults.A hypercoagulable state is associated with minor trauma in children. More work is needed to determine the functional significance of these changes and to establish normal pediatric reference ranges.

Background. In a model of traumatic brain injury (TBI), 2 protocols compared changes in intracranial pressure (ICP), coagulation, and neurologic outcome after intravenous fluid (IVF) resuscitation with either Hextend (HEX, 6% hetastarch in lactated electrolyte injection) or standard of care, crystalloid plus mannitol (MAN). Methods. In the nonsurvivor protocol, swine (n = 28) received a fluid percussion TBI and hemorrhage (27 ± 3 mL/kg). At 30 minutes, resuscitation began with lactated Ringer’s (LR) or HEX. After 60 minutes, MAN (1 g/kg) or placebo was given plus supplemental IVF to maintain cerebral perfusion pressure (CPP) $70 mm Hg for 240 minutes. Swine in the survivor group (n = 15) also underwent TBI and hemorrhage, and resuscitation with HEX was compared to that of normal saline (NS)+MAN. Neurologic outcome and coagulation were evaluated for 72 hours. Results. In the nonsurvivor protocol, HEX, LR+MAN, and HEX+MAN attenuated the time-related rise of ICP and prevented ICP >20 mm Hg versus LR alone (P < .05). HEX alone maintained CPP (relative to baseline) and decreased total IVF by 50% versus LR ± MAN (P < .05). MAN had no additive effect with HEX. Coagulation, measured by thromboelastograph reaction time (R), was 11 ± 1 and 9 ± 1 minutes at baseline and after TBI (before randomization). At 240 minutes after HEX or LR+MAN, R was 6 ± 1o r 7± 2 minutes, which indicates a hypercoagulable state, but there was no difference between treatments. In the survivor protocol, ICP and CPP were similar with NS+MAN versus HEX, but IVF requirement was 161 ± 20 versus 28 ± 3 mL/kg (P < .05). Motor scores were higher on days 2 and 3 with HEX (P < .05). At 72 hours, R was 28 ± 14 versus 26 ± 6 minutes with NS+MAN versus HEX, which indicates a hypocoagulable state, but there was no difference between treatments. Conclusions. Hextend as the sole resuscitation fluid after severe TBI reduces fluid requirement, obviates the need for mannitol, improves neurologic outcome, and has no adverse effect on the coagulation profile relative to the crystalloid plus mannitol standard of care. (Surgery 2004;136:355-63.)

Background Three different protocols tested the hypothesis that hind limb muscle tissue O2 saturation (StO2), measured noninvasively with near-infrared spectroscopy (NIRS), is as reliable as invasive systemic oxygenation indices to guide fluid resuscitation. Methods In series 1, swine (n = 30) were hemorrhaged, then received either no fluid, a fixed volume of colloid (15 mL/kg), or shed blood plus lactated Ringer's (LR) titrated to MAP >60 mm Hg. In series 2, swine (n = 16) received a penetrating femur injury, a 47% to 55% hemorrhage to determine a median lethal dose (LD50) then shed blood plus LR titrated to MAP >60 mm Hg. In series 3, swine (n = 5) received the femur injury plus LD50 hemorrhage, and were resuscitated with LR titrated to StO2 >50%. Results In series 1, StO2 tracked mixed venous O2 saturation (SvO2), but discriminated between 3 survivor groups better than SvO2, arterial lactate, or arterial base excess. In series 2, StO2 tracked SvO2 but discriminated between 2 survivor groups better than SvO2, arterial lactate, or arterial base excess. In series 3, animals survived to extubation when resuscitated to an StO2 target. Conclusions Noninvasive muscle StO2 determined by NIRS was more reliable than invasive oxygenation variables as an index of shock. Because muscle StO2 can be easily monitored in emergency situations, it may represent an improved method to gauge the severity of shock or the adequacy of fluid resuscitation after trauma.

The San Antonio Vasopressin Symposium reviewed substantial accumulated data concerning vasopressin in haemorrhagic, septic, and cardiac arrest shock conditions and found that there is considerable evidence to support the use of vasopressin in overcoming vasopressin deficiency or insufficiency. The value of vasopressin in the setting of trauma requires further investigation. It was concluded that a large, multicenter controlled trial of vasopressin is needed to assess the therapeutic benefit of vasopressin replacement in the setting of trauma with haemorrhagic shock that is prolonged and profound.

Background: We have reported that treatment with exogenous granulocyte colony-stimulating factor (G-CSF) improves abscess localization and reduces mortality without aggravating neutrophil (PMN)-mediated reperfusion injury in a model of septic abdominal trauma. The purpose of this study was to determine actions of G-CSF on PMN function in the peritoneum. Methods: Anesthetized swine were pretreated with broad-spectrum antibiotics and underwent cecal ligation and incision and 35% hemorrhage (trauma). After 1 hour they were resuscitated with shed blood, crystalloid, and either G-CSF (n = 10) or saline solution vehicle (n = 9). The animals were observed for 72 hours. Results: After trauma, saline solution treatment increased PMN infiltration into the peritoneum within 2 hours ( P = .035), increased peritoneal PMN elastase production (ie, cytotoxicity) by 24 hours ( P = .004), and decreased adherence of peritoneal PMNs to an artificial substrate from 4 to 72 hrs ( P = .043). The mean autopsy score was 7.0 ± 0.5. With G-CSF treatment peritoneal neutrophilia was enhanced (maximum 48 hours, P = .002) and PMN cytotoxicity was augmented and delayed (maximum 48 hours, P = .004). Despite these changes, adherence of peritoneal PMNs was not significantly changed and there was no evidence for PMN-mediated damage in the lung as judged by bronchoalveolar lavage protein, bronchoalveolar lavage PMNs, lung tissue myeloperoxidase, or histologic changes. The mean autopsy score was improved to 4.1 ± 0.3 ( P Conclusions: G-CSF in resuscitation fluids improved localization of an intra-abdominal septic focus by increased production of circulating PMNs, increased PMN extravasation into the peritoneal cavity, and increased PMN cytotoxicity at the abdominal septic focus, without exaggerating PMN-dependent reperfusion injury in the lung. Therefore these data further support the idea that G-CSF in resuscitation fluids might reduce septic complications in the multiply injured trauma patient. (Surgery 1999;126:305-13.)

Background: The goals were (1) to characterize physiologic changes after a combined insult of hemorrhage plus sepsis in a large animal model and (2) to determine whether transient inhibition of the neutrophil CD18 adherence receptor during fluid resuscitation impairs host defense during recovery from this injury. Methods: Two series of experiments were performed in anesthetized swine. In the first series (n = 22), the cecum was ligated and incised immediately before 35% hemorrhage. After 1 hour, shed blood plus supplemental fluid was administered to restore and stabilize hemodynamics. On the basis of these results, a second series examined effects of anti-CD18 (2 mg/kg R15.7; n = 9) or its saline placebo (n = 10) administered during fluid resuscitation. Results: In the first series the mortality rate was 41% (9 of 22). Early deaths occurred 3.0 ± 0.8 days after injury and were distinguished by significantly lower neutrophil counts on resuscitation. Those alive at 7 days had intraabdominal abscesses and bacteremia. Alveoli and peribronchial spaces were congested, with edema and fibrin deposition in capillaries and alveoli. Livers were congested with biliary stasis. Despite these pathologic findings, hemodynamic, electrolyte, and serum enzyme changes were minimal. In the second series the mortality rate at 4 days was 30% with placebo (3 of 10) versus 33% with anti-CD18 (3 of 9). Lung changes (i.e., pneumonia, pleuritis, thrombosis, and edema) were similar in both groups, but liver congestion and hemorrhage were attenuated by anti-CD18. Some aspects of host defense were altered by anti-CD18. At 24 and 48 hours the oxidative burst potential for circulating granulocytes was 208% ± 57% and 383% ± 73% with placebo versus 1273% ± 351% and 762% ± 226% in anti-CD18. At 72 hours the granularity of circulating neutrophils was unchanged from baseline with placebo but was reduced to 82% ± 5% by anti-CD18. At 48 hours lipopolysaccharide-evoked tumor necrosis factor production in vitro was reduced to 62% ± 22% with placebo but was increased to 148% ± 16% with anti-CD18. Conclusions: Anti-CD18 during fluid resuscitation did not increase vulnerability to endogenous pathogens because the transient inhibition of neutrophil demargination was balanced by enhanced oxidative burst, degranulation, and production of tumor necrosis factor in circulating cells later during recovery. Thus a single administration of antiadhesion therapy does not worsen posttrauma outcome even if given during ongoing sepsis. (Surgery 1998;123:679-91.)

Background. The purpose of this experimental study was to test whether transfusion potentiated physiologic changes associated with fluid resuscitated trauma in controlled conditions. Methods. Anesthetized and ventilated mongrel pigs were subjected to soft-tissue injury plus 35% hemorrhage and 1 hour shock and then were resuscitated with either autologous (shed) or heterologous (crosstransfused) fresh whole blood. Leukocyte differential counts, T-lymphocyte subsets, neutrophil adherence molecule (CD18) expression, granulocyte oxidative burst, plasma cortisol, and serum chemistries were monitored in awake animals with indwelling catheters on 3 consecutive days. Changes were referenced to preinjury baseline values and to a control group that received heterologous transfusion but no shock. To determine whether these changes might have influenced host defense, a low-dose challenge with Escherichia coli endotoxin (lipopolysaccharide [LPS]; 1 to 2 μg/kgfor 30 minutes) was administered on day 4. Results. During recovery, neutrophil counts, neutrophil CD18 expression, and granulocyte oxidative burst were generally increased, but the changes were not potentiated by transfusion. Lymphocyte subpopulations remained relatively constant. Serum enzyme markers were elevated with trauma plus shed blood or trauma plus cross-transfusion, but they remained essentially unchanged after heterologous transfusion only. Plasma cortisol, a nonspecific index of stress, peaked at 3 to 6 times higher than baseline. The increases tended to be higher and later with heterologous transfusion only, relative to trauma plus shed blood or trauma plus cross-transfusion. The delayed LPS challenge evoked profound but transient pulmonary hypertension and leukopenia, followed by subsequent hypoxemia; the time courses and magnitude of these changes were similar in all groups. Conclusions. If these measured variables before and after LPS challenge are a valid index of host defense in this species, then a 35% transfusion does not potentiate the risk for posttrauma immune dysfunction when the magnitude of injury is constant. Thus the predisposition to infection after human trauma might be due to cold storage of blood, separation of blood into components, or other transfusion-related practices rather than to transfusion per se.

We have shown that therapy directed at polymorphonuclear neutrophil (PMN) CD18 receptors attenuates sequelae associated with a post-trauma endotoxin (lipopolysaccharide [LPS]) challenge. Platelet activating factor (PAF) stimulates PMNs by CD18-independent pathways, and WEB-2086, a PAF receptor antagonist, blunts septic symptoms in many experimental models. This study tested the hypothesis that the blockade of non-CD18 dependent PMN adherence attenuates trauma- and LPS-evoked pulmonary dysfunction.We performed three experiments. First, anesthetized swine were subjected to hind-limb trauma and 30% hemorrhage. After 1 hour animals were resuscitated with shed blood, lactated Ringer's solution (LRS), and WEB-2086 (10 mg/kg/hr) or vehicle. After a 72-hour recovery period, LPS was administered. LPS was then administered without an earlier episode of traumatic shock to animals treated with WEB-2086 or vehicle. Finally, PAF was infused before and after trauma and a dose response curve was obtained.Surprisingly, PAF blockade increased mortality after trauma (5 of 11 WEB-2086 animals versus 1 of 9 vehicle animals; p = 0.15) and depressed cardiac index and O2 delivery at 72 hours (p0.05). After LPS administration WEB-2086 treated pigs were unable to manifest the hyperdynamic circulatory compensation seen in the vehicle pigs. In the absence of traumatic shock, WEB-2086 was associated with reduced mortality (four of five WEB-2086 treated pigs versus two of five vehicle pigs survived 5 hours; p = 0.07) and improved arterial PO2 (p = 0.05) and base excess (p = 0.04) 60 minutes after LPS administration. The dose response curve for PAF infusion on the cardiac index was altered after trauma compared with the nontraumatized state.Because WEB-2086 had unexpected and fundamentally opposite properties before and after trauma, PAF may have a previously undescribed homeostatic role in the compensatory response to injury. These results also suggest that blockade of endogenous inflammatory mediators can have a positive or negative action, depending on the timing of administration and the preexisting condition.

Background. Histamine H 2 antagonists (e.g., ranitidine) are generally thought to specifically reduce gastric acid secretion and are commonly used for stress ulcer prophylaxis in critically ill patients because of their efficacy and safety profile. A few reports suggest that ranitidine might also bind to extragastric sites and/or act as an immunomodulator. The potential effects on posttraumatic sepsis are unknoum. Methods. Mongrel pigs (n=24) were anesthetized with fentanyl, injured by a 10 kg steel bar dropped from a height of 1 m onto the fleshy portion of the posterior thigh, and then 35% of their blood volume was drained through the arterial catheter. All the shed blood plus two times the hemorrhage volume as lactated Ringer's solution was infused after a 1-hour shock period. Either vehicle or ranitidine (1.5 mg/kg) was intravenously administered at the time of resuscitation and every 12 hours thereafter in a blinded fashion. After 72 hours a septic challenge was administered (15 μg/kg Escherichia coli lipopolysaccharide [LPS]×30 min). Serial gastroscopy, gastric pH, hemodynamics leukocyte counts, cortisol, and tumor necrosis factor were recorded for 180 minutes after LPS. Results. Immediately before LPS all hemodynamic variables were identical between treatments, but gastric pH was slightly higher and stress gastritis was marginally lower with ranitidine. LPS caused profound leukopenia and a hyperdynamic circulatory response (i.e., tachycardia, increased cardiac output, and decreased peripheral vascular resistance at relatively constant blood pressure); these changes were not altered by ranitidine. Gastric pH remained elevated after LPS with ranitidine, but LPS-induced gastritis was not modified. Ranitidine delayed the LPS-induced ventilation-perfusion imbalance and attenuated the peak increase in the proinflammatory cytokine, tumor necrosis factor, without altering its antiinflammatory opponent, cortisol. Similar changes were observed in four additional animals treated with cimetidine. The proportion of circulating neutrophils and lymphocytes was slightly altered 180 minutes after LPS, but there was no obvious effect on T lymphocytes in vivo, and no effect on the LPS-induced increase in neutrophil CD18 expression in vitro was seen. Conclusions. (1) Ranitidine increased gastric pH, which blunted the stress gastritis caused by trauma but not that caused by LPS; (2) ranitidine delayed the early LPS-evoked pulmonary changes and reduced the tumor necrosis factor spike, which is consistent with a favorable immunomodulatory action that has been reported in patients who are critically ill or are undergoing an elective abdominal surgical procedure; (3) the mechanism is probably related to H 2 receptor antagonism rather than to a nonspecific side effect of ranitidine, which suggests that histamine may have a previously unrecognized role in posttraumatic septic responses; and (4) the site of action is probably not in the heart or peripheral resistance vessels, but salutary effects on circulating lymphocytes or neutrophils cannot be excluded.

The role of oxygen-derived free radicals in the local control of blood flow (BF) was evaluated in the microcirculation of the hamster cremaster muscle superfused with the enzymatic radical scavengers superoxide dismutase (SOD, 10 μg/ml) and catalase (CAT, 20 μg/ml). A bioassay of the cheek pouch microcirculation, using a previously described fluorescent microscopic technique, verified the in vivo activity of SOD and CAT. Increased superfusate O2 content to 95% O2 was correlated with an arteriolar vasoconstriction of approximately 50% and a 70% reduction in estimated BF, neither of which was affected by SOD-CAT treatment. These data suggest that free radicals do not mediate the vasoactive effect of O2. SOD-CAT did not alter vascular reactivity because a twofold vasodilation and a fourfold BF increase after topical adenosine application and a fivefold vasoconstriction after topical norepinephrine were unaffected by enzyme treatment. A twofold vasodilation accompanied striated muscle contraction, but there was no effect of SOD-CAT. Assuming SOD and CAT are not excluded from the striated muscle interstitial space, we conclude that the release of superoxide radicals into the extracellular space does not participate in local microvascular control of cremaster muscle BF.