Effect of allopurinol on venous endothelial dysfunction after resuscitated hemorrhagic shock.

BACKGROUND: Blood flow deficits contribute to organ dysfunction in patients resuscitated from hemorrhage. AIM: To determine the contribution of xanthine oxidase mediated reperfusion injury to venous endothelial function after resuscitated hemorrhagic shock. METHODS: Rats were prepared for intravital microscopic study then bled to 50% of baseline blood pressure for 60 min. Treatment animals received a 50mg/kg bolus and a 25mg/kg/h infusion of the xanthine oxidase inhibitor allopurinol (allo) after shock but before resuscitation with shed blood and an equal volume of Ringer's lactate. A similarly resuscitated group (Std) and a non-hemorrhage group (No HS) served as control. Endothelial function was quantified at baseline, 30 min (R30) and 90 min (R90) post resuscitation as a change in mesenteric vessel diameter after topical application of acetylcholine (Ach), an endothelial dependent vasodilator. RESULTS: Resuscitation restored cardiac output and blood pressure in both hemorrhage groups. First order venules (V1) demonstrated a 39% and a 36% reduction in ability to dilate to Ach at R30 and R90 after resuscitation with shed blood and Ringer's lactate (Std). Second order venules (V2) demonstrated a 20% and a 25% reduction in ability to dilate to Ach at R30 and R90 after resuscitation with shed blood and Ringer's lactate (Std). Addition of allopurinol to standard resuscitation attenuated this response resulting in the preservation of endothelial dependent venous vasodilation. CONCLUSIONS: These data suggest that xanthine oxidase mediated ischemia-reperfusion injury contributes to venous endothelial dysfunction in the mesenteric microcirculation after resuscitated hemorrhagic shock. Endothelial function can be preserved by the addition of the xanthine oxidase inhibitor allopurinol to standard resuscitation lending support for its inclusion as an adjunct to resuscitation after hemorrhagic shock.

Is colostomy always necessary in the treatment of open pelvic fractures?

BACKGROUND: Wound management in open pelvic fractures has used fecal diversion, debridement, and closure by secondary intention to prevent pelvic sepsis. Colostomy care and takedown adds to the morbidity and resource utilization of this approach. We reviewed our experience to determine if a selective approach to fecal diversion based on wound location was possible. METHODS: Retrospective analysis of patients admitted to a Level I trauma center during an 8-year period. Fractures were classified as open if the fracture was in continuity with the wound. Wounds were classified as perineal if they involved the rectum, ischiorectal fossa, or genitalia, and as nonperineal if they involved the pubis anteriorly, iliac crest, or anterior thigh. Pelvic sepsis was defined as cellulitis, fasciitis, or infection of a pelvic hematoma. Diversion consisted of loop or end colostomy. RESULTS: Eighteen patients with open fractures were identified. Four died from closed head injury and blood loss. The remaining 14 were treated as follows. Five patients with perineal wounds had diversion of their fecal stream. Their Injury Severity Score was 34 +/- 8.3 and their Revised Trauma Score was 7.69 +/- 0.15. No patient developed pelvic sepsis. Nine patients with nonperineal wounds did not undergo diversion. Their Injury Severity Score was 28.6 +/- 5.3 and their Revised Trauma Score was 7.36 +/- 0.45. No patients developed pelvic sepsis in the nondiverted group. CONCLUSION: No patients with anterior wounds and an intact fecal stream developed pelvic sepsis. Colostomy may not be necessary in all patients with open pelvic fracture. Protocols using fecal diversion based on wound location appear to be safe and may decrease resource utilization and subsequent morbidity related to colostomy closure.

Xanthine oxidase inhibition after resuscitated hemorrhagic shock restores mesenteric blood flow without vasodilation.

To determine the contribution of xanthine oxidase-mediated reperfusion injury to the blood flow deficits seen in the intestinal microcirculation after resuscitated hemorrhagic shock, rats were prepared for intravital microscopic study then bled to 50% of baseline blood pressure for 60 min. Treatment animals received a 50 mg/kg bolus and a 25 mg/kg/h infusion of the xanthine oxidase inhibitor allopurinol after shock but before standard resuscitation with shed blood and an equal volume of Ringer's lactate. A similarly resuscitated group served as control. Blood flow and vessel diameters were measured in the neurovascularly intact terminal ileum using intravital microscopy and doppler velocimetry. Resuscitation restored cardiac output and blood pressure in both groups. Blood flow in first order arterioles 120 min postresuscitation was 41% of baseline in the standard resuscitation group and 77% of baseline in the allopurinol-treated group. A1 arteriolar diameter was not significantly different between the two groups, being 73 and 82% of baseline, respectively. These data suggest that xanthine oxidase-mediated ischemia-reperfusion injury contributes to blood flow deficits in the small intestinal microcirculation after resuscitated hemorrhagic shock and that the improvement in blood flow seen with allopurinol is not due to vasodilation within the microvasculature.

Delayed hyphema and intravitreal blood following intrableb autologous blood injection after trabeculectomy.

PURPOSE: To report delayed hyphema and intravitreal blood as complications following intrableb autologous blood injection after trabeculectomy. METHODS: Case report. A 44-year-old woman with hypotony and maculopathy after trabeculectomy with mitomycin C received an intrableb autologous blood injection. RESULTS: Three days after the blood injection, a hyphema formed and subsequently dispersed into the vitreous. CONCLUSIONS: Although immediate hyphema from autologous blood injection is common, hyphema may be delayed and associated with intravitreal blood.

Xanthine oxidase inhibition prevents mesenteric blood flow deficits after resuscitated hemorrhagic shock by preserving endothelial function.

To determine the contribution of xanthine oxidase-mediated endothelial dysfunction to the blood flow deficits seen in the mesenteric circulation after resuscitated hemorrhagic shock, rats were prepared for intravital microscopic study then bled to 50% of baseline blood pressure for 60 min. Treatment animals received a 50 mg/kg bolus and a 25 mg/kg/hr infusion of the xanthine oxidase inhibitor allopurinol (allo) after shock but before resuscitation with shed blood and an equal volume of Ringer's lactate. A similarly resuscitated group (Std Res) and a nonhemorrhage group served as controls. Endothelial function was quantified at baseline, 30 min (R30), and 90 min (R90) postresuscitation as a change in mesenteric vessel diameter after topical application of acetylcholine (Ach), an endothelial-dependent vasodilator. Resuscitation restored cardiac output and blood pressure in both groups. First-order arteriolar blood flow (A1) remained depressed in the Std Res group but was restored to baseline in the group treated with allo. A1 arterioles demonstrated a 22 and a 27% reduction in ability to dilate to Ach at R30 and R90 after Std Res. V1 venules demonstrated a 39 and a 36% reduction in ability to dilate to Ach at R30 and R90 after Std Res. Endothelial-dependent vasodilation and blood flow were preserved in the group receiving Std Res plus allo. The preservation of endothelial function correlated with the restoration of microvascular blood flow postresuscitation. These data suggest that xanthine oxidase-mediated ischemia-reperfusion injury contributes to endothelial dysfunction and blood flow deficits in the mesenteric microcirculation after resuscitated hemorrhagic shock, the effect of which can be attenuated by the addition of the xanthine oxidase inhibitor allopurinol to standard resuscitation.

Laser synechialysis to prevent membrane recurrence on silicone intraocular lenses.

PURPOSE: To determine whether laser posterior synechialysis will prevent recurrence of pigmented membranes that can form on the anterior surface of silicone intraocular lenses. METHODS: Three patients (four eyes) had posterior synechiae and silicone intraocular lens surface membranes that required long-term corticosteroid treatment. Posterior synechiae were lysed by an Nd:YAG laser (1 to 2 mJ per burst; 148 to 485 applications; total energy, 296 to 896 mJ). RESULTS: All four eyes remained free of recurrence from 12 to 14 months. CONCLUSIONS: Silicone intraocular lens surface membranes emanated from posterior synechiae. The Nd:YAG laser synechialysis prevented recurrence and allowed discontinuation of corticosteroids.

Mitomycin trabeculectomy: the microsurgical sponge difference.

OBJECTIVE: A reproducible method for mitomycin application during glaucoma surgery is necessary to compare clinical results among investigators. To evaluate the potential reliability in drug delivery characteristics, mitomycin absorption and release from microsurgical sponges was studied. METHODS: Four brands of commercially available sponges were compared using a 0.5 mg/ml concentration of mitomycin. First, the maximum volume each sponge could absorb was measured. Second, 0.2 ml was applied to each sponge and then the expansion width was measured. Finally, 0.2 ml was applied to each sponge, the sponge was placed on filter paper, and then the amount (by weight) each sponge released during a 31/2-min period was measured. RESULTS: The volume absorbed was similar for each brand; the means ranged from 0.44 to 0.52 ml. The expansion width was variable between the brands; the means ranged from 4.0 to 10.4 mm. The amount released to filter paper was also variable between the brands; the means ranged from 19 to 54 mg. CONCLUSIONS: The difference in delivery characteristics suggests that the microsurgical sponge may be an important variable in mitomycin application. In absence of a standardized method, more detailed descriptions about specific mitomycin techniques are needed.

Allopurinol plus standard resuscitation preserves hepatic blood flow and function following hemorrhagic shock.

To determine the contribution of ischemia-reperfusion injury (IRI) to the blood flow deficit and hepatocellular dysfunction seen after resuscitation from hemorrhagic shock, the xanthine oxidase inhibitor allopurinol was given to rats as a 50 mg/kg bolus after shock but before resuscitation and continued as a 25 mg/kg/h infusion. Resuscitation with shed blood and lactated Ringer's restored cardiac output and blood pressure in both groups. Control animals demonstrated a reduction in total hepatic and effective hepatic blood flow to 59% and 43% of baseline values, respectively. Allopurinol resulted in a return to baseline values of both variables. Allopurinol treatment resulted in a 350% increase in xanthine, a 630% increase in hypoxanthine, and a 70% reduction in uric acid concentrations. These data suggest that IRI contributes to the organ dysfunction and blood flow deficits seen after resuscitated hemorrhagic shock the effect of which can be attenuated by the addition of the xanthine oxidase inhibitor allopurinol to standard resuscitation.

Retinal vein occlusions: case reviews of USAF aviators.

Retinal vein occlusions are primarily a disease of the elderly, frequently with permanent visual abnormalities. However, both branch and central retinal vein occlusions occur rarely in young individuals. Reported here are a series of retinal vein occlusions in USAF aviators. Seven cases were identified from records of the USAF Armstrong Laboratory Aeromedical Consultation Service from 1976-91. Four cases of central retinal vein occlusions and three cases of branch occlusions are summarized. Initial visual acuity ranged from 20/15 to 20/400. All seven aviators recovered 20/15 vision and returned to flying status. Hyperlipidemia was found in four of the seven aviators, and hypertension was diagnosed in two aviators. Included is a discussion of current concepts in the natural history, associated systemic conditions, treatment options, and aeromedical implications of retinal vein occlusions.

Brain injury causes loss of cardiovascular response to hemorrhagic shock.

The combined cardiovascular effects of hemorrhagic shock and mechanical brain injury were modeled in five groups of pigs. Standard and hypertonic saline resuscitation of hypotension were evaluated. Changes in mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), intracranial pressure (ICP), and brain water were measured. Brain injury (BI) was produced with a fluid percussion device that generated an extradural pressure of 3.5 x 10(5) N/m2 for 400 msec. Shock was caused by bleeding to a MAP of 60 mm Hg for 60 minutes and then resuscitated with shed blood only or shed blood plus 0.9% or 1.8% saline. Brain-injured only and shocked-only pigs served as controls. We found that brain injury alone caused refractory hypotension. Less shed blood was required to produce shock in brain injured animals (p < .05). Shock accompanied by brain injury was not reversed with crystalloid solutions. Volumes of saline required to restore blood pressure were large (> 6 L in 3 hours). 1.8% saline produced less rise in ICP than 0.9% saline but was less effective in restoring blood pressure. Brain edema was not decreased with 1.8% saline. Brain injury altered vascular compensation to hemorrhage and made accepted resuscitative measures ineffective.

Intestinal blood flow is restored with glutamine or glucose suffusion after hemorrhage.

Intestinal blood flow has been shown to be impaired after resuscitated hemorrhagic shock. Enteral feeding has been proposed as an adjunct for preserving mucosal integrity and decreasing translocation-related morbidities during stress. The purpose of this study was to determine if an ileal mucosal suffusion with an isotonic glucose or glutamine solution begun after resuscitation would prevent development of this blood flow impairment. The distal ileum of anesthetized Sprague-Dawley rats was prepared for in vivo videomicroscopy. Animals were bled to 50% of baseline blood pressure for 60 min and then resuscitated with their shed blood and an equal volume of lactated Ringer's. After resuscitation was complete, the mucosa was suffused with isotonic glucose, glutamine, or saline (control). Resuscitation restored cardiac output and mean arterial pressure to baseline in all groups; however, first-order arteriolar blood flow remained 50% below baseline in the saline group. Glucose-treated animals demonstrated a 34% increase over baseline in first-order arteriolar blood flow 120 min after resuscitation due to submucosal and previllus arteriolar dilation. This effect became evident 30 min after initiating the suffusion, suggesting an effect mediated via locally generated vasodilators. Glutamine suffusion attenuated the flow impairment by dilation of previllus arterioles but to a lesser degree than that observed in glucose-treated animals. These data demonstrate that mucosal suffusion with an isotonic glucose solution overrides the residual effects of hemorrhagic shock on the intestinal microcirculation and suggest a mechanism for preserving mucosal integrity with the addition of glutamine to standard enteral formulations.

Pentoxifylline restores intestinal microvascular blood flow during resuscitated hemorrhagic shock.

We studied the intestinal microvascular blood flow responses to hemorrhage and resuscitation with pentoxifylline by in vivo video microscopy. Male Sprague-Dawley rats were hemorrhaged to 50% of baseline mean arterial pressure for 45 minutes and then blindly randomized to receive pentoxifylline (25 mg/kg bolus + 0.2 mg/kg/minute) or an equivalent volume of saline plus return of shed blood and an additional bled volume of Ringer's lactate solution. Hemorrhage caused intestinal microvascular blood flow to decrease to 10% to 15% of baseline values. In the control group, resuscitation restored cardiac output and mean arterial pressure to baseline values, but intestinal microvascular blood flow remained at 30% of baseline values. In contrast, addition of pentoxifylline to the resuscitation regimen resulted in an immediate hyperemic response with an increase in intestinal microvascular blood flow to significantly greater than baseline values followed by return to baseline. Arteriolar dilation was not responsible for the improvement in flow implicating improved flow dynamics between erythrocytes, granulocytes, and vascular endothelia within the microcirculation. We conclude that addition of pentoxifylline to resuscitation from hemorrhagic shock restores intestinal microvascular blood flow.

Pentoxifylline but not saralasin restores hepatic blood flow after resuscitation from hemorrhagic shock.

After determining that hepatic blood flow remains impaired after resuscitation from hemorrhagic shock, we used the angiotensin II receptor antagonist saralasin and pentoxifylline to investigate their respective effects on hepatic blood flow responses after resuscitation from hemorrhagic shock. Rats were bled to 50% of baseline blood pressure for 60 min and resuscitated with shed blood and an equal volume of lactated Ringer's solution. Saralasin [10 micrograms/kg per min (n = 6)], pentoxifylline [25 mg/kg bolus and 12.5 mg/kg per hr (n = 7)], or saline (n = 11) were started with the onset of resuscitation. Total hepatic blood flow measured by ultrasonic transit time flow meter, effective nutrient hepatic blood flow measured by galactose clearance, mean arterial pressure, and cardiac output were recorded at 15-min intervals for 2 hr after resuscitation. Hemorrhage decreased cardiac output 57% below baseline and decreased total hepatic blood flow 64% below baseline. Resuscitation restored cardiac output to baseline levels in all three groups. Despite restoration of cardiac output, total hepatic and effective hepatic blood flow remained significantly below baseline in the saline control and saralasin groups but was restored to baseline levels in the pentoxifylline group. These data indicate that angiotensin II does not contribute significantly to the hepatic blood flow impairment after resuscitation from hemorrhagic shock. Improvement in flow with pentoxifylline implies that hemorrhage and resuscitation impair hepatic microvascular hemorrheology and that addition of pentoxifylline to standard resuscitation corrects the impairment.

Reappraisal of pancreatic and duodenal injury management based on injury severity.

We evaluated the effectiveness of treatment protocols for pancreatic and duodenal injuries according to the severity of injury. Of 81 patients, 65 survived initial injury. Pancreatic injuries without ductal involvement occurred in 21 patients and were treated by drainage. No late deaths occurred. Pancreatic injuries with ductal disruption occurred in 18 patients and were treated by pancreatic resection. Abscesses developed in seven (39%) of the patients, but no late deaths occurred. Nineteen patients had duodenal injuries without pancreatic injury, and no duodenal complications occurred. Simple closure sufficed for injuries affecting up to 40% of the duodenal circumference. Wounds affecting up to 40% of the duodenal circumference can be treated by suture closure alone. Adjunctive duodenal tube decompression should be reserved for wounds affecting greater than 40% of the duodenal circumference, closure under tension, and associated injuries to the head of the pancreas. Pyloric exclusion was rarely necessary in our patients.

Soft contact lens wear at altitude: effects of hypoxia.

In the U.S. Air Force, aircraft can be divided into two categories--those with cabin pressures equivalent to high altitudes and aircraft with cabin pressures equivalent to lower altitudes, with longer duration exposures. The purpose of this study was to determine the effects of soft contact lens wear under atmospheric pressures simulating these two types of aircraft environments. Ten subjects were tested to 7620 m (25,000 ft) in hypobaric chamber flights of 75 min and eight subjects were tested in hypobaric chamber flights at 3048 m (10,000 ft) for 4 h. Four subjects were also tested in dry air to further simulate cabin conditions. Vision and physiologic response were monitored by measurements of visual acuity, contrast sensitivity, and slit-lamp biomicroscopy examinations. The results of this study indicate that the physiologic responses of the cornea to soft contact lens wear at altitude are subject to higher levels of manifested stresses, but these occurred without measurable degradation in vision and did not preclude normal wear of soft contact lenses.

Contact lens wear at altitude: subcontact lens bubble formation.

A concern in the past regarding contact lens wear in aviation has been the fear of subcontact lens bubble formation. Previous reports have documented the occurrence of bubbles with hard (PMMA) lenses. Reported here are the results of contact lens bubble studies with soft hydrophilic and rigid gas-permeable lenses. Testing was accomplished in hypobaric chambers and onboard USAF transport aircraft. Hypobaric chamber flights were of three types: high-altitude flights up to 7,620 m (25,000 ft); explosive rapid decompressions from 2,438.4 m (8,000 ft) to 7,620 m (25,000 ft); and 4-h flights at 3,048 m (10,000 ft). Flights aboard transport aircraft typically had cabin pressures equivalent to 1,524-2,438.4 m (5,000-8,000 ft), and ranged in duration from 3 to 10 h. For subjects wearing rigid gas-permeable lenses, central bubbles were detected in 2 of 10 eyes and occurred at altitudes greater than 6,096 m (20,000 ft). With soft contact lenses, bubble formation was detected in approximately 24% (22 of 92 eyes) of the eyes tested, sometimes occurring at altitudes as low as 1,828.8 m (6,000 ft). Soft lens bubbles were always located at the limbus and were without sequela to vision or corneal epithelial integrity. Bubbles under the rigid lenses were primarily central, with potential adverse effects on vision and the corneal epithelium.

Effect of positive acceleration (+Gz) on soft contact lens wear.

The effects of positive acceleration on soft contact lens wear were tested on a human centrifuge to +8 Gz. There were 11 subjects who participated in this study; 5 were myopic subjects fit with low-, medium-, and high-water-content spherical soft lenses; 3 were astigmatic subjects fit with various designs of toric soft lenses and 3 were emmetropic control subjects. As an additional control, the contact lens subjects were tested with spectacles for comparison. Video photography was used to monitor lens position during the centrifuge rides and visual acuity was checked at +1, +2, +4, +6, and +8 Gz with a reduced Snellen eye chart. Each lens type and control run was evaluated in straight-ahead, lateral, and vertical gaze. No visually significant decentration was noted for any of the lens types tested up to the maximum level of +8 Gz. Visual acuity was reduced at the higher +Gz levels for contact lenses, and spectacle trials, and with the emmetropic controls--all to similar levels. Contact lens wear did not produce any corneal insult due to the +Gz exposure.