Effect of age and disc size on rim order rules by Heidelberg Retina Tomograph.

PURPOSE: The ISNT rule for nonglaucomatous eyes suggests that the neuroretinal rim is thickest at the inferior quadrant (I), followed by the superior (S), nasal (N), and temporal (T) quadrants. This study aimed to use Heidelberg Retina Tomograph (HRT III) measurements to assess (a) fulfillment of the ISNT rule and its derivatives in a large normative database and (b) effect of disc size and age on rule fulfillment. PATIENTS AND METHODS: A multicenter, prospective, cross-sectional study of a Caucasian normative database consisting of 280 subjects with normal comprehensive biomicroscopic examination, intraocular pressure <21 mm Hg, and normal automated visual field testing was conducted. Right eye neuroretinal rim and disc area, measured by HRT III, for each of the 4 quadrants were analyzed. Compliance of the rim area to the ISNT rule (I≥S≥N≥T) and its derivates was determined. Effect of age and disc area on rule compliance was further determined. RESULTS: Only 18% of normal eyes had rim areas that complied with the ISNT rule; however, a majority complied to IS (77%) and IST (73%) rules. The temporal quadrant had the smallest rim area [(I,S,N)>T] in 91% of patients. The likelihood of ISNT rule violation was increased in larger discs (χ², P=0.003) but was not affected by age. CONCLUSIONS: The ISNT rule does not apply to neuroretinal rim area as measured by HRT, as only 18% of the eyes complied with the ISNT rule in this normative database. Although the ISNT rule may be more applicable to normal eyes with a smaller disc area, the IS and IST rules seem to better represent the normative database.

Topical glaucoma therapy and ocular surface disease: a prospective, controlled cohort study.

OBJECTIVE: To evaluate the association between the intensity and duration of glaucoma topical therapy and severity of signs and symptoms of ocular surface disease (OSD). DESIGN: Single-site, prospective, controlled, cross-sectional study. PARTICIPANTS: Sixty-one patients with no diagnosis of or previous treatment for OSD were identified. METHODS: Patients were assigned to 2 groups: the glaucoma group with 31 patients diagnosed with primary open-angle glaucoma and using at least 1 topical intraocular pressure (IOP)-lowering medication and the control group including 30 patients with no diagnosis of glaucoma or history of topical therapy usage. The right eye of each patient was arbitrarily chosen. Each patient completed an Ocular Surface Disease Index (OSDI) questionnaire and underwent evaluation of the ocular surface by conjunctival and corneal lissamine green (LG) staining and tear breakup time (TBUT). The intensity index (drops/wk × therapy duration in years) was calculated to quantify the topical therapy. RESULTS: OSDI scores of the glaucoma group correlated to the intensity index (r = 0.46, CI 0.13-0.69). The glaucoma group had a higher mean OSDI score than the control group (18.97 ± 9.5 versus 6.25 ± 5.7, p = 5.85E-08). Abnormal TBUT and LG staining scores were prevalent in the glaucoma group compared with the control group (68% vs 17%, p = 0.000078; 65% vs 3%, p = 2.9E-07). CONCLUSIONS: Patients on glaucoma therapy have a greater prevalence of OSD symptoms, and their intensity index correlates to the OSDI score. The intensity index reflects quantitatively the amount of treatment and can be further validated in future studies as a predicting tool for OSD development.

New Technique of Exposed Glaucoma Drainage Tube Repair: Report of a Case.

We present the case of successful repair of an exposed glaucoma drainage tube by cornea graft fixation with tissue adhesive, and without subsequent coverage by adjacent conjunctiva or donor tissues. Patient with history of keratoglobus with thin cornea and sclera, and phthisical contralateral eye, underwent three unsuccessful corneal grafts followed by Boston type 1 keratoprosthesis in the right eye. Ahmed drainage device with sclera patch graft was implanted to control the intraocular pressure. Two years later the tube eroded through sclera graft and conjunctiva. Repair was performed by covering the tube with a corneal patch graft secured by tissue adhesive after the conjunctiva in this area was dissected away. The cornea graft was left uncovered due to fragility of adjacent conjunctiva. The healing of ocular and graft surfaces was complete prior to the 1 month follow-up. Conjunctival epithelium covered the corneal patch graft. At 12 months follow-up, the graft and the tube remained stable. Our report suggests that corneal patch graft fixation to the sclera by means of tissue adhesive, without closing the conjunctiva, can be considered as an effective alternative surgical approach for managing exposed glaucoma drainage tube, accompanied by adjacent conjunctiva tissue deficiency. How to cite this article: Berezina TL, Fechtner RD, Cohen A, Kim EE, Chu DS. New Technique of Exposed Glaucoma Drainage Tube Repair: Report of a Case. J Curr Glaucoma Pract 2015;9(2):62-64.

Repeat selective laser trabeculoplasty can be effective in eyes with initial modest response.

PURPOSE: To evaluate the effectiveness of repeat selective laser trabeculoplasty (SLT) in eyes exhibiting only a modest response upon initial treatment. MATERIALS AND METHODS: Retrospective chart review was conducted of 51 eyes that received initial 360 degree SLT (SLT1) and subsequent SLT (SLT2) from 2003-2011 at a large academic ophthalmology practice. Successful response (S) was a post-treatment 12 month mean IOP reduction ≥ 20% from baseline, while modest response (M) was <20% reduction over the same time. Chi-squared and log rank analyses were used to determine if success after SLT2 depended on having successful (S1) or modest (M1) response after SLT1. RESULTS: IOP was significantly reduced from baseline in both SLT1 and SLT2. The proportion of eyes with S2 was not significantly different between those with initial M1 or S1 (36.67% vs. 52.38%, respectively; P = 0.26). Log rank analysis revealed no differences between M1 and S1 in determining SLT2 success (P = 0.41). This outcome was similar when the analyses were performed for the right and left eye independently. CONCLUSION: The proportion of eyes that successfully responded to repeat SLT did not differ based upon whether the response to initial SLT was successful or modest. This raises the possibility that repeat SLT should not be excluded as an option for those eyes that have only a modest initial response.

Long term efficacy of repeat selective laser trabeculoplasty.

PURPOSE: To evaluate long term intraocular pressure (IOP) control after repeat selective laser trabeculoplasty (SLT). METHODS: This single center study retrospectively reviews the electronic medical records of patients with open angle glaucoma undergoing repeat SLT. Eyes with prior argon laser trabeculoplasty, or incisional surgery before or during the study period were excluded. Demographics, laser parameters, number of glaucoma medications and IOP at baseline and after 1, 4, 8, 12, 18 and 24 months were collected. The percentage of subjects with IOP reduction >20% and ≥15% from baseline was determined. RESULTS: A total of 45 eyes of 25 subjects with mean age of 73 ± 9 years undergoing repeat SLT were included. Repeat SLT was performed at a mean interval of 28.3 ± 12.7 months after initial treatment. Mean IOP reductions were statistically significant with repeat SLT as compared to baseline at 1, 4, 8, 12, 18 and 24 months' follow-up. Change in IOP after first and repeat SLT were comparable at most time points except at 4, 8 and 12 months when initial treatment had yielded significantly greater reductions. At 24 months, 29% and 39% of eyes achieved IOP reduction >20% and ≥15% respectively after repeat SLT as compared to 36% and 54% of eyes following initial treatment (P > 0.05). CONCLUSION: Repeat SLT is effective in lowering IOP up to 24 months. Long term IOP control was achieved in 29-39% of eyes following repeat treatment in this cohort of patients.

Does recombinant factor XIII eliminate early manifestations of multiple-organ injury after experimental burn similarly to gut ischemia-reperfusion injury or trauma-hemorrhagic shock?

The authors have previously shown that recombinant factor XIII (rFXIII) eliminates early manifestations of multiple-organ injury caused by experimental superior mesenteric artery occlusion or trauma-hemorrhagic shock. The aim of the present study was to test the hypothesis that rFXIII provides similar protective effect in experimental burn injury. Rats were randomly divided into five groups (eight animals per group): group 1: burn + placebo treatment; group 2: burn + rFXIII pretreatment; group 3: burn + rFXIII treatment; group 4: sham burn + placebo treatment, and group 5: sham burn + rFXIII treatment. Burn (40% of TBSA) was achieved by immersing the back and abdomen of a rat into 97°C water for 10 and 5 seconds, respectively. Infusion of rFXIII (1 mg/kg) or placebo was performed immediately after burn/sham burn in treatment groups or 24 hours before burn and repeated immediately after it in pretreatment group. Endpoint parameters measured 3 hours after burn/sham burn included muscle blood flow and PO2, lung permeability, gut histology, lung and gut myeloperoxidase activity, neutrophil respiratory burst, and FXIII activity. Both treatment and pretreatment with rFXIII partially preserved microvascular blood flow in the muscle. Muscle PO2 in pretreated rats did not differ from that in shams. Pretreatment but not treatment with rFXIII preserved lung permeability. rFXIII did not have any protective effect on other endpoint parameters. In contrast to superior mesenteric artery occlusion and trauma-hemorrhagic shock experimental models, rFXIII at the doses tested has a limited effect on preventing early manifestations of multiple-organ injury after experimental burn.

Visual field and ocular safety during short-term vigabatrin treatment in cocaine abusers.

PURPOSE: To evaluate the ocular safety of short-term vigabatrin treatment of cocaine abuse. DESIGN: Multicenter, prospective, randomized, placebo-controlled, double-masked, parallel assignment study. METHODS: Cocaine addicts were randomized to receive vigabatrin 3000 mg/day, cumulative dose 218 g (n = 92), or placebo (n = 94) for 12 weeks. Subjects underwent examination of visual acuity (ETDRS) and peripheral visual field (PVF) by Humphrey Field Analyzer (HFA) 60-4 program before and after treatment. Reliable PVF tests (fixation loss, false positive, and false negative <33%) for 103 subjects were included for the analysis. The threshold visual sensitivity (TVS) was analyzed by points, rings and zones. Main outcome measures included visual acuity decrease by 15 letters and/or significant PVF alteration, defined as 5 or more visual field location points having greater than or equal to 15 dB reduction in TVS or decline (≥33% loss) in posttreatment TVS for 1 or more rings. RESULTS: Visual acuity decrease was detected in 1 eye of a subject receiving placebo and in none receiving vigabatrin. Posttreatment reduction in TVS more than 15 dB in 5 or more adjacent visual field location points combined with reduction in TVS greater than 33% in 1 or more of the rings was detected in 2 of 54 subjects (3.7%) from the vigabatrin group and in 1 of 49 subjects (2%) from the placebo group (P = .9, NS). None of the PVF changes were bilateral or concentric. CONCLUSIONS: Short-term use of vigabatrin did not cause a decrease in visual acuity or significant peripheral visual field changes in cocaine abusers.

Recombinant factor XIII mitigates hemorrhagic shock-induced organ dysfunction.

BACKGROUND: Plasma factor XIII (FXIII) is responsible for stabilization of fibrin clot at the final stage of blood coagulation. Since FXIII has also been shown to modulate inflammation, endothelial permeability, as well as diminish multiple organ dysfunction (MOD) after gut ischemia-reperfusion injury, we hypothesized that FXIII would reduce MOD caused by trauma-hemorrhagic shock (THS). MATERIALS AND METHODS: Rats were subjected to a 90 min THS or trauma sham shock (TSS) and treated with either recombinant human FXIII A(2) subunit (rFXIII) or placebo immediately after resuscitation with shed blood or at the end of the TSS period. Lung permeability, lung and gut myeloperoxidase (MPO) activity, gut histology, neutrophil respiratory burst, microvascular blood flow in the liver and muscles, and cytokine levels were measured 3 h after the THS or TSS. FXIII levels were measured before THS or TSS and after the 3-h post-shock period. RESULTS: THS-induced lung permeability as well as lung and gut MPO activity was significantly lower in rFXIII-treated than in placebo-treated animals. Similarly, rFXIII-treated rats had lower neutrophil respiratory burst activity and less ileal mucosal injury. rFXIII-treated rats also had a higher liver microvascular blood flow compared with the placebo group. Cytokine response was more favorable in rFXIII-treated animals. Trauma-hemorrhagic shock did not cause a drop in FXIII activity during the study period. CONCLUSIONS: Administration of rFXIII diminishes THS-induced MOD in rats, presumably by preservation of the gut barrier function, limitation of polymorphonuclear leukocyte (PMN) activation, and modulation of the cytokine response.

Peripheral visual field thresholds using Humphrey Field Analyzer program 60-4 in normal eyes.

PURPOSE: Various methods have been used for testing peripheral visual field disturbances such as defects caused by drug toxicity. Static threshold perimetry with Humphrey Field Analyzer (HFA) is widely available. The aim of this study was to better define the normal thresholds for peripheral visual field (PVF) sensitivity and to refine analysis strategies. METHODS: Automated PVF testing was performed with HFA 60-4 program in 33 normal subjects. Test locations were organized into inner, middle, and outer eccentricity rings and divided into 4 zones: nasal, temporal, superior, and inferior. The threshold visual sensitivity (TVS) in decibels was established for each point. RESULTS: The majority of points with the lowest TVS and highest between-subject variability were located within the nasal area of the outer ring. Points with the highest TVS and least variability were detected in the inner ring and in the temporal area of the middle and outer rings. Mean zone TVS decreased and variability increased with increasing eccentricity. CONCLUSIONS: The areas that demonstrate the highest between-subject consistency and thus might best reveal peripheral visual abnormalities with HFA 60-4 are the inner ring, inferior and temporal zone of the middle ring, and temporal zone of the outer ring. These observations may be useful for developing strategies to detect peripheral field loss at an early stage when central vision is not yet affected.

Augmenting regional cerebral blood flow using external-to-internal carotid artery flow diversion method.

The objective of this study was to assess the effect of flow diversion by external carotid artery (ECA) occlusion on ipsilateral regional cerebral blood flow (rCBF). Local cerebral hyperperfusion in rats (n = 12) was induced by ligating the right ECA. Ipsilateral rCBF was determined pre- and post-ligation for 120 min using a laser Doppler flow meter. Sham animals (n = 6) were subjected to the craniotomy without ligation of the right ECA. In a separate series of rats (n = 5), brain tissue oxygen levels (pO(2)) in the right and left brain hemispheres were determined before and 90 min after ligation of the right ECA using a tissue oxygenation monitoring unit. We investigated the effect of ECA occlusion hemispheric changes in rCBF in one clinical case as a proof of concept. Ligation of ECA resulted in a statistically significant increase in rCBF on the ipsilateral side compared to the sham-operated rats (p < 0.0001). On average we observed a 34% increase (95% CI: 24-45%) in rCBF in the ipsilateral territory in the treated group compared with sham-operated rats. There was no significant variation in MAP for the treated animals. Vascular permeability and cerebral water content in the right hemisphere after ligation of ECA did not significantly differ from the contralateral hemisphere. Ipsilateral hemisphere tissue pO(2) was significantly higher compared to the contralateral area (p < 0.002) post-ligation or to the ipsilateral area (p < 0.001) prior to ligation. In the clinical case, occlusion of ECA resulted in 3.6% and 12.1% increase in peak value and rise-time of the time-density curves. Flow diversion by temporary occlusion of the ECA can result in increased rCBF and cerebral pO(2) on the ipsilateral side. The strategy may represent a viable option to augment rCBF in focal cerebral ischemia.

Trauma-hemorrhagic shock-induced red blood cell damage leads to decreased microcirculatory blood flow.

OBJECTIVE: To test the hypothesis that trauma-hemorrhagic shock (T/HS)-induced changes in red blood cells (RBC) contribute to the reduction of blood flow in distant organs. DESIGN: Laboratory study. SETTING: Academic medical center laboratory. SUBJECTS: Specific pathogen-free male Sprague-Dawley rats weighing between 250 and 350 g. INTERVENTIONS: Rats were transfused with trauma-sham shock (T/SS), or T/HS whole blood, or RBC-depleted blood (blood with the RBC removed and consisting of white blood cells and plasma). MEASUREMENTS AND MAIN RESULTS: Cardiac output and organ blood flow were measured by the radioactive microsphere technique. RBC tissue trapping, deformability, and RBC aggregation and adhesion were studied. Measurements of RBC adenosine triphosphate (ATP) and plasma fibrinogen were performed. Exchange transfusion with T/SS blood did not alter cardiac output or organ blood flow. However, cardiac output and blood flow in several organs were decreased when T/HS whole blood was used and RBCs were trapped in the organs that evidenced decreased blood flow. T/HS also increased RBC aggregation and adhesion, and decreased deformability. The ability of T/HS exchange transfusion to decrease microcirculatory blood flow did not appear to be due to plasma factors or non-RBC elements (i.e., white blood cell), because organ blood flow was not reduced after exchange transfusion with T/HS RBC-depleted blood. Likewise, neither decreased RBC ATP nor increased plasma fibrinogen explained the T/HS-induced changes that were observed. There was no change in fibrinogen levels during or after shock. Although there was a transient decrease in T/HS erythrocyte ATP levels during the early shock period, in contrast to RBC function, the ATP levels had returned to normal with resuscitation. CONCLUSIONS: T/HS induces significant changes in RBC functions and the injection of T/HS, but not T/SS, RBC leads to decreased organ blood flow. These findings confirm the hypothesis that T/HS-induced RBC alterations will directly cause organ hypoperfusion and suggest that T/HS-induced RBC damage contributes to this process. Thus, T/HS-induced changes in RBC function may contribute to the development of shock-induced multiple organ failure.

Recombinant factor XIII diminishes multiple organ dysfunction in rats caused by gut ischemia-reperfusion injury.

Plasma factor XIII (FXIII) is responsible for stabilization of fibrin clot at the final stage of blood coagulation. Because FXIII has also been shown to modulate inflammation and endothelial permeability, we hypothesized that FXIII diminishes multiple organ dysfunction caused by gut I/R injury. A model of superior mesenteric artery occlusion (SMAO) was used to induce gut I/R injury. Rats were subjected to 45-min SMAO or sham SMAO and treated with recombinant human FXIII A2 subunit (rFXIII) or placebo at the beginning of the reperfusion period. Lung permeability, lung and gut myeloperoxidase activity, gut histology, neutrophil respiratory burst, and microvascular blood flow in the liver and muscles were measured after a 3-h reperfusion period. The effect of activated rFXIII on transendothelial resistance of human umbilical vein endothelial cells was tested in vitro. Superior mesenteric artery occlusion-induced lung permeability as well as lung and gut myeloperoxidase activity was significantly lower in rFXIII-treated versus untreated animals. Similarly, rFXIII-treated rats had lower neutrophil respiratory burst activity and ileal mucosal injury. Rats treated with rFXIII also had higher liver microvascular blood flow compared with the placebo group. Superior mesenteric artery occlusion did not cause FXIII consumption during the study period. In vitro, activated rFXIII caused a dose-dependent increase in human umbilical vein endothelial cell monolayer resistance to thrombin-induced injury. Thus, administration of rFXIII diminishes SMAO-induced multiple organ dysfunction in rats, presumably by preservation of endothelial barrier function and the limitation of polymorphonuclear leukocyte activation.

The influence of the type of resuscitation fluid on gut injury and distant organ injury in a rat model of trauma/hemorrhagic shock.

BACKGROUND: Recognition that resuscitation with Ringers lactate (RL) potentiates trauma-hemorrhagic shock (T/HS)-induced organ injury and systemic inflammation has led to a search for improved initial fluid resuscitation regimens. However, one relatively neglected component in the search for new and novel resuscitation strategies is a determination of what fluid resuscitation therapy (i.e., control group) the new experimental regimen of interest should be tested against. Thus, we tested the effects of three commonly used resuscitation strategies on trauma-shock-induced gut and lung injury, as well as neutrophil activation and red blood cell (RBC) function. METHODS: Male Sprague Dawley rats were subjected to a laparotomy (trauma) and 90 minutes of sham shock (trauma-sham shock [T/SS]) or a laparotomy plus hemorrhagic shock (T/HS), followed by a reperfusion period of 3 hours. The T/HS groups were resuscitated either with their shed blood (SB), or half the SB and 1.5 times the SB volume as RL (SB/RL), or 3 times the SB volume as RL (3RL). The T/SS groups received either no resuscitation or RL at 1.5 times the SB volume of the T/HS rats. Gut injury was quantified by measuring intestinal permeability to flourescein dextran (FD-4), as well as by histologic analysis of the terminal ileum. Lung injury was assessed histologically and by the magnitude of neutrophil sequestration as reflected in myeloperoxidase levels. Neutrophil activation was measured by quantitating the level of CD11b expression using flow cytometry. RBC injury was analyzed by measuring the RBC deformability. RESULTS: As compared with the T/SS groups, all three T/HS resuscitation regimens were associated with morphologic evidence of gut and lung injury, increased gut permeability, pulmonary leukosequestration, systemic neutrophil activation, and decreased RBC deformability (p < 0.05). However, the effect of the resuscitation regimens varied based on the tissues and cells tested. Morphologically, gut and lung injury as well as pulmonary neutrophil sequestration was worse in the 3RL T/HS group than the other two T/HS groups. As compared with the other two T/HS resuscitation regimens, resuscitation with the SB/RL combination was associated with less of an increase in gut permeability, systemic neutrophil activation, and RBC rigidification (p < 0.05). CONCLUSIONS: The type of resuscitation regimen used influenced the extent of organ injury and cellular activation or dysfunction observed after T/HS with different resuscitation regimens showing varying effects depending on the cell or organ tested. Thus, when testing novel fluid resuscitation regimen, attention must be paid to the control resuscitation regimen used.

Microscopic and macroscopic evaluation of emboli captured during angioplasty and stent procedures in extracranial vertebral and internal carotid arteries.

PURPOSE: To compare the quantities of emboli dislodged during percutaneous transluminal angioplasty/stenting in the vertebral artery (VA) with those released during stent placement in the internal carotid artery (ICA). METHODS: Macroscopic images of distal protection devices (DPD) used during 30 stent procedures in 16 ICAs (11 men; mean age 64.6+/-10.6 years) and 14 VAs (9 men; mean age 67.1+/-9.8 years) were reviewed. The amount of captured embolic debris was calculated and expressed as a proportion to the size of the filter. Histological examinations were performed to characterize the material trapped in the filters. RESULTS: Relative to the size of the filter, the proportion of captured debris ranged from 0.1% to approximately 22% in the ostial VA filters and from 0.1% to approximately 21% in the filters used in the ICA procedures (p = NS). Plaque fragments with or without thrombus were discovered in the histological examinations of captured material. There were no significant differences in the characteristics of the debris between the 2 vascular regions, nor did sex, race, or plaque morphology correlate significantly with the proportion of captured debris. However, the severity of stenosis was significantly (p<0.029) greater in the ICA (73%+/-0.11%) than the VA (63%+/-0.09%) territory. CONCLUSION: The study suggests that the frequency and amount of captured emboli during stent procedures in ICA and ostial VAs are comparable. Therefore, the use of a DPD for stent placement in the vertebral artery may be advisable.

Resistance of the female, as opposed to the male, intestine to I/R-mediated injury is associated with increased resistance to gut-induced distant organ injury.

We tested the hypothesis that the female intestine is more resistant to gut I/R injury than the male intestine by comparing the effects of the isolated pure gut I/R superior mesenteric artery occlusion (SMAO) model on gut morphology and whether SMAO-induced distant organ injury (lung, bone marrow [BM], neutrophils, and red blood cells [RBCs]) would differ between male and proestrus female rats. At 6 or 24 h after SMAO or sham SMAO, gut injury, lung permeability, pulmonary neutrophil sequestration, RBC deformability, and BM RBC and white blood cell progenitor growth were measured, as was the ability of the plasma from these rats to activate naive rat neutrophils. At both 6 and 24 h after SMAO, the female rats had significantly less intestinal injury and reduced gut-induced lung injury, BM suppression, RBC dysfunction, and neutrophil activation than male rats subjected to SMAO. These results indicate that the resistance of proestrus female rats to gut injury and gut-induced distant organ injury is greater than that observed in male rats.

Adenosine A2A receptor activation reduces lung injury in trauma/hemorrhagic shock.

OBJECTIVE: Hemorrhagic shock and resuscitation trigger a global ischemia/reperfusion phenomenon, in which various inflammatory processes critically contribute to the ensuing tissue damage. Adenosine is an endogenous nucleoside that is released during shock. Activation of adenosine A(2A) receptors can broadly inactivate inflammatory cascades. The current study was designed to evaluate the effect of A(2A) receptor activation on organ injury and inflammation in the setting of global ischemia/reperfusion elicited by trauma/hemorrhagic shock and resuscitation. DESIGN: Prospective animal study with concurrent control. SETTING: Small animal laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: The rats were subjected to a laparotomy (trauma) and 90 mins of hemorrhagic shock or trauma/sham shock. The selective A(2A) receptor agonist CGS-21680 (2-p-(2-carboxyethyl) phenethylamino-5'-N-ethyl-carboxamidoadenosine; 0.5 mg/kg) or its vehicle was injected 30 mins before shock or immediately after resuscitation. At 3 hrs following resuscitation, animals were killed and tissue was harvested for analysis. Lung permeability and pulmonary myeloperoxidase levels were used to quantitate lung injury. Intestinal injury was determined by histologic analysis of terminal ileum. Red blood cell deformability was measured by a laser-assisted ektacytometer. In this assay, a decrease in the elongation index is a marker of decreased red blood cell deformability. MEASUREMENTS AND MAIN RESULTS: Pretreatment with CGS-21680 protected the lung but not the gut against shock-induced injury and prevented the shock-induced decrease in red blood cell deformability. Posttreatment with CGS-21680 ameliorated shock-induced lung injury but failed to prevent gut injury and preserve red blood cell deformability. CONCLUSION: A(2A) receptor agonists may represent a novel therapeutic approach in preventing organ injury following trauma/hemorrhagic shock.

Small volume resuscitation with hypertonic saline is more effective in ameliorating trauma-hemorrhagic shock-induced lung injury, neutrophil activation and red blood cell dysfunction than pancreatitic protease inhibition.

BACKGROUND: Recognition of the limitations of standard crystalloid resuscitation has led to the search for alternative resuscitation strategies that might better limit the development of trauma-hemorrhage-induced organ dysfunction and systemic inflammation. Thus, the goal of this study was to compare the effects of two resuscitation strategies alone, and in combination, with those of standard resuscitation with Ringers lactate (RL). The two strategies were small volume resuscitation with hypertonic saline (HTS) and intraluminal inhibition of pancreatic proteases with the serine protease inhibitor nafamostat. METHODS: Male rats were subjected to trauma-hemorrhagic shock (T/HS) or trauma sham-shock (T/SS) and resuscitated with RL, HTS, nafamostat, or the combination of HTS and nafamostat. The T/HS model consisted of a laparotomy plus 90 minutes of shock (MAP 30 mm Hg). Three hours after the end of the shock or sham-shock period, lung permeability, pulmonary neutrophil sequestration, neutrophil activation, red blood cell deformability, and gut injury were assessed. RESULTS: Both HTS and nafamostat reduced T/HS-induced pulmonary permeability and neutrophil sequestration, as well as neutrophil activation as compared with resuscitation with RL. However, HTS was more effective than nafamostat in reducing T/HS-induced acute lung injury and neutrophil activation. Additionally, HTS, but not nafamostat, reduced T/HS-induced RBC rigidification. Lastly, gut injury after T/HS was reduced to the greatest extent by the combination of HTS plus nafamostat. CONCLUSION: Small volume resuscitation with HTS is more effective than RL and nafamostat in limiting T/HS-induced acute lung injury, neutrophil activation and red blood cell injury.

Amiloride combined with small-volume resuscitation with hypertonic saline is superior in ameliorating trauma-hemorrhagic shock-induced lung injury in rats to the administration of either agent alone.

OBJECTIVE: Recognition of the limitations of standard crystalloid resuscitation has led to exploration for alternative resuscitation strategies that might better prevent the development of trauma-hemorrhage-induced organ dysfunction and systemic inflammation. Thus, the goal of this study was to compare the effects of two resuscitation strategies alone and in combination with that of standard resuscitation with Ringer's lactate. These two strategies were intravenous injection of amiloride, an inhibitor of Na/H exchange and epithelial Na channels, and resuscitation with hypertonic saline. DESIGN: Prospective animal study with concurrent control. SETTING: Small animal laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Rats injected with amiloride or its vehicle were subjected to trauma-hemorrhagic shock (T/HS) or trauma sham-shock (T/SS) and resuscitated with Ringer's lactate or hypertonic saline. The T/HS model consisted of a laparotomy plus 90 mins of shock (mean arterial pressure 30 mm Hg). Three hours after the end of the shock or sham-shock period, lung permeability, lung histology, pulmonary neutrophil sequestration, neutrophil CD11b expression, gut injury, and red blood cell rigidification were assessed. MEASUREMENTS AND MAIN RESULTS: Both amiloride and hypertonic saline reduced T/HS-induced pulmonary permeability and neutrophil sequestration, and coadministration of these two agents was more efficacious than administration of the individual agents. In contrast, whereas gut injury was attenuated by both amiloride and hypertonic saline, combined administration of amiloride and hypertonic saline failed to further protect the gut. Additionally, hypertonic saline reduced both neutrophil CD11b expression and red blood cell rigidification, whereas amiloride was without effect. CONCLUSIONS: Combined administration of amiloride and small-volume resuscitation with hypertonic saline may be a strategy worthy of further evaluation in the therapy of shock-induced distant organ injury.

Mesenteric lymph duct ligation decreases red blood cell alterations caused by acute pancreatitis.

BACKGROUND: Both experimental and clinical studies have shown that acute pancreatitis (AP) causes a significant decrease in red blood cell (RBC) deformability. The mechanisms by which AP induces RBC injury are unknown. The purpose of this study was to test the hypothesis that factors carried in the mesenteric lymph after an attack of AP significantly contribute to the RBC injury observed in AP. METHODS: RBC deformability was determined by means of laser-assisted ektacytometry in mesenteric lymph duct-ligated and non-ligated rats subjected to AP and in sham-operated animals. RESULTS: AP was associated with significant alterations of RBC deformability indices, namely the elongation index and half maximal RBC elongation. Pancreatitis-induced RBC deformability changes were partially prevented by mesenteric lymph duct ligation. CONCLUSIONS: Mesenteric lymph in AP contains factors that cause RBC damage, which is manifested by decreased deformability. Interruption of the lymph flow from the injured gut into the bloodstream decreases these RBC alterations.

Pancreatic duct ligation reduces lung injury following trauma and hemorrhagic shock.

OBJECTIVE: To determine whether pancreatic digestive enzymes released into the ischemic gut during an episode of T/HS are involved in the generation of distant organ injury. This hypothesis was tested by examining the effect of PDL on T/HS-induced intestinal injury, lung injury, and RBC deformability. SUMMARY BACKGROUND DATA: The effect of pancreatic duct ligation (PDL) on distant organ injury following trauma/hemorrhagic shock (T/HS) was examined. PDL before T/HS decreases lung and red blood cell (RBC) injury and exerts a limited protective effect on the gut. Pancreatic proteases in the ischemic gut appear to be involved in gut-induced lung and RBC injury. Based on recent work, it appears that proinflammatory and/or toxic factors, which are generated by the ischemic intestine, play an important role in the pathogenesis of multiple organ failure. The process by which these toxic factors are generated remains unknown. Previous experimental work has clearly documented that intraluminal inhibition of pancreatic proteases decreases the degree of T/HS-induced lung injury and neutrophil activation. One possible explanation for this observation is that the toxic factors present in intestinal lymph are byproducts of interactions between pancreatic proteases and the ischemic gut. METHODS: Male Sprague-Dawley rats were subjected to a laparotomy (trauma) and 90 minutes of sham (T/SS) or T/HS with or without PDL. At 3 and 24 hours following resuscitation, animals were killed and samples of gut, lung, and blood were collected for analysis. Lung permeability, pulmonary myeloperoxidase levels, and bronchoalveolar fluid protein content were used to quantitate lung injury. Intestinal injury was determined by histologic analysis of terminal ileum (% villi injured). To assess RBC injury, RBC deformability was measured, as the RBC elongation index (RBC-EI), using a LORCA device. RESULTS: At 3 and 24 hours following resuscitation, PDL prevented shock-induced increases in lung permeability to both Evans blue dye and protein in addition to preventing an increase in pulmonary myeloperoxidase levels. T/HS-induced impairments in RBC deformability were significantly reduced at both time points in the PDL + T/HS group, but deformability did not return to T/SS levels. PDL did reduce the magnitude of ileal injury at 3 hours after T/HS, but the protective effect was lost at 24 hours after T/HS. CONCLUSIONS: PDL prior to T/HS decreases lung injury and improves RBC deformability but exerts a limited protective effect on the gut. Thus, the presence of pancreatic digestive enzymes in the ischemic gut appears to be involved in gut-induced lung and RBC injury.