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Preston B Rich

Publications and source records attributed to Preston B Rich.

17 recordsLinked to original sources
PubMed2006

Nucleotides induce IL-6 release from human airway epithelia via P2Y2 and p38 MAPK-dependent pathways.

Extracellular nucleotides can mediate a variety of cellular functions via interactions with purinergic receptors. We previously showed that mechanical ventilation (MV) induces airway IL-6 and ATP release, modifies luminal nucleotide composition, and alters lung purinoceptor expression. Here we hypothesize that extracellular nucleotides induce secretion of IL-6 by small airway epithelial cells (SAEC). Human SAEC were stimulated with nucleotides in the presence or absence of inhibitors. Supernatants were analyzed for IL-6 and lysates for p38 MAPK activity by ELISA. RNA was analyzed by real-time RT-PCR. Rats (n=51) were randomized to groups as follows: control, small-volume MV, large-volume MV, large-volume MV-intratracheal apyrase, or small-volume MV-intratracheal adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS). After 1 h of MV, bronchoalveolar lavage fluid was analyzed for ATP and IL-6 by luminometry and ELISA. ATP and ATPgammaS increased SAEC IL-6 secretion in a time- and dose-dependent manner, an effect inhibited by apyrase. Agonists were ranked in the following order: ATPgammaS>ATP=UTP>ADP=adenosine>2-methylthio-ADP=control. SB-203580, but not U-0126 or JNK1 inhibitor, decreased nucleotide effects. Additionally, nucleotides induced p38 MAPK phosphorylation. Inhibitors of Ca2+ signaling, phospholipase C, transcription, and translation decreased IL-6 release. Furthermore, nucleotides increased IL-6 expression. In vivo, large-volume MV increased airway ATP and IL-6 concentrations. IL-6 release was decreased by apyrase and increased by ATPgammaS. Extracellular nucleotides induce P2Y2-mediated secretion of IL-6 by SAEC via Ca2+, phospholipase C, and p38 MAPK-dependent pathways. This effect is dependent on transcription and translation. Our findings were confirmed in an in vivo model, thus demonstrating a novel mechanism of nucleotide-induced IL-6 secretion by airway epithelia.

Adenosine Triphosphate↗
PubMed2006

Performance of a dose-defining insulin infusion protocol among trauma service intensive care unit admissions.

BACKGROUND: Among critically ill patients, glycemic control reduces mortality and morbidities, but the use of intravenous insulin infusion is complicated by hypoglycemia. Having a standardized algorithm increases the likelihood of effective and safe utilization of intravenous insulin therapy. A tabular dose-defining protocol for intravenous insulin infusion is described, containing design elements intended to minimize risk for hypoglycemia while seeking control in a narrow target range, and performance is evaluated among critically ill trauma service patients. METHODS: The protocol assigns insulin infusion rate (IR) for ranges of blood glucose (BG). The columns are arranged in order of increasing maintenance rate (MR) for insulin infusion. Patient column assignment is determined according to rate of change of BG. During stable column assignment, the IR is a function of column MR and BG. Within-column, the protocol formula provides that (a) for BG between 70 mg/dL and target BG, the IR increases exponentially to the column MR; and (b) for BG above upper target BG range, the IR increases linearly as an adaptation of the rule of 1800, with slope determined by the column MR. Values for IR calculated by formula are rounded to correspond to BG ranges of the table. Performance was assessed in 27 sequential runs among 24 trauma service patients admitted to a surgical intensive care unit (2004-2005). RESULTS: Using point-of-care measurements, mean preinfusion BG was 230.0 +/- 67.9 mg/dL. BG < 140 mg/dL was reached during all 27 runs (median time 5.0 h), and target BG was < 110 mg/dL during 25 runs (median time 11.0 h). For the group of runs attaining target before interruption of insulin infusion, the average +/- SD of the principal measure of glycemic control, the within-run mean BG, was 113.7 +/- 14.8 mg/dL (coefficient of variation 13%, n = 25 runs). After attaining target, the average within-run SD for BG was 22.9 mg/dL. The within-run frequency of hypoglycemic measurements (BG < 70 mg/dL) as a percentage of BG determinations was 2.4%. In this series, no instance of BG <50 mg/dL was seen. CONCLUSIONS: This report describes a nurse-implemented tabular protocol for intravenous insulin infusion having the advantages of efficacy, safety, and simplicity of use. Wide variability of IR in the neighborhood of BG 110 mg/dL is associated with stable BG response, and protection against hypoglycemia is achieved by rapid decline of IR at BGs in or below the target range.

Adult↗
PubMed2006

A randomized trial of intermittent lorazepam versus propofol with daily interruption in mechanically ventilated patients.

OBJECTIVE: To compare duration of mechanical ventilation for patients randomized to receive lorazepam by intermittent bolus administration vs. continuous infusions of propofol using protocols that include scheduled daily interruption of sedation. DESIGN: A randomized open-label trial enrolling patients from October 2001 to March 2004. SETTING: Medical intensive care units of two tertiary care medical centers. PATIENTS: Adult patients expected to require mechanical ventilation for >48 hrs and who required > or =10 mg of lorazepam or a continuous infusion of a sedative to achieve adequate sedation. INTERVENTIONS: Patients were randomized to receive lorazepam by intermittent bolus administration or propofol by continuous infusion to maintain a Ramsay score of 2-3. Sedation was interrupted on a daily basis for both groups. MEASUREMENTS AND MAIN RESULTS: The primary outcome was median ventilator days. Secondary outcomes included 28-day ventilator-free survival, intensive care unit and hospital length of stay, and hospital mortality. Median ventilator days were significantly lower in the daily interruption propofol group compared with the intermittent bolus lorazepam group (5.8 vs. 8.4, p = .04). The difference was largest for hospital survivors (4.4 vs. 9.0, p = .006). There was a trend toward greater ventilator-free survival for patients in the daily interruption propofol group (median 18.5 days for propofol vs. 10.2 for lorazepam, p = .06). Hospital mortality was not different. CONCLUSIONS: For medical patients requiring >48 hrs of mechanical ventilation, sedation with propofol results in significantly fewer ventilator days compared with intermittent lorazepam when sedatives are interrupted daily.

Drug Administration Schedule↗
PubMed2005

ATP stimulates MMP-2 release from human aortic smooth muscle cells via JNK signaling pathway.

Aortic smooth muscle cell release of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) has been implicated in aortic aneurysm pathogenesis, but proximal modulation of release is poorly understood. Extracellular nucleotides regulate vascular smooth muscle cell metabolism in response to physiochemical stresses, but nucleotide modulation of MMP and/or TIMP release has not been reported. We hypothesized that nucleotides modulate MMP-2 and TIMP-2 release from human aortic smooth muscle cells (HASMCs) via distinct purinergic receptors and signaling pathways. We exposed HASMCs to exogenous ATP and other nucleotides with and without interleukin-1beta (IL-1beta). HASMCs were pretreated in some experiments with apyrase, which degrades ATP, and inhibitors of ERK1/2, JNK, and p38 MAPK. MMP-2 and TIMP-2 released into supernatant were assessed using ELISA and Western blotting. ATP, adenosine, and UTP significantly stimulated MMP-2 release in the presence of IL-1beta (300 nM ATP: 181 +/- 22%, P = 0.003; 30 microm adenosine: 244 +/- 150%, P = 0.001; and 200 microm UTP: 153 +/- 40%, P = 0.015; vs. 100% constitutive). ATP also stimulated MMP-2 release in the absence of IL-1beta (100 microm ATP: 148 +/- 38% vs. 100% constitutive). Apyrase significantly reduced ATP-stimulated MMP-2 release (apyrase + 500 nM ATP: 59 +/- 3% vs. 124 +/- 7% with 500 nM ATP). Rank-order agonist potency for MMP-2 release was consistent with ATP activation of PAY and PAY receptors. ATP induced phosphorylation of intracellular JNK, and inhibition of the JNK pathway blocked ATP-stimulated MMP-2 release, indicating signaling via this pathway. Nucleotides are thus novel stimulants of MMP-2 release from HASMCs and may provide a mechanistic link between physiochemical stress in the aorta and aneurysms, especially in the context of inflammation.

Adenosine Triphosphate↗
PubMed2005

Blood transfusion is an independent predictor of increased mortality in nonoperatively managed blunt hepatic and splenic injuries.

BACKGROUND: Management strategies for blunt solid viscus injuries often include blood transfusion. However, transfusion has previously been identified as an independent predictor of mortality in unselected trauma admissions. We hypothesized that transfusion would adversely affect mortality and outcome in patients presenting with blunt hepatic and splenic injuries after controlling for injury severity and degree of shock. METHODS: We retrospectively reviewed records from all adults with blunt hepatic and/or splenic injuries admitted to a Level I trauma center over a 4-year period. Demographics, physiologic variables, injury severity, and amount of blood transfused were analyzed. Univariate and multivariate analysis with logistic and linear regression were used to identify predictors of mortality and outcome. RESULTS: One hundred forty-three (45%) of 316 patients presenting with blunt hepatic and/or splenic injuries received blood transfusion within the first 24 hours. Two hundred thirty patients (72.8%) were selected for nonoperative management, of whom 75 (33%) required transfusion in the first 24 hours. Transfusion was an independent predictor of mortality in all patients (odds ratio [OR], 4.75; 95% confidence interval [CI], 1.37-16.4; p = 0.014) and in those managed nonoperatively (OR, 8.45; 95% CI, 1.95-36.53; p = 0.0043) after controlling for indices of shock and injury severity. The risk of death increased with each unit of packed red blood cells transfused (OR per unit, 1.16; 95% CI, 1.10-1.24; p < 0.0001). Blood transfusion was also an independent predictor of increased hospital length of stay (coefficient, 5.45; 95% CI, 1.64-9.25; p = 0.005). CONCLUSION: Blood transfusion is a strong independent predictor of mortality and hospital length of stay in patients with blunt liver and spleen injuries after controlling for indices of shock and injury severity. Transfusion-associated mortality risk was highest in the subset of patients managed nonoperatively. Prospective examination of transfusion practices in treatment algorithms of blunt hepatic and splenic injuries is warranted.

Adolescent↗
PubMed2005

Multidisciplinary approach to abdominal wall reconstruction after decompressive laparotomy for abdominal compartment syndrome.

INTRODUCTION: Decompressive laparotomy for abdominal compartment syndrome has been shown to reduce mortality in critically ill patients, but little is known about the outcome of abdominal wall reconstruction. This study investigates the role of plastic surgeons in the management and reconstruction of these abdominal wall defects. METHODS: We performed a retrospective review of 82 consecutive critically ill patients who underwent decompressive laparotomy for abdominal compartment syndrome, at a university level 1 trauma center, from April 2000 to May 2004. Patients reconstructed by trauma surgeons alone (n = 15) were compared with patients reconstructed jointly with plastic surgeons (n = 12), using Student t test and chi analysis. RESULTS: Eighty-two patients underwent decompressive laparotomy for abdominal compartment syndrome, yielding 50 survivors (61%). Of the 27 patients who underwent abdominal wall reconstruction, 6 had early primary fascial repair, and 21 had staged reconstruction with primary fascial closure (n = 4), components separation alone (n = 3), components separation with mesh (n = 10), or permanent mesh only (n = 4). Compared with patients whose reconstruction was performed by trauma surgeons, patients who underwent a combined approach with plastic surgeons were older (50.5 versus 31.7 years, P < 0.05), had more comorbidities (P < 0.001), were less likely to have a traumatic etiology (P < 0.001), had a longer delay to reconstruction (407 versus 119 days, P < 0.05), and were more likely to undergo components separation (P < 0.05). Mean follow-up of 11.5 months revealed 2 recurrent hernias in the combined reconstruction group, both of which were successfully repaired. CONCLUSIONS: A multidisciplinary approach is essential to the successful management of abdominal wall defects after decompressive laparotomy for abdominal compartment syndrome. Although carefully selected patients can undergo early primary fascial repair, most of reconstructed patients had staged closure of the abdominal wall via components separation, with a low rate of recurrent hernia. High-risk patients with large defects and comorbidities appear to benefit from the involvement of a plastic surgeon.

Abdomen↗
PubMed2005

Superselective catheterization and embolization as first-line therapy for lower gastrointestinal bleeding.

Emergent operative intervention for lower gastrointestinal bleeding (LGIB) is associated with significant morbidity and mortality. Advances in endovascular techniques have made superselective catheterization and embolization (SSCE) of small visceral arterial branches possible. We hypothesized that SSCE for LGIB would be an effective first-line therapy and associated with low mortality. We identified all patients that underwent visceral angiography at our institution from 1997 to 2003. Records from all patients with documented LGIB and in whom SSCE was used as first-line therapy were reviewed. Twenty-three patients (69 +/- 11 years) were treated with SSCE as an initial intervention for LGIB. A definitive bleeding site was identified in 95 per cent of cases (22/23). Eleven patients (48%) developed an early complication [recurrent bleeding (n=5; two required surgery), asymptomatic ischemic colonic mucosa (n=3), acute renal insufficiency (n=1; resolved), and femoral pseudo-aneurysm (n=2; one treated operatively)]. Long-term (mean 19 months) follow-up was available for 17 patients. Five patients (22%) experienced recurrent LGIB, and three patients had evidence of colonic ischemic. One patient required endoscopic dilation of a stricture, and three underwent surgical resection. There was no mortality in our series. In this series, SSCE was an effective first-line therapy for LGIB. Rebleeding and ischemia rates were low.

Age Factors↗
PubMed2004

Mechanical ventilation alters airway nucleotides and purinoceptors in lung and extrapulmonary organs.

Extracellular nucleotides are stress-responsive ligands that mediate a variety of cellular processes via purinoceptors. We hypothesized that mechanical ventilation (MV) would alter the extracellular adenyl-nucleotide profile and purinoceptor expression in lung and extrapulmonary tissues. Twenty-eight rats were randomized to: (i) unventilated control animals; (ii) tidal volume (VT; 6 ml/kg); (iii) VT (6 ml/kg) and positive end-expiratory pressure (PEEP; 5 cm H20); (iv) VT (12 ml/kg); or (v) VT (12 ml/kg) and PEEP (5 cm H20). Bronchoalveolar lavage (BAL) was analyzed for adenyl-nucleotides. Pulmonary, hepatic, and renal tissues were assessed for P2Y4, P2Y6, P2X7, A3, and A2b receptor expression by real-time reverse transcriptase-polymerase chain reaction and Fas/Fas ligand mRNA was quantified in the lung. MV produced volume-dependent changes in BAL nucleotides; AMP and adenosine increased, whereas ATP and ADP proportions decreased. Large-volume MV increased A2b mRNA and decreased P2X7 in the lung; mRNA changes in lung Fas ligand paralleled P2X7. PEEP normalized BAL nucleotide profiles and A2b expression. Injurious MV reduced hepatic and renal P2X7 mRNA; PEEP normalized these levels in both tissues. Large-volume MV also decreased renal A2b mRNA. MV alters the BAL adenyl-nucleotide profile and purinoceptor patterns in lung, liver, and kidney. PEEP normalizes the BAL nucleotide profile and receptor patterns in lung and extrapulmonary tissues.

Adenosine↗
PubMed2004

Infrared thermography: a rapid, portable, and accurate technique to detect experimental pneumothorax.

RATIONALE AND OBJECTIVE: Pneumothorax (Ptx) is a life-threatening complication that can result from trauma, mechanical ventilation, and invasive procedures. Infrared thermography (IRT), a compact and portable technology, has become highly sensitive. We hypothesized that IRT could detect Ptx by identifying associated changes in skin temperature. MATERIALS AND METHODS: Bilateral nonpenetrating chest incisions or needle punctures were performed in 21 anesthetized rats. Rats were then randomized to no, bilateral, left, or right Ptx by either open (n = 16) or closed percutaneous (n = 5) puncture through selected pleurae. Real-time thermographic images and surface temperature data were acquired with a noncooled infrared camera. RESULTS: In all cases, blinded observers correctly identified each Ptx with real-time grayscale image analysis. When compared to either the ipsilateral baseline or an abdominal reference, experimental Ptx produced a significantly greater decrease in surface temperature when compared to non-Ptx control. CONCLUSIONS: These results demonstrate that portable infrared imaging can rapidly and accurately detect changes in thoracic surface temperature associated with experimental pneumothorax.

Animals↗
PubMed2004

Intrapleural tissue plasminogen activator for complicated pleural effusions.

BACKGROUND: This study is aimed at evaluating the safety and efficacy of intrapleural tissue plasminogen activator (TPA) for complicated pleural effusions, including posttraumatic hemothorax. METHODS: Data were retrospectively collected from hospitalized patients over a 4-year period (1999-2003) who were treated with intrapleural TPA after failing drainage by tube thoracostomy. Pre- and post-TPA imaging studies were reviewed and scored by a blinded radiologist. RESULTS: Forty-one consecutive patients with 42 effusions were identified with the following indications: 6 traumatic hemothoraces (14%), 22 loculated pleural effusions (52%), 2 line-associated hemothoraces (5%), and 12 empyemas (29%). Nine patients (22%) required operative drainage including two with posttraumatic hemothoraces. All patients managed nonoperatively demonstrated radiographic improvement after TPA administration. One patient (2.4%) developed hematuria, requiring transfusion. No trauma patient required TPA-related blood transfusion and no deaths were attributable to TPA therapy. CONCLUSION: Intrapleural TPA administration appears safe for use in complicated pleural effusions and may decrease the need for operative intervention.

Adolescent↗
PubMed2003

Effect of ventilatory rate on airway cytokine levels and lung injury.

BACKGROUND: Controversy exists regarding the effect of large-volume mechanical ventilation (MV), as a sole stimulus, on the pulmonary cytokine milieu. We used a well described experimental model of ventilator-induced lung injury (VILI) to examine the impact of large volume ventilation on pulmonary cytokines in vivo and to study the effect of respiratory rate (RR) variation on these levels. MATERIALS AND METHODS: Sixty rats (410 +/- 47 g) were randomized to: 1) non ventilated control; 2) V(t) = 40 ml/kg, RR = 40 bpm; 3) V(t) = 40 ml/kg, RR = 20 bpm; 4) V(t) = 7 ml/kg, RR = 40 bpm; or 5) V(t) = 7 ml/kg, RR = 20 bpm. After 1 h of MV, bronchoalveolar lavage (BAL) and serum were collected. BAL was analyzed for urea, protein, lactate dehydrogenase (LDH), tumor necrosis factor (TNF)alpha and interleukin (IL)-6. Epithelial lining fluid volume (ELF) was calculated. RESULTS: Regardless of RR, animals ventilated at 7 ml/kg did not differ from control in any outcome. In contrast, MV at 40 ml/kg V(t) with 40 bpm produced lung injury characterized by significant elevations of BAL TNFalpha, IL-6, protein, ELF, and LDH. At 40 ml/kg V(t), RR reduction (20 bpm) significantly reduced all injury measures. CONCLUSION: This study confirms that large-volume MV, as a sole stimulus, produces lung injury and cytokine release. Whereas increasing RR at low V(t) has little impact on injury parameters, RR reduction under VILI-promoting conditions significantly limits lung injury.

Animals↗
PubMed2003

Extracorporeal life support for severe adult respiratory failure.

PURPOSE OF REVIEW: The past 35 years have provided a wealth of evidence that mechanical ventilation, although potentially life saving, can injure the lungs. Recent evidence suggests that limiting ventilating gas volumes can reduce patient mortality, but may result in progressive parenchymal derecruitment and alveolar hypoventilation, potentially aggravating systemic hypercarbia and hypoxemia. This review summarizes the current recommendations on a controversial, invasive technique termed 'extracorporeal life support' as a means to provide temporary pulmonary support during 'lung-protective' strategies. RECENT FINDINGS: Extracorporeal life support has been implemented since the origins of cardiopulmonary bypass in the 1950s, but differs in several important ways from cardiopulmonary bypass, including its prolonged duration of application. Because extracorporeal life support serves only to supplement physiological derangements and is not therapeutic, patient selection critically impacts results. Whereas reversible neonatal processes such as meconium aspiration and persistent fetal circulation have fostered clinical trials demonstrating the efficacy of extracorporeal life support, adult cardiopulmonary failure extracorporeal life support trials have proved less compelling. Despite two prospective randomized trials that failed to demonstrate its efficacy, adult extracorporeal life support continues in limited centers of excellence. Adult extracorporeal life support survival rates for respiratory failure average 50% when strict criteria are met, but it remains unclear whether these results represent improved outcomes. SUMMARY: Extracorporeal life support is an invasive technique that can provide support to the failing lung. Clinical trials have demonstrated its efficacy in neonatal and pediatric patients, but data in adults are less clear. An ongoing trial in the UK will soon address this important issue.

Journal Article↗
PubMed2003

Postoperative pulmonary complications.

PURPOSE OF REVIEW: Postoperative pulmonary complications, including pneumonia, bronchospasm, respiratory failure and prolonged mechanical ventilation, occur commonly and are a significant source of morbidity and mortality. This review will discuss the etiology of postoperative pulmonary complications and the interventions that reduce their risk. RECENT FINDINGS: General anesthesia and surgery produce changes in the respiratory system and are responsible, along with underlying conditions, for postoperative pulmonary complications. Risk factors include upper abdominal or thoracic surgery, cigarette smoking, chronic respiratory disease, emergency surgery, anesthetic time of 180 min or more, age greater than 70 years, renal failure, poor nutritional status, and significant intraoperative blood loss. The inhibition of phrenic nerve output results in postoperative diaphragmatic dysfunction. Sleep-disordered breathing occurs after surgery even in patients without obstructive sleep apnea, but patients with obstructive sleep apnea may have a worsening of their disease after surgery. A clear advantage of one anesthetic technique over another in reducing postoperative pulmonary complications has not been demonstrated. Conflicting results have been obtained regarding the value of epidural analgesia in preventing postoperative pulmonary complications. Incentive spirometry decreases rates of postoperative pulmonary complications and hospital lengths of stay. SUMMARY: Understanding risk factors for the development of postoperative pulmonary complications allows targeted interventions aimed at reducing their frequency and severity. Further research is needed to define the role of regional analgesic and anesthetic techniques in reducing postoperative pulmonary complications, and also to define the nature of risk factors and develop better predictive models of patients at risk of developing postoperative pulmonary complications.

Journal Article↗
PubMed2003

Adenosine triphosphate is released during injurious mechanical ventilation and contributes to lung edema.

BACKGROUND: Extracellular nucleotides mediate many cellular functions and are released in response to mechanical stress in vitro. It is unknown whether adenosine triphosphate (ATP) is released in vivo during mechanical ventilation (MV). We hypothesized that stress from high-pressure MV would increase airway ATP, contributing to MV-associated lung edema. METHODS: Rats were randomized to nonventilated control (n = 6) or 30 minutes of MV with low (15 cm H(2)0, n = 7) or high (40 cm H(2)0, n = 6) pressure. Additional groups received intratracheal ATP (n = 7) or saline (n = 7) before low-pressure MV. RESULTS: Low-pressure MV did not affect lung edema or bronchoalveolar lavage (BAL) ATP levels. In contrast, high-pressure MV significantly increased BAL ATP and produced alveolar edema; lactate dehydrogenase was unchanged. Intratracheal ATP administration significantly increased lung water during low-pressure MV. CONCLUSION: High-pressure MV increases BAL ATP concentration without altering lactate dehydrogenase, suggesting that release is not from cell lysis. Intratracheal ATP increases lung water, implicating nucleotides in MV-associated lung edema.

Adenosine Triphosphate↗
PubMed2002

Partial liquid ventilation and positive end-expiratory pressure reduce ventilator-induced lung injury in an ovine model of acute respiratory failure.

OBJECTIVE: To examine the isolated and combined effects of positive end-expiratory pressure (PEEP) and partial liquid ventilation (PLV) on the development of ventilator-induced lung injury in an ovine model. DESIGN: Prospective controlled animal study. SETTING: University-based cardiovascular animal physiology laboratory. SUBJECTS: Thirty-eight anesthetized supine sheep weighing 22.3 +/- 2.2 kg. INTERVENTIONS: Animals were ventilated for 6 hrs (respiratory rate, 15; FIO2, 1.0, inspiratory/expiratory ratio, 1:1) with one of five pressure-controlled strategies, expressed as peak inspiratory pressure (PIP)/PEEP: low-PIP, 25/5 cm H2O (n = 8); high-PIP, 50/5 cm H2O (n = 8); high-PIP-PLV, 50/5 cm H2O-PLV (n = 8); high-PEEP, 50/20 cm H2O (n = 7); and high-PEEP-PLV, 50/20 cm H2O-PLV (n = 7). MEASUREMENTS AND MAIN RESULTS: Compared with the low-PIP control, high-PIP ventilation increased airleak, shunt, histologic evidence of lung injury, neutrophil infiltrates, and wet lung weight. Maintaining PEEP at 20 cm H2O or adding PLV reduced the development of physiologic shunt and dependent histologic injury indexes. Neither higher PEEP nor PLV reduced the high incidence of barotrauma observed in high-PIP animals. CONCLUSIONS: We conclude that application of PLV or PEEP at 20 cm H2O may improve gas exchange and afford lung protection from ventilator-induced lung injury during high-pressure mechanical ventilation in this model.

Acute Disease↗
PubMedDate not supplied

Measurement of free and bound fractions of extracellular ATP in biological solutions using bioluminescence.

Measurement of extracellular ATP in biological solutions is complicated by protein-binding and rapid enzymatic degradation. We hypothesized that the concentration of extracellular ATP could be determined luminometrically by limiting degradation and measuring the free and protein-bound fractions. ATP was added (a) at constant concentration to solutions containing varying albumin concentrations; (b) at varying concentrations to a physiological albumin solution (4 gm/dL); (c) at varying concentrations to plasma. After centrifugation, a fraction of each supernatant was heated. ATP in heated and unheated samples was measured luminometrically. Blood was drawn into saline or an ATP-stabilizing solution and endogenous plasma ATP measured. ATP-albumin binding was a linear function of albumin concentration (3.5% ATP bound at 100 micromol/L to 33.2% ATP bound at 1000 micromol/L) but independent of ATP concentration (29.3%, 10-1000 nmol/L ATP in 602 micromol/L albumin). Heating released the majority of bound ATP from albumin-containing solutions (94.8 +/- 1.7%) and plasma (97.6 +/- 5.1%). Total endogenous plasma ATP comprised 93 +/- 27 nmol/L (free) and 150 +/- 40 nmol/L (total fraction). Without stabilizing solution, degradation of free endogenous plasma ATP occurred. Within a physiological range (10-1000 nmol/L), ATP binds albumin independently of ATP concentration. Heating releases bound ATP, enabling accurate luminometric measurement of total extracellular ATP (free and bound) in biological samples.

Adenosine Triphosphate↗