Biomedical subjects

M C Chang

Publications and source records attributed to M C Chang.

At least 91 records · Page 5Linked to original sources

PubMed1998

Effects of EGb 761 on fatty acid reincorporation during reperfusion following ischemia in the brain of the awake gerbil.

Transient cerebral ischemia (5 min) releases unesterified fatty acids from membrane phospholipids, increasing brain concentrations of fatty acids for up to 1 h following reperfusion. To understand the reported anti-ischemic effect of Ginkgo biloba extract (EGb 761), we monitored its effect on brain fatty acid reincorporation in a gerbil-stroke model. Both common carotid arteries in awake gerbils were occluded for 5 min, followed by 5 min of reperfusion. Animals were infused intravenously with labeled arachidonic (AA) or palmitic acid (Pam), and rates of incorporation of unlabeled fatty acid from the brian acyl-CoA pool were calculated by the model of Robinson et al. (1992), using quantitative autoradiography and biochemical analysis of brain acyl-CoA. Animals were treated for 14 d with 50 or 150 mg/kg/d EGb 761 or vehicle. Ischemia-reperfusion had no effect on the rate of unlabeled Pam incorporation into brain phospholipids from palmitoyl-CoA; this rate also was unaffected by EGb 761. In contrast, ischemia-reperfusion increased the rate of incorporation of unlabeled AA from brain arachidonoyl-CoA by a factor of 2.3-3.3 compared with the control rate; this factor was further augmented to 3.6-5.0 by pretreatment with EGb 761. There is selective reincorporation of AA compared with Pam into brain phospholipids following ischemia. EGb 761 further accelerates AA reincorporation, potentially reducing neurotoxic effects of prolonged exposure of brain to high concentrations of AA and its metabolites.

Animals↗

PubMed1998

Cloning and sequence analysis of the Candida tropicalis URA3 gene encoding orotidine-5'-phosphate decarboxylase.

An integrative transformation system was established for a phenol-utilizing strain of Candida tropicalis M4. The system is based on an auxotrophic mutant host of C. tropicalis U-6 that is defective in orotidine-5'-phosphate decarboxylase (ODCase). As a selectable marker, we isolated and characterized the C. tropicalis URA3 gene, which codes for ODCase. The gene was cloned by complementation of the ura3 mutation of Sachharomyces cerevisiae SHY-3 and the pyrF mutation of Escherichia coli. The C. tropicalis U-6 was transformed by plasmid containing the C. tropicalis URA3 gene at a frequency of 1 to 10 transformants per microgram of plasmid DNA. When the URA3 gene was expressed in E. coli minicells, a 30-kDa protein was identified. Nucleotide sequence analysis revealed the presence of an open reading frame, encoding a protein of 268 amino acids with a calculated molecular mass of 29.7 kDa. The nucleotide sequence of URA3 gene and its deduced amino acid sequence showed significant homology to those of the ODCase of other fungal species.

Base Sequence↗

PubMed1998

Detection of human papillomavirus types in cervical adenocarcinoma by the polymerase chain reaction.

OBJECTIVE: To determine the human papillomavirus (HPV) types in cervical adenocarcinoma of patients from Taiwan. METHODS: DNA was extracted from fixed tissues and polymerase chain reaction was performed in conjunction with a unique probe, pRSA I, allowing simultaneous detection of HPV types 6, 11, 16, 18, 31 and 33 from amplified HPV DNAs after endonuclease, RsaI, digestion. RESULTS: Of 69 tissues examined, 31.9% (22/69) were found to contain HPV DNA. Among 22 HPV-positive specimens, no HPV types 6, 11, 31 and 33 were detected. On the other hand, HPV 16 and HPV 18 were found in 11 (15.9%) and 10 (14.5%) of HPV-positive specimens, respectively. One specimen (1.5%) was found to contain both HPV 16 and 18 DNAs. CONCLUSIONS: Our findings support that HPV 18, along with HPV 16, may play a certain role in the adenocarcinoma pathogenesis of the uterine cervix.

Adenocarcinoma↗

PubMed1998

Pharmacokinetics of methyl palmoxirate, an inhibitor of beta-oxidation, in rats and humans.

Recent studies from our laboratory have shown that methyl palmoxirate (MEP), an inhibitor of mitochondrial beta-oxidation of long chain fatty acids, can be used to increase incorporation of radiolabeled palmitic acid into brain lipids and reduce beta-oxidation of the fatty acid. Thus, MEP allows the use of carbon labeled palmitate for studying brain lipid metabolism in animals and humans by quantitative autoradiography or positron emission tomography (PET). As it is essential to pretreat human subjects with an acute dose of MEP prior to intravenous injection of [1-11C]palmitate for PET scanning, this study was undertaken to determine the plasma elimination half-life of MEP in rats and human subjects and to provide insight about the drug's absorption and metabolism. A gas chromatographic method was developed to measure MEP in body fluids. Following oral administration of MEP to rats (2.5 and 10 mg/kg) and to humans, the unmetabolized drug could not be detected in plasma or urine (sensitivity of detection was 1 ng). However, when MEP was injected intravenously (10 mg/kg) in rats, a peak initial concentration could be measured in plasma (7.7 microg/mL), the clearance of the drug from plasma was rapid (t1/2 = 0.6 min), which indicates that MEP readily enters tissue lipid pools or is metabolized like long-chain fatty acids. As no adverse experience occured in the 11 human subjects studied, oral administration of a single dose of MEP was safe under the conditions of this study and may be used to increase the incorporation of positron labeled palmitic acid for studying brain lipid metabolism in vivo by PET.

Administration, Oral↗

PubMed1998

Thrombin-induced DNA synthesis of cultured human dental pulp cells is dependent on its proteolytic activity and modulated by prostaglandin E2.

To clarify the roles of alpha-thrombin and prostaglandin E2 (PGE2) in the healing and inflammatory processes of dental pulp, their effects on the DNA synthesis of human pulp cells were investigated by measurement of [3H]thymidine incorporation. At a concentration range of 1 to 25 units/ml, alpha-thrombin stimulated DNA synthesis of the pulp cells by 1.5 to 2.6-fold. On the contrary, PGE2 (> 0.05 microgram/ml) suppressed DNA synthesis by 24 to 39%. Using reverse transcriptase-polymerase chain reaction, thrombin receptor mRNA expression was identified in the pulp cells. Furthermore, alpha-thrombin-induced DNA synthesis could be inhibited by antithrombin III (2 units/ml) with heparin (2 units/ml) or D-Phe-Pro-ArgCH2Cl (50 micrograms/ml). PGE2 (0.1 to 0.5 microgram/ml) also inhibited the thrombin-induced DNA synthesis by 39 to 64%. These results imply that pulp cells express the thrombin receptor that is activated by the serine protease activity of thrombin. Interactions of thrombin and PGE2 are important in modulating the inflammatory and healing processes of the pulp.

Cells, Cultured↗

PubMed1998

Elevated arterial base deficit in trauma patients: a marker of impaired oxygen utilization.

BACKGROUND: In trauma patients, the admission value of arterial base deficit stratifies injury severity, predicts complications, and is correlated with arterial lactate concentration. In theory, elevated base deficit and lactate concentrations after shock are related to oxygen transport imbalance at the cellular level. The purpose of this study was to test the hypothesis that an elevated base deficit in trauma patients is indicative of impaired systemic oxygen utilization and portends poor outcomes. METHODS: This study was a retrospective analysis of a prospectively collected database. The study population included all patients admitted to the trauma intensive care unit at a Level 1 trauma center during a 12-month period who were monitored with a pulmonary artery catheter and serial measurements of lactate and base deficit, and who achieved a normal arterial lactate concentration (< 2.2 mmol/L) with resuscitation. The patients were divided into those who maintained a persistently high base deficit (> or = 4 mmol/L) and those who achieved a low base deficit (< 4 mmol/L) during resuscitation. RESULTS: One-hundred patients (mortality 20%) were monitored with a pulmonary artery catheter and achieved a normal arterial lactate concentration. The mean age+/-SD (SEM) of the group was 37+/-17 years and the Injury Severity Score was 25+/-11. Subgroup analysis revealed that patients with a persistently high base deficit (n=26) had higher rates of multiple organ failure (35% versus 5%, p < 0.001) and death (50% versus 9%, p < 0.00001) compared with patients who achieved a low base deficit. Patients with a persistently high base deficit also had lower oxygen consumption (126+/-40 mL/m2 versus 156+/-30 mL/m2, p=0.01 at 48 hours) and a lower oxygen utilization coefficient (0.20+/-0.05 versus 0.24+/-0.03, p=0.01 at 48 hours) compared with patients with a low base deficit. At 48 hours, both oxygen consumption (r=-0.44, [r, correlation coefficient] p=0.002) and oxygen utilization (r=-0.46, p=0.001) had a significant negative correlation with base deficit. CONCLUSIONS: In trauma patients, a persistently high arterial base deficit is associated with altered oxygen utilization and an increased risk of multiple organ failure and mortality. Serial monitoring of base deficit may be useful in assessing the adequacy of oxygen transport and resuscitation.

Acid-Base Imbalance↗

PubMed1998

Cytotoxicity of sodium fluoride on human oral mucosal fibroblasts and its mechanisms.

Because sodium fluoride (NaF) is widely used for prevention of dental caries, pathobiological effects of NaF were investigated on human oral mucosal fibroblasts. The results showed that NaF was cytotoxic to oral mucosal fibroblasts at concentrations of 4 mmol/L or higher. Exposure of cells to NaF for 2 h also inhibited protein synthesis, cellular ATP level and functional mitochondrial activities in a dose-dependent manner. However, incubation of cells with NaF up to 12 mmol/L for 2 h depleted only 13% of cellular glutathione level. The IC50 of NaF on cellular ATP level was about 5.75 mmol/L. Preincubation of the cells with pyruvate and succinate did not protect cells from NaF-induced ATP depletion. At concentrations of 4 mmol/L, 8 mmol/L and 12 mmol/L, NaF inhibited 31%, 56% and 57% of mitochondrial functions, respectively, after 2 h incubation. No significant inhibition for NaF was found at concentrations lower than 2 mmol/L (40 ppm). These results indicate that NaF can be toxic to oral mucosal fibroblasts in vitro by its inhibition of protein synthesis, mitochondrial function and depletion of cellular ATP. Because of repeated and long-term usage of NaF, more detailed studies should be undertaken to understand its toxic effects in vitro and in vivo.

Adenosine Triphosphate↗

PubMed1998

Expression and export of Pseudomonas putida NTU-8 creatinase by Escherichia coli using the chitinase signal sequence of Aeromonas hydrophila.

The gene for the creatinase from Pseudomonas putida NTU-8 was sequenced and revealed an open reading frame (ORF) of 1209 base pairs encoding a polypeptide of 403 amino acids with a calculated molecular weight (M(r)) of 45,691. The deduced amino acid sequence is very similar to that of the creatinase of Pseudomonas putida and Flavobacterium sp. An overproduction system for the chitinase signal peptide--creatinase hybrid gene was constructed by using the pQE-51 expression vector in E. coli JM109. The amount of this fusion enzyme was about 50% exported into the periplasmic space of E. coli.

Aeromonas hydrophila↗

PubMed1998

Manoalide, a phospholipase A2 inhibitor, inhibits arachidonate incorporation and turnover in brain phospholipids of the awake rat.

The Fatty Acid method was used to determine whether incorporation of plasma radiolabeled arachidonic acid into brain phospholipids is controlled by phospholipase A2. Awake rats received an i.v. injection of a phospholipase A2 inhibitor, manoalide (10 mg/kg), and then were infused i.v. with [1-(14)C]arachidonate or [3H]arachidonate. Animals were killed after infusion by microwave irradiation, and tracer distribution was analyzed in brain phospholipid, neutral lipid and acyl-CoA pools. Calcium-independent phospholipase A2 activity in brain homogenate was reduced by manoalide, whereas phospholipase C activity was unaffected. At 60 min but not at 20 or 40 min after its injection, manoalide had significantly decreased by 50% incorporation of unesterified arachidonate into and turnover within brain phospholipids, taking into account dilution of the brain arachidonoyl-CoA pool by recycled arachidonate. Manoalide also increased by 100% the net rate of unesterified arachidonate incorporation into brain triacylglycerol. This study indicates that manoalide can be used to inhibit brain phospholipase A2 in vivo, and that phospholipase A2 plays a critical role in arachidonate turnover in brain phospholipids and neutral lipids.

Acyl Coenzyme A↗

PubMed1998

Chronic lithium treatment decreases brain phospholipase A2 activity.

Chronic lithium administration decreases the turnover of arachidonic acid (AA) in several brain phospholipids. This suggests that lithium may attenuate phospholipase A2 (PLA2) activity in brain. We now report effects of chronic lithium treatment on PLA2 activity in postnuclear supernatant from rat brain: Enzyme activity was determined by two assay methods, radiometric and fluorometric, and measured the release of the fatty acid on the second acyl position (sn2) from choline and ethanolamine phospholipids. PLA2 activity in brain postnuclear supernatant from rats chronically treated with lithium in the diet was significantly decreased (20-50%) when compared with controls. In vehicle or lithium-treated rats, PLA2 activity was not significantly augmented or attenuated by the addition of calcium chelators, divalent cations or LiCl supplementation (1.0 mM) to postnuclear supernatant. These results suggest that a major therapeutic effect of lithium is to attenuate brain PLA2 activity involved in signal transduction.

Animals↗

PubMed1998

Selective acceleration of arachidonic acid reincorporation into brain membrane phospholipid following transient ischemia in awake gerbil.

Awake gerbils were subjected to 5 min of forebrain ischemia by clamping the carotid arteries for 5 min and then allowing recirculation. Radiolabeled arachidonic or palmitic acid was infused intravenously for 5 min at the start of recirculation, after which the brains were prepared for quantitative autoradiography or chemical analysis. Dilution of specific activity of the acyl-CoA pool was independently determined for these fatty acids in control gerbils and following 5 min of ischemia and 5 min of reperfusion. Using a quantitative method for measuring regional in vivo fatty acid incorporation into and turnover within brain phospholipids and determining unlabeled concentrations of acyl-CoAs following recirculation, it was shown that reperfusion after 5 min of ischemia was accompanied by a threefold increase compared with the control in the rate of reincorporation of unlabeled arachidonate that had been released during ischemia, whereas reincorporation of released palmitate was not different from the control. Selective and accelerated reincorporation of arachidonate into brain phospholipids shortly after ischemia may ameliorate specific deleterious effects of arachidonate and its metabolites on brain membranes.

Acyl Coenzyme A↗

PubMed1998

Diagnosis and initial management of blunt pancreatic trauma: guidelines from a multiinstitutional review.

OBJECTIVE: The authors' objective was to resolve the current controversies surrounding the diagnosis and management of blunt pancreatic trauma (BPT). SUMMARY BACKGROUND DATA: The diagnosis of BPT is notoriously difficult: serum amylase has been claimed to be neither sensitive nor specific, and recent anecdotal reports have suggested a role for computed tomography. The therapy of BPT has been controversial, with some suggesting selective observation and others advocating immediate exploration to prevent a delay-induced escalation in morbidity and death. METHODS: The authors conducted a retrospective chart review of documented BPT from six institutions, using a standardized binary data form composed of 187 items and 237 data fields. RESULTS: A significant correlation between pancreas-specific morbidity and injury to the main pancreatic duct (MPD) was noted. Patients requiring delayed surgical intervention after an unsuccessful period of observation demonstrated notably higher pancreas-specific mortality and morbidity rates, principally because of the incidence of unrecognized injuries to the MPD. Although detection of MPD injuries by computed tomography was no better than flipping a coin, endoscopic pancreatography was accurate in each of the five cases in which it was used. CONCLUSIONS: The principal cause of pancreas-specific morbidity after BPT is injury to the MPD. Parenchymal pancreatic injuries not involving the ductal system rarely result in pancreas-specific morbidity or death. Delay in recognizing MPD injury leads to increased mortality and morbidity rates. CT is unreliable in diagnosing MPD injury and should not be used to guide therapy. Initial selection of patients with isolated BPT for observation or surgery can be based on the determination of MPD integrity.

Cholangiopancreatography, Endoscopic Retrograde↗

PubMed1998

Right ventricular end-diastolic volume index as a predictor of preload status in patients on positive end-expiratory pressure.

OBJECTIVE: To evaluate the clinical utility of right ventricular end-diastolic volume index (RVEDVI) and pulmonary artery occlusion pressure (PAOP) as measures of preload status in patients with acute respiratory failure receiving treatment with positive end-expiratory pressure. DESIGN: Prospective, cohort study. SETTING: Surgical intensive care unit in a Level I trauma center/university hospital. PATIENTS: Sixty-four critically ill surgical patients with acute respiratory failure. INTERVENTIONS: All patients were treated for acute respiratory failure with titrated levels of positive end-expiratory pressure (PEEP) with the goal of increasing arterial oxygen saturation to > or =0.92, reducing FIO2 to <0.5, and reducing intrapulmonary shunt to < or =0.2. Serial determinations of RVEDVI, PAOP, and cardiac index (CI) were recorded. MEASUREMENTS AND MAIN RESULTS: Two hundred-fifty sets of hemodynamic variables were measured in 64 patients. The level of PEEP ranged from 5 to 50 cm H2O (mean 12+/-9 [SD] cm H2O). At all levels of PEEP, CI correlated significantly better with RVEDVI than with PAOP. At levels of PEEP > or =15 cm H2O, CI was inversely correlated with PAOP, but remained positively correlated with RVEDVI. CONCLUSIONS: CI correlates significantly better with RVEDVI than PAOP at all levels of PEEP up to 50 cm H2O. RVEDVI is a more reliable predictor of volume depletion and preload recruitable increases in CI, especially in patients receiving higher levels of PEEP where PAOP is difficult to interpret.

Acute Disease↗

PubMed1998

Randomized, prospective comparison of increased preload versus inotropes in the resuscitation of trauma patients: effects on cardiopulmonary function and visceral perfusion.

OBJECTIVE: To evaluate the effects of maintaining increased levels of preload on cardiopulmonary function and visceral perfusion during resuscitation. METHODS: Randomized, prospective study of 39 consecutive trauma patients with a low right ventricular ejection fraction (<40%) admitted to a university Level I trauma center during a 10-month period. Patients were randomized to one of two groups: increased preload (PL), or normal preload with inotropes (INO). The PL group received fluid administration to maintain a target right ventricular end-diastolic volume index (RVEDVI) > or = 120 mL/m2 during resuscitation. The INO group had inotropes added according to a prospectively determined protocol and was maintained at a RVEDVI of 90 to 100 mL/m2. Systemic perfusion was assessed using oxygen transport and acid-base parameters, and pulmonary function was evaluated with PaO2/FiO2 ratio, dynamic compliance, ventilator days, and incidence of adult respiratory distress syndrome. Gut perfusion was assessed by measuring gastric intramucosal pH (pHi). Data are expressed as means +/- SD. RESULTS: The mean RVEDVI was significantly higher in the PL group (n = 19) than in the INO group (n = 20) during resuscitation (119+/-18 vs. 103+/-22 mL/m2, p = 0.01). There was no difference in oxygen delivery, mixed venous oxygen saturation, lactate, PaO2/FiO2 ratio, dynamic compliance, or ventilator days between the groups. The incidence of adult respiratory distress syndrome was not significantly different (PL 31% vs. INO 50%, p > 0.1). In the patients who had pHi measured sequentially during resuscitation (PL = 13, INO = 17), the final pHi was significantly higher in the PL group (7.31+/-0.1 vs. 7.16+/-0.2, p = 0.03). CONCLUSION: Patients resuscitated at higher levels of preload have significantly better visceral perfusion than those resuscitated at normal preload with addition of inotropes. This higher preload does not adversely affect pulmonary function.

Adult↗

PubMed1998

Effects of abdominal decompression on cardiopulmonary function and visceral perfusion in patients with intra-abdominal hypertension.

OBJECTIVE: Increased intra-abdominal pressure (IAP) compromises cardiopulmonary function and visceral perfusion. Our goal was to characterize acute changes in these subsystems associated with operative abdominal decompression. PATIENT POPULATION: A series of 11 consecutive injured patients monitored with a pulmonary artery catheter and nasogastric tonometer in whom operative decompression was performed. Indications for decompression included oliguria or progressive acidosis despite aggressive resuscitation in the presence of elevated IAP (>25 mm Hg). MAIN OUTCOME MEASURES: Studied hemodynamic variables included pulmonary artery occlusion pressure (PAOP), right ventricular end-diastolic volume index (RVEDVI), and cardiac index (CI). Pulmonary variables included shunt fraction (Qs/Qt) and dynamic compliance (Cdyn). Visceral perfusion was assessed using hourly urine output 4 hours before and after decompression (UOP) and gastric intramucosal pH (pHi). Mean values before and after decompression were compared using the paired t test. Linear regression and Fisher's z transformation were used to evaluate the relationships between RVEDVI, PAOP, CI, and IAP. IAP was transduced via bladder pressures. Significance was defined as p < 0.05. Data are expressed as means+/-SD. RESULTS: IAP decreased with decompression (49+/-11 to 19+/-6.8 mm Hg; p < 0.0001). RVEDVI improved independent of CI and correlated better (p < 0.01) with CI (r =0.49, p=0.04) than PAOP did (r=-0.36, p=0.09). PAOP correlated significantly with IAP (r=0.45, p=0.04). Decompression resulted in significant improvements in Qs/Qt, Cdyn, UOP, and pHi. CONCLUSION: Abdominal decompression in patients with increased IAP improves preload, pulmonary function, and visceral perfusion. Elevated IAP has important effects on PAOP, which makes the PAOP an unreliable index of preload in these patients.

Abdominal Injuries↗

PubMed1998

Redefining cardiovascular performance during resuscitation: ventricular stroke work, power, and the pressure-volume diagram.

OBJECTIVES: (1) To compare left ventricular stroke work index (SW) and left ventricular power output (LVP), hemodynamic variables that encompass blood pressure as well as blood flow, with the purely flow-derived hemodynamic and oxygen transport variables as markers of perfusion and outcome in critically injured patients during resuscitation. (2) To use the ventricular pressure-volume diagram to define characteristic hemodynamic patterns in the determinants of SW and LVP that are associated with survival. METHODS: This was a cohort study at a university Level I trauma center during the course of 1 year. A consecutive series of patients was monitored with a volumetric pulmonary artery catheter during the initial 48 hours of resuscitation. Heart rate, SW, LVP, cardiac index, and oxygen delivery and consumption during resuscitation were compared using multivariate logistic regression analysis with regard to the ability to clear lactate in less than 24 hours and survival. Receiver operating characteristic curves were constructed to determine threshold values for SW and LVP. Ventricular pressure-volume diagrams were used to describe characteristic patterns in the determinants of SW and LVP in survivors and nonsurvivors. Preload was expressed as left ventricular end-diastolic volume index, afterload as aortic input impedance (Ea), and contractility as ventricular end-systolic elastance (Ees). The ratio of Ea/Ees (RATIO) was used as a measure of ventricular-arterial coupling, which describes the efficacy of energy transfer from the heart to the vascular system. RESULTS: One hundred eleven patients (87 survivors, 24 nonsurvivors) met study criteria. Survivors had a significantly higher SW (4,510 +/- 1,070 vs. 3,440 +/- 980 mm Hg x mL x m(-2); p < 0.0001) and LVP (370 +/- 94 vs. 270 +/- 81 mm Hg x L x min(-2) x m(-2); p < 0.0001) than nonsurvivors. Heart rate, SW, and LVP were the only studied variables that were significantly related to lactate clearance and survival by logistic regression. Threshold values determined by the receiver operating characteristic curves were 4,000 mm Hg x mL x m(-2) for SW and 320 mm Hg x L x min(-1) x m(-2) for LVP. Survivors had better ventricular-arterial coupling than nonsurvivors, indicated by a lower RATIO (0.32 +/- 0.22 vs. 0.54 +/- 0.38; p = 0.003). This lower RATIO was attributable to lower levels of Ea (2.7 +/- 0.7 vs. 3.4 +/- 0.8 mm Hg x mL(-1) x m(-2); p = 0.0003) and a trend toward higher levels of Ees (13 +/- 11 vs. 9.9 +/- 7.3 mm Hg x mL(-1) x m(-2); p = 0.12). CONCLUSION: Thermodynamic perfusion variables that encompass both pressure and flow, such as SW and LVP, are more closely related to perfusion and outcome than the purely flow-derived variables. The higher SW and LVP in survivors is related to better ventricular-arterial coupling, and therefore more efficient cardiac function. Cutoff values for LVP of 320 mm Hg x L x min(-1) x m(-2) and for SW of 4,000 mm Hg x mL x m(-2) may be useful thresholds for evaluating hemodynamic performance during resuscitation.

Adolescent↗

PubMed1998

Threshold values of intramucosal pH and mucosal-arterial CO2 gap during shock resuscitation.

BACKGROUND: The gastric intramucosal pH (pHi) and gastric mucosal-arterial CO2 gap (GAP) estimate visceral perfusion and predict outcome. Threshold values of these variables for use during resuscitation, however, remain poorly defined. The purpose of this study was to develop clinically derived cutoffs for both pHi and GAP for predicting death and multiple organ failure (MOF) in trauma patients. METHODS: This was a cohort study of 114 consecutive trauma patients who had pHi determined at 24 hours after intensive care unit admission. The corresponding GAP for each of these values of pHi was obtained through chart review. Receiver operating characteristic curves were constructed for both pHi and GAP with respect to death and MOF. These curves were used to determine the value of each variable that maximized the sum of sensitivity and specificity in predicting outcome. chi2 tests and odds ratios were used to determine if significant differences in outcome occurred above and below these cutoff values. RESULTS: Of 114 patients who had pHi determined at 24 hours after admission, 108 had corresponding GAP values available. The values of pHi and GAP that maximized sensitivity and specificity were 7.25 and 18 mm Hg, respectively. The odds ratio for pHi versus death was 4.6 and for pHi versus MOF was 4.3. The odds ratios for GAP versus death and MOF were 2.9 and 3.3, respectively. CONCLUSION: In trauma patients, the ability to predict death and MOF is maximized at values of pHi less than 7.25 and GAP greater than 18 mm Hg. These values represent clinically derived cutoffs that should be useful for evaluating the adequacy of intestinal perfusion during resuscitation.

Acid-Base Equilibrium↗

PubMed1998

Enalaprilat improves gut perfusion in critically injured patients.

Inadequate splanchnic perfusion, detected as a low gastric intramucosal pH (pHi), in the face of normal systemic perfusion predicts an increased risk for multiple organ failure after trauma. Although the exact etiology of this low pHi is unknown, angiotensin II is thought to be an important regulator of gut perfusion during and after resuscitation from shock. The purpose of this study is to determine whether enalaprilat, an angiotensin-converting enzyme inhibitor, improves gut perfusion in critically injured patients. To test this hypothesis, 18 trauma patients monitored with a nasogastric tonometer and a pulmonary artery catheter were enrolled in a prospective study. A single dose of enalaprilat, .625 mg, was given as an i.v. bolus or a 4 h infusion following systemic resuscitation. Pre- and postdrug tonometric and hemodynamic data, including cardiac index, mean arterial pressure, right ventricular end-diastolic volume index, systemic vascular resistance index, and oxygen transport variables were compared using the paired t test. Results demonstrate that pHi was significantly improved after 4 h (7.13 +/- .04 to 7.19 +/- .03, p = .03) and after 24 h compared with baseline (7.14 +/- .04 to 7.25 +/- .04, p = .04). Overall, pHi increased in 12 of 18 patients. No significant differences were observed in any of the studied hemodynamic or systemic perfusion variables including mean arterial pressure (92 +/- 4 to 87 +/- 4, p = .24) and oxygen delivery (669 +/- 33 to 675 +/- 32, p = .82). In examining the determinants of pHi, the intramucosal-arterial PCO2 difference was improved after enalaprilat administration (27 +/- 6 to 17 +/- 3 mmHg, p = .04) while no difference was observed in arterial bicarbonate (19.5 +/- .7 to 19.7 +/- .8, p = .90). Additionally, the change in pHi observed with enalaprilat correlated with predrug intramucosal-arterial PCO2 difference (r = .74, r2 = .55, p = .0005). These results demonstrate that enalaprilat improves gut perfusion as measured by gastric tonometry in critically injured patients, and that this effect appears to be independent of changes in systemic perfusion.

Adult↗