Biomedical subjects

N L Polissar

Publications and source records attributed to N L Polissar.

At least 19 recordsLinked to original sources

PubMed2005

Carotid plaque composition differs between ethno-racial groups: an MRI pilot study comparing mainland Chinese and American Caucasian patients.

OBJECTIVE: Ethnicity-based research may identify new clues to the pathogenesis of atherosclerotic disease. Therefore, we sought to determine whether carotid lesions differ between 20 Chinese and 20 Caucasian Americans by MRI. METHODS AND RESULTS: Inclusion criteria were >50% stenosis as measured by duplex ultrasound and recent symptoms attributed to carotid artery disease. The patients were imaged in 2 centers (Beijing, China and Seattle, Wash) using a standardized protocol. Both carotid arteries were reviewed quantitatively (lumen, wall, outer wall, tissue components) and morphologically (lesion types, fibrous cap status). Significant differences between the Chinese and Americans were found for the mean size of the lipid/necrotic core (13.6 versus 7.8 mm2; P=0.002), percentage of slices with calcified type VII lesions (1.6 versus 12.4%; P=0.03), and percentage of slices with early type III lesions (19.3 versus 9.3%; P=0.02). Furthermore, the mean outer wall area in the common carotid artery was larger in the Chinese population (P=0.007). CONCLUSIONS: This pilot study suggests that composition and morphology of atherosclerotic lesions in symptomatic carotid disease differ between ethno-racial groups. Quantitative MRI-based review of carotid atherosclerosis comparing plaque morphology and composition between ethno-racial groups is feasible, and future MRI studies may improve our understanding of the pathophysiology of this disease.

Aged↗

PubMed2004

Quantitative evaluation of carotid plaque composition by in vivo MRI.

OBJECTIVE: This study evaluates the ability of MRI to quantify all major carotid atherosclerotic plaque components in vivo. METHODS AND RESULTS: Thirty-one subjects scheduled for carotid endarterectomy were imaged with a 1.5T scanner using time-of-flight-, T1-, proton density-, and T2-weighted images. A total of 214 MR imaging locations were matched to corresponding histology sections. For MRI and histology, area measurements of the major plaque components such as lipid-rich/necrotic core (LR/NC), calcification, loose matrix, and dense (fibrous) tissue were recorded as percentages of the total wall area. Intraclass correlation coefficients (ICCs) were computed to determine intrareader and inter-reader reproducibility. MRI measurements of plaque composition were statistically equivalent to those of histology for the LR/NC (23.7 versus 20.3%; P=0.1), loose matrix (5.1 versus 6.3%; P=0.1), and dense (fibrous) tissue (66.3% versus 64%; P=0.4). Calcification differed significantly when measured as a percentage of wall area (9.4 versus 5%; P<0.001). Intrareader and inter-reader reproducibility was good to excellent for all tissue components, with ICCs ranging from 0.73 to 0.95. CONCLUSIONS: MRI-based tissue quantification is accurate and reproducible. This application can be used in therapeutic clinical trials and in prospective longitudinal studies to examine carotid atherosclerotic plaque progression and regression.

Aged↗

PubMed2002

Relative sensitivity of the Montgomery-Asberg Depression Rating Scale, the Hamilton Depression rating scale and the Clinical Global Impressions rating scale in antidepressant clinical trials.

Although early antidepressant clinical trials simply relied on a clinician's judgment as to whether a depressed patient clinically improved or not, the Hamilton Depression (HAM-D) rating scale has become the 'gold standard' to assess the efficacy of new antidepressants. The alternative Montgomery-Asberg Depression Rating Scale (MADRS) has not achieved general acceptance. However, its ease of use warrants evaluation as to whether it is comparable to HAM-D in its sensitivity in detecting antidepressant-placebo differences in antidepressant clinical trials. A retrospective chart review was performed on the records of 208 depressed adult patients that participated in eight randomized, placebo-controlled, double-blind antidepressant clinical trials at the Northwest Clinical Research Center between 1996 and 2000. We compared the effect sizes of the HAM-D, MADRS and Clinical Impressions Rating Scale (CGI-S for severity and CGI-I for improvement) for patients assigned to placebo or an established antidepressant. The effect size (measured as the mean change in rating with antidepressants minus the mean change for placebo divided by the pooled SD of change, adjusted for age, gender and initial scores) was 0.49 with MADRS, 0.53 with HAM-D, 0.55 with CGI-S and 0.59 with CGI-I. The four rating scales had similar effect sizes regardless of the type of antidepressant evaluated. These data suggest that MADRS is as sensitive an instrument as HAM-D for detecting antidepressant efficacy in clinical trials. Thus, MADRS may be a desirable tool in large-scale, pivotal antidepressant clinical trials.

Adolescent↗

PubMed2001

In vivo accuracy of multispectral magnetic resonance imaging for identifying lipid-rich necrotic cores and intraplaque hemorrhage in advanced human carotid plaques.

BACKGROUND: High-resolution MRI has been shown to be capable of identifying plaque constituents, such as the necrotic core and intraplaque hemorrhage, in human carotid atherosclerosis. The purpose of this study was to evaluate differential contrast-weighted images, specifically a multispectral MR technique, to improve the accuracy of identifying the lipid-rich necrotic core and acute intraplaque hemorrhage in vivo. METHODS AND RESULTS: Eighteen patients scheduled for carotid endarterectomy underwent a preoperative carotid MRI examination in a 1.5-T GE Signa scanner using a protocol that generated 4 contrast weightings (T1, T2, proton density, and 3D time of flight). MR images of the vessel wall were examined for the presence of a lipid-rich necrotic core and/or intraplaque hemorrhage. Ninety cross sections were compared with matched histological sections of the excised specimen in a double-blinded fashion. Overall accuracy (95% CI) of multispectral MRI was 87% (80% to 94%), sensitivity was 85% (78% to 92%), and specificity was 92% (86% to 98%). There was good agreement between MRI and histological findings, with a value of kappa=0.69 (0.53 to 0.85). CONCLUSIONS: Multispectral MRI can identify the lipid-rich necrotic core in human carotid atherosclerosis in vivo with high sensitivity and specificity. This MRI technique provides a noninvasive tool to study the pathogenesis and natural history of carotid atherosclerosis. Furthermore, it will permit a direct assessment of the effect of pharmacological therapy, such as aggressive lipid lowering, on plaque lipid composition.

Carotid Arteries↗

PubMed2001

Age-related radical-induced DNA damage is linked to prostate cancer.

We measured concentrations and ratios of mutagenic (8-OH) lesions to putatively nonmutagenic formamidopyrimidine (Fapy) lesions of adenine (Ade) and guanine (Gua) to elucidate radical (.OH)-induced changes in DNA of normal, normal from cancer, and cancer tissues of the prostate. The relationship between the lesions was expressed using the mathematical model log(10)[(8-OH-Ade + 8-OH-Gua)/(FapyAde + FapyGua)]. Logistic regression analysis of the log ratios for DNA of normal and cancer tissues discriminated between the two tissue groups with high sensitivity and specificity. Correlation analysis of log ratios for normal prostates revealed a highly significant increase in the proportion of mutagenic base lesions with age. Data from correlation analysis of the log ratios for normal tissues from cancer were consistent with an age-dependent, dose-response relationship. The slopes for both correlations intersected at approximately 61 years, an age when prostate cancer incidence is known to rise sharply. The age-related increase in the proportion of.OH-induced mutagenic base lesions is likely a significant factor in prostate cancer development.

Adenine↗

PubMed2001

The etiology of community-acquired pneumonia at an urban public hospital: influence of human immunodeficiency virus infection and initial severity of illness.

In a prospective study, the etiology of community-acquired pneumonia (CAP) was investigated among consecutive patients admitted to an academic, urban public hospital in Seattle. The study population was uniquely young, was predominantly male, and had high rates of homelessness, cigarette smoking, alcoholism, injection drug use, and human immunodeficiency virus (HIV) infection. Leading causes of CAP among HIV-negative patients were aspiration, followed by Streptococcus pneumoniae, Legionella species, and Mycoplasma pneumoniae. Among HIV-positive patients, Pneumocystis carinii, Mycobacterium tuberculosis, S. pneumoniae, and M. pneumoniae were the most common etiologic agents. Severe CAP was associated with typical bacterial infections and aspiration pneumonia but not Legionella infection among HIV-negative patients and with Pseudomonas aeruginosa infections among HIV-positive patients. These findings emphasize the need to tailor empirical antibiotic therapy according to local patient populations and individual risk factors and highlight the importance of recognizing underlying HIV infection in patients who are hospitalized with CAP.

Adult↗

PubMed2001

Comparison of carotid vessel wall area measurements using three different contrast-weighted black blood MR imaging techniques.

Measuring carotid artery plaque burden from MRI is a reliable method for monitoring regression and progression of atherosclerosis. However, to measure all available images would be very time consuming, and in practice the image quality (IQ) of these images may be inconsistent, which can directly impact the quality of measurement. It is hypothesized that if IQ is comparable among different contrast weighted images, then carotid artery area measurements obtained from different contrast images of the same location will produce identical results. To test this, T1, proton density and T2 weighted images were acquired from ten patients (51 +/- 7 years old). Carotid lumen and vessel wall area was measured using a custom designed software program. The results showed strong agreement evidenced with only small differences on both lumen (mean: 40.5 mm(2)) and wall (mean: 52.6 mm(2)) area measurement among different weighted images. The maximum absolute mean differences are less than 2.7 mm(2) and 4.4 mm(2), and 90(th) percentile of the absolute differences are 5.6 mm(2) and 8.2 mm(2) respectively. In conclusion, different contrast weighted images with high and comparable IQ will yield similar results in lumen and vessel wall area measurement. At each matched location, it is recommended that the image with the highest IQ be used for area measurement.

Carotid Arteries↗

PubMed2001

Effects of vaporized perfluorocarbon on pulmonary blood flow and ventilation/perfusion distribution in a model of acute respiratory distress syndrome.

BACKGROUND: Perfluorocarbon (PFC) liquids are known to improve gas exchange and pulmonary function in various models of acute respiratory failure. Vaporization has been recently reported as a new method of delivering PFC to the lung. Our aim was to study the effect of PFC vapor on the ventilation/perfusion (VA/Q) matching and relative pulmonary blood flow (Qrel) distribution. METHODS: In nine sheep, lung injury was induced using oleic acid. Four sheep were treated with vaporized perfluorohexane (PFX) for 30 min, whereas the remaining sheep served as control animals. Vaporization was achieved using a modified isoflurane vaporizer. The animals were studied for 90 min after vaporization. VA/Q distributions were estimated using the multiple inert gas elimination technique. Change in Qrel distribution was assessed using fluorescent-labeled microspheres. RESULTS: Treatment with PFX vapor improved oxygenation significantly and led to significantly lower shunt values (P < 0.05, repeated-measures analysis of covariance). Analysis of the multiple inert gas elimination technique data showed that animals treated with PFX vapor demonstrated a higher VA/Q heterogeneity than the control animals (P < 0.05, repeated-measures analysis of covariance). Microsphere data showed a redistribution of Qrel attributable to oleic acid injury. Qrel shifted from areas that were initially high-flow to areas that were initially low-flow, with no difference in redistribution between the groups. After established injury, Qrel was redistributed to the nondependent lung areas in control animals, whereas Qrel distribution did not change in treatment animals. CONCLUSION: In oleic acid lung injury, treatment with PFX vapor improves gas exchange by increasing VA/Q heterogeneity in the whole lung without a significant change in gravitational gradient.

Algorithms↗

PubMed2001

Determination of regional ventilation and perfusion in the lung using xenon and computed tomography.

We propose a model to measure both regional ventilation (V) and perfusion (Q) in which the regional radiodensity (RD) in the lung during xenon (Xe) washin is a function of regional V (increasing RD) and Q (decreasing RD). We studied five anesthetized, paralyzed, mechanically ventilated, supine sheep. Four 2.5-mm-thick computed tomography (CT) images were simultaneously acquired immediately cephalad to the diaphragm at end inspiration for each breath during 3 min of Xe breathing. Observed changes in RD during Xe washin were used to determine regional V and Q. For 16 mm(3), Q displayed more variance than V: the coefficient of variance of Q (CV(Q)) = 1.58 +/- 0.23, the CV of V (CV(V)) = 0.46 +/- 0.07, and the ratio of CV(Q) to CV(V) = 3.5 +/- 1.1. CV(Q) (1.21 +/- 0.37) and the ratio of CV(Q) to CV(V) (2.4 +/- 1.2) were smaller at 1,000-mm(3) scale, but CV(V) (0.53 +/- 0.09) was not. V/Q distributions also displayed scale dependence: log SD of V and log SD of Q were 0.79 +/- 0.05 and 0.85 +/- 0.10 for 16-mm(3) and 0.69 +/- 0.20 and 0.67 +/- 0.10 for 1,000-mm(3) regions of lung, respectively. V and Q measurements made with CT and Xe also demonstrate vertically oriented and isogravitational heterogeneity, which are described using other methodologies. Sequential images acquired by CT during Xe breathing can be used to determine both regional V and Q noninvasively with high spatial resolution.

Algorithms↗

PubMed2000

Single 8-oxo-guanine and 8-oxo-adenine lesions induce marked changes in the backbone structure of a 25-base DNA strand.

Structural changes in a 25-base DNA strand, induced by single 8-oxo-guanine or 8-oxo-adenine substitutions, were shown by using Fourier transform-infrared spectroscopy with multivariate statistics. Pronounced differences were demonstrated between the parent and derivatives with respect to base interactions and changes in the phospho-deoxyribose backbone. The greatest degree of change in the backbone likely occurred immediately adjacent to the 8-oxo group, potentially altering the stereochemistry at a distance. The 8-oxo lesions, formed from reactive oxygen species (e.g., hydroxyl radicals), may appreciably alter the conformational properties of strands at the replication fork, thus affecting the selectivity of polymerases, the proofreading capability of repair enzymes, and the fidelity of the transcriptional machinery.

Adenine↗

PubMed2000

Visualization of fibrous cap thickness and rupture in human atherosclerotic carotid plaque in vivo with high-resolution magnetic resonance imaging.

BACKGROUND: The results of studies of advanced lesions of atherosclerosis suggest that the thickness of the fibrous cap that overlies the necrotic core distinguishes the stable lesion from one that is at high risk for rupture and thromboembolic events. We have developed a high-resolution MRI technique that can identify the fine structure of the lesion, including the fibrous cap, in vivo. The aim of the present study was to determine the agreement between in vivo MRI and lesion architecture as seen on histology and gross tissue examination to identify fibrous cap thickness and rupture. METHODS AND RESULTS: Twenty-two subjects who were scheduled for carotid endarterectomy underwent MRI with a 3-dimensional multiple overlapping thin slab angiography protocol. The appearance of the fibrous cap was categorized as (1) an intact, thick, (2) an intact, thin, or (3) a ruptured fibrous cap on MRI, gross, and histological sections. Thirty-six sites were available for comparison between MRI and histology. There was a high level of agreement between MRI and histological findings: 89% agreement, kappa (95% CI)=0.83 (0.67 to 1. 0), weighted kappa=0.87. Spearman's correlation coefficient was 0.88 (significant to the 0.01 level). CONCLUSIONS: These findings indicate that high-resolution MRI with a 3-dimensional multiple overlapping thin slab angiography protocol is capable of distinguishing intact, thick fibrous caps from intact thin and disrupted caps in atherosclerotic human carotid arteries in vivo. This noninvasive technique has the potential to permit studies that examine the relationship between fibrous cap changes and clinical outcome and to permit trials that evaluate therapy intended to "stabilize" the fibrous cap.

Carotid Arteries↗

PubMed2000

Analysis of the measurement precision of arterial lumen and wall areas using high-resolution MRI.

High-resolution MRI may be used to monitor the progression of human carotid atherosclerosis by measuring the lumen and wall area changes over time. The purpose of this study was to analyze the precision of quantitative measurements of lumen and wall areas. Two independent MR scans near the carotid bifurcation were conducted on eight patients within 2 weeks. The error of lumen area measurement was 6. 2%, 9.2%, and 9.7% for T(1), proton density, and T(2)-weighted images, respectively, and the error of wall area measurement was 10. 8%, 10.9%, and 12.0%. The precision of area measurement correlates strongly with image quality.

Algorithms↗

PubMed2000

Factors critical to the design and execution of epidemiologic studies and description of an innovative technology to follow the progression from normal to cancer tissue.

The results obtained from experimental studies of estrogen carcinogenesis need validation in epidemiologic studies. Such studies present additional challenges, however, because variations in human populations are much greater than those in experimental systems and in animal models. Because epidemiologic studies are often used to evaluate modest differences in risk factors, it is essential to minimize sources of errors and to maximize sensitivity, reproducibility, and specificity. In the first part of this chapter, critical factors in designing and executing epidemiologic studies, as well as the influence of sample collection, processing, and storage on data reliability, are discussed. One of the most important requirements is attaining sufficient statistical power to assess small genetic effects and to evaluate interactions between genetic and environmental factors. The second part of this chapter describes innovative technology, namely, Fourier transform-infrared (FT-IR) spectra of DNA that reveal major structural differences at various stages of the progression from normal to cancer tissue. The structural differences become evident from wavenumber-by-wavenumber statistical comparisons of the mean FT-IR spectra of DNA from normal to cancer tissues. This analysis has allowed distinguishing benign tissues from cancer and metastatic tissues in human breast, prostate, and ovarian cancers. This analysis, which requires less than 1 microg of DNA, is predicted to be used for detecting early cancer-related changes at the level of DNA, rather than at the cellular level.

DNA, Neoplasm↗

PubMed2000

Spinal nerve function in five volunteers experiencing transient neurologic symptoms after lidocaine subarachnoid anesthesia.

UNLABELLED: The etiology of transient neurologic symptoms (TNS) after 5% lidocaine spinal anesthesia remains undetermined. Previous case reports have shown that patients acutely experiencing TNS have no abnormalities on neurologic examination or magnetic resonance imaging. The aim of our study was to determine whether volunteers with TNS would exhibit abnormalities in spinal nerve electrophysiology. Twelve volunteers with no history of back pain or neurologic disease underwent baseline electromyography (EMG), nerve conduction studies, and somatosensory-evoked potential (SSEP) testing. Then, the volunteers were administered 50 mg of 5% hyperbaric lidocaine spinal anesthesia and were placed in a low lithotomy position (legs on four pillows). The next day, all volunteers underwent follow-up EMG, nerve conduction, and SSEP testing and were questioned and examined for the presence of complications including TNS (defined as pain or dysthesia in one or both buttocks or legs occurring within 24 h of spinal anesthesia). Volunteers who had TNS underwent additional EMG testing 4-6 wk later. Five of the 12 volunteers reported TNS. No volunteer had an abnormal EMG, nerve conduction study, or SSEP at 24 h follow up, nor were there any changes in EMG studies at delayed testing in the five volunteers experiencing TNS. On statistical analysis, the right peroneal and the right tibial nerve differed significantly for all volunteers from pre- to postspinal testing. When comparing pre- and postspinal testing of the TNS and non-TNS volunteers, statistically significant changes occurred in the nerve conduction tests of the right peroneal and left tibial nerve. There was no difference in measurements of F response, H reflex latency, amplitude, or velocity for either leg. Multivariate analysis of variance showed no significant difference between TNS and non-TNS volunteers for the changes in the nine nerve conduction tests when considered together (P = 0.4). We conclude that acute TNS after lidocaine spinal anesthesia did not result in consistent abnormalities detectable by EMG, nerve conduction studies, or SSEP in five volunteers. IMPLICATIONS: Electrophysiologic testing in volunteers experiencing transient neurologic symptoms is not abnormal.

Adult↗

PubMed2000

The 400 microsphere per piece "rule" does not apply to all blood flow studies.

Microsphere experiments are useful in measuring regional organ perfusion as well as heterogeneity of blood flow within organs and correlation of perfusion between organ pieces at different time points. A 400 microspheres/piece "rule" is often used in planning experiments or to determine whether experiments are valid. This rule is based on the statement that 400 microspheres must lodge in a region for 95% confidence that the observed flow in the region is within 10% of the true flow. The 400 microspheres precision rule, however, only applies to measurements of perfusion to a single region or organ piece. Examples, simulations, and an animal experiment were carried out to show that good precision for measurements of heterogeneity and correlation can be obtained from many experiments with <400 microspheres/piece. Furthermore, methods were developed and tested for correcting the observed heterogeneity and correlation to remove the Poisson "noise" due to discrete microsphere measurements. The animal experiment shows adjusted values of heterogeneity and correlation that are in close agreement for measurements made with many or few microspheres/piece. Simulations demonstrate that the adjusted values are accurate for a variety of experiments with far fewer than 400 microspheres/piece. Thus the 400 microspheres rule does not apply to many experiments. A "rule of thumb" is that experiments with a total of at least 15,000 microspheres, for all pieces combined, are very likely to yield accurate estimates of heterogeneity. Experiments with a total of at least 25,000 microspheres are very likely to yield accurate estimates of correlation coefficients.

Animals↗

PubMed2000

Effects of inertial load and countermeasures on the distribution of pulmonary blood flow.

We assessed the influence of cranial-to-caudal inertial force (+G(z)) and the countermeasures of anti-G suit and positive pressure breathing during G (PBG), specifically during +G(z), on regional pulmonary blood flow distribution. Unanesthetized swine were exposed randomly to 0 G(z) (resting), +3 G(z), +6 G(z), and +9 G(z), with and without anti-G suit and PBG with the use of the Air Force Research Laboratory centrifuge at Brooks Air Force Base (the gravitational force of the Earth, that is, the dorsal-to-ventral inertial force, was present for all runs). Fluorescent microspheres were injected into the pulmonary vasculature as a marker of regional pulmonary blood flow. Lungs were excised, dried, and diced into approximately 2-cm(3) pieces, and the fluorescence of each piece was measured. As +G(z) was increased from 0 to +3 G(z), blood flow shifted from cranial and hilar regions toward caudal and peripheral regions of the lung. This redistribution shifted back toward cranial and hilar regions as anti-G suit inflation pressure increased at +6 and +9 G(z). Perfusion heterogeneity increased with +G(z) stress and decreased at the higher anti-G suit pressures. The distribution of pulmonary blood flow was not affected by PBG. ANOVA indicated anatomic structure as the major determinant of pulmonary blood flow.

Animals↗

PubMed1999

Comparative efficacy and safety of ondansetron, droperidol, and metoclopramide for preventing postoperative nausea and vomiting: a meta-analysis.

UNLABELLED: Postoperative nausea and vomiting are important causes of morbidity after anesthesia and surgery. We performed a meta-analysis of published, randomized, controlled trials to determine the relative efficacy and safety of ondansetron, droperidol, and metoclopramide for the prevention of postoperative nausea and vomiting. We performed a literature search of English references using both the MEDLINE database and a manual search. Double-blinded, randomized, controlled trials comparing the efficiency of the prophylactic administration of ondansetron, droperidol, and/or metoclopramide therapy during general anesthesia were included. A total of 58 studies were identified, of which 4 were excluded for methodological concerns. For each comparison of drugs, a pooled odds ratio (OR) with a 95% CI was calculated using a random effects model. Ondansetron (pooled OR 0.43, 95% CI 0.31, 0.61; P < 0.001) and droperidol (pooled OR 0.68, 95% CI 0.54, 0.85; P < 0.001) were more effective than metoclopramide in preventing vomiting. Ondansetron was more effective than droperidol in preventing vomiting in children (pooled OR 0.49; P = 0.004), but they were equally effective in adults (pooled OR 0.87; P = 0.45). The overall risk of adverse effects was not different among drug combinations. We conclude that ondansetron and droperidol are more effective than metoclopramide in reducing postoperative vomiting. IMPLICATIONS: We performed a systematic review of published, randomized, controlled trials to determine the relative efficacy and safety of ondansetron, droperidol, and metoclopramide for preventing postoperative nausea and vomiting. Ondansetron and droperidol were more effective than metoclopramide in reducing postoperative vomiting. The overall risk of adverse effects did not differ.

Adult↗

PubMed1999

Hemodilution during venous gas embolization improves gas exchange, without altering V(A)/Q or pulmonary blood flow distributions.

BACKGROUND: Isovolemic anemia results in improved gas exchange in rabbits with normal lungs but in relatively poorer gas exchange in rabbits with whole-lung atelectasis. In the current study, the authors characterized the effects of hemodilution on gas exchange in a distinct model of diffuse lung injury: venous gas embolization. METHODS: Twelve anesthetized rabbits were mechanically ventilated at a fixed rate and volume. Gas embolization was induced by continuous infusion of nitrogen via an internal jugular venous catheter. Serial hemodilution was performed in six rabbits by simultaneous withdrawal of blood and infusion of an equal volume of 6% hetastarch; six rabbits were followed as controls over time. Measurements included hemodynamic parameters and blood gases, ventilation-perfusion (V(A)/Q) distribution (multiple inert gas elimination technique), pulmonary blood flow distribution (fluorescent microspheres), and expired nitric oxide (NO; chemoluminescence). RESULTS: Venous gas embolization resulted in a decrease in partial pressure of arterial oxygen (PaO2) and an increase in partial pressure of arterial carbon dioxide (PaCO2), with markedly abnormal overall V(A)/Q distribution and a predominance of high V(A)/Q areas. Pulmonary blood flow distribution was markedly left-skewed, with low-flow areas predominating. Hematocrit decreased from 30+/-1% to 11+/-1% (mean +/- SE) with hemodilution. The alveolar-arterial PO2 (A-aPO2) difference decreased from 375+/-61 mmHg at 30% hematocrit to 218+/-12.8 mmHg at 15% hematocrit, but increased again (301+/-33 mmHg) at 11% hematocrit. In contrast, the A-aPO2 difference increased over time in the control group (P < 0.05 between groups over time). Changes in PaO2 in both groups could be explained in large part by variations in intrapulmonary shunt and mixed venous oxygen saturation (SvO2); however, the improvement in gas exchange with hemodilution was not fully explained by significant changes in V(A)/Q or pulmonary blood flow distributions, as quantitated by the coefficient of variation (CV), fractal dimension, and spatial correlation of blood flow. Expired NO increased with with gas embolization but did not change significantly with time or hemodilution. CONCLUSIONS: Isovolemic hemodilution results in improved oxygen exchange in rabbits with lung injury induced by gas embolization. The mechanism for this improvement is not clear.

Animals↗