Biomedical subjects

R N Pierson

Publications and source records attributed to R N Pierson.

At least 73 records · Page 4Linked to original sources

PubMed1998

Percentage body fat determination in hemodialysis and peritoneal dialysis patients: a comparison.

OBJECTIVE: To evaluate percentage body fat in hemodialysis (HD) and peritoneal dialysis (PD) patients. DESIGN: A prospective study of 20 HD patients and 20 PD patients. SETTING: Sol Goldman Renal Therapy Center, Lenox Hill Hospital, New York, NY; Baumritter Kidney Center Albert Einstein College of Medicine, Bronx, NY; Body Composition Unit, St Luke's Roosevelt Hospital, Columbia University, New York, NY. PATIENTS: Twenty HD (10 men, 10 women) patients, mean age 41.8 +/- 2.4 years and 20 PD (12 men, 8 women) patients, mean age 48.6 years +/- 3.0 years. INTERVENTION: This is a noninterventional study. PATIENTS signed consent to undergo dual-energy x-ray absorptiometry, total body potassium counting bioelectrical impedance analysis, total body water determination, and anthropmetric evaluation. MAIN OUTCOME MEASURES: Present and compare percentage body fat between HD and PD patients as determined by the methods used. RESULTS: Percentage fat is not different between HD and PD patients. Differences in absolute values of percent fat between techniques exist. CONCLUSION: HD patients and PD patients may be evaluated by the methods of body composition used. Percentage body fat will vary among techniques; therefore the same method should be used to follow a patient over time.

Absorptiometry, Photon↗

PubMed1998

Six-compartment body composition model: inter-method comparisons of total body fat measurement.

OBJECTIVE: To compare 16 currently used total body fat methods to a six-compartment criterion model based on in vivo neutron activation analysis. DESIGN: Observational, inter-method comparison study. SUBJECTS: Twenty-three healthy subjects (17 male and 6 female). MEASUREMENTS: Total body water (TBW) was measured by tritium dilution; body volume by underwater weighing (UWW); total body fat and bone mineral by dual-energy X-ray absorptiometry (DXA), total body potassium (TBK) by whole-body 40K counting; total body carbon, nitrogen, calcium, phosphorus, sodium and chlorine by in vivo neutron activation analysis; skinfolds/circumferences by anthropometry (Anth); and resistance by single-frequency bioimpedance analysis (BIA). RESULTS: The average of total body fat mass measurements by the six-compartment neutron activation model was 19.7+/-10.2kg (mean+/-s.d.) and comparable estimates by other methods ranged from 17.4-24.3 kg. Although all 16 methods were highly correlated with the six-compartment criterion model, three groups emerged based on their comparative characteristics (technical error, coefficient of reliability, Bland-Altman analysis) relative to criterion fat estimates, in decreasing order of agreement: 1. multi-compartment model methods of Baumgartner (19.5+/-9.9 kg), Heymsfield (19.6+/-9.9 kg), Selinger (19.7+/-10.2 kg) and Siri-3C (19.6+/-9.9 kg); 2. DXA (20.0+/-10.8 kg), Pace-TBW (18.8+/-10.1 kg), Siri-2C (20.0+/-9.9 kg), and Brozek-UWW (19.4+/-9.2 kg) methods; and 3. Segal-BIA (17.4+/-7.2 kg), Forbes-TBN (21.8+/-10.5 kg), Durnin-Anth (22.1+/-9.5 kg), Forbes-TBK (22.9+/-11.9 kg), and Steinkamp-Anth (24.3+/-9.5 kg) methods. CONCLUSION: Relative to criterion fat estimates, body composition methods can be organized into three groups based on inter-method comparisons including technical error, coefficient of reliability and Bland-Altman analysis. These initial groupings may prove useful in establishing the clinical and research role of the many available fat estimation methods.

Absorptiometry, Photon↗

PubMed1998

Improvement of the prompt-gamma neutron activation facility at Brookhaven National Laboratory.

The prompt-gamma neutron activation facility at Brookhaven National Laboratory was upgraded to improve both the precision and accuracy of its in vivo determinations of total body nitrogen. The upgrade, guided by Monte Carlo simulations, involved elongating and modifying the source collimator and its shielding, repositioning the system's two NaI(Tl) detectors, and improving the neutron and gamma shielding of these detectors. The new source collimator has a graphite reflector around the 238PuBe neutron source to enhance the low-energy region of the neutron spectrum incident on the patient. The gamma detectors have been relocated from positions close to the upward-emerging collimated neutron beam to positions close to and at the sides of the patient. These modifications substantially reduced spurious counts resulting from the capture of small-angle scattered neutrons in the NaI detectors. The pile-up background under the 10.8 MeV 14N(n, gamma)15N spectral peak has been reduced so that the nitrogen peak-to-background ratio has been increased by a factor of 2.8. The resulting reduction in the coefficient of variation of the total body nitrogen measurements from 3% to 2.2% has improved the statistical significance of the results possible for any given number of patient measurements. The new system also has a more uniform composite sensitivity.

Gamma Rays↗

PubMed1998

Anthropometric equations for studying body fat in pregnant women.

Anthropometric data from 200 pregnant women were used to estimate body fat at gestation weeks 14 and 37 and changes in body fat from week 14 to week 37 with four formulas from the literature. The resulting estimates were evaluated against the estimation of fat by a four-compartment model that determined fat from weight, total body water, bone mineral mass, and body density. The estimates of fat by existing anthropometric models were statistically different from those by the four-compartment model in both early and late pregnancy. Most importantly, the change in body fat estimated by the anthropometric models (all > 4 kg) was considerably higher than that estimated by the four-compartment model (3.3 kg). Two new anthropometric equations were developed, both of which used the four-compartment model as the reference method. The equation for predicting change in fat mass from week 14 to 37 of pregnancy was as follows: 0.77 (change in weight, kg)+ 0.07 (change in thigh skinfold thickness, mm)-6.13 (r2 = 0.73). The equation for determining fat (kg) at term was as follows: 0.40 (weight at week 37, kg)+ 0.16 (biceps skinfold thickness at week 37, mm) + 0.15 (thigh skinfold thickness at week 37, mm)-0.09 (wrist circumference at week 37. mm)+ 0.10 (prepregnancy weight.kg)-6.56 (r2 = 0.89). Both equations were derived on a randomly selected half of the total sample and validated on the remaining half. Both equations were found to be valid for use in studying pregnant women with different prepregnancy body mass indexes, different gestational weight gains, different ethnicities, and different socioeconomic status.

Adipose Tissue↗

PubMed1998

Fraction of carbon-free body mass as oxygen is a constant body composition ratio in men.

Although elements are the foundation of the human body, information concerning the atomic level of body composition is still limited. The aim of this study was to explore potentially constant relationships among elements found in vivo. Based on the known stoichiometries of relevant chemical components, a theoretical model was derived, suggesting the existence of a relatively constant ratio of total body oxygen to carbon-free body mass (TBO/CFM) in men. Eight elements (C, H, N, Ca, P, K, Na and Cl ) were measured in 22 healthy male subjects by using in vivo neutron activation-40K whole-body counting, and TBO was calculated as the difference between body mass and the sum of the eight measured elements. TBO (in kg) was significantly correlated with CFM (in kg): TBO = 0.829 x CFM - 1.8; r = 0.998, P < 0.001, standard error of estimate = 0.4 kg. The ratio of TBO to CFM was relatively constant, mean +/- SD at 0. 800 +/- 0.009 with a CV of 1.1%. Oxygen and carbon are the two most abundant elements in the human body. The discovery of a constant relationship between oxygen and carbon is not only helpful for understanding the atomic level of body composition, but also provides the possibility of estimating the content of specific elements in vivo.

Adult↗

PubMed1998

Complement inhibition by FUT-175 and K76-COOH in a pig-to-human lung xenotransplant model.

Two complement inhibitors, FUT-175 (FUT) and K76-COOH (K76), were studied as single agents in an ex vivo, in situ model of pig lung rejection by human blood. Pulmonary toxicity (primarily increased pulmonary vascular resistance [PVR]) was seen with FUT at a dose which inhibited complement in vitro (0.4 mg/ml); a lower dose (0.1 mg/ml) was therefore used. K76 had little apparent toxicity at a dose which inhibited complement in vitro (6 mg/ml), but activated complement, leading to C3a elaboration. Efficacy was then assessed by 1) deposition of complement pathway components in the lung and 2) lung survival during perfusion with human blood. Neither agent consistently prolonged median lung survival (FUT: 50 min. +/- 28 SEM; K76: 37 +/- 16), blocked thromboxane production, or prevented PVR elevation compared to experiments using unmodified human blood (survival 9 min. +/- 2). At the doses used, both agents prevented deposition of terminal complement complex (TCC) in the lung. This finding demonstrates that the various phenomena associated with hyperacute lung rejection (thromboxane release, PVR elevation, capillary leak, and intraalveolar hemorrhage) can all occur despite abrogation of membrane attack complex formation. We can not exclude a contribution by drug toxicity or complement damage (mediated by C3a or other complement pathway components proximal to TCC) to the observed lung injury. We conclude that, although both FUT and K76 inhibit deposition of TCC in the lung, at the dose tested neither drug is useful as a single agent to prolong survival in a pig-to-human lung xenograft model.

Animals↗

PubMed1998

Calcium supplementation suppresses bone turnover during weight reduction in postmenopausal women.

Bone mobilization, lowering of bone mineral density (BMD), and osteoporotic fractures are recognized in postmenopausal women with weight loss. Because a high-calcium intake suppresses bone loss in peri- and postmenopausal women, the present randomized, double-blind, placebo-controlled study was designed to test the hypothesis that calcium supplementation prevents net bone mobilization and consequent bone mineral loss during voluntary weight reduction in obese postmenopausal women. Subjects were placed on a moderate energy-restricted diet and either calcium supplementation (1 g/day) or placebo for 6 months. Body weight, bone turnover markers (pyridinium cross-links), osteocalcin, and parathyroid hormone (PTH) were measured at treatment weeks 1-5, 7, 10, 13, 16, 20, and 25. Total body BMD, insulin-like growth factor, 25-hydroxyvitamin D, and sex hormone binding globulin (SHBG) were measured at baseline and week 25. The calcium supplemented (n = 15; age 60.9 +/- 9.4 years, body mass index [BMI] 33.2 +/- 4.6 kg/m2) and placebo (n = 16; age 55.8 +/- 8.3 years, BMI 32.9 +/- 4.5 kg/m2) groups lost similar amounts of weight over the study interval (10.2 +/- 5.3% vs. 10.0 +/- 5.2%) and both groups increased SHBG (p < 0.001). There was a statistical effect of calcium supplementation during weight loss to suppress pyridinium cross-links, osteocalcin, and PTH (p < 0.05, < 0.01, and < 0.05, respectively). Loss of BMD tended to be greater in the placebo group by 1.4% (p < 0.08) after weight loss. One gram per day calcium supplementation normalizes the increased calcium-PTH axis activity and the elevated bone turnover rate observed during moderate voluntary energy restriction in postmenopausal women.

Adult↗

PubMed1997

Hyperacute lung rejection in a pig-to-human transplant model: the role of anti-pig antibody and complement.

BACKGROUND: The physiology of hyperacute rejection of pig lung by human blood and the role of antispecies antibody and complement in this phenomenon have not previously been characterized. METHODS: Human blood was perfused through an ex vivo pig heart-lung preparation. In the treatment groups, blood was either unmodified or modified to deplete alternative pathway complement (heat treatment), anti-pig antibody, or both. Control experiments were performed with unmodified and heat-treated pig blood. Physiologic parameters, organ survival, and immunohistology were the primary outcome measures assessed. RESULTS: Pig lung was consistently damaged by human blood within 45 min (median 20 min), as evidenced by elevated pulmonary vascular resistance and parenchymal injury. Immunohistologic studies of perfused lungs showed prominent deposition of IgM and classical pathway component, C4, and weaker deposition of alternative pathway component, properdin. Heat treatment did not impede the rise in pulmonary vascular resistance or significantly prolong survival. Depletion of anti-pig antibody prolonged survival (median 90 min) and attenuated the rise in pulmonary vascular resistance. Antibody absorption, combined with heat treatment of plasma, prevented the elevation in pulmonary vascular resistance and yielded median graft survival (210 min) similar to pig blood perfusion (approximately 240 min). CONCLUSIONS: These results show that elevated pulmonary vascular resistance and pulmonary parenchymal injury are mediated at least in part by antispecies antibody and heat-sensitive pathways. They are consistent with the hypothesis that complement activation contributes significantly to acute lung damage in the pig-to-human species combination.

Animals↗

PubMed1997

Anthropometrics do not influence dual X-ray absorptiometry (DXA) measurement of fat in normal to obese adults: a comparison with in vivo neutron activation analysis (IVNA).

Dual-energy X-ray absorptiometry (DXA) is now a commonly used method for the determination of bone mineral status and body composition in humans. The purposes of this study were to compare fat mass by in vitro neutron activation analysis (FMIVNA) with that by DXA (FMDXA) in an anthropometrically heterogeneous sample of healthy adult men (n = 33) and women (n = 36) (19 < or = BMI < or = 39), and to determine whether differences in fat mass estimates between the two methods (delta FM) were attributable to subject anthropometry as defined by several circumference (waist, iliac crest, thigh) and skinfold thickness (umbilical, suprailiac, abdominal) measurements. No significant differences between FMDXA and FMIVNA were observed in men (p = 0.46) or women (p = 0.09). The two methods were very highly correlated in both sexes (women r2 = 0.97, p < 0.001, men r2 = 0.91, p < 0.001), although the regression line for men was significantly different from the line of identity (p = 0.043). These results suggest modest trends toward underestimation of FMDXA in men when FMIVNA < 18 kg, and overestimation in men when FMIVNA > 18 kg. delta FM (IVNA-DXA) was not significantly related to any combination of skinfold thickness and circumferences in either gender. Age explained 27% of the variance in delta FM for the men (p = 0.008). Furthermore, delta FM was not significantly related to inter-method disparity in total-body bone mineral measurements in men or women (p < 0.05). The present study demonstrates strong correlation in fat measurements between IVNA and DXA in men and women ranging from normal to markedly obese. Correction for subject anthropometry does not significantly improve this relationship.

Absorptiometry, Photon↗

PubMed1997

Body fat and water changes during pregnancy in women with different body weight and weight gain.

OBJECTIVE: To determine the fat deposited during pregnancy in women gaining according to recommendations of the Institute of Medicine and the relationship of weight gain to fat gain in women of different starting weights (classified by their body mass index). METHODS: A cohort study of healthy, nonsmoking women, 18-36 years of age, identified during prenatal visits at three hospital clinics and one birthing center in New York City. From a pool of 432 eligible volunteers who signed a consent form, body composition measurements were performed on 200 women at weeks 14 (+/-2) and 37+ of pregnancy, and bone mineral mass was measured at 2-4 weeks postpartum. Body fat was estimated with a model that used total body water, weight, and density and bone mineral mass. RESULTS: In women gaining as recommended by the Institute of Medicine, fat gains during pregnancy for women underweight, normal weight, overweight, or obese before pregnancy were 6.0 +/- 2.6 kg, 3.8 +/- 3.4 kg, 3.5 +/- 4.1 kg, and -0.6 +/- 4.6 kg, respectively. Higher weight gain increased fat gain. Body water gain was not different among the four prepregnancy weight groups. CONCLUSION: Recommended weight gain should not cause obesity in any weight group. Underweight women will normalize their body composition if they gain as recommended, whereas obese women will have little or no change in body fat. A majority of women do not gain as recommended during pregnancy.

Adipose Tissue↗

PubMed1997

A multi-center comparison of dual energy X-ray absorptiometers: in vivo and in vitro soft tissue measurement.

OBJECTIVE: To assess intra- and inter-site soft tissue variability by dual energy X-ray absorptiometry (DXA). DESIGN: Cross-sectional trial. SETTING: Three medical research institutions. SUBJECTS: Five humans (in vivo) and four phantoms (in vitro), configured from two whole body phantoms with artificial skeletons and thickness overlays. INTERVENTIONS: Duplicate total-body DXA scans were performed on all subjects at each institution within a 15 d period. RESULTS: All intra-site coefficients of variation (CV) were < 0.5% for total tissue mass, but in vitro and in vivo Cvs were 7.2% and 2.3% for fat mass (FM) and 2.5% and 0.9% for lean mass (LM), respectively. Several total-body and regional FM and LM measurements were significantly different between sites (P < 0.05), with percent differences between sites ranging from 2.6-13.3% for FM and from 1.6-13.6% for LM. Site 2 was consistently lower for FM and Site 3 was consistently lower for LM. CONCLUSIONS: These results stress the need for both rigorous and standardized cross-calibration procedures for soft tissue measurement by DXA.

Absorptiometry, Photon↗

PubMed1997

A modified bottle manikin phantom for in vivo neutron activation analysis.

An artificial skeleton was designed and placed inside a bottle manikin absorber phantom to provide a new reference standard for measurements of total body calcium by in vivo neutron activation analysis at Brookhaven National Laboratory. The composition of the epoxy-based calcium and phosphorus mixture used to construct the skeleton, the dimensions and weight of each bone are given for two phantoms representing an adult male and female. Also, the dimensions, composition, and weights of overlays designed to simulate the influence of obesity on in vivo neutron activation analysis are given for each.

Adult↗

PubMed1997

Density of fat-free body mass: relationship with race, age, and level of body fatness.

The two-compartment body composition method assumes that fat-free body mass (FFM) has a density of 1.100 kg/l. This study tested the hypothesis that FFM density is independent of race, age, and body fatness. Subjects were 703 black and white subjects, ages 20-94 yr, with body mass index (BMI) 17-35 kg/m2. Body composition was assessed using a four-compartment model based on tritium dilution volume, body density by underwater weighing, bone mineral by dual-energy X-ray absorptiometry, and body weight. No relationship was observed between FFM density and race or BMI. A tendency was observed for a lower FFM density only in older white women. The difference in percent body fat (delta fat) between the four-compartment model and underwater weighing was < 2% for all groups. Race, age, and BMI explained only 2.3 (women) and 1.4% (men) of the variance in delta fat, whereas the total body water fraction of FFM explained 77%. In contrast to current thinking, these results show that the assumption of constant FFM density is valid in black, elderly, and obese subjects.

Adipose Tissue↗

PubMed1997

Appendicular skeletal muscle mass: effects of age, gender, and ethnicity.

This study tested the hypothesis that skeletal muscle mass is reduced in elderly women and men after adjustment first for stature and body weight. The hypothesis was evaluated by estimating appendicular skeletal muscle mass with dual-energy X-ray absorptiometry in a healthy adult cohort. A second purpose was to test the hypothesis that whole body 40K counting-derived total body potassium (TBK) is a reliable indirect measure of skeletal muscle mass. The independent effects on both appendicular skeletal muscle and TBK of gender (n = 148 women and 136 men) and ethnicity (n = 152 African-Americans and 132 Caucasians) were also explored. Main findings were 1) for both appendicular skeletal muscle mass (total, leg, and arm) and TBK, age was an independent determinant after adjustment first by stepwise multiple regression for stature and weight (multiple regression model r2 = approximately 0.60); absolute decrease with greater age in men was almost double that in women; significantly larger absolute amounts were observed in men and African-Americans after adjustment first for stature, weight, and age; and >80% of within-gender or -ethnic group between-individual component variation was explained by stature, weight, age, gender, and ethnicity differences; and 2) most of between-individual TBK variation could be explained by total appendicular skeletal muscle (r2 = 0.865), whereas age, gender, and ethnicity were small but significant additional covariates (total r2 = 0.903). Our study supports the hypotheses that skeletal muscle is reduced in the elderly and that TBK provides a reasonable indirect assessment of skeletal muscle mass. These findings provide a foundation for investigating skeletal muscle mass in a wide range of health-related conditions.

Absorptiometry, Photon↗

PubMed1997

Measurement of body composition: applications in hormone research.

Measurements of body composition are fundamental to the diagnosis and management of a number of diseases. However, these measurements must be appropriate and accurate. Accuracy can now be achieved, but at the expense of invasiveness (mainly radiation) and cost. Some methods for measuring body composition, such as bioimpedance analysis, are inexpensive, simple, harmless and infinitely repeatable. The remaining methods fall within a scale of increasing discriminating power and increasing cost/risk/difficulty. In this review, a number of methods of measuring body composition are discussed. Both traditional and new methods are included, which vary in ease of use, invasiveness and cost. The choice of technique depends on the needs of a particular study.

Absorptiometry, Photon↗

PubMed1997

Expression of human decay accelerating factor may protect pig lung from hyperacute rejection by human blood.

BACKGROUND: Hyperacute rejection currently prevents clinical application of discordant lung xenografts. Pigs transgenic for human regulators of complement activation offer one promising potential solution to this problem. METHODS: Using fresh human blood in an ex vivo lung perfusion model, we studied eight different strains of pigs transgenic for human decay accelerating factor. Survival (by blood flow and gas transfer criteria) were correlated with immunohistologic evidence of pulmonary human decay accelerating factor expression and complement activation. RESULTS: With human blood perfusion, blood flow through the unmodified pig lung rapidly falls and is not restored by continuous infusion or high-dose bolus of prostacyclin. Airway pressure also rises rapidly and is followed promptly by loss of gas transfer. Four of the transgenic pig strains showed no difference from this pattern. Immunohistochemistry for human decay accelerating factor revealed low or no pulmonary expression in these lungs. In contrast, two of five transgenic pig lungs that had significant decay accelerating factor expression demonstrated recovery of pulmonary blood flow within 1 hour, and rejection was delayed, from less than 20 minutes in controls to about 1 hour. Complement activation, particularly the alternative pathway, was inhibited in lungs with high levels of endothelial decay accelerating factor expression. CONCLUSIONS: Lungs from some strains of pig transgenic for human decay accelerating factor demonstrate incomplete physiologic and histologic protection from hyperacute rejection. Although complement-independent pathogenic mechanisms may present a formidable obstacle, pig lungs transgenic for human complement regulatory proteins may facilitate discordant lung transplantation in human beings.

Animals↗

PubMed1996

Hemodynamic exercise testing. A valuable tool in the selection of cardiac transplantation candidates.

BACKGROUND: Peak exercise oxygen consumption (Vo2), a noninvasive index of peak exercise cardiac output (CO), is widely used to select candidates for heart transplantation. However, peak exercise Vo2 can be influenced by noncardiac factors such as deconditioning, motivation, or body composition and may yield misleading prognostic information. Direct measurement of the CO response to exercise may avoid this problem and more accurately predict prognosis. METHODS AND RESULTS: Hemodynamic and ventilatory responses to maximal treadmill exercise were measured in 185 ambulatory patients with chronic heart failure who had been referred for cardiac transplantation (mean left ventricular ejection fraction, 22 +/- 7%; mean peak Vo2, 12.9 +/- 3.0 mL. min-1.kg-1). CO response to exercise was normal in 83 patients and reduced in 102. By univariate analysis, patients with normal CO responses had a better 1-year survival rate (95%) than did those with reduced CO responses (72%) (P < .0001). Survival in patients with peak Vo2 of > 14 mL.min-1.kg-1 (88%) was not different from that of patients with peak Vo2 of < or = 14 mL.min-1.kg-1 (79%) (P = NS). However, survival was worse in patients with peak Vo2 of < or = 10 mL.min-1.kg-1 (52%) versus those with peak Vo2 of > 10 mL.min-1.kg-1 (89%) (P < .0001). By Cox regression analysis, exercise CO response was the strongest independent predictor of survival (risk ratio, 4.3), with peak Vo2 dichotomized at 10 mL. min-1.kg-1 (risk ratio, 3.3) as the only other independent predictor. Patients with reduced CO responses and peak Vo2 of < or = 10 mL.min-1.kg-1 had an extremely poor 1-year survival rate (38%). CONCLUSIONS: Both CO response to exercise and peak exercise Vo2 provide valuable independent prognostic information in ambulatory patients with heart failure. These variables should be used in combination to select potential heart transplantation candidates.

Analysis of Variance↗

PubMed1996

Thrombin inhibition in an ex vivo model of porcine heart xenograft hyperacute rejection.

Prominent components of vascularized xenograft rejection such as platelet activation and microvascular thrombosis may be dependent upon thrombin generation in vivo. To study potential therapeutic benefits of a synthetic low-molecular-weight thrombin inhibitor, SDZ MTH 958, in hyperacute porcine heart rejection by human blood ex vivo, a working model of hyperacute rejection of porcine by fresh, heparinized (6 microM/ml) human blood with or without 1 microM SDZ MTH 958 was used. Thrombin-antithrombin complexes (TAT) and prothrombin fragment F1.2 levels as markers of thrombin activation were determined, and biopsies from rejected hearts were analyzed by immunohistopathology. Control porcine hearts (n=8) underwent a rapid and consistent decline in cardiac output, ceasing function by 60 min. Experimental cardiac output values of 14 ml/g (SEM 1.2) were significantly higher than seen in controls (5 ml/g SEM 0.6) after 5 min of cardiac work, and prolonged survival times up to 120 min were noted (P<0.05). Activity of SDZ MTH 958 was confirmed by functional assays throughout perfusion. Levels of TAT and F1.2 increased consistently in control samples when compared with plasma samples containing SDZ MTH 958. Immunohistopathological examination confirmed diminished fibrin deposition, reduced leukocyte adherence to endothelium, impaired diapedesis and less tissue necrosis in the hearts perfused with SDZ MTH 958. SDZ MTH 958, in this xenoperfusion model, prolonged survival, enhanced function of the explanted organ, and improved histological features at the time of rejection. Effective and specific antagonism of thrombin may be useful as an adjunct therapy to complement inhibition for xenograft rejection

Acute Disease↗