Biomedical subjects

M Nagashima

Publications and source records attributed to M Nagashima.

At least 55 records · Page 3Linked to original sources

PubMed2000

Patch augmentation of the pulmonary artery with bioabsorbable polymers and autologous cell seeding.

OBJECTIVE: In recent years bioabsorbable synthetic or biologic materials have been used to augment the pulmonary artery or the right ventricular outflow tract. However, each of these polymers has one or more shortcomings. None of these patch materials has been seeded with cells. Thus, we have tested a fast-absorbing biopolymer, poly-4-hydroxybutyric acid, with autologous cell seeding for patch augmentation of the pulmonary artery in a juvenile sheep model. METHODS: Vascular cells were isolated from ovine peripheral veins (n = 6). Bioabsorbable porous poly-4-hydroxybutyric acid patches (porosity > 95%) were seeded on 3 consecutive days with a mixed vascular cell suspension (21.3 +/- 1.3 x 10(6) cells). Forty-five (+/- 2) days after the vessel harvest, 1 unseeded and 6 autologously seeded control patches were implanted into the proximal pulmonary artery. The animals received no postoperative anticoagulation. Follow-up was performed with echocardiography after 1 week and before explantation after 1, 7, and 24 weeks (2 animals each) for the seeded control patches and after 20 weeks for the nonseeded control patch. RESULTS: All animals survived the procedure. Postoperative echocardiography of the seeded patches demonstrated a smooth surface without dilatation or stenosis. Macroscopic appearance showed a smooth internal surface with increasing tissue formation. Histology at 169 days demonstrated a near-complete resorption of the polymer and formation of organized and functional tissue. Biochemical assays revealed increasing cellular and extracellular matrix contents. The control patch showed a slight bulging, indicating a beginning dilatation. CONCLUSION: This experiment showed that poly-4-hydroxybutyric acid is a feasible patch material in the pulmonary circulation.

Absorbable Implants↗

PubMed2000

Effects of combinations of anti-rheumatic drugs on the production of vascular endothelial growth factor and basic fibroblast growth factor in cultured synoviocytes and patients with rheumatoid arthritis.

OBJECTIVE: To examine whether different combinations of disease-modifying anti-rheumatic drugs (DMARDs), including bucillamine (BUC), gold sodium thiomalate (GST), methotrexate (MTX), salazosulphapyridine (SASP) and dexamethasone (DEX; a steroid), act by inhibiting the production of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in cultured synoviocytes, causing a decrease in their serum concentrations in patients with rheumatoid arthritis (RA). METHODS: The VEGF and bFGF concentrations in cultured synoviocytes and peripheral blood from patients with RA were measured by enzyme-linked immunosorbent assay and their serum concentrations were measured at two time points. RESULTS: BUC and GST inhibited VEGF production even when given alone, and a combination of BUC, GST and MTX with DEX also inhibited VEGF production. None of the DMARDs or DEX inhibited bFGF production when given alone, but a combination of SASP and GST inhibited the production of bFGF in cultured synoviocytes. Serum VEGF concentrations were significantly decreased 6 months after the commencement of medication compared with their concentrations before medication. CONCLUSION: Our results show that the effects of a combination of DEX with any two of BUC, GST, SASP and MTX on the production of VEGF and bFGF in cultured synoviocytes and on the serum concentrations of VEGF in patients with RA may be based on synergistic or additive effects of the drugs.

Anti-Inflammatory Agents↗

PubMed2000

Heterogeneous distribution of thrombomodulin and von Willebrand factor in endothelial cells in the human pulmonary microvessels.

Laser scanning confocal fluorescence microscopy techniques were used to study the localization of von Willebrand factor (vWf; Factor VIII-related antigen) and thrombomodulin (transmembrane receptor for thrombin) in the microvascular endothelial cells in the normal human lung. Tissues were obtained from lobectomy specimens resected for solitary nodules (7 adenocarcinomas and 4 hamartomas) from 11 patients. The plasma membranes of the capillary endothelial cells in the alveolar zones (A-zones) showed red linear fluorescence for thrombomodulin. However, their cytoplasm was mostly unreactive for vWf. The microvessels which were located in the connective tissue (C-zones), including peribronchial, and subpleural areas and large vascular walls, consistently demonstrated band-like green fluorescence for vWf in their cytoplasm, and their plasma membranes usually lacked reactivity for thrombomodulin. Only a limited number of peribronchial capillaries measuring <10 microm in diameter showed a mosaic-like appearance, in which red fluorescence along the plasma membranes was found together with green fluorescence in the subjacent cytoplasm. In the juxtaalveolar (J-zones) microvessels located along the borders between A- and C-zones, and measuring up to 40 microm in diameter, the endothelial cells showed a mosaic-like pattern of distribution of the two antigens. However, the localization of thrombomodulin in the J-zone microvessels was separate and independent from that of vWf. The thrombomodulin-reactive cells were directly connected to the alveolar capillary endothelial cells. Heterogeneous patterns of distribution of thrombomodulin and vWf suggest that topographic differences of endothelial function occur to maintain a balance of coagulation and anticoagulation in the normal human lung.

Adult↗

PubMed2000

Cloning and expression of a gene encoding N-glycosyltransferase (ngt) from Saccarothrix aerocolonigenes ATCC39243.

In the course of our bioconversion studies on the derivatives of an indolocarbazole, J-104303, Saccharothrix aerocolonigenes ATCC39243 was found to convert J-104303, which was added into the culture medium, to its glycosylated derivative, J-109384. In order to clone the gene having the ability to convert J-104303 to J-109384, a library of Saccharothrix aerocolonigenes ATCC39243 DNA fragments was constructed using Streptomyces lividans TK21 and pIJ702 as host strain and vector, respectively. By examining more than 5,000 transformants, one was found to convert J-104303 to J-109384. Sequence analysis of the inserted DNA fragment revealed an open reading frame with 1,245 base pairs, named ngt. The transformant containing this ngt gene was also found to introduce a D-glucose moiety into 6-N-methylarcyriaflavin C. Furthermore, when ngt was introduced into Streptomyces mobaraensis BA13793, a producer of J-104303, the resulting transformant produced J-109384 directly.

Actinomycetales↗

PubMed2000

[Comparison of the circadian variation of the time of onset of acute myocardial infarction and of attack of vasospastic angina without significant stenosis].

OBJECTIVES: To study the involvement of vasospasm as the trigger of acute myocardial infarction without significant stenosis, the circadian variation of the time of onset of acute myocardial infarction was compared with that of vasospastic angina without significant stenosis. METHODS: The subjects consisted of 3 groups, 64 patients with acute myocardial infarction without significant stenosis, 101 patients with acute myocardial infarction with one vessel disease and 98 patients with vasospastic angina without significant stenosis. The times of onset of acute myocardial infarction and spontaneous attack of vasospastic angina were recorded and classified according to the 4 periods (0:00-6:00, 6:00-12:00, 12:00-18:00, 18:00-24:00) and the pattern of distribution was compared between the 3 groups. RESULTS: The time distribution of acute myocardial infarction without significant stenosis showed a double peaked pattern at 6:00-12:00 and 18:00-24:00 and was similar to the pattern of acute myocardial infarction with one vessel disease(p = 0.93). Only a single peak in 0:00-6:00 was found in the pattern of distribution of vasospastic angina without significant stenosis and differed significantly from acute myocardial infarction(p < 0.01). CONCLUSIONS: The circadian variation of the time of onset of acute myocardial infarction was similar in patients with or without significant stenosis, and differed significantly from that in patients with vasospastic angina.

Angina Pectoris↗

PubMed2000

Imbalance in production between vascular endothelial growth factor and endostatin in patients with rheumatoid arthritis.

OBJECTIVE: To clarify whether synovial cell proliferation indicates an imbalance in production between angiogenic growth factors and angiogenesis inhibitors in rheumatoid arthritis (RA), we investigated the production of basic fibroblast growth factor (b-FGF) and vascular endothelial growth factor (VEGF) as representative angiogenic growth factors and endostatin as a representative angiogenesis inhibitor. METHODS: The b-FGF, VEGF, and endostatin levels in 90 samples of peripheral blood (PB) and 15 samples of joint fluid obtained from patients with RA and 30 samples of PB and 10 samples of joint fluid from patients without RA, including 20 patients with inflammatory arthritis without purulent arthritis, and 10 patients with osteoarthritis were measured by ELISA. VEGF and endostatin levels in blood samples from 22 patients with RA were measured at 2 points: before and 4 or 5 months after the commencement of medication. RESULTS: The b-FGF and VEGF levels in the PB and joint fluid samples from patients with RA were markedly elevated compared to samples from patients without RA. In contrast, endostatin levels in PB and joint fluid samples from patients with RA were almost the same as in the samples from patients without RA. VEGF levels in blood samples obtained 4 or 5 months after the commencement of medication (combination of prednisolone 5 mg/day and disease modifying antirheumatic drugs: either bucillamine 100 mg/day or salazosulfapyridine 1,000 mg/day) were significantly decreased from 27.1 +/- 8.5 pg/ml in samples obtained before commencement of medication to 18.1 +/- 16.2 pg/ml. Endostatin levels in the corresponding samples were significantly increased, from 31.5 +/- 7.0 to 57.1 +/- 22.8 ng/ml [correction]. CONCLUSION: Our results reveal significant differences in b-FGF and VEGF levels in PB and joint fluid samples, but no difference in endostatin levels, between patients with RA and those without RA, suggesting that angiogenesis in RA occurs as a result of an imbalance in production between angiogenic growth factors and angiogenesis inhibitors.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1999

Induction of human beta-defensin-2 mRNA expression by Helicobacter pylori in human gastric cell line MKN45 cells on cag pathogenicity island.

Helicobacter pylori is an etiological agent of gastritis, peptic ulcer, and gastric cancer. Human beta-defensin-2 (hBD-2) is an antimicrobial peptide which belongs to one of the most important host defense systems against bacterial infection in several epithelial tissues. We studied the effect of H. pylori on the expression of hBD-2 mRNA in MKN45 gastric mucosal cells. H. pylori, but not culture filtrate, increased the hBD-2 mRNA level in MKN45 cells; the inductive effect of H. pylori was not detected with Intestine 407 cells. Among H. pylori strains, strain OHPC0002, which lacks a cag Pathogenicity Island (PAI), did not induce hBD-2 mRNA in MKN45 cells. These results suggested that H. pylori cag PAI is critical for the induction of hBD-2 mRNA in MKN45 cells. Exposure of MKN45 cells to Salmonella typhimurium, S. enteritidis, S. typhi, and S. dublin, but not Escherichia coli ML35, also resulted in induction of hBD-2 mRNA.

Blood Bactericidal Activity↗

PubMed1999

Thrombin interacts with thrombomodulin, protein C, and thrombin-activatable fibrinolysis inhibitor via specific and distinct domains.

A collection of 56 purified thrombin mutants, in which 76 charged or polar surface residues on thrombin were mutated to alanine, was used to identify key residues mediating the interactions of thrombin with thrombomodulin (TM), protein C, and thrombin-activatable fibrinolysis inhibitor (TAFI). Comparison of protein C activation in the presence and absence of TM identified 11 residues mediating the thrombin-TM interaction (Lys(21), Gln(24), Arg(62), Lys(65), His(66), Arg(68), Thr(69), Tyr(71), Arg(73), Lys(77), Lys(106)). Three mutants (E25A, D51A, R89A/R93A/E94A) were found to have decreased ability to activate TAFI yet retained normal protein C activation, whereas three other mutants (R178A/R180A/D183A, E229A, R233A) had decreased ability to activate protein C but maintained normal TAFI activation. One mutant (W50A) displayed decreased activation of both substrates. Mapping of these functional residues on thrombin revealed that the 11 residues mediating the thrombin-TM interaction are all located in exosite I. Residues important in TAFI activation are located above the active-site cleft, whereas residues involved in protein C are located below the active-site cleft. In contrast to the extensive overlap of residues mediating TM binding and fibrinogen clotting, these data show that distinct domains in thrombin mediate its interactions with TM, protein C, and TAFI. These studies demonstrate that selective enzymatic properties of thrombin can be dissociated by site-directed mutagenesis.

Animals↗

PubMed1999

Predominant germ-line mutation of the hMSH2 gene in Japanese hereditary non-polyposis colorectal cancer kindreds.

By means of PCR-SSCP and direct sequencing, we detected 12 germ-line mutations of hMSH2 or hMLH1 in 37 Japanese hereditary non-polyposis colorectal cancer (HNPCC) kindreds, of whom 15 satisfied the Amsterdam and 22 the Japanese criteria. The germ-line mutation detection rate of hMSH2 was much higher than that of hMLH1 (11/37 vs. 1/37). The total mutation detection rate of hMSH2 and hMLH1 in the Amsterdam criteria group was significantly higher than that in the Japanese criteria group (9/15 vs. 3/22). Furthermore, the mean age of the HNPCC patients in the mutation-positive group was lower than that in the mutation-negative one; the rates of both vertical transmission and multiplicity of tumors in the mutation-positive group were higher than those in the mutation-negative one. In addition, the number of patients with microsatellite instability-positive cancers in the mutation-positive group was higher than that in the mutation-negative one. Our results suggest firstly that the hMSH2 gene plays a much more important role than hMLH1 in the carcinogenesis of Japanese HNPCC patients, secondly that the rate of hMSH2 and hMLH1 mutations is high in the kindreds satisfying the Amsterdam criteria and thirdly that both the clinical phenotypes (early onset, vertical transmission and multiplicity of tumors) and the microsatellite instability status are important for the genetic screening of HNPCC.

Colorectal Neoplasms, Hereditary Nonpolyposis↗

PubMed1999

RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides.

S100/calgranulin polypeptides are present at sites of inflammation, likely released by inflammatory cells targeted to such loci by a range of environmental cues. We report here that receptor for AGE (RAGE) is a central cell surface receptor for EN-RAGE (extracellular newly identified RAGE-binding protein) and related members of the S100/calgranulin superfamily. Interaction of EN-RAGEs with cellular RAGE on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators. Blockade of EN-RAGE/RAGE quenches delayed-type hypersensitivity and inflammatory colitis in murine models by arresting activation of central signaling pathways and expression of inflammatory gene mediators. These data highlight a novel paradigm in inflammation and identify roles for EN-RAGEs and RAGE in chronic cellular activation and tissue injury.

Amino Acid Sequence↗

PubMed1999

Cortical neurite outgrowth and growth cone behaviors reveal developmentally regulated cues in spinal cord membranes.

Corticospinal axon outgrowth in vivo and the ability to sprout or regenerate after injury decline with age. This developmental decline in growth potential has been correlated with an increase in inhibitory myelin-associated proteins in older spinal cord. However, previous results have shown that sprouting of corticospinal fibers after contralateral lesions begins to diminish prior to myelination, suggesting that a decrease in growth promoting and/or an increase in inhibitory molecules in spinal gray matter may also regulate corticospinal axon outgrowth. To address this possibility, we carried out in vitro experiments to measure neurite outgrowth from explants of 1-day-old hamster forelimb sensorimotor cortex that were plated onto membrane carpets or membrane stripe assays prepared from white or gray matter of 1-to 22-day-old cervical spinal cord. On uniform carpets and in the stripe assays cortical neurites grew robustly on young but not older membranes from both white and gray matter. Mixtures of membranes from 1- and 15-day spinal cord inhibited neurite outgrowth, suggesting that the presence of inhibitory molecules in the 15-day cord overwhelmed permissive or growth promoting molecules in membranes from 1-day cord. Video microscopic observations of growth cone behaviors on membrane stripe assays transferred to glass coverslips supported this view. Cortical growth cones repeatedly collapsed at borders between permissive substrates (laminin or young membrane stripes) and nonpermissive substrates (older membrane stripes). Growth cones either turned away from the older membranes or reduced their growth rates. These results suggest that molecules in both the gray and white matter of the developing spinal cord can inhibit cortical neurite outgrowth.

Aging↗

PubMed1999

Mutational analysis of p73 and p53 in human cancer cell lines.

p73 is a candidate tumor suppressor gene with substantial DNA and protein homology to the p53 tumor suppressor gene. We have investigated two hypotheses: (a) p73 is mutated in diverse types of human cancer, and (b) p73 is functionally redundant with p53 in carcinogenesis so that mutations would be exclusive in these two genes. The entire coding region and intronic splice junctions of p73 were examined in 54 cancer cell lines. Three lung cancer cell lines contained mutations that affected the amino acid sequence. One amino acid substitution was in a region with homology to the specific DNA binding region of p53 and two microdeletions were outside the region of homology. Two of the cell lines with p73 mutations also carried p53 mutations. Although our results are inconsistent with the two hypotheses tested, p73 mutations may contribute infrequently to the molecular pathogenesis of human lung cancer.

DNA Mutational Analysis↗

PubMed1999

COOH-terminal domain of p53 modulates p53-mediated transcriptional transactivation, cell growth, and apoptosis.

The tumor suppressor protein p53 contributes to the control of cell cycle checkpoints and stress-induced apoptosis and is frequently mutated in many different types of human cancers. The COOH terminus of p53 modulates the transcriptional and apoptotic activities of the protein. Although COOH-terminal mutants of p53 are uncommon, we proposed that these p53 mutants nevertheless contributed to the selective clonal expansion of the cancer cells. Therefore, we analyzed the tumor-derived p53 COOH-terminal domain (CTD) mutants (352D/H, 356G/W, 342-stop, 360-del, and 387-del) functionally. The results have revealed that all mutants have impaired apoptotic activity when compared with wild-type p53. However, some of these mutants still transcriptionally transactivate p21Waf/Cip1 and inhibit cell growth. Interestingly, of the tumor-derived CTD mutants, oligomerization-defective mutant 342-stop was the only one that did not exhibit sequence-specific DNA binding or failed to transactivate p21Waf1/Cip1, Bax, and IGF-BP3 transcriptionally. The failure to inhibit cell growth by this tumor-derived CTD mutant supports the hypothesis that p53 sequence-specific transcriptional transactivity to p21Waf1/Cip1 is correlated with induction of cell cycle arrest and that the p53 transcriptional transactivity requires oligomerization of the p53 protein. These and other data indicate that the CTD of p53 is an important component of p53-mediated apoptosis and cell growth arrest and that inactivation of the apoptotic function, but not the inhibition of growth, is an important step during human tumorigenesis.

Apoptosis↗

PubMed1999

Characteristics of current fluctuations originating from activities of inward-rectifier K+ channels in guinea-pig heart cells.

Although outward current through inward-rectifier K+ channels has been observed in the whole-cell mode of the patch-clamp technique, no outward unitary current in single-channel studies has been recorded with the physiological ionic conditions. Hence, the relationship between single-channel activities and the inward rectification of the whole-cell current has been poorly understood. Therefore, characteristics of inward-rectifier K+ channels in guinea-pig ventricular myocytes were assessed by the noise analysis of the K+ current using the whole-cell patch clamp method. Partial blockade of the inward-rectifier K+ current by Ba2+ was used to obtain different levels of mean current and current fluctuation as needed for variance-to-mean analysis. The plot of variance of current fluctuation against mean currents was well fitted by theoretical parabolic curves, and the unitary conductance, the open probability, and the density of functional channels were deduced. The unitary conductance of the inward-rectifier K+ channel exhibited an inward-rectification, although the channel open probability and the density of functional channels were not much different at various holding potentials used. The unitary conductance was not changed when the intrapipette concentration of Mg2+ was reduced, but tended to be smaller when the pipette contained high Mg2+ concentration. Spermine also tended to reduce the outward unitary conductances, although the reduction was not statistically significant. These results suggest that the inward rectification in the whole-cell current was due to the inward-rectifying property of the unitary conductance of the K+ channels. Inward rectification of the unitary conductance may be caused by blocking of the channels by both Mg2+ and polyamines.

Animals↗

PubMed1999

Oxygen uptake efficiency slope as a useful measure of cardiorespiratory functional reserve in adult cardiac patients.

In this study we aimed to elucidate the validity and usefulness of the oxygen uptake efficiency slope (OUES) in the evaluation of adult cardiac patients. Cardiopulmonary exercise tests were performed on a treadmill by 50 adult patients with chronic heart failure. The OUES was calculated from data for the first 75%, 90%, and 100% of exercise duration. The OUES is derived from the following equation: VO(2)=ax logV(E)+b, where VO(2) is oxygen uptake (ml/kg/min), V(E) is minute ventilation (l/kg/min), and the constant "a" represents OUES. We also determined the ventilatory anaerobic threshold (VAT). The correlation coefficient of the logarithmic curve-fitting model was [mean (SD)] 0.986 (0.009). The OUES could be used to discriminate effectively between New York Heart Association functional classes (P < 0.001). OUES and maximum VO(2) were significantly correlated (r=0.78, P < 0.01). Agreement between the OUES values for the first 90%, 75%, and 100% of the exercise was excellent (intraclass correlation coefficient = 0.99). Our results suggest that OUES is applicable to adult cardiac patients as an objective, effort-independent estimation of cardiorespiratory functional reserve.

Aged↗

PubMed1999

A patient with rectal cancer associated with ulcerative colitis in whom endoscopic ultrasonography was useful for diagnosis.

Endoscopic ultrasonography (EUS) was helpful for the diagnosis of rectal cancer associated with ulcerative colitis. The patient was a 38-year-old Japanese man with a 19-year history of relapsing-remitting type ulcerative colitis involving the entire colon. Routine colonoscopy revealed multiple polypoid prominences in the upper portion of the rectum. EUS revealed a hypoechoic mass in the submucosa beneath and around the polypoid lesion on the most oral side. Signet ring cells were found in a biopsy specimen from this lesion. Subtotal colectomy was performed. A depressed lesion was observed around the prominence on the most oral side; histologically, this lesion was poorly differentiated mucinous and signet ring cell carcinoma extending into the subserosa. The polypoid lesion on the most anal side was well differentiated adenocarcinoma, which was limited to the mucosa. Our findings suggest that EUS is helpful for detecting invasive cancer associated with ulcerative colitis.

Adenocarcinoma↗

PubMed1999

A novel amino acid substitution at the receptor-binding site on the hemagglutinin of H3N2 influenza A viruses isolated from 6 cases with acute encephalopathy during the 1997-1998 season in Tokyo.

We analyzed the hemagglutinin (HA) genes of influenza A viruses consisting of 6 strains isolated from cerebrospinal fluids of patients with encephalopathy and 3 isolates from throat washes of patients without central nervous system symptoms during the 1997-1998 season in Tokyo. Aligned 9 amino acid sequences showed 7 common substitutions compared with A/Wuhan/359/95 (vaccine strain used in the season in Japan), which were allocated to three different antigenic sites on the H3 HA molecule. It is noted that a novel substitution at the receptor-binding site (Tyr-137 to Phe) was found exclusively in the isolates from the patients with encephalopathy.

Amino Acid Sequence↗

PubMed1999

Effects of cyanosis and hypothermic circulatory arrest on lung function in neonatal lambs.

BACKGROUND: Lung function is often impaired after cardiac surgery and cardiopulmonary bypass (CPB), particularly in chronically cyanotic patients. This study aimed to evaluate lung function in a surgically created chronic cyanotic neonatal lamb model after CPB and deep hypothermic circulatory arrest (DHCA) and to assess the role of nitric oxide (NO) in the pathogenesis of increased pulmonary vascular resistance. METHODS: A chronic cyanosis model was surgically created in 7 lambs (4.7+/-0.8 days old) by anastomosing the pulmonary artery (PA) to the left atrium (LA). Another 7 lambs underwent a sham operation (control). One week later, the animals underwent shunt takedown and CPB with 90 minutes of DHCA at 18 degrees C. Cardiac index (CI), pulmonary vascular resistance index (PVRI), lung dynamic compliance (Cdyn), alveolar-arterial oxygen difference (AaDO2), left atrial plasma nitrate/nitrite (NO metabolites) levels, and pulmonary cGMP production (concentration difference between LA and PA) were measured before CPB and at 1 and 2 hours after reperfusion. RESULTS: The cyanosis model consistently produced significantly lower arterial oxygen tension (34.8+/-2.3 vs 93.1+/-8.8 torr in control, p < 0.001) and Qp/Qs (0.6+/-0.1 vs 1.0+/-0.0 in control, p < 0.001) than controls. Postoperative PVRI was significantly lower in the cyanosis group than in controls, although CPB with DHCA significantly elevated PVR in both cyanotic and control animals. There were no significant differences in AaDO2 and Cdyn after CPB between groups. The level of NO metabolites did not change before or after CPB in either cyanotic or acyanotic animals. NO metabolite levels tended to be higher in the cyanotic animals (p = 0.08). There was no significant difference in pulmonary cGMP production between both groups. CONCLUSIONS: These findings suggest that CPB with DHCA, per se, does not affect NO production in cyanotic or acyanotic neonatal lambs but causes increased PVR in both groups. Chronic cyanosis does not result in reduced pulmonary function after CPB with DHCA, and is associated with lower PVR. The mechanism may involve an increased NO production in cyanotic animals.

Animals↗