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Biomedical subjects

Y Kawashima

Publications and source records attributed to Y Kawashima.

At least 127 records · Page 7Linked to original sources
PubMed1998

Degenerated lens epithelial cells in rabbit and human eyes after intraocular lens implantation.

PURPOSE: To evaluate the role of lens epithelial cells (LECs) in posterior capsule opacification. SETTING: Departments of Ophthalmology and Pathology, Wakayama Medical College, Department of Anatomy, Kansai Shinkyu College, and Department of Ophthalmology, Kobe Kaisei Hospital, Japan. METHODS: We examined the presence of degenerated LECs on the capsules of the eyes of rabbits and a patient after intraocular lens (IOL) implantation. Phacoextraction of a crystalline lens and IOL implantation were done in 5 albino rabbits under general anesthesia. The animals were killed after 2 months. Lens capsules were removed and fixed. During vitreous surgery, a lens capsule with an IOL was removed from a patient. Ultrathin sections of specimens were studied by transmission electron microscopy. RESULTS: Presumed LECs proliferated between the posterior capsule and the IOL in association with collagenous matrix. Debris from the degenerated cells and destroyed intracellular organelles was also seen. CONCLUSION: Lens epithelial cells proliferating on the posterior capsule cannot survive indefinitely.

Aged↗
PubMed1998

Properties of a peptide containing DL-lactide/glycolide copolymer nanospheres prepared by novel emulsion solvent diffusion methods.

Novel emulsion solvent diffusion methods in water or oil were developed to prepare the peptide (TRH and elcatonin)-loaded PLGA nanospheres, via the coprecipitation of drug and polymer in the emulsion droplets induced by the diffusion of solvent. The PLGA nanospheres prepared by the emulsion solvent diffusion method in water were unimodally dispersed particles with an average diameter of about 250 nm, whereas those prepared by the emulsion solvent diffusion method in oil and the phase separation method exhibited bimodal distribution with average diameter of about 700 and 800 nm, respectively. The content and recovery of the peptide and nanospheres prepared by the emulsion solvent diffusion method in oil were superior to those of nanospheres prepared using other methods. The drug release properties from nanospheres depended strongly on their preparation processes. The nanospheres prepared by the emulsion solvent diffusion method in oil, released the drug continuously over 14 days, the rate of which was determined by the diffusion of drug in the rigid matrix structure of the nanosphere. The drug release behavior of nanospheres prepared by the phase separation method exhibited a triphasic release pattern with an initial burst and an induction period followed by the diffusion of drug through the walls of the reservoir type nanospheres, which were produced via the phase separation of polymer deposited around the emulsion droplets of the drug.

Biocompatible Materials↗
PubMed1998

Attenuation of ischemic liver injury by prostaglandin E1 analogue, misoprostol, and prostaglandin I2 analogue, OP-41483.

BACKGROUND: Prostaglandin has been reported to have protective effects against liver injury. Use of this agent in clinical settings, however, is limited because of drug-related side effects. This study investigated whether misoprostol, prostaglandin E1 analogue, and OP-41483, prostaglandin I2 analogue, which have fewer adverse effects with a longer half-life, attenuate ischemic liver damage. STUDY DESIGN: Thirty beagle dogs underwent 2 hours of hepatic vascular exclusion using venovenous bypass. Misoprostol was administered intravenously for 30 minutes before ischemia and for 3 hours after reperfusion. OP-41483 was administered intraportally for 30 minutes before ischemia (2 microg/kg/min) and for 3 hours after reperfusion (0.5 microg/kg/min). Animals were divided into five groups: untreated control group (n=10); high-dose misoprostol (total 100 microg/kg) group (MP-H, n=5); middle-dose misoprostol (50 microg/kg) group (MP-M, n=5); low-dose misoprostol (25 microg/kg) group (MP-L, n=5); and OP-41483 group (OP, n=5). Animal survival, hepatic tissue blood flow (HTBF), liver function, and histology were analyzed. RESULTS: Two-week animal survival rates were 30% in control, 60% in MP-H, 100% in MP-M, 80% in MP-L, and 100% in OP. The treatments with prostaglandin analogues improved HTBF, and attenuated liver enzyme release, adenine nucleotrides degradation, and histologic abnormalities. In contrast to the MP-H animals that exhibited unstable cardiovascular systems, the MP-M, MP-L, and OP animals experienced only transient hypotension. CONCLUSIONS: These results indicate that misoprostol and OP-41483 prevent ischemic liver damage, although careful dose adjustment of misoprostol is required to obtain the best protection with minimal side effects.

Analysis of Variance↗
PubMed1998

A new powder design method to improve inhalation efficiency of pranlukast hydrate dry powder aerosols by surface modification with hydroxypropylmethylcellulose phthalate nanospheres.

PURPOSE: A new particle design method to improve the aerosolization properties of a dry powder inhalation system was developed using surface modification of hydrophobic drug powders (pranlukast hydrate) with ultrafine hydrophilic particles, hydroxypropylmethylcellulose phthalate (HPMCP) nanospheres. The mechanism of the improved inhalation properties of the surface-modified particles and their deposits on carrier particles (lactose) was clarified in vitro. METHODS: Drug particles were introduced to aqueous colloidal HPMCP dispersions prepared by emulsion-solvent diffusion techniques followed by freeze- or spray-drying of the resultant aqueous dispersions. The surface-modified powders obtained with HPMCP nanospheres and their mixture with lactose powders were aerosolized by Spinhaler and their mode of deposition in lung was evaluated in vitro using a twin impinger. To elucidate the inhalation mechanism of these surface modified particles, we measured their modified micromeritic properties, such as surface topography, specific surface area, dissolution rate, and dispersibility in air. RESULTS: Dramatically improved inhalation properties of the surface modified powder, i.e. a two-fold increase in emission and a three-fold increase in delivery to deep lung, were found in vitro compared with the original unmodified powder. Improved inhalation was also found with the surface-modified drug deposited on lactose particles. Those improvements were attributed to the increased surface roughness and hydrophilicity of the surface-modified particles, and the resultant increased dispersibility in air. CONCLUSIONS: Surface modification of hydrophobic drug particles with HPMCP nanospheres to improve hydrophilicity was extremely useful in increasing the inhalation efficiency of the drug itself and the drug deposited on carrier; this was attributed to increased dispersibility in air and emission from the device, for spray- and freeze-dried particles, respectively.

Administration, Inhalation↗
PubMed1998

Surface-modified antiasthmatic dry powder aerosols inhaled intratracheally reduce the pharmacologically effective dose.

PURPOSE: The aim of this study was to construct a reliable dry powder inhalation (DPI) testing system for use in guinea pigs. Using this system, we were able to demonstrate the superiority of pulmonary administration of hydrophilically surface-modified pranlukast hydrate powder (SM-DP) over IV and PO administration as reflected in improved pharmacological action. Our ultimate aim is the development of an ideal treatment system for bronchial asthma involving topical administration to the lung. METHODS: The reliability of the present DPI system was validated by continuously monitoring the concentration and particle size distribution of aerosols generated with an ambient particulate monitor and an Andersen air sampler, respectively. The pharmacological effect of SM-DP intratracheally administered to guinea pig was investigated by measuring the degree of bronchoconstriction and microvascular leakage induced by leukotriene D4. RESULTS: The mass concentration of aerosols generated by the DPI system was stable and the mass median aerodynamic diameter of aerosols insufflated from the respirator of the DPI system ranged from 1.4 to 1.7 microm, within respirable limits. Inhibition of bronchoconstriction and airway microvascular leakage induced by leukotriene D4 was achieved successfully with a dramatically lower dose of DP, or a further lower dose of SM-DP, comparable with that of the drug solution injected intravenously. The plasma pranlukast hydrate level with SM-DP at 50% inhibition of bronchoconstriction and airway microvascular leakage was reduced to 1/10 or less that following IV and PO administration. CONCLUSIONS: The hydrophilically surface-modified pranlukast hydrate powders were ideally aerosolized by the present DPI system, and were uniformly deposited in the lung lobes after inhalation. The pulmonary administration system with SM-DP is strongly recommended as an ideal system for the treatment of bronchial asthma in order to avoid systemic side-effects due to a dramatically reduced ED50, comparable with or lower than IV, and the low plasma concentration of drug, 1/12 or less than that following IV and PO administration.

Administration, Inhalation↗
PubMed1998

Serum thrombopoietin level is mainly regulated by megakaryocyte mass rather than platelet mass in human subjects.

A patient with idiopathic thrombocytopenic purpura (ITP) developed T-cell lymphoma while undergoing steroid therapy. We examined the relationship between the patient's serum thrombopoietin (Tpo) level, platelet count, megakaryocyte number and CFU-Meg number during the second 5 d course of chemotherapy for lymphoma in which megakaryopoiesis switched from ITP phase to amegakaryocytic phase. The patient's platelet count was temporarily elevated but CFU-Meg numbers were markedly suppressed, and megakaryocyte numbers were decreased in this period, whereas serum Tpo level was not suppressed despite an increased platelet count, indicating that serum Tpo level is mainly regulated by megakaryocyte mass.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Postinfarction left-ventricular aneurysm: regional stress, function, and remodeling after aneurysmectomy.

BACKGROUND: Left-ventricular (LV) aneurysm formation after myocardial infarction (MI) leads to LV remodeling with global and regional cardiac dysfunction. LV aneurysmectomy (LVA) can often improve LV function, but changes of regional wall stress and systolic function in the noninfarcted segment before and after the operation remain poorly understood. The purpose of this study was to assess the effects of LVA on regional stress and systolic function in the noninfarcted region and to examine this procedure's impact on the LV remodeling in patients with LV aneurysm after myocardial infarction (MI). METHODS: Using quantitative left ventriculography and pressure measurements, 11 patients with an anterior LV aneurysm were studied before and 8 months after standard linear repair (LVA group), and 10 patients with an anterior transmural infarction who received coronary artery bypass grafting were also studied (CABG group) in an attempt to separate the effects of aneurysmectomy from the effects of bypass surgery. Regional end-systolic (ESS) and end-diastolic (EDS) stresses of the contractile segment (CS) were computed by Janz's method. RESULTS: The total ejection fraction (EF) increased (p < 0.01) in the LVA group, whereas it did not change in the CABG group at 8 months after surgery. Both the end-diastolic and end-systolic volume indices of CS decreased (p < 0.01 and p < 0.01, respectively) in the LVA group, whereas both remained unchanged in the CABG group. The mean velocity of circumferential fiber shortening (mean Vcf) of CS increased substantially (p < 0.01) in the LVA group and, less significantly (p < 0.05), in the CABG group. Regional ESS and EDS decreased (p < 0.01 and p < 0.05, respectively) in the LVA group, whereas both remained unchanged in the CABG group. The increase in mean Vcf correlated strongly with the magnitude of decrease in ESS (r = -0.63, p < 0.01) in the LVA group but not in the CABG group. CONCLUSIONS: LVA can reduce regional afterload and improve ejection performance of the noninfarcted myocardium in many patients with a large anterior LV aneurysm and, moreover, may favorably affect the LV remodeling process after MI.

Cardiac Catheterization↗
PubMed1998

Recombinant TIMP-1 and -2 enhance the proliferation of rabbit corneal epithelial cells in vitro and the spreading of rabbit corneal epithelium in situ.

PURPOSE: The repair of the corneal epithelium is modulated by matrix metalloproteinases. The present study examined the effects of recombinant (r-) tissue inhibitors of metalloproteinases-1 and -2 (TIMP-1 and -2) on the proliferation of cultured epithelial cells from rabbit cornea, and on the spreading of a sheet of squamous epithelium of rabbit cornea placed in an organ culture system. METHODS: DNA synthesis of the cells, with or without r-TIMPs, was determined by an immunoassay for BrdU incorporation. Cell proliferation was assayed by measuring MTT mitochondrial activity. Epithelial spreading was evaluated by culturing small corneal blocks for 24 h in the presence or absence of each agent. Cryosections were prepared and the epithelial growth on the cut stromal surface was measured. RESULTS: Each agent, r-TIMP-1 (at 50 and 100 ng/ml) and r-TIMP-2 (at 50 ng/ml) significantly enhanced the DNA synthesis and MTT activity of the corneal epithelial cells in vitro. Relative to the untreated control cells, DNA synthesis was increased 2.4-fold by r-TIMP-1 and 2.3-fold by r-TIMP-2. r-TIMP-1 (at 100 and 200 ng/ml) and r-TIMP-2 (at 10 and 50 ng/ml) each significantly enhanced the spreading of the corneal epithelium. Relative to the untreated control tissue, spreading of the epithelial sheet was increased 1.7-fold by r-TIMP-1 and 1.4-fold by r-TIMP-2. Higher concentrations of r-TIMP-1 and r-TIMP-2 did not further enhance either the DNA synthesis of the cultured cells or the spreading of the epithelium. CONCLUSIONS: Exogenous TIMPs enhanced the spreading of the corneal epithelium and proliferation of cultured corneal epithelial cells. Findings suggest that endogenous TIMPs may influence the healing of corneal epithelium in vivo.

Animals↗
PubMed1998

Beta adrenergic antagonist permeation across cultured rabbit corneal epithelial cells grown on permeable supports.

PURPOSE: To determine whether cultured rabbit corneal epithelial cells (RCEC), grown on permeable supports, provide a suitable in vivo model for characterizing transcellular drug permeation and metabolism. METHODS: Primary rabbit corneal epithelial cells grown in DMEM-F12 were seeded on Transwell-COL inserts coated with fibronectin. The epithelial barrier integrity was evaluated, based on measurements of 14C-mannitol and 3H-PEG900, and their transepithelial electrical resistance (TEER). Ultrastructure evaluation was based on scanning electron microscopy and transmission electron microscopy, which were performed 8 days after seeding. Measurements of beta adrenergic antagonist permeability were performed to assess transcellular permeability. RESULTS: Eight days after seeding, the TEER reached a peak of 144 omega.cm2 and the 14C-mannitol and 3H-PEG900 permeabilities were 6.8 x 10(-6) and 2.9 x 10(-6) cm/sec, respectively. Ultrastructural analysis revealed a multilayered structure with numerous microplicae and typical cytoplasmic organelles along with desmosomes. The relationship between permeation of beta-blockers and lipophilicity resembled the intact isolated cornea. CONCLUSIONS: This is the first description of cultured RCEC grown on permeable support. Many of its properties mimic those described in the intact corneal epithelium. Even though its electrical tightness is less than that of the intact cornea, the transcellular permeability to lipophilic beta-antagonists is comparable to the isolated preparation. Therefore, this model will facilitate characterization of ocular permeation mechanisms of hydrophobic drugs whose route of permeation is transcellular.

Adrenergic beta-Antagonists↗
PubMed1998

OPC-15161 suppresses the proliferation of Tenon's capsule fibroblasts and the production of type I collagen and fibronectin stimulated by TGF-beta1 in vitro.

PURPOSE: We investigated the effects of OPC-15161 on the growth of cultured human Tenon's capsule fibroblasts (TCFs), as well as on the production of type I procollagen, fibronectin, and laminin. These effects were examined in the presence or absence of TGF-beta1. METHODS: Cell proliferation was assayed by counting cell number and assay of DNA synthesis. Cytotoxicity was determined by the MTT method. Matrix components were assayed by enzyme immunoassay of material in the medium and in the cell lysate with or without OPC-15161. Total protein content was determined. Cellular ultrastructure was also evaluated. RESULTS: Treatment with OPC-15161 (up to 100.0 microg ml(-1)) significantly reduced the proliferation and DNA synthesis of TCFs. No significant decrease in MTT values was observed in confluent TCF cultures with OPC-15161 (up to 100.0 microg ml(-1)). TGF-beta1 enhanced the TCF production of procollagen I and fibronectin. OPC-15161 significantly decreased the procollagen I content in both the medium, in the cell lysate of TGF-beta1-stimulated cells, and fibronectin content in the lysate. OPC-15161 did not affect the laminin or total protein content, either with or without TGF-beta1. No ultrastructural evidence of cytotoxicity was observed. CONCLUSIONS: OPC-15161 inhibited the proliferation of TCFs, and reduced their production of procollagen I and fibronectin in the presence of TGF-beta1 without evidence of cytotoxicity. OPC-15161 may be useful in inhibiting the excessive fibrosis produced in the wound in response to filtering surgery.

Adult↗
PubMed1998

Immunolocalization of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human subconjunctival tissues.

PURPOSE: To evaluate the roles of fibroblast proteins in the remodeling of the subconjunctival connective tissue, we immunohistochemically assessed the expression of matrix metalloproteinases (MMP)-1 and -2, and the tissue inhibitors of matrix metalloproteinases (TIMP)-1 and -2 in cultured human subconjunctival fibroblasts and in normal and healing human subconjunctival connective tissue. METHODS: Cultured fibroblasts derived from human subconjunctival connective tissue and surgical specimens of normal and healing conjunctiva were immunostained with monoclonal antibodies directed against human MMPs and TIMPs and examined by light and electron microscopy. RESULTS: In the cultured fibroblasts, MMP-1 and TIMP-1 antibodies stained the cytoplasm in a fine granular pattern, suggesting localization of those proteins in the endoplasmic reticulum (ER) and Golgi apparatus. Antibodies to MMP-2 and TIMP-2 reacted with fibroblast cytoplasm in a granular pattern. Electron microscopy of those fibroblasts revealed MMP-1 and TIMP-1 immunoreactivity in the ER cisternae or on the membrane of the ER. In surgical samples, MMP-1 and TIMP-1 were immunohistochemically detected in healing subconjunctival tissue, but not in conjunctival epithelium or normal subconjunctival tissue. CONCLUSIONS: MMPs and TIMPs may be involved in remodeling of subconjunctival connective tissue and in fibroblast population after surgical interventions. These proteins may play a crucial role in the post-operative fibrotic process occurring during scar formation in subconjunctival tissue.

Adult↗
PubMed1998

Efficacy of hypothermic perfusion using University of Wisconsin solution in extended hepatectomy with hepatic inflow occlusion in a canine model.

This study was designed to elucidate the efficacy of University of Wisconsin (UW) solution for preventing liver injury, when used as a hypothermic perfusate infused into the systemic circulation during extended hepatectomy with hepatic inflow occlusion. Adult mongrel dogs (9.5-17.5 kg, n = 14) were subjected to 75% hepatectomy under 60 min hepatic inflow occlusion. The animals were divided into two groups. The UW group (n = 7) underwent hypothermic perfusion using 4 degrees C UW solution (core temperature of the liver: 12.3 +/- 0.2 degrees C). The control group designated as the Ringer's lactate (LR) group (n = 7) underwent hypothermic perfusion using 4 degrees C LR solution. The perfusate was introduced into the systemic circulation via the hepatic vein. Blood from the hepatic vein was sampled, and alanine aminotransferase, purine nucleoside phosphorylase activities and the ammonia concentration were measured. The 7 day survival rate was higher in the UW group than in the LR group. The parameters of liver function were less significantly altered in the UW group than in the LR group. The plasma ammonia concentration was significantly (P < 0.05) lower 6 h after reperfusion in the UW group than in the LR group. A small volume of hypothermic perfusion of the liver using UW solution was safe if it returned to systemic circulation. Hypothermic perfusion of the liver using UW solution may be effective for preventing hepatic tissue injury during extended hepatectomy with hepatic vascular occlusion.

Adenosine↗
PubMed1998

Effects of sphingomyelin and cholesterol on lipoprotein lipase-mediated lipolysis in lipid emulsions.

Lipoprotein lipase (LPL) hydrolyzes triacylglycerol (TG) of TG-rich lipoproteins. We investigated the effects of sphingomyelin (SM) and cholesterol (Chol) on the lipolysis of lipid emulsions by LPL using human apolipoprotein C-II (apoC-II) or plasma as an activator. Kinetic studies of the lipolysis rates clearly demonstrated that the primary effect of the activator on the LPL reaction was not to increase the affinity of LPL for the emulsion surface, but to enhance LPL catalytic activity. Incorporation of SM into the emulsion surface caused increases in Km(app) and decreases in Vmax(app), indicating that SM inhibited lipolysis by decreasing both affinity for substrates and catalytic activity of LPL. SM was also found to affect possible factors related to the lipolysis rates; that is, SM increased TG solubility in surface layers and decreased apoC-II binding to the emulsion surface. Interestingly, Chol did not affect the lipolysis rates even though it decreased TG solubility and apoC-II binding. These results indicated that neither TG solubility nor amount of apoC-II binding were determinate factors in LPL-mediated lipolysis under physiological conditions. Our results suggest that the content of SM in the lipoprotein surface plays an important role by controlling lipoprotein lipase-mediated lipolysis, and that cholesterol enrichment in the lipoprotein surface has no influence on lipolysis, but may affect other metabolic processes such as uptake by the liver through the selectivity of apolipoprotein binding.

Apolipoprotein C-II↗
PubMed1998

Afferent reinnervation after lung transplantation in the rat.

Denervation at lung transplantation results in loss of cough reflex and attenuated local defense mechanisms, accounting for increased incidence and severity of infection after lung transplantation. We studied the presence or absence of spontaneous afferent reinnervation in rats at various intervals after orthotopic left pulmonary isografting (n = 52). Normal rats (n = 21) and rats undergoing left hilar stripping (n = 14) served as control subjects. Afferent reinnervation was tested physiologically by reflex bradycardia in response to intravenous infusion of capsaicin (30 microg/kg), an extract of paprika stimulating pulmonary C-fibers. Injection of capsaicin was repeated before and after right pulmonary artery occlusion to divert all pulmonary blood flow to the left lung or isograft. Whereas rats early after surgical denervation lost the reflex after right pulmonary artery occlusion, rats examined 8 months or longer after surgery showed potent reflex bradycardia in response to capsaicin, as did the control rats. Immunohistochemical staining for sensory neuron-specific substances, such as calcitonin gene-related peptide and substance P, were identified only in the right native lung and left pulmonary isografts 2 months or longer after transplantation. Fluorogold was found only in the ipsilateral nodose ganglion after left lung intrapleural injection of the neuron-specific tracer in rats 8 months or longer after denervation. These experiments provide physiological, morphologic, and neurologic evidence suggesting that afferent lung innervation, abolished early after transplantation, is spontaneously reestablished and functioning in the ipsilateral vagus nerve by 8 months after pulmonary isografting in the rat.

Animals↗
PubMed1998

Effects of taltirelin hydrate (TA-0910), a novel thyrotropin-releasing hormone analog, on in vivo dopamine release and turnover in rat brain.

Effects of taltirelin hydrate (CAS 103300-74-9, TA-0910), a novel thyrotropin-releasing hormone (TRH) analog, on the cerebral monoamine systems, especially the release and turnover of dopamine (DA) in rat brain were compared with those of TRH by intraperitoneal administration. Taltirelin hydrate (1-10 mg/kg) increased the extracellular levels of DA and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens and corpus striatum for 3 h in a microdialysis study. TRH (30 mg/kg) also increased the levels of these substances, the potency of TRH being the same as that of taltirelin hydrate at doses of 1-3 mg/kg. Taltirelin hydrate (10 mg/kg) also caused an increase in 3-methoxytyramine (3-MT: DA metabolite) until 6 h after the treatment and L-3-dihydroxyphenylalanine (DOPA: precursor of DA and noradrenaline). Taltirelin hydrate also increased the 3-methoxy-4-hydroxyphenylglycol (MHPG: noradrenaline metabolite) level in the frontal cortex and hypothalamus, and 5-hydroxytryptophan (5-HTP: serotonin precursor) accumulation and 5-hydroxyindoleacetic acid (5-HIAA: serotonin metabolite) level in the nucleus accumbens or corpus striatum. These results suggest that taltirelin hydrate possesses not only an enhancing effect on DA release, but also a stimulating effect on the monoamine system. Moreover, these actions were 10-30 times stronger and also longer-lasting than those of TRH. In addition, the mechanisms of DA release induced by these drugs were different from those induced by methamphetamine.

5-Hydroxytryptophan↗
PubMed1998

[Does mixed venous desaturation during a bed bath indicate cardiopulmonary decompensation in postoperative cardiac patients?].

The bed bath procedure consists of cleansing patients' body, passive position change, changing gown and making a bed. During the procedure, mixed venous desaturation was observed consistently in postoperative cardiac patients. We investigated the cause of the phenomenon in 22 patients undergoing cardiac surgery in their first postoperative day. The patients were breathing oxygen-enriched air via a Venturi mask. Cardiac index (CI), transluminal SvO2, arterial blood gas, Hb, DO2, VO2, FIO2, A-aDO2 and Qp/Qs were measured before and during the bed bath, while the patients were in the supine and left lateral position, respectively. Mean 8.5 +/- 1.5 minutes were required to complete the bed bath. During the bed bath, SvO2 decreased from 71 +/- 7% to 59 +/- 9% (P < 0.001), and returned to the baseline 6.5 +/- 7.4 minutes after the completion of the bed bath. VO2 increased markedly from 128 +/- 27 to 194 +/- 47 ml.min-1.m-2 (P < 0.001), while DO2 increased slightly from 480 +/- 91 to 513 +/- 110 ml.min-1.m-2 (P < 0.05). Among the determinants of DO2, CI increased slightly from 3.3 +/- 0.6 to 3.6 +/- 0.8 l.min-1.m-2, Hb remained unchanged and SaO2 decreased from 98.5 +/- 0.8 to 98.0 +/- 1.1%. FIO2 also decreased, while A-aDO2 and Qp/Qs remained unchanged. There was a negative correlation between VO2 change and SvO2 change, but no correlation between DO2 change and SvO2 change. There was a positive correlation between SaO2 change and SvO2 change, as well as between FIO2 change and SaO2 change. Therefore, the major cause of mixed venous desaturation was not the decreased DO2 or cardiopulmonary decompensation but the increased VO2 due to increased activity of the skeletal muscles. However, the decrease in SaO2 due to markedly increased O2 demand and the limited increase in CI might partially contribute to the marked decline in SvO2 through the limited increase in DO2.

Aged↗
PubMed1997

Coagulation and fibrinolysis system in aortic surgery under deep hypothermic circulatory arrest with aprotinin: the importance of adequate heparinization.

BACKGROUND: Coagulation and fibrinolysis parameters were compared between two strategies of heparinization during cardiopulmonary bypass (CPB) in patients who underwent aortic surgery with deep hypothermic circulatory arrest (DHCA) and retrograde cerebral perfusion (RGCP) with aprotinin. METHODS AND RESULTS: From January 1994 to January 1996, 94 patients underwent aortic surgery with DHCA with aprotinin; replacement of the ascending aorta took place in 14 patients, arch in 69, and descending aorta in 11. Two million units of aprotinin was administrated in the priming of CPB, and 3 mg/kg heparin was given before CPB. During CPB, 49 patients had an additional 1 mg/kg/h heparin regardless of activated clotting time (ACT) [group A], whereas 45 patients had an additional 1 mg/kg/h heparin when ACT was less than 500 seconds [group B]. ACT, PT, aPTT, fibrinogen, AT-3, plasminogen, alpha2-PI (plasmin inhibitor), fibrin/fibrinogen degradation products (FDP), DD (D dimer), TAT (thrombin-antithrombin complex), PIC (plasmin-plasmin inhibitor complex), beta-TG (thromboglobulin), and PF-4 (platelet factor-4) were assayed. No difference was detected between the two groups regarding the duration of operation, CPB, aortic cross-clamping, DHCA, RGCP, and time from the end of CPB to admission to ICU. The heparin dose was greater in group A, but the protamine dose was similar. There was no difference in bleeding after perfusion or in ICU. Levels of TAT, fibrinogen, and DD were lower in group A. PIC, alpha-PI, and FDP value showed no difference. PF-4 and beta-TG were lower in group A, and the platelet count at the end of operation and the day after the operation was higher in group A. CONCLUSIONS: Platelets were better preserved and activation of the coagulation system during CPB was less severe in patients who had a regular additional constant heparin regimen irrespective of ACT in surgery for the aortic aneurysm with DHCA and aprotinin usage. An accurate monitoring system for heparinization is necessary to maintain appropriate anticoagulation during CPB in patients who are undergoing aortic surgery with DHCA using aprotinin.

Adult↗