Biomedical subjects

Koichi Sato

Publications and source records attributed to Koichi Sato.

At least 73 records · Page 4Linked to original sources

PubMed2003

Ki16425, a subtype-selective antagonist for EDG-family lysophosphatidic acid receptors.

Lysophosphatidic acid (LPA) exerts a variety of biological responses through specific receptors: three subtypes of the EDG-family receptors, LPA1, LPA2, and LPA3 (formerly known as EDG-2, EDG-4, and EDG-7, respectively), and LPA4/GPR23, structurally distinct from the EDG-family receptors, have so far been identified. In the present study, we characterized the action mechanisms of 3-(4-[4-([1-(2-chlorophenyl)ethoxy]carbonyl amino)-3-methyl-5-isoxazolyl] benzylsulfanyl) propanoic acid (Ki16425) on the EDG-family LPA receptors. Ki16425 inhibited several responses specific to LPA, depending on the cell types, without any appreciable effect on the responses to other related lipid receptor agonists, including sphingosine 1-phosphate. With the cells overexpressing LPA1, LPA2, or LPA3, we examined the selectivity and mode of inhibition by Ki16425 against the LPA-induced actions and compared them with those of dioctyl glycerol pyrophosphate (DGPP 8:0), a recently identified antagonist for LPA receptors. Ki16425 inhibited the LPA-induced response in the decreasing order of LPA1 >/= LPA3 >> LPA2, whereas DGPP 8:0 preferentially inhibited the LPA3-induced actions. Ki16425 inhibited LPA-induced guanosine 5'-O-(3-thio)triphosphate binding as well as LPA receptor binding to membrane fractions with a same pharmacological specificity as in intact cells. The difference in the inhibition profile of Ki16425 and DGPP 8:0 was exploited for the evaluation of receptor subtypes involved in responses to LPA in A431 cells. Finally, Ki16425 also inhibited LPA-induced long-term responses, including DNA synthesis and cell migration. In conclusion, Ki16425 selectively inhibits LPA receptor-mediated actions, especially through LPA1 and LPA3; therefore, it may be useful in evaluating the role of LPA and its receptor subtypes involved in biological actions.

Animals↗

PubMed2003

Long-term effects of donepezil on P300 auditory event-related potentials in patients with Alzheimer's disease.

The P300, one of the cognitive event-related potentials (ERPs) of the cerebral cortex, reflects the functioning of the neurochemical system involved in cognitive processes. We investigated clinical significance of the components of auditory P300 ERPs, in comparison with neuropsychologic tests including the Mini-Mental State Examination and the Japanese version of the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-J cog), for evaluating of the effect of donepezil (DPZ) (5 mg daily for 6 months), an acetylcholinesterase inhibitor, in patients with Alzheimer's disease (AD). Reduction of P300 latency associated with a parallel improvement of ADAS-J cog scores was observed after administration of 5 mg/day of DPZ in patients with AD. P300 latency gives very useful information on the progression of AD, especially in the longitudinal follow-up of patients with AD during treatment with DPZ acting on cholinergic pathways.

Aged↗

PubMed2003

A comparison of hyperbaric 1% and 3% solutions of small-dose lidocaine in spinal anesthesia.

UNLABELLED: We examined whether the concentration of hyperbaric lidocaine affected the regression of motor block when the dose of lidocaine was kept constant at 30 mg. We also examined the spread, duration, and regression of sensory block. Sixty-five patients (ASA physical status I or II), scheduled for elective perineum or lower limb surgery, were enrolled in this study. Patients received spinal anesthesia with 1 mL of 3% lidocaine or 3 mL of 1% lidocaine. Adequate level of block was obtained for surgery in 63 of 65 patients. Whereas the administration of 3 mL of hyperbaric 1% lidocaine solution produced a level of sensory block similar to that produced by the administration of 1 mL of hyperbaric 3% lidocaine solution in spinal anesthesia, the administration of 3 mL of hyperbaric 1% lidocaine solution resulted in shorter times to full motor recovery and to urination and produced less motor block compared with 1 mL of hyperbaric 3% lidocaine solution. Two patients receiving 1% lidocaine and four patients receiving 3% lidocaine required IV ephedrine because of hypotension. Our results showed the clinical advantages of hyperbaric 1% lidocaine spinal anesthesia compared with hyperbaric 3% lidocaine spinal anesthesia for surgery of short duration. IMPLICATIONS: When the dose of lidocaine was kept constant at 30 mg, hyperbaric 1% lidocaine solution resulted in shorter times for recovery from motor block and to urination than did hyperbaric 3% lidocaine solution. Levels of sensory block were similar. Therefore, the more dilute lidocaine for spinal anesthesia may be suitable for day-care surgery and short duration surgery.

Aged↗

PubMed2003

Circulating thrombomodulin levels are related to latent progression of atherosclerosis in hypertensive patients.

The present study was designed to test the hypothesis that circulating levels of thrombomodulin are elevated in patients with hypertension in proportion to the severity of the vascular damage. A cross-sectional study was carried out using a population consisting of 96 patients with essential hypertension without clinically evident cardiovascular disease (mean age: 65 +/- 10 years) and 99 healthy normotensive control subjects (64 +/- 9 years). Blood was sampled and serum concentrations of soluble thrombomodulin were measured using an enzyme immunoassay method. We calculated the ratio of the concentration of thrombomodulin to that of creatinine, because soluble thrombomodulin is excreted by the kidney and the serum level of thrombomodulin was correlated with that of creatinine (p < 0.05). The association between the ratio and other clinical variables was investigated. The ratio of the thrombomodulin to creatinine concentrations was higher in hypertensive (29.3 +/- 10.9) than in control subjects (24.4 +/- 5.9; p < 0.0001). Systolic blood pressure was correlated with the ratio but the ratio showed no correlation with serum lipid levels when analyzed using data from all subjects. In hypertensive patients, the ratio correlated with the grade of sclerotic, but not hypertensive, changes in the fundus oculi (Scheie's classification, p < 0.001). Furthermore, the ratio correlated with brachial-ankle pulse wave velocity (p < 0.001). However, no correlation was detected between the ratio and blood pressure. These results suggest that circulating levels of thrombomodulin are elevated in hypertensive patients as compared to normotensive subjects and that the thrombomodulin level may be a molecular marker of the latent progression of atherosclerosis in hypertensive patients.

Aged↗

PubMed2003

Candesartan reduces oxidative stress and inflammation in patients with essential hypertension.

The present study was designed to test the hypothesis that blockade of angiotensin II type-1 receptors reduces oxidative stress and inflammation in patients with essential hypertension. The study population comprised 132 hypertensive patients, some receiving and others not receiving medical treatment. At enrollment their systolic and/or diastolic blood pressures were > or = 140 and/or > or = 90 mmHg, respectively. The serum concentration of C-reactive protein, and the urine concentrations of 8-epi-prostaglandin F2alpha and 8-hydroxydeoxyguanosine were measured at baseline and after 12 weeks of treatment either with an angiotensin II type-1 receptor blocker, candesartan (8 mg daily) (age 64 +/- 12 years; male/female 28/39; n = 67), or other antihypertensive agents that do not block the renin-angiotensin system (age 65 +/- 10 years, male/female 25/40, n = 65). Candesartan reduced the levels of C-reactive protein (from 0.07 +/- 0.04 [median value +/- median absolute deviation] to 0.06 +/- 0.03 mg/dl, p < 0.0001), 8-epi-prostaglandin F2alpha (from 210 +/- 92 to 148 +/- 59 pg/mg creatinine, p < 0.0001), and 8-hydroxydeoxyguanosine (from 5.7 +/- 1.9 to 4.0 +/- 1.3 ng/mg creatinine, p < 0.0001), while the levels of these markers were not altered after the treatment with other antihypertensive agents. Blood pressure decreased by a similar amount in both groups, and the reductions in the levels of the markers did not correlate with that of blood pressure. These results suggest that candesartan reduces oxidative stress and inflammation in hypertensive patients independently of its effects on blood pressure. This may provide useful information for determining therapeutic strategies to minimize tissue injury by inflammation and oxidative stress in hypertensive patients.

Adult↗

PubMed2003

Increased endogenous endothelin-1 in coronary circulation is associated with restenosis after coronary angioplasty.

BACKGROUND: The relationship between vasoactive substances, including endothelin-1, nitric oxide, serotonin, angiotensin II and noradrenaline, and coronary restenosis after percutaneous transluminal coronary angioplasty (PTCA) is not clear. OBJECTIVE: To determine whether any vasoactive substance may be a marker of coronary restenosis after PTCA. METHODS: Twenty-nine patients with angina pectoris underwent elective PTCA. Three months after PTCA, coronary angiography was performed again to study the patency of the lesions. Seven patients had coronary restenosis (greater than 50% stenosis) (restenosis group) and the rest of the patients were without restenosis (patency group). Their blood samples were obtained from the coronary sinus before, immediately after and three months after PTCA. RESULTS: Endothelin-1 levels obtained immediately after PTCA (3.44+/-0.26 pg/mL) and three months after PTCA (3.57+/-0.29 pg/mL) were significantly higher than those obtained before PTCA (3.00+/-0.26 pg/mL) in the restenosis group, but not in the patency group (3.34+/-0.15 pg/mL, 3.02+/-0.17 pg/mL and 3.14+/-0.18 pg/mL, respectively). A transient decrease in nitrite/nitrate levels was observed immediately after PTCA in both groups. The serotonin levels three months after PTCA were significantly decreased in the patency group, but not in the restenosis group, and the levels of angiotensin II and noradrenaline did not change in either group throughout the study. CONCLUSIONS: Among several vasoactive substances, endothelin-1 seems to be associated with the process of coronary restenosis after PTCA. Increased endothelin-1 levels in the coronary circulation after PTCA may indicate an increased risk of coronary restenosis.

Aged↗

PubMed2002

Decreased endothelial nitric-oxide synthase (eNOS) activity resulting from abnormal interaction between eNOS and its regulatory proteins in hypoxia-induced pulmonary hypertension.

In the pulmonary artery isolated from 1-week hypoxia-induced pulmonary hypertensive rats, endothelial NO production stimulated by carbachol was decreased significantly in in situ visualization using diaminofluorescein-2 diacetate and also in cGMP content. This change was followed by the decrease in carbachol-induced endothelium-dependent relaxation. Protein expression of endothelial NO synthase (eNOS) and its regulatory proteins, caveolin-1 and heat shock protein 90, did not change in the hypoxic pulmonary artery, indicating that chronic hypoxia impairs eNOS activity at posttranslational level. In the hypoxic pulmonary artery, the increase in intracellular Ca(2+) level stimulated by carbachol but not by ionomycin was reduced. We next focused on changes in Ca(2+) sensitivity of the eNOS activation system. A morphological study revealed atrophy of endothelial cells and a peripheral condensation of eNOS in hypoxic endothelial cells preserving co-localization between eNOS and Golgi or plasma membranes. However, eNOS was tightly coupled with caveolin-1, and was dissociated from heat shock protein 90 or calmodulin in the hypoxic pulmonary artery in either the presence or absence of carbachol. Furthermore, eNOS Ser(1177) phosphorylation in both conditions significantly decreased without affecting Akt phosphorylation in the hypoxic artery. In conclusion, chronic hypoxia impairs endothelial Ca(2+) metabolism and normal coupling between eNOS and caveolin-1 resulted in eNOS inactivity.

Animals↗

PubMed2002

Xestospongin C, a novel blocker of IP3 receptor, attenuates the increase in cytosolic calcium level and degranulation that is induced by antigen in RBL-2H3 mast cells.

1. We evaluated the role of the cross-linking of Fc epsilon RI-mediated inositol 1,4,5-triphosphate (IP(3)) in the increase in cytosolic Ca(2+) level ([Ca(2+)](i)) using xestospongin C, a selective membrane permeable blocker of IP(3) receptor, in RBL-2H3 mast cells. 2. In the cells sensitized with anti-dinitrophenol (DNP) IgE, DNP-human serum albumin (DNP-HSA) and thapsigargin induced degranulation of beta-hexosaminidase and a sustained increase in [Ca(2+)](i). Xestospongin C (3 - 10 microM) inhibited both of these changes that were induced by DNP-HSA without changing those induced by thapsigargin. 3. In the absence of external Ca(2+), DNP-HSA induced a transient increase in [Ca(2+)](i). Xestospongin C (3 - 10 microM) inhibited this increase in [Ca(2+)](i). 4. In the cells permeabilized with beta-escin, the application of IP(3) decreased Ca(2+) in the endoplasmic reticulum (ER) as evaluated by mag-fura-2. Xestospongin C (3 - 10 microM) inhibited the effect of IP(3). 5. After the depletion of Ca(2+) stores due to stimulation with DNP-HSA or thapsigargin, the addition of Ca(2+) induced capacitative calcium entry (CCE). Xestospongin C (3 - 10 microM) inhibited the DNP-HSA-induced CCE, whereas it did not affect the thapsigargin-induced CCE. 6. These results suggest that Fc epsilon RI-mediated generation of IP(3) contributes to Ca(2+) release not only in the initial phase but also in the sustained phase of the increase in [Ca(2+)](i), resulting in prolonged Ca(2+) depletion in the ER. The ER Ca(2+) depletion may subsequently activate CCE to achieve a continuous [Ca(2+)](i) increase, which is necessary for degranulation in the RBL-2H3 mast cells. Xestospongin C may inhibit Ca(2+) release and consequently may attenuate degranulation.

Animals↗

PubMed2002

FcepsilonRI cross-linking-induced actin assembly mediates calcium signalling in RBL-2H3 mast cells.

1. To determine the role of actin assembly in the Ca(2+) signalling of mast cells activated by cross-linking of FcepsilonRI, we examined the effects of cytochalasin D, an inhibitor of actin polymerization. 2. In the RBL-2H3 cells, F-actin content was increased by sensitization with anti-dinitrophenol (DNP) IgE. In these cells, cytochalasin D induced oscillatory increases in cytosolic Ca(2+) ([Ca(2+)](i)); these increase were inhibited by jasplakinolide, a stabilizer of actin filaments. 3. In the IgE-sensitized RBL-2H3 cells, DNP-human serum albumin (DNP-HSA) augmented actin assembly. DNP-HSA also increased the production of IP(3), [Ca(2+)](i) and degranulation. Cytochalasin D enhanced all of these DNP-HSA-induced effects. 4. In a Ca(2+)-free solution, DNP-HSA induced a transient increase in [Ca(2+)](i), and this increase was accelerated by cytochalasin D. After cessation of the DNP-HSA-induced Ca(2+) release, the re-addition of Ca(2+) induced a sustained increase in [Ca(2+)](i) through capacitative Ca(2+) entry (CCE), and this increase was enhanced by cytochalasin D. 5 The effect of cytochalasin D in enhancing the CCE activity was prevented by xestospongin C. 6. In contrast, neither the Ca(2+) release nor the CCE activation that was induced by thapsigargin was affected by cytochalasin D. 7. These results suggest that actin de-polymerization stimulates the FcepsilonRI-mediated signalling to augment the release of Ca(2+) from the endoplasmic reticulum in RBL-2H3 cells.

Actins↗

PubMed2002

At least thirty-four days of animal continuous perfusion by a newly developed extracorporeal membrane oxygenation system without systemic anticoagulants.

We developed an extracorporeal membrane oxygenation (ECMO) system with high antithrombogenicity and durability characteristics for prolonged continuous cardiopulmonary support. The oxygenator consists of a special hollow-fiber-type polyolefin gas-exchange membrane, which has an ultrathin dense layer in contact with the blood, in order to prevent plasma leakage during protracted use (Platinum Cube NCVC). The centrifugal pump (RotaFlow) is free of seals. The entire blood-contacting surface of the system is coated with a newly developed heparin material (Toyobo-NCVC coating). We performed a venoarterial bypass in a goat, and the ECMO system was driven for 34 days without systemic anticoagulants. Plasma leakage from the oxygenator did not occur, and sufficient gas exchange performance was maintained. Thrombus formation was hardly observed in the ECMO system except in the casing margins of the oxygenator. This ECMO system showed potential for long-term cardiopulmonary support with minimal or no use of systemic anticoagulants.

Animals↗

PubMed2002

Prostaglandin synthesis inhibitor affects humoral conditions and oxygen metabolism during normothermic cardiopulmonary bypass.

We have reported that infusion of prostaglandin synthesis inhibitor (PGSI) reduced the severity of hypotension during normothermic cardiopulmonary bypass (CPB). In the present study, we investigated the effects of PGSI on humoral conditions and whole body oxygen metabolism during normothermic CPB conducted for 60 min in 8 adult goats. The PGSI group (n = 4) was administered 100 to 150 mg of flurbiprofen, a potent PGSI, before and during CPB, and the control group (n = 4) was administered noradrenaline (NA) to restore hypotension. The prostaglandin E2 (PGE2) and NA concentrations in the PGSI group were significantly lower than those of the control group (PGE2 8.8 +/- 1.0 versus 30.3 +/- 11.5 pg/ml, NA 431 +/- 197 versus 3847 +/- 2,153 pg/ml). The adrenaline concentration was not significantly different between the groups. The oxygen consumption and the oxygen extraction rate were not significantly different between the groups, but the blood lactate level in the PGSI group was lower than that of the control group (34.3 +/- 7.6 versus 43.7 +/- 3.8 mg/dl). In conclusion, PGSI improves humoral disorder and thus prevents inadequate tissue oxygen delivery.

Analysis of Variance↗

PubMed2002

Morphological changes of the arterial systems in the kidney under prolonged continuous flow left heart bypass.

We investigated morphological changes of the arterial systems in the kidneys under prolonged continuous flow left heart bypass. Twelve goats were subjected to 2 weeks of pulsatile left heart bypass followed by 4 weeks of continuous flow left heart bypass (group CF). After autopsy, the kidneys underwent pathological evaluation. Six normal healthy goats were used as controls. The media of the afferent arterioles of group CF were frequently thickened by an increase in the number of the mature smooth muscle cells (SMCs). The juxtaglomerular areas (JGA) were expanded because of an increase in the number and size of SMCs and/or SMC-like cells. Furthermore, the percentage of anti-proliferating cell nuclear antigen antibody-positive cells in the JGA of group CF (9.9 +/- 1.9%) was significantly higher (p = 0.025) than that of the control group (4.6 +/- 3.4%), indicating active proliferation in group CF. We concluded that prolonged continuous flow left heart bypass causes proliferation of SMCs and/or SMC-like cells in the afferent arterioles and their perivascular tissue.

Animals↗

PubMed2002

Effect of troglitazone on endothelial function in type 2 diabetic patients.

Lysophosphatidylcholine (lysoPC), a component of oxidized low-density lipoprotein cholesterol (LDL-C), has been reported to impair nitric oxide production and endothelium-dependent vasorelaxation. The effects of troglitazone (CAS 97322-87-7), which is an antidiabetic agent with antioxidant properties, on serum levels of lysoPC and nitrite/nitrate (NOx) have been studied. Eight patients with Type 2 diabetes (non-insulin dependent diabetes mellitus, NIDDM) were studied (age: 61.5 +/- 2.8 years; diabetes duration: 10.2 +/- 1.6 years). They were additionally given troglitazone (200 mg once daily) since their fasting plasma glucose (FPG) and HbA1c levels had been increased in spite of conventional medications. Before and after 12 weeks of treatment with troglitazone their blood pressure, FPG, HbA1c, lipid profiles and NOx were measured. Troglitazone treatment had a slight depressor effect (decreasing the blood pressure from 133 +/- 5/72 +/- 3 to 127 +/- 4/68 +/- 1 mmHg; p < 0.05). FPG and HbA1c were significantly decreased with the therapy (181 +/- 10 to 160 +/- 10 mg/dl; p < 0.05 and 9.1 +/- 0.6 to 8.1 +/- 0.5%; p < 0.05, respectively). In contrast, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and LDL-C were maintained within normal limits throughout the study. Although lysoPC and NOx levels were not altered, a negative correlation between lysoPC and NOx levels was observed. These results suggest that troglitazone is a beneficial agent improving FPG and HbA1c levels in NIDDM patients, while its effects on serum lysoPC and NOx levels, at least for 12 weeks, seem to be minimal.

Aged↗

PubMed2002

Altered effect of cyclopiazonic acid on endothelium-dependent relaxation in femoral arteries from hypertensive rats.

The function of endoplasmic reticulum in hypertensive vascular endothelium has not been intensively studied. The current study was designed to investigate a role of intracellular Ca2+ stores in endothelium-dependent relaxations to acetylcholine using femoral arteries obtained from Wistar-Kyoto (WKYs) and spontaneously hypertensive rats (SHRs). Rings were prepared from the femoral arteries and changes in isometric tension were recorded. Endothelium-dependent relaxations induced by acetylcholine in rings contracted with serotonin were identical in WKYs and SHRs. Cyclopiazonic acid (CPA) inhibited the relaxation in SHRs but not in WKYs. In WKYs, acetylcholine evoked smaller relaxations in rings contracted with KCl than in those contracted with serotonin, whereas in SHRs the relaxation was not affected by the contractile agonists used. The relaxation in rings contracted with KCl was abolished by Nw-nitro-l-arginine methyl ester (l-NAME) and was reduced by CPA to a similar extent in both strains. In rings contracted with serotonin, l-NAME abolished the relaxation in SHRs, but the inhibitor only partially reduced the relaxation in WKYs. CPA did not alter the relaxation in the presence of l-NAME. Endothelium-independent relaxations to sodium nitroprusside were not affected by CPA. These results suggest that acetylcholine relaxes rat femoral arteries by releasing both nitric oxide and endothelium-derived hyperpolarizing factor (EDHF). In SHRs, the relaxation is preserved, but the release of EDHF is absent. CPA inhibits the relaxation mediated by nitric oxide, but not EDHF and, thus, inhibits the relaxation in SHRs but not in WKYs. Functional alteration of endoplasmic reticulum in the hypertensive endothelium cannot be detected.

Acetylcholine↗

PubMed2002

Inhibitors of pentose phosphate pathway cause vasodilation: involvement of voltage-gated potassium channels.

Cytosolic reducing cofactors, such as NADPH and NADH, are thought to regulate vascular smooth muscle ion channel activity and vascular tone. In this study, the effects of pentose phosphate pathway (PPP) inhibitors, 6-aminonicotinamide (6-AN), epiandrosterone (EPI), and dehydroepiandrosterone (DHEA), on vascular tone were studied in isolated perfused lungs and pulmonary artery (PA) and aortic rings from rats. In addition, effects of 6-AN on voltage-gated K(+) (K(v)) current in PA smooth muscle cells (SMCs) were also examined. Pretreatment of lungs with 6-AN and EPI reduced the pressor response to acute hypoxia and decreased tissue NADPH levels. 6-AN, EPI, and DHEA relaxed isolated PA and aortic rings precontracted with 30 mM KCl in a dose-dependent manner. The PPP inhibitor-induced PA relaxations were reduced in PA rings precontracted with 80 mM KCl but not by pretreatment with nitro-L-arginine or endothelial removal. Pretreatment of PA rings with tetraethylammonium chloride or 4-aminopyridine caused rightward shifts of concentration-relaxation curves for 6-AN, EPI, and DHEA. In contrast, glybenclamide, charybdotoxin, or apamin did not inhibit the relaxant effects of 6-AN, EPI, and DHEA. 6-AN caused an increase in K(v) current in PASMC. These results indicate that reduction of NADPH by the PPP inhibitors causes vasodilation at least partly through opening of K(v) channels.

6-Aminonicotinamide↗

PubMed2002

Changes in the temporal organization of autobiographical memories.

The temporal organization of autobiographical memories was examined through the event-cueing technique. Participants were presented a word indicating a life-time period and asked to recall autobiographical events sequentially. Temporal relations between recalled events were analyzed. Analysis suggested that recent autobiographical memories are organized temporally. As time passes, however, organization becomes ambiguous, and old autobiographical memories can evoke temporally distant memories sharing the person, life theme, or other distinctive features.

Adult↗

PubMedDate not supplied

Prostaglandin synthesis inhibitor prevents hypotension without impairing gut perfusion during normothermic cardiopulmonary bypass.

Aortic pressure declines during cardiopulmonary bypass (CPB), particularly at normothermia. It has been reported that administering vasoconstrictors during normothermic CPB (NCPB) to restore perfusion pressure might induce hypoperfusion of splanchnic organs. We have reported that prostaglandin (PG), metabolized in the lung but increased during CPB, might have played a substantial role in hypotension, and that a PG synthesis inhibitor (PGSI) could improve hypotension during CPB. This study was designed to examine whether regional perfusion of splanchnic organs was reduced when PGSI restored systemic perfusion pressure during NCPB. NCPB was performed in eight adult goats for 60 minutes (body weight 57.0 +/- 5.9 kg). PGSI was administered in group P (n = 4), while norepinephrine was administered in group C (n = 4), to keep aortic pressure in the range of 50 to 80 mm Hg. The total systemic flow was maintained at approximately 70 ml/kg/min. Tissue blood flow was measured by means of the colored microsphere method before and 30 and 60 minutes after the start of CPB. In group P, gut blood flows after the start of CPB were higher than those before CPB, significantly in the stomach and jejunum at 30 minutes (p < 0.05), whereas gut blood flows in group C were decreased or not changed. In conclusion, PGSI prevents hypotension without impairing gut perfusion during NCPB.

Animals↗

PubMedDate not supplied

Ultrastructural alterations in red blood cell membranes exposed to shear stress.

In the mechanism of damage to red blood cells (RBCs) caused by a centrifugal pump, the prolonged effects to the RBC membrane caused by exposure to shear stress remain unclear. We focused on the band 3 protein (B3), one of the major proteins in the membrane skeleton, and investigated the ultrastructural alterations of the RBC membrane with loaded shear stress. Using flow cytometry, the relative amount of B3 was examined in relation to RBC deformability. The results, with continuous exposure to low shear stress, showed cell downsizing, an increase in B3 density, and a decrease in the deformability of the RBC membrane. Exposure to high shear stress does not appear to exert any influence on the membrane skeleton of the RBC. Therefore, in addition to conventional processes including the instantaneous destruction of a cell due to intense shear stresses, the results of the present study indicate the presence of another process based on changes in membrane proteins leading to cell fragmentation. Under low shear stress, the RBC membrane skeleton shows delayed destruction, which is exhibited as a disorder of B3 distribution, and the related membrane dysfunction includes decreases in RBC deformability and stability.

Animals↗