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Biomedical subjects

K Kubo

Publications and source records attributed to K Kubo.

At least 595 records · Page 33Linked to original sources
PubMed1988

Effects of hypobaria on lung fluid balance in awake sheep.

Effects of hypobaria on lung fluid balance were studied in five awake sheep with chronic lung lymph fistulas using a decompression chamber. Each sheep was exposed to three conditions of 6,600-m-simulated high altitude in random order as follows: 1) 6,600-m-simulated hypoxic hypobaria (barometric pressure 326 Torr, 21% inspired O2 fraction), 2) 6,600-m-simulated normoxic hypobaria (barometric pressure 326 Torr, 65% inspired O2 fraction), and 3) 6,600-m-simulated normoxic hypobaria (barometric pressure 326 Torr, 65% inspired O2 fraction) after pretreatment with a 2-h pure O2 inhalation (i.e., denitrogenation) to allow elimination of dissolved gases, especially N2, from the blood and tissues. We observed that under both hypoxic hypobaria and normoxic hypobaria, lung lymph flow (Qlym) significantly increased from the base-line values of 6.4 +/- 0.3 to 13.0 +/- 1.0 ml/h and 6.0 +/- 0.2 to 9.4 +/- 0.3 ml/h, respectively (P less than 0.05) and that the lymph-to-plasma protein concentration ratio remained unchanged. Moreover, pretreatment with a 2-h denitrogenation inhibited the increase in Qlym. These results suggest that rapid exposure to hypobaria causes an increase in pulmonary vascular permeability and that intravascular air bubble formation may account for this permeability change.

Altitude↗
PubMed1988

Role of barometric pressure in pulmonary fluid balance and oxygen transport.

To examine the role of barometric pressure in high-altitude pulmonary edema, we randomly exposed five unanesthetized chronically instrumented sheep with lung lymph fistulas in a decompression chamber to each of three separate conditions: hypobaric hypoxia, normobaric hypoxia, and normoxic hypobaria. A combination of slow decompression and/or simultaneous adjustment of inspired PO2 provided three successive stages of simulated altitudes of 2,600, 4,600, and 6,600 m during which hemodynamics and lymph flow were monitored. Under both hypoxic conditions we noted significant and equivalent elevations in pulmonary arterial pressure (Ppa), cardiac output, and heart rate, with left atrial and systemic pressures remaining fairly constant. Normoxic hypobaria was also accompanied by a smaller but significant rise in Ppa. Lymph flow increased to a highly significant maximum of 73% above base line, accompanied by a slight but significant decrease in lung lymph-to-plasma protein ratio, only under conditions of combined hypobaric hypoxia but not under equivalent degrees of alveolar hypoxia or hypobaria alone. Arterial hypoxemia was noted under all three conditions, with arterial PO2 being uniformly lower under hypobaric conditions than when identical amounts of inspired PO2 were delivered at normal atmospheric pressure. We therefore hypothesize that alveolar pressure significantly alters the Starling forces governing transcapillary fluid flux in the lung and may affect the alveolar-arterial gradient for O2 as well.

Altitude↗
PubMed1988

Effects of coronary ischemia on lung fluid balance in conscious sheep.

It has been suggested that coronary ischemia increases extravascular lung water. To determine whether pulmonary microvascular permeability is increased by coronary ischemia, we measured pulmonary hemodynamics, lung lymph flow (QL), and lymph-to-plasma protein concentration ratio (L/P) in 12 sheep with chronic lung lymph fistulas. Studies were done in 3 groups: in group 1 (n = 7) a marginal branch of the left circumflex artery (Lcx) was occluded, in group 2 (n = 5) left atrial pressure (Pla) was mechanically raised by 10 mmHg, and in group 3 (n = 5) Lcx was occluded and Pla was raised by 10 mmHg. In group 1, coronary occlusion increased QL (4.6 +/- 0.4 to 8.3 +/- 2.6 ml/h) without changes in L/P. In group 2, elevated Pla increased QL (5.1 +/- 1.2 to 10.1 +/- 3.0 ml/h) with decreases in L/P (0.71 +/- 0.02 to 0.61 +/- 0.02). In group 3, coronary occlusion with elevated Pla caused a further increase in QL (5.0 +/- 1.5 to 16.9 +/- 4.6 ml/h) without significant decreases in L/P (0.71 +/- 0.01 to 0.65 +/- 0.06). Lung lymph concentrations of 6-keto-prostaglandin F1 alpha (a degradation product of prostacyclin) increased transiently after coronary occlusion. These results indicate that coronary occlusion can increase transcapillary protein transport in lungs of conscious sheep and simultaneously increase prostacyclin production in the lung.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Alterations in insulin receptor autophosphorylation in insulin resistance: correlation with altered sensitivity to glucose transport and antilipolysis to insulin.

We studied insulin binding, receptor autophosphorylation, and insulin action in isolated adipocytes from 23 Pima Indians with varying degrees of obesity over a range of glucose tolerance. [125I]Insulin binding varied widely and did not correlate with fasting plasma immunoreactive insulin levels or insulin sensitivity, as assessed by the ED50 values of insulin stimulation of glucose transport or insulin inhibition of lipolysis in isolated abdominal wall adipocytes obtained by biopsy from the patients. In contrast there was a significant correlation between loss of stimulation of autophosphorylation in solubilized receptors and loss of insulin sensitivity for both stimulation of glucose transport (r = -0.59; P less than 0.005) and inhibition of lipolysis (r = -0.54; P less than 0.01). There was also a significant inverse correlation between insulin's ability to stimulate receptor autophosphorylation and in vivo insulin resistance, as assessed by fasting plasma insulin levels (r = -0.46; P less than 0.05). These data indicate a significant correlation between changes in sensitivity of glucose transport and antilipolysis to insulin and receptor kinase activity in those patients and suggest that defective coupling of insulin binding to insulin action at the level of phosphorylation of the insulin receptor may cause the insulin resistance in this group of patients.

Adipose Tissue↗
PubMed1988

Inhibitory effect of KW-3049, a new 1,4-dihydropyridine calcium antagonist, on the reduction of myocardial creatine kinase activity and high-energy phosphate content in rats subjected to coronary artery ligation.

The effect of KW-3049, (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarb oxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride on myocardial infarction in rats was examined, in comparison with some other drugs. Extension of myocardial infarction was assessed by separately determining the tissue creatine kinase (CK) activity of left ventricular free wall (LVFW) and that of interventricular septum. Loss of CK activity was limited to LVFW until 6 h after the ligation of the left main coronary artery, while 24 h after the ligation, it extended to the septum. Therefore, the effects of drugs were examined mainly in rats following 6 h of coronary artery ligation. Pretreatments with KW-3049 at 1 and 3 mg/kg (p.o.), given 1 h before coronary artery ligation, significantly reduced the loss of CK activity of LVFW by 45.3 and 39.7%, respectively. Also, posttreatment with KW-3049 at 30 micrograms/kg (i.p.), given 10 min after the ligation, significantly reduced the loss of CK activity by 30.6%. On the other hand, nifedipine (3, 10 mg/kg, p.o.), propranolol (100 mg/kg, p.o.), OKY-1581 (100 mg/kg, p.o.) and BM 13.177 (100 mg/kg, p.o.), each of which was given 1 h before coronary ligation, did not significantly reduce the loss of CK activity. Coronary artery ligation for 6 h significantly decreased the myocardial contents of adenosine triphosphate (ATP) and creatine phosphate (CP). Pretreatments with KW-3049 at 1 and 3 mg/kg (p.o.) reduced the decrease in ATP and CP. These results suggest that KW-3049 possesses a superior cardioprotective effect in comparison with the other drugs examined. The possible implications for the protection by KW-3049 are discussed.

Adenosine Triphosphate↗
PubMed1988

Calcium antagonistic effects and the in vitro duration of actions of KW-3049, a new 1,4-dihydropyridine derivative, in isolated canine coronary arteries.

The newly-developed 1,4-dihydropyridine derivative KW-3049 was investigated for calcium antagonistic effects in isolated canine coronary arteries. KW-3049 relaxed the arteries contracted by KCI-depolarization with an IC50 of 7.4 x 10(-9) M, while the IC50 of nifedipine, verapamil and diltiazem were 9.1 x 10(-9) M, 1.7 x 10(-7) M and 3.1 x 10(-7) M, respectively. Comparison with negative inotropic activities examined in electrically-driven canine papillary muscles indicated that KW-3049 was more selective for vasorelaxing versus negative inotropic activities than nifedipine, verapamil and diltiazem. KW-3049 inhibited 45Ca-uptake induced by depolarization without affecting 45Ca-uptake in polarized arteries. Inhibitory effects of KW-3049 at 10(-9) and 10(-8) M on depolarization-induced contractions of arteries exhibited no recovery for up to 4 hr after washout of the tissues, whereas those of nifedipine, nitrendipine, verapamil and diltiazem at vasoinhibitory concentrations disappeared within 1 to 4 hr after washout. The uptake and efflux of [3H]compounds of KW-3049, nitrendipine, verapamil and diltiazem were examined. The uptake of compound after 2 hr of incubation was the highest for nitrendipine. The efflux rate of KW-3049 was 1/10 or less than those of the other compounds examined. In summary, the present results in isolated coronary arteries demonstrate that KW-3049 is a potent, vasculoselective calcium antagonist whose effects persist long even after washout of tissues presumably due to its slow dissociation rate from arteries.

Animals↗
PubMed1988

The increased sympathoadrenal activity in patients with high altitude pulmonary edema is centrally mediated.

To assess the role of catecholamines in the pathogenesis of high altitude pulmonary edema (HAPE), 24-hour urinary catecholamine excretions and plasma catecholamine concentrations were measured. We also performed brain computed tomography (CT) in the same 8 serial patients with HAPE. 24-hour urinary norepinephrine excretion showed a statistically high value on admission compared with that after recovery (396.9 +/- 92.9 micrograms/24 hr, decreasing to 93.0 +/- 31.1 micrograms/24 hr, mean +/- S.E., p less than 0.01). 24-hour urinary epinephrine excretion on admission was also remarkably high, and returned later normal (62.9 +/- 25.8 micrograms/24 hr, decreasing to 12.7 +/- 4.2 micrograms/24 hr, p less than 0.05). Plasma norepinephrine concentration was also high, but returned to normal (0.260 +/- 0.073 ng/ml, to 0.11 +/- 0.043 ng/ml) by the time of discharge. Brain CT scans revealed diffuse low density of the entire cerebrum, small ventricles, disappearance of sulci, and small cistern, suggesting cerebral edema. These findings may suggest that the heightened sympathoadrenal activity that occurred in the patients concomitant with cerebral edema was related to the high altitude illness rather than to simple exposure to high altitude.

Adrenal Glands↗
PubMed1988

Effects of flunarizine on induced nystagmus and cochlear blood flow.

The effects of flunarizine on induced nystagmus and cochlear blood flow were compared with those of cinnarizine and diphenidol. Flunarizine significantly inhibited caloric (cool water)-induced nystagmus frequency and duration of nystagmus in rabbits at 5 mg/kg i.v., whereas cinnarizine and diphenidol only slightly decreased the frequency of nystagmus at 5 mg/kg, i.v. As for optokinetic stimuli-induced nystagmus in rabbits, flunarizine significantly decreased the amplitude of nystagmus at 2.5 mg/kg i.v., and cinnarizine and diphenidol inhibited nystagmus at 5 mg/kg, i.v. Flunarizine had no effect on nystagmus induced by electrical stimulation of the lateral geniculate body in rabbits at doses up to 5 mg/kg, i.v. Flunarizine increased the cochlear blood flow in anesthetized guinea pigs dose-dependently (0.312-1.25 mg/kg i.v.) On the other hand, cinnarizine (0.625-2.5 mg/kg i.v.) and diphenidol (0.625-2.5 mg/kg i.v.) increased cochlear blood flow, but the duration of action of both cinnarizine and diphenidol was shorter than that of flunarizine at the same dose. As stated above, flunarizine inhibited nystagmus experimentally induced by caloric or optokinetic stimuli. Increased cochlear blood flow suggested that the enhancement of vestibular blood flow might play an important role in the treatment of vestibular dysfunctions with this drug.

Animals↗
PubMed1988

New 1,4-dihydropyridines with vasoconstrictor action through activation of Ca++-channels.

We found four new phenylcarbamoyl-substituted 1,4-dihydropyridines which produced vasoconstrictor and vasopressor effects and we further investigated the mode of vasoconstrictor action of one of the derivatives, 2-(2-pyridil)ethyl-4-(2-chlorophenyl)-2,6-dimethyl-5-phenylcarbamo yl-1, 4-dihydropyridine-3-carboxylate (YC-170). In anesthetized dogs. YC-170 (0.1-3 mg/kg i.v.) produced dose-dependent increases in blood pressure, total peripheral resistance and maximum dLVP/dt with slight reductions of heart rate and aortic blood flow. Intracoronary injection of YC-170 (10-1000 micrograms) produced not only a decrease in coronary blood flow but also an immediate reversal of the coronary vasodilation induced by nicardipine (3 micrograms). YC-170 (0.1-3 mg/kg i.v.) also produced a dose-dependent and reversible vasopressor effect in both anesthetized and pithed rats. The vasopressor response to YC-170 in pithed rats was not attenuated by either hexamethonium, prazosin, yohimbine, ketanserin or reserpine but was antagonized by either nicardipine, nifedipine, verapamil or diltiazem. In isolated rabbit aorta, YC-170 (3 X 10(-6) to 3 X 10(-5) M) induced a dose-dependent and reversible contraction which was not affected by either phentolamine, prazosin, mepyramine, ketanserin or atropine but removed by either nicardipine, verapamil or a Ca++-free medium. YC-170 (1 X 10(-6) to 3 X 10(-5) M) displaced [3H]nitrendipine binding to the canine cardiac membrane in an apparently competitive manner with a Ki value of 1.7 X 10(-6) M. The results suggest that the new phenylcarbamoyl-substituted dihydropyridines, including YC-170, exert a direct vasoconstrictor effect, which appears to be associated with an influx of Ca++ through Ca++ channels.

Animals↗
PubMed1988

[A case of HBs antigen negative hepatocellular carcinoma without liver cirrhosis in a young woman].

A 27-year-old woman, post parturition, was admitted to hospital because of epigastric pain. Ultrasonography and abdominal computerized tomography revealed a giant mass in the left lobe of the liver. Celiac angiography showed a hypervascular mass with irregular vascularity. Serum HBs antigen proved negative. A left hepatic lobectomy was performed in March, 1985. Histology of the tumor revealed the trabecular type of a hepatocellular carcinoma with Edmondson grade 2 atypism, whereas the non-cancerous region of the liver showed chronic inactive hepatitis. This case is presented, because of the rarity of a hepatocellular carcinoma developing in such a young patient. In addition, reported cases of a hepatocellular carcinoma in the young in Japan are reviewed.

Adult↗
PubMed1988

Antihypertensive effects of the new calcium antagonist benidipine hydrochloride in rats.

Using spontaneously hypertensive rats (SHR), DOCA-NaCl hypertensive rats (DHR) and normotensive rats (NTR), the antihypertensive action of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dic arb oxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) was comparatively evaluated with those of nicardipine and hydralazine. Administration of KW-3049 at 0.5, 1 and 3 mg/kg (p.o.) showed dose-dependent antihypertensive action. This action appeared gradually and it lasted longer than those of nicardipine and hydralazine. The administration of KW-3049 at 0.5 mg/kg (p.o.) did not show any effect on the blood pressure of NTR, but a long-lasting blood pressure lowering action was observed by the administration at 1 and 3 mg/kg (p.o.). This antihypertensive action specific to the hypertensive animals was similar to that of nicardipine, however, it was different from that of hydralazine, with which the blood pressure in SHR, DHR and NTR was lowered in similar degrees. Also, administration of KW-3049 caused tachycardia concomitant with the fall of blood pressure, however, it was mild as compared with those of nicardipine and hydralazine. When KW-3049 at doses of 3 and 10 mg/kg (p.o.) once a day was continuously administered to SHR for 31 days and changes of the antihypertensive action were observed, no tolerance developed and rebound hypertension following the discontinuation of medication did not occur. When the effect on the urinary volume and electrolyte excretion was evaluated in rats loaded with physiological saline solution, a natriuretic effect was observed by the administration of KW-3049 at 0.5, 1 and 3 mg/kg (p.o.).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

[Tissue distribution of beta-lactam antibiotics, cefotiam and cefmenoxime in the lungs of sheep].

The present study was performed to investigate the distribution of beta-lactam antibiotics, cefotiam (CTM) and cefmenoxime (CMX) in pulmonary tissue of sheep. The animals were prepared to form chronic lung-lymph fistula for the collection of lung lymph. CTM and CMX were administered bolus-intravenously at doses of 20 mg/kg and 40 mg/kg, respectively, and serum and lymph levels of each drug were measured by bioassay method. Antibiotic levels of serum or lymph increased to a peak within 15 minutes after injection and then decreased rapidly. Measurable concentrations persisted for 240 minutes after the injection. Ratios of lung lymph to serum concentrations of CTM and CMX within 1 hour after the injection ranged 0.7 to 1.3, and 0.9 to 1.3, respectively. In addition, CMX levels in serum, lung lymph and tissues of both right and left lung were compared in anesthetized sheep to which CMX 50 mg/kg was given. Ratios of lung lymph and tissue concentrations of CMX in right and left lung to serum concentration were 0.76, 0.14 and 0.13, respectively. These results indicate that CTM and CMX were well distributed in interstitial fluid (lung lymph), and the levels of CMX in tissues of both right and left lung were markedly lower than those of lung lymph.

Animals↗
PubMed1988

A case of high altitude pulmonary edema followed by brain computerized tomography and electroencephalogram.

A case of high altitude pulmonary edema with high altitude cerebral edema was reported. A young Japanese male complained of severe palpitation and shortness of breath on the third day of climbing at 3,000 m above sea level. During the next 2 d at altitude, the following symptoms occurred: cough with foamy sputum, cyanosis, and loss of consciousness. Soon after evacuation, he showed severe hypoxemia and deep coma with decerebrate rigidity; electroencephalogram showed diffuse alpha waves, indicating "alpha wave coma." Brain computerized tomography revealed brain edema, showing small compressed ventricles and diffuse low density of the cerebrum. Pulmonary edema on chest roentgenogram disappeared by the fifth hospital day, and his consciousness recovered gradually during the next 2 weeks after the admission. He was examined serially by electroencephalography and brain computerized tomography. He recovered fully, but there were transient psychological abnormalities soon after discharge and mild brain atrophy was observed by brain computerized tomography 6 years later.

Adult↗