Search PubMed⌕ Search

Biomedical subjects

T Kumazawa

Publications and source records attributed to T Kumazawa.

At least 145 records · Page 8Linked to original sources

Effects of intravenous anesthetics on function and metabolism in the reperfused working rat heart.

We investigated the comparative effects of ketamine, flunitrazepam, diazepam and midazolam on function and metabolism in reperfused rat hearts. Seventy-two hearts were rapidly excised and perfused with buffer as a Neely's working model. Whole heart ischemia was induced for 15 min followed by reperfusion for 20 min. Four intravenous anesthetics in 2 different concentrations (10 and 50 times of therapeutic concentrations) were administered during reperfusion. The data were compared to a control group in which intravenous anesthetics were not used. At the end of reperfusion, myocardial metabolites were measured by liquid chromatography. Cardiac outputs in the both groups given lower and higher doses of ketamine and flunitrazepam and in the groups given the higher dose of diazepam and midazolam were significantly lower than that in the control group [at the end of reperfusion: control: 60.4; ketamine: 48.8 (lower) and 14.6 (higher); flunitrazepam: 50.2 (lower) and 50.6 (higher); diazepam: 62.6 (lower) and 42.5 (higher); midazolam: 59.5 (lower) and 51.2 (higher), ml/min]. The levels of ATP in all higher concentration anesthetic groups were significantly lower than those in the control group (control: 23.7, ketamine: 17.8, flunitrazepam: 17.8, diazepam: 17.7, midazolam: 17.7, mumol/g). These results suggest that ketamine and flunitrazepam moderately depress cardiac function more than diazepam and midazolam when they are given during reperfusion.

Anesthetics↗

Effects of prostaglandin E1 on intra-operative central and peripheral temperatures during upper abdominal surgery.

Effects of prostaglandin E1 (PGE1) on temperatures during upper abdominal surgery under isoflurane anaesthesia were studied. Forty-five patients were randomly assigned to one of three groups (15 patients per group). One group received 0.05 micrograms kg-1 min-1 of PGE1, the second group received 0.1 microgram kg-1 min-1 of PGE1 just after the induction of anaesthesia, and the third group received no PGE1 during anaesthesia (control). Tympanic membrane (central) temperatures, forearm temperatures, and fingertip temperatures were recorded during surgery every 30 min. Tympanic membrane temperatures in the 0.05 micrograms kg-1 min-1 group during and at the end of surgery were significantly higher than those in the control group. In the 0.1 microgram kg-1 min-1 group, maximum decrease of tympanic membrane temperature was significantly larger than that in the control group. Fingertip temperatures in the 0.05 micrograms kg-1 min-1 group during surgery were significantly higher than those in the control group. This result suggests that 0.05 micrograms kg-1 min-1 of PGE1 may be superior to 0.1 microgram kg-1 min-1 of PGE1 for maintaining central and peripheral temperatures during surgery and general anaesthesia.

Abdomen↗

[Effect of ritodrine hydrochloride on uterine and umbilical blood flow in patients with preeclampsia and IUGR].

Ritodrine hydrochloride is clinically used to prevent uterine contraction in preterm labor. Pregnancy toxemia is known to be a cause of intrauterine growth retardation (IUGR) due to disturbance of utero-placental circulation. In the present study, patients with preterm labor or pregnancy toxemia associated with IUGR were infused with ritodrine and the effects of ritodrine on uterine and umbilical blood flow were determined by using 2-D color Doppler. The effects of ritodrine infusion on fetal growth were also evaluated. Increases in fetal heart rate and maternal heart rate were observed following ritodrine infusion, but there was no other apparent side effect. The resistance index (RI) of the uterine and umbilical arteries of patients with preterm labor were significantly decreased by ritodrine infusion. The RI of both arteries of the patients associated with toxemia and IUGR was also decreased. A significant increase in FTA and EFBW was observed in IUGR fetuses following treatment with ritodrine for 2 weeks given to patients with toxemia when compared with the non-treated control. These results indicate that ritodrine administration may be effective not only in preventing preterm labor but also in treating IUGR by improving utero-placental blood flow.

Female↗

[Anesthesia with transesophageal echocardiography for removal of pheochromocytoma].

A 45-year-old female was scheduled for left adrenalectomy because of a pheochromocytoma. Preoperative general condition was well controlled with alpha- and beta-blockers. Anesthesia was induced with thiamylal and vecuronium, and maintained with isoflurane (0.5-3%) and nitrous oxide in oxygen. Blood pressure was controlled with nicardipine and alpha-blocker during the manipulation of the tumor. After removal of the tumor, dopamine and norepinephrine were used. We used transesophageal echocardiography (TEE) to determine the fluid administration rate and doses of catecholamine. We could observe the wall motion and the mass of the heart, and see changes of the left ventricular enddiastolic volume, the cardiac output and the stroke volume. TEE monitoring seems to be very useful during the resection of pheochromocytoma.

Adrenal Gland Neoplasms↗

[Alterations of cardiac function and metabolism in the rat heart-lung preparation by methyl methacrylate (MMA) and their protection by ulinastatin].

We have assessed the deleterious effects of methyl methacrylate (MMA) on cardiac function and metabolism in the isolated heart-lung preparation and their protection by ulinastatin. Twenty-four male Wistar rats were prepared for the heart-lung model. They were randomly divided into 3 groups. In the MMA (M) and ulinastatin (U) groups, MMA 1000 micrograms.ml-1 was administered 7 minutes after the start of perfusion. At the end of the experimental period, the hearts were freeze-clamped and then myocardial high energy phosphates, lactate and glycogen were measured. Cardiac output decreased significantly in the M and U groups. Po2 of the perfusion blood in the M and U groups was significantly lower than that in the control (C) group. Myocardial ATP in the M and U groups was significantly lower than that in the C group. ADP and AMP in the M and U groups were higher than those in the C group. Although there was no significant difference in lactate levels among the 3 groups, glycogen in the U and C groups was significantly higher than that in the M group. MMA 1000 micrograms.ml-1 is much higher than the blood level (0.05-31.89 micrograms.ml-1) reported clinically in patients who had femoral prosthesis. Ulinastatin increased myocardial glycogen content which had been reduced by MMA. This may suggest that ulinastatin has a protective effect on heart damaged by MMA.

Adenosine Diphosphate↗

[Anesthetic management of a neonate with primary cardiac rhabdomyoma].

We have experienced anesthetic management for cardiac rhabdomyoma in a 21-day-old male, whose pulmonary trunk was obstructed by the tumor. He was anesthetized with fentanyl 70 micrograms.kg-1 and oxygen. The operative and post-operative courses were uneventful. Cardiac tumor, especially cardiac rhabdomyoma, in infant is rare. Anesthesia for the resection of the cardiac tumor must be carried out carefully, because sudden death due to arrhythmias as well as cardiac or respiratory failure is the most dangerous complication.

Anesthesia↗

[Anesthetic management of a patient with cardiac sarcoidosis].

We report the anesthetic management of a patient with cardiac sarcoidosis. Cardiac sarcoidosis is characterized by a high incidence of complete atrioventricular block, right bundle branch block, and ventricular arrhythmias. Cases of sudden death during stable cardiac function have been reported. Therefore, careful anesthetic management is necessary. The patient was premedicated with scopolamine, intramuscularly. Before the induction, he received lidocaine, propranolol, and pentazocine, intravenously. Anesthesia was induced with midazolam and vecuronium, and the trachea was intubated. Anesthesia was maintained with nitrous oxide, sevoflurane in oxygen. Anesthetic method adapted to prevent severe complications including sudden death resulted in good condition of the patient during the perioperative period.

Adult↗

Effects of kainic acid in the parabrachial region for ongoing respiratory activity and reflexive respiratory suppression.

We previously reported that the electrical stimulation of gastrocnemius muscle nerve afferents given at a suprathreshold intensity for C-fiber afferents induces naloxone-reversible reflexive respiratory suppression ('after suppression'). The effects of kainic acid (KA) microinjections into the parabrachial area (nucleus parabrachialis lateralis: NPBL and nucleus parabrachialis medialis: NPBM) on (1) ongoing respiratory activity and (2) the 'after suppression' were studied in chloralose-urethane anesthetized, bivagotomized, paralyzed, and artificially ventilated cats. A large dose of KA (1.91 nmol in 0.1 microliters) microinjected into the unilateral NPBL induced significant long-lasting respiratory facilitation, while a subsequent KA injection into the ipsilateral NPBM induced significant, long-lasting respiratory depression. A small dose of KA (0.48 nmol in 0.1 microliters) into the unilateral NPBL (right side) induced significant respiratory facilitation, and the 'after suppression' effect was eliminated. A small dose into the unilateral NPBM (right side) caused initial transient respiratory facilitation followed by respiratory depression before 'after suppression' was restored. Subsequent KA injections into the NPBL on the other side (left side) significantly augmented respiration. The 'after suppression' effect was again eliminated after an injection of KA into the bilateral NPBL. It was concluded that NPBL may exhibit tonic inhibitory activities on respiration and play a critical role in the 'after suppression' effect, since an injection of KA into the NPBM counteracted both of these effects in the NPBL.

Animals↗

Norepinephrine excitation of cutaneous nociceptors in adjuvant-induced inflamed rats does not depend on sympathetic neurons.

To test the contribution of sympathetic postganglionic neurons (SPGNs) to adrenergic excitation of cutaneous nociceptor activities in adjuvant-inflamed rats (AI rats), we studied the effects of norepinephrine (NE) in a group of sympathectomized AI rats. Sympathectomy was complete in 4-6 weeks by guanethidine (30-50 mg/kg). NE excited polymodal receptor units in the saphenous nerve at an incidence (25-30%) similar to that in AI rats, while CH-38083 blocked such excitation. These results show that alpha 2-adrenoceptors in SPGNs are not involved in the norepinephrine excitation of cutaneous nociceptors in AI rats.

Adrenergic alpha-Antagonists↗

Possible involvement of the EP2 receptor subtype in PGE2-induced enhancement of the heat response of nociceptors.

Prostaglandin E2 augments bradykinin- and heat-induced discharges of polymodal receptors as studied in vitro preparations. Our previous study revealed the involvement of the EP3 receptor subtype in the PGE2 induced enhancement of the BK response [Brain Res. 632 (1993) 321-324]. The agonist for EP2 (butaprost; 10(-8) M) significantly augmented heat responses, but did not augment the BK responses at concentrations from 10(-8) to 10(-5) M; however, the agonist for EP3 (M&B28767) or EP1 (17-phenyl-trinor-PGE2) at 10(-7) M did not affect the heat responses. These findings indicate the involvement of the EP2 receptor subtype in the augmenting effect of PGE2 on heat responses.

Alprostadil↗

Inhibitors of acyl-CoA:cholesterol acyltransferase. 1. Synthesis and hypocholesterolemic activity of dibenz[b,e]oxepin-11-carboxanilides.

A series of N-phenyl-6,11-dihydrodibenz[b,e]oxepin-11-carboxamides and related derivatives were prepared on the basis of structures of the reported inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). These compounds were tested for their ability to inhibit ACAT (liver microsomes from cholesterol-fed rabbits) in vitro and to decrease serum total cholesterol in cholesterol-fed golden hamsters in vivo. The structure-activity relationships in vitro were as follows. Substitution at positions 2 and 6 in the anilide resulted in potent inhibitory activity, and the potency increased with increasing size of the substituents, with maximum potency being obtained with a 2,6-diisopropyl substitution. The position of the substituent on the dibenz[b,e]oxepin ring system influenced the activity, and substitution at position 2 was critical for potent activity. The electronic effect of the substituent at position 2 does not influence activity, but bulkiness seems to be a significant factor. The lipophilicity of the compounds also plays an important role in determining ACAT inhibitory activity. Among the compounds tested, 2-bromo-N-(2,6-diisopropylphenyl)-6,11-dihydrodibenz-[b,e]++ +oxepin-11- carboxamide (33, KF17828) showed significant in vitro activity (rabbit liver microsomes IC50 = 23 nM) and the most potent in vivo activity (complete reduction in elevated serum total cholesterol levels at a dose of 10 mg/kg in hamsters).

Animals↗

Histamine-induced sensitization of the heat response of canine visceral polymodal receptors.

In elucidating the possible involvement of histamine (His) in hyperalgesia to heat, the effects of His on the heat response of testicular polymodal receptors were studied in vitro in canine testis-spermatic nerve preparations. His (100 and 1000 microM) induced discharges > 0.5 impulses/s (high-responders) in about one third of units tested. His (> or = 10 microM) facilitated the heat response irrespective of whether His alone induced substantial excitation, and the magnitude of facilitation at 100 microM did not differ between high- and low-responders (His-induced discharges < or = 0.5 impulses/s). Conduction velocity of high-responders at 100 microM (2.2 +/- 0.9 m/s, n = 5) was slower on average than that of low-responders (12.9 +/- 1.6 m/s, n = 9). The sensitizing effect of His reported in this paper suggests that His plays a role in hyperalgesia.

Animals↗

Forskolin does not augment the bradykinin response of canine visceral polymodal receptors in vitro.

In clarifying the possible involvement of cyclic AMP (cAMP) in prostaglandin (PG) E2-induced sensitization of the bradykinin response of canine testicular polymodal receptors, the effects of forskolin, an activator of adenylyl cyclase, were studied in the presence and absence of acetylsalicylic acid (ASA, 550 microM) which blocks PG production. Forskolin (10 microM) seldom induced discharges in polymodal receptors. An unexpected outcome of this study was that forskolin induced no facilitation of the bradykinin (0.1 microM) response, both in the absence and presence of ASA. A slight yet significant suppression of the bradykinin response was instead observed in the absence of ASA. These results suggest that intracellular cAMP may be related with PG E2-induced sensitization of the bradykinin response through its decrease.

Adenylyl Cyclases↗

Pharmacokinetics of doxorubicin and its active metabolite in patients with normal renal function and in patients on hemodialysis.

The comparative pharmacokinetics of doxorubicin (DOX) were investigated in five hemodialysis (HD) and eight non-hemodialysis (non-HD) patients who were infused with a 40- to 60-mg dose of DOX at a constant rate over 30 min. A significant difference was observed in the total body clearance (Cl tot) of DOX between HD and non-HD patients. The area under the curve (AUC) for both DOX and doxorubicinol (DOXol), an active metabolite, showed increases of approximately 1.5 and 3 times in HD patients as compared with non-HD patients. Although these differences were not statistically significant (P < 0.1), the mean residence time (MRT) of DOX and DOXol in HD patients showed a 2-fold increase in comparison with those in non-HD patients. Compartmental analysis indicated that the greater AUC values and longer MRT of DOX and DOXol in HD patients resulted from the lesser DOXol formation and disappearance of rate constants. As a consequence of the decrease in Cl tot for DOX and the marginal hemodialysis clearance of both DOX and DOXol, the present study suggests that the exposure to DOX and DOXol obtained in HD patients greater than achieved in non-HD patients. Careful attention should therefore be paid to HD patients receiving DOX.

Aged↗

Receptor mechanisms of bitter substances.

The receptor mechanism of bitter substances was discussed from the following points of views. (a) Both electrostatic and hydrophobic interactions of bitter substances with taste receptor membranes contribute to reception of bitter substances having a positive charge. (b) In the frog, the responses to bitter substances are easily adapted. The presence of Ca ion in the medium prolongs the responses. (c) Bitter substances elicit electrical responses in nongustatory cells such as neuroblastoma cells and olfactory cells, suggesting that bitter substances induce the response by nonreceptor-mediated mechanism. (d) There is also a possibility that receptors for some bitter substances are G-protein coupled. We cloned G-protein coupled receptors from bovine taste tissues. (e) A specific inhibitor of bitter taste has been desired in pharmaceutical and food sciences, but it has not been available. We found that a lipoprotein made of phosphatidic acid and beta-lactoglobulin selectively inhibits the responses to bitter substances in the frog and humans. Binding of the lipoprotein to the receptor sites for bitter substances leads to suppression of the response.

Amino Acid Sequence↗

Effects of artificial blood (FC-43 emulsion) on myocardial energy metabolism in the rat heart-lung preparation.

We have assessed the effects of artificial blood (FC-43 emulsion) on myocardial energy metabolism in the rat heart-lung preparation. Animals were allocated to four groups (n = 8 each group) according to the ratio of perfusion blood and FC-43 as follows: group 1 = control, perfusion blood only; group 2 = 50% FC-43; group 3 = 75% FC-43; and group 4 = 100% FC-43. Hearts were perfused initially to a cardiac output of 30 ml min-1 and mean arterial pressure of 50 mm Hg. Thirty minutes after perfusion, the hearts were freeze-dried for 6 days. Myocardial high energy phosphates (ATP, ADP and AMP) were measured by high pressure liquid chromatography. Myocardial lactate and glycogen concentrations were measured by enzymatic methods. There were almost no significant differences in cardiac output, systolic pressure, right atrial pressure and heart rate among the groups. Oxygen contents of the perfusate in all FC-43 groups were significantly lower than those in the control group. Myocardial ATP concentrations in rats receiving 50%, 75% and 100% FC-43 were significantly lower than those in the control group. In addition, myocardial ADP and AMP concentrations in rats receiving 75% and 100% FC-43 were significantly higher than those in the control group. Although there is adequate oxygen-carrying capacity in FC-43 to maintain cardiac function during perfusion, the energy levels in the hearts perfused with FC-43 were lower than those in normal hearts.

Adenosine Diphosphate↗

Effects of inhalation anesthetics on myocardial and hepatic energy metabolism in normotensive and spontaneously hypertensive rats subjected to hemorrhage.

Forty spontaneously hypertensive rats (SHRs) and forty normotensive Wistar-ST rats (NRs) were used to assess the influence of anesthetics on myocardial and hepatic energy metabolism after hemorrhage. They were divided into five pairs of groups: a control group (pentobarbital 6 mg.100 g BW-1 ip), and four others which received 1.2% halothane, 2.2% enflurane, 1.4% isoflurane, and 3.3% sevoflurane, respectively. Following a 10 min stabilization period, blood (2 ml.100 g BW-1) was gradually withdrawn over a 5 min period from a femoral artery. Thirty min after the induction of hemorrhage, the heart and liver were removed and myocardial and hepatic metabolites (ATP, lactate, pyruvate and glycogen) were measured by enzymatic methods. There were no significant differences in myocardial metabolites among either the anesthetic groups or between SHRs and NRs. However, hepatic ATP levels in all SHR groups were significantly lower than those in NR groups. Moreover, ATP levels in the inhalation anesthetic groups of SHRs were significantly higher than that in the control group of SHRs. All inhalation anesthetics, especially isoflurane, may reduce metabolic deterioration of the liver during hemorrhage when compared to barbiturate anesthesia.

Adenosine Triphosphate↗

Incomplete suppressive effects of acetylsalicylic acid on the heat sensitization of canine testicular polymodal receptor activities.

1. Using canine testis-spermatic nerve preparations in vitro, we studied the effects of acetylsalicylic acid (ASA), an inhibitor of cyclooxygenase, on the polymodal receptor response to heat stimulation itself and on the sensitizing effects on the heat and bradykinin responses induced by strong heat stimulation (55 degrees C for 30 s). 2. Greater heat responses tended to be strongly suppressed by ASA (550 microM), with a significant correlation observed between the response magnitude and the magnitude of the suppression (r = 0.88 for the response at 45 degrees C; r = 0.83 for the response at 48 degrees C). The change in the heat response at 48 degrees C from 1.18 +/- 0.19 to 0.62 +/- 0.11 imp/s was statistically significant (n = 21, P < 0.01). 3. After stimulation at 55 degrees C in the presence of ASA, resting discharges at 34 degrees C appeared in only 2 of the 21 units tested. The responses at 45 and 48 degrees C, however, were significantly potentiated after this stimulation (those at 45 degrees C from 0.12 +/- 0.05 to 2.19 +/- 0.51 imp/s, mean +/- SE; those at 48 degrees C from 0.62 +/- 0.11 to 2.42 +/- 0.49 imp/s; P < 0.01, n = 21 for both). Sensitization was observed up to 50 min after stimulation at 55 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗