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Biomedical subjects

A Mitani

Publications and source records attributed to A Mitani.

At least 55 records · Page 3Linked to original sources
PubMed1992

Acidic fibroblast growth factor delays in vitro ischemia-induced intracellular calcium elevation in gerbil hippocampal slices: a sign of neuroprotection.

Using microfluorometry, effects of acidic fibroblast growth factor (aFGF) on the in vitro ischemia-induced intracellular calcium elevation were investigated in gerbil hippocampal slices at 35 degrees C. When slices were superfused with hypoxic and glucose-free medium, the mean latency of the in vitro ischemia-induced calcium elevation was 209 +/- 51 s. The addition of aFGF in medium (25 micrograms/l) delayed the calcium elevation throughout the experiments: the mean latency was 541 +/- 94 s. This retardation in calcium elevation may be indicative of neuroprotective nature of aFGF.

Animals↗
PubMed1992

Selective vulnerability of hippocampal CA1 neurons cannot be explained in terms of an increase in glutamate concentration during ischemia in the gerbil: brain microdialysis study.

Ischemia-induced selective neuronal injury to field CA1 is not attributable to selective glutamate release in field CA1 during ischemia. Excessive release of glutamate has been proposed to play a major role in ischemia-induced selective neuronal death in field CA1 of the hippocampus. It is well known that, following carotid arterial occlusion of 5 min duration in the gerbil, the pyramidal neurons in field CA1 show delayed neuronal death, whereas the neurons in field CA3 do not show any neuronal degeneration. In the present study, we measured the levels of released glutamate during ischemia in field CA1 and field CA3, separately, and evaluated whether there are subregional differences in the concentration of released glutamate which could be a satisfactory explanation for the selective vulnerability of hippocampal neurons to ischemia. Extracellular glutamate levels were significantly increased during ischemia in both field CA1 and field CA3. No significant differences were detected in the time-course of change in glutamate release and the levels of glutamate between field CA1 and field CA3. This result indicates that the increased glutamate levels do not play a pivotal part in the detrimental effect of glutamate during 5-min ischemia. Some differentiated post-synaptic organization may act as a crucial factor in the development of ischemia-induced selective neuronal death in the gerbil hippocampus.

Analysis of Variance↗
PubMed1992

Effects of propentofylline on hypoxia-hypoglycemia-induced calcium accumulation in gerbil hippocampal slices.

The xanthine derivative propentofylline (HWA 285) has been reported to show protective effects against neuronal damage induced by cerebral ischemia. In the present study, microfluorometry was used to investigate the effect of propentofylline on the hypoxia-hypoglycemia-induced intracellular calcium accumulation in gerbil hippocampal slices. When slices were superfused with hypoxic-hypoglycemic medium that did not contain propentofylline, an acute increase in calcium accumulation was detected 75-200 s (mean latency of 123 s) after the beginning of hypoxia-hypoglycemia. When slices were superfused with hypoxic-hypoglycemic mediums that contained 10 microM, 100 microM, and 1 mM propentofylline, the latency of the acute increase in calcium accumulation was prolonged in all subregions of the hippocampus in a dose-dependent manner: mean latencies in field CA1 were 146, 168, and 197 s after hypoxia-hypoglycemia, respectively. This retardation in calcium accumulation may be involved in the mechanisms by which propentofylline diminishes ischemic injury.

Animals↗
PubMed1992

Effects of diltiazem and noradrenaline on extracellular potassium changes in the globally ischaemic rat heart.

OBJECTIVE: The aim was to investigate the effects of a calcium antagonist (diltiazem) and a catecholamine (noradrenaline) on extracellular potassium accumulation during global ischaemia. METHODS: Extracellular potassium concentration ([K+]e) was measured during 30 min global ischaemia in the isolated rat heart using a valinomycin potassium sensitive electrode. Contracture development during ischaemia was measured throughout with an intraventricular balloon inserted into the left ventricle and myocardial adenine nucleotides were measured in separate series of hearts. RESULTS: In control hearts, [K+]e showed a characteristic triphasic change during 30 min global ischaemia. This consisted of an early rising phase followed by a transient falling phase after the initial peak of [K+]e, and then a late rising phase. Diltiazem suppressed the rate of rise of [K+]e during early ischaemia, but extended the time course of the early [K+]e rise with the higher dose, abolishing the transient falling phase of [K+]e. During late ischaemia, the rise in [K+]e was attenuated by diltiazem. Noradrenaline also suppressed the early extracellular potassium accumulation, but in contrast to diltiazem, hastened the time course of the late [K+]e rise. CONCLUSIONS: Although diltiazem suppresses the early potassium loss during ischaemia as previously described, the drug also decreases the [K+]e fall by some as yet unknown mechanism, so that the [K+]e level becomes higher than control during the falling phase.

Adenosine Triphosphate↗
PubMed1992

Role of Na-activated K channel, Na-K-Cl cotransport, and Na-K pump in [K]e changes during ischemia in rat heart.

The contribution of Na-activated K channel, the furosemide-sensitive (Na-K-Cl) cotransport, and Na-K pump to extracellular potassium accumulation during global ischemia was investigated using pharmacological blockade of these pathways. R 56865 (a blocker of the Na-activated K channel), furosemide, or ouabain was included in the perfusate before ischemia in the isolated rat heart preparation, and the extracellular K concentration ([K]e) was monitored during 30 min of global ischemia. In control hearts, [K]e showed an early rise (up to 9.0 +/- 0.2 mM from the baseline of 5.9 mM), a fall (to a minimum of 6.7 +/- 0.2 mM), and a late rise (to 14.1 +/- 0.4 mM by the end of ischemia). R 56865 (0.1 and 1 microM) suppressed the early [K]e rise to 50% of the control level. The late rise in [K]e was also significantly suppressed by the higher dose of R 56865. Furosemide (0.1 and 1 mM) reduced the early K accumulation by 35% but did not affect the rise of [K]e during the late ischemic phase. Blockade of Na-K pump by 10 microM ouabain did not increase [K]e during any phase of ischemia and, in fact, 100 microM ouabain profoundly suppressed the early rise in [K]e. We therefore suggest that the Na-activated K channel, the furosemide-sensitive cotransport, and changes in the activity of the Na-K pump may all contribute to extracellular K accumulation during ischemia. However, in addition to these pathways, it seems likely that other pathways for transsarcolemmal K efflux contribute to cellular K loss during ischemia in the isolated rat heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Effects of propentofylline on hypoxia-hypoglycemia-induced calcium accumulation in gerbil hippocampal slices].

The xanthine derivative propentofylline (HWA 285) has been reported to show protective effects against neuronal damage induced by cerebral ischemia. In the present study, we investigated the effect of propentofylline on the hypoxia-hypoglycemia-induced intracellular calcium accumulation in gerbil hippocampal slices using microfluorometry. When slices were superfused with hypoxic-hypoglycemic medium that did not contain propentofylline, an acute increase in calcium accumulation was detected 75-200s (mean latency of 123s) after the start of hypoxic-hypoglycemia. When slices were superfused with hypoxic-hypoglycemic medium that contained 10 microM, 100 microM and 1mM propentofylline, the latency period before acute increase in calcium accumulation was prolonged in all subregions of the hippocampus in a dose-dependent manner: mean latencies in field CA 1 were 146, 168, and 197s after hypoxic-hypoglycemia, respectively. This retardation in calcium accumulation may be involved in the mechanisms by which propentofylline diminishes ischemic injury.

Animals↗
PubMed1992

The myocardial recovery mode after cold storage for transplantation with Collins' solution and cardioplegic solution. A functional and metabolic study in the rat heart.

Mechanisms and kinetics of the effects of the ionic composition of two different storage solutions, an intracellular type and an extracellular type, were analyzed by examining the myocardial functional and metabolic recovery processes during the early reperfusion periods after 3 hours of cold storage using an isolated perfused working rat heart model. The hearts were stored either in our own cardioplegic solution (group 1) or in Collins' solution (group 2) for 3 hours at 4 degrees C and were then reperfused. The electromechanical activity in group 1 was elevated, as indicated by a higher incidence of ventricular fibrillation at 5 minutes of reperfusion (group 1: 5/6; group 2: 0/5; p < 0.05). The coronary flow rate in group 2 was significantly lower, at least for the first 15 minutes after reperfusion, than that of group 1, suggesting the possible existence of vasoconstriction in group 2. Although myocardial oxygen uptake during this period was smaller in group 2, the recovery of myocardial high-energy phosphate levels was better and creatine kinase leakage was less in group 2. The recovery of aortic flow after 30 minutes of reperfusion was significantly better in group 2 (group 1, 59.1 +/- 5.8%; group 2, 71.7 +/- 6.0%; p < 0.01), although the early recovery was somewhat worse in group 2. These data suggest that the heart stored in an intracellular-type solution, compared with one stored in an extracellular-type solution, recovers in an electromechanically suppressed fashion during the early reperfusion phase, associated with a better metabolic recovery and a slower but larger functional recovery. The disadvantage of the intracellular-type solution, however, may be its effect on the increase of coronary vascular resistance during the early reperfusion period.

Animals↗
PubMed1992

Collins' solution for cold storage of the heart for transplantation must be reversed with cardioplegic solution before reperfusion. A functional and metabolic study in the rat heart.

The following hypotheses were tested using an isolated perfused working rat heart model: (1) Collins' solution for cold storage of the heart is harmful for the heart during reperfusion; (2) a "reverse" of the intracellular-type Collins' solution with an extracellular-type cardioplegic solution before reperfusion is able to prevent this disadvantage of Collins' solution. The following two major groups (I and II) and five subgroups (-a to -e) in each group were prepared. In group I (reversed group); the hearts were initially stored in Collins' solution but were reversed by a 1-minute flush with cardioplegic solution followed by storage in cardioplegic solution for the last 1 to 180 minutes of the total 3-hour storage, that is, groups I-a (reversed for 1 minute), I-b (10 minutes), I-c (30 minutes), I-d (90 minutes), and I-e (180 minutes). In group II (nonreversed control group); the hearts were stored in Collins' solution throughout 3 hours and were also divided into five subgroups of groups II-a, II-b, II-c, II-d, and II-e in which only a 1-minute flush with Collins' solution was performed at the point corresponding to group I. The coronary flow in any of group II showed a marked decrease during the early reperfusion period. In group I, however, the coronary flow increased significantly in proportion to the duration of the reversing phase. The recovery of the aortic flow and the cardiac output in group I showed a bell-shaped pattern in relation to the duration of the reversing phase, reaching their peak values when reversed for 30 minutes (group I-c). The prolonged reverse (180 minutes) resulted in a deterioration of functional recovery associated with a poorer preservation of high-energy phosphates and a larger enzyme leakage. These results suggest that the beneficial effects of intracellular-type Collins' solution for cold storage of the heart were further improved by reversing Collins' solution with the extracellular-type cardioplegic solution for the last 30 minutes of the 3-hour cold storage because the disadvantageous vasoconstriction due to Collins' solution during reperfusion was successfully prevented by the replacement of intravascular and extravascular Collins' solution with cardioplegic solution before the reperfusion.

Animals↗
PubMed1992

[Optimal pH and PaCO2 during moderate hypothermia].

Effects of pH and PaCO2 on cerebral as well as systemic hemodynamics and oxygen consumption were investigated during moderate hypothermia under 0.5% halothane anesthesia. Twenty-seven adult mongrel dogs were cooled to 28 degrees C (brain temperature) with a surface cooling method. They were divided into 3 groups, pH-stat (pH 7.35 n = 9), alpha-stat (pH 7.48 n = 9), and alkalosis (pH 7.70 n = 9). During hypothermia cardiac index fell to 74%, 56%, and 45%, and cerebral blood flow to 54%, 42%, and 36% in pH-stat, alpha-stat and alkalosis groups, respectively. Cerebral and systemic oxygen consumptions decreased to approximately 54% and 47%, respectively in all groups. Cerebrospinal fluid pH rose from 7.36 precooling to 7.49 (pH-stat), 7.53 (alpha-stat), and 7.72 (alkalosis). We concluded from these results that pH-stat and alpha-stat management have no significant effect on either hemodynamics or metabolism during moderate hypothermia but alkalosis management has deleterious effects because of the alkalinity itself and of the hyperventilation by which the alkalosis is induced.

Animals↗
PubMed1991

Temperature dependence of hypoxia-induced calcium accumulation in gerbil hippocampal slices.

Microfluorometry was used to investigate temperature dependence of hypoxia-induced intracellular calcium accumulation in gerbil hippocampal slice. When slices were superfused with hypoxic medium at 37 degrees C, 35 degrees C, 33 degrees C or 31 degrees C, latencies of acute increase of calcium accumulation, which was accompanied by a large negative shift of extracellular DC potentials, were delayed in a dose-dependent manner: mean latencies in field CA1 were 130 s, 182 s, 232 s and 277 s after hypoxia, respectively. This retardation in calcium accumulation may be involved in the mechanisms by which hypothermia diminishes ischemic injury.

Animals↗
PubMed1991

Transient forebrain ischemia of three-minute duration consistently induces severe neuronal damage in field CA1 of the hippocampus in the normothermic gerbil.

We examined the effect of transient forebrain ischemia of 2-, 3-, 4- and 5-min duration on the development of delayed neuronal death in field CA1 of the hippocampus in the gerbil whose brain temperature was maintained at 37 degrees C. Transient ischemia of 3- and 4-min duration caused almost the same maximal damage in field CA1 as observed in the gerbils subjected to 5-min ischemia. A detrimental factor inducing delayed neuronal death in field CA1 may be already set up during the first 3 min after the onset of ischemia in the gerbil whose brain temperature is maintained at normothermic levels.

Animals↗
PubMed1991

Visualization of hypoxia-induced glutamate release in gerbil hippocampal slice.

Microfluorometry was used to investigate distribution of hypoxia-induced release of glutamate. Mongolian gerbil hippocampal slice was perfused in a medium containing glutamate dehydrogenase and NAD+. Release of glutamate into extracellular space caused an increase in fluorescence due to the formation of NADH. The hypoxia-induced release of glutamate was gradually increased throughout the slice: no significant difference was detected among CA1 region, CA3 region and the dentate gyrus.

Animals↗
PubMed1991

Critical levels of extracellular glutamate mediating gerbil hippocampal delayed neuronal death during hypothermia: brain microdialysis study.

When the brain temperature was lowered by 2 degrees C from normothermic temperature, a protective effect on postischemic neuronal death was exhibited and levels of extracellular glutamate were attenuated to about half of those at normothermic brain temperature in the gerbil hippocampus. Hypothermia has been reported to confer a protective effect on ischemia-induced delayed neuronal death. The present study was carried out to quantify this protective effect of hypothermia on the degree of alteration in extracellular release of glutamate during ischemia and the final histopathological outcome in the hippocampus. Extracellular glutamate levels were measured by microdialysis. In gerbils whose brain temperature was maintained at normothermia (37 degrees C), glutamate increased during ischemia and the early period of recirculation (by 15-fold), and CA1 neurons were consistently damaged. In animals whose brain temperature was maintained at 35 or 33 degrees C during ischemia, the release of glutamate was significantly attenuated to half or a quarter, respectively, at 37 degrees C. In animals whose brain temperature was maintained at 31 degrees C during ischemia, the release of glutamate was slightly lower than that at 33 degrees C. No CA1 ischemic neuronal damage was seen in 60% of gerbils at 35 degrees C and none was seen in any gerbils at 33 and 31 degrees C. In animals whose brain temperature was maintained at 39 degrees C during ischemia, the release of glutamate was slightly higher than that at 37 degrees C, and a high mortality rate of animals (75%) was observed. Our results reinforce other recent evidence suggesting that one of the mechanisms by which lowering of the brain temperature by only a few degrees during ischemia exerts a protective effect in the hippocampus, involves the reduction of ischemia-induced glutamate release.

Animals↗
PubMed1991

Delayed neuronal death is induced without postischemic hyperexcitability: continuous multiple-unit recording from ischemic CA1 neurons.

It has been proposed that neuronal hyperexcitability during postischemic chronic stage mediates delayed neuronal death in the hippocampal CA1 region. In the present study, multiple-unit spike discharges were continuously recorded from hippocampal CA1 neurons of the awake Mongolian gerbil for 5 days after 5 min of ischemia. Before ischemia, CA1 neurons showed burst-like spike discharges (so-called complex spikes). Spike discharges disappeared 8-40 s after the onset of 5-min ischemia and reappeared 5-30 min after recirculation. The frequency of discharges gradually increased but did not return to the preischemic level. The amplitude of the spike discharges was smaller than that recorded before ischemia and the number of spikes composing the burst-like discharges diminished. CA1 neurons did not show any hyperexcitability for 5 days. However, histological examinations revealed widespread neuronal death in the CA1 region. These results indicate that the delayed neuronal death in the hippocampal CA1 region is induced without postischemic neuronal hyperexcitability.

Animals↗
PubMed1991

Effects of glibenclamide and nicorandil on cardiac function during ischemia and reperfusion in isolated perfused rat hearts.

We examined influences of a blocker (glibenclamide) and an opener (nicorandil) of the ATP-sensitive potassium (KATP) channel on extracellular K concentration [( K+]e), as well as the myocardial function and metabolites during global ischemia and reperfusion in Langendorff-perfused rat heart preparation. In control hearts, [K+]e began to rise 20 s after the onset of ischemia up to an initial peak (8.3 +/- 0.3 mM) at 2.5 +/- 0.7 min, then fell to 6.0 +/- 0.8 mM after 8.2 +/- 0.7 min, and then rose progressively to 14.6 +/- 0.8 mM at the end of 30 min of ischemia. Glibenclamide (50 microM) reduced the initial peak of [K+]e to 7.2 +/- 0.3 mM (P less than 0.01), and nicorandil (200 microM) increased it to 9.4 +/- 0.6 mM (P less than 0.01). There were no significant differences in [K+]e values among all groups at the end of ischemia. During ischemia, nicorandil decreased the time to mechanical arrest from 1.9 +/- 0.1 min to 1.5 +/- 0.1 min, whereas it was increased by glibenclamide to 2.7 +/- 0.4 min. In control hearts, the time to onset of ischemic contracture was 14.7 +/- 1.8 min. Nicorandil delayed onset of contracture and glibenclamide accelerated it. Thus we have confirmed that some part of the early increase in [K+]e during ischemia is attributable to K+ efflux through the KATP channel in our model, and opening of the KATP channel may contribute to a rapid reduction of the contractility of the ischemic myocardium that subsequently protects the myocardium against further ischemic injury.

Adenosine Triphosphate↗
PubMed1991

Difference in pressor responses to NG-monomethyl-L-arginine between conscious and anesthetized rats.

NG-Monomethyl-L-arginine (L-NMMA; 0.1-10 mg/kg, i.v.), a selective inhibitor of nitric oxide (NO) synthesis derived from L-arginine, elicited a greater increase in blood pressure in urethane/alpha-chloralose- and pentobarbital-anesthetized rats than in conscious Wistar rats. The pressor response to phenylephrine was almost equivalent in both conscious and anesthetized rats. These findings suggest that the experimental conditions (anesthetized or conscious) modify the spontaneously released NO's contribution to blood pressure regulation in vivo.

Anesthetics↗
PubMed1991

Beneficial effect of pericardial meshing on left ventricular pump performance in dogs.

To evaluate the effects of pericardial meshing (multiple incisions on the pericardium) on cardiac function, we examined left ventricular pump performance before and after pericardial meshing in six open chest dogs. We evaluated left ventricular systolic properties with the slope of end-systolic pressure-volume relation and diastolic properties with end-diastolic pressure-volume relation (chamber compliance). Overall left ventricular performance was assessed with end-diastolic pressure versus cardiac output relation. Left ventricular chamber compliance was increased (31.3%) with pericardial meshing compared with direct closure of the pericardium, and cardiac output was increased (26.7%) for any given left ventricular end-diastolic pressure. The slope of the end-systolic pressure-volume relation was not altered in pericardial meshing. These results suggest that pericardial meshing improves left ventricular pump performance as a result of increasing left ventricular chamber compliance. This technique may benefit cardiac pump performance that is depressed by the direct closure of the pericardium after cardiac operations.

Animals↗