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M Shirahata

Publications and source records attributed to M Shirahata.

53 records · Page 3Linked to original sources
PubMed1990

Chemical respiratory control in chronically hyperoxic cats.

Chemical control of respiration in cats after chronic normobaric hyperoxia (NH; inhalation of 100% O2 for 60-67 h) was compared with that of control rats, anesthetized with pentobarbital. After chronic hyperoxia, induction of moderate hypoxia (PaO2 = 50-60 Torr) increased inspiratory time (TI) often without increasing tidal volume (VT). More intense hypoxia (PaO2 = 40-50 Torr) depressed tidal volume and further increased TI, diminishing the respiratory drive (VT/TI). Hypercapnia, on the other hand, increased tidal volume and shortened respiratory cycle time; but these responses were subnormal. The normal stimulatory effects of intravenous nicotine and inhibitory effect of dopamine on carotid chemo-receptor activity and ventilation were preserved in the NH cats. Cyanide, however, did not stimulate carotid chemoreceptor activity and ventilation. Thus, the changes in the carotid and aortic chemosensory activities elicited appropriate reflex ventilation responses, indicating that the central component of the chemoreflex was not impaired. The ventilatory depression during hypoxia despite an active chemosensory input is consistent with the lack of carotid chemosensory response to and a central depressant effect of hypoxia in the NH cats, and was presumably associated in part with an increased responsiveness of airway reflexes. We conclude that chronic hyperoxia selectively attenuated carotid chemosensory and chemoreflex responses to hypoxia.

Animals↗
PubMed1990

Amiloride and carotid body chemoreception of hypercapnia and hypoxia.

The sodium-proton (Na(+)-H+) antiporter has been found in virtually every tissue where its presence has been investigated. Its principal physiological role is to regulate intracellular pH (pHi). Amiloride (10(-3)-10(-4) M) is a known blocker of the antiporter when Na is present in normal physiological concentrations (130-140 x 10(-3) M). In order to determine if the Na(+)-H+ antiporter participated in the chemoreception of hypercapnia or hypoxia anesthetized, paralyzed, artificially ventilated cats were fitted with a loop in the right common carotid artery for the selective perfusion of the carotid body. Neural activity (imp/10 sec) was recorded from single or few fiber preparations during hypercapnia (PaCO2 = 48-64 Torr) while the carotid body was perfused with Krebs-Ringer bicarbonate solution for 2.5 min, then with its own hypercapnic arterial blood (4 min), then with Krebs-Ringer bicarbonate solution containing 0.6-0.8 x 10(-3) M amiloride (2.5 min), then with its own hypercapnic blood (4 min). After 20 min of rest the protocol was repeated during hypoxia (PaO2 = 35-45 Torr). The carotid body response to hypercapnic blood was unaffected by a preceding perfusion of the amiloride-containing solution but the response to hypoxic blood was decreased by 25% by the amiloride-containing solution. The data suggest the possibility of different mechanisms being involved in the chemoreception of hypercapnia and hypoxia.

Amiloride↗
PubMed1988

Carotid body chemoreceptor and ventilatory responses to sustained hypoxia and hypercapnia in the cat.

To understand the role of carotid chemoreceptor activity in the ventilatory responses to sustained hypoxia (30 min) the following measurements were made in cats anesthetized with alpha-chloralose: (1) carotid chemoreceptor and ventilatory responses to isocapnic hypoxia and to hypercapnia during hyperoxia; (2) carotid chemoreceptor responses to isocapnic hypoxia after dopamine receptor blockade; and (3) ventilatory responses to hypoxia after bilateral section of carotid sinus nerves (CSN). Transition to hypoxia (PaO2 approximately equal to 52 Torr) from hyperoxia gradually increased carotid chemoreceptor activity by ten fold and ventilation by two fold without any detectable overshoot. Termination of isocapnic hypoxia with hyperoxia (PaO2 greater than 300 Torr) at 30 min promptly restored the carotid chemoreceptor activity to prehypoxic level. Ventilation also decreased promptly, but remained above the control value. Induction of hypercapnia (from 31.8 Torr to 43.9 Torr) during hyperoxia was followed by a prompt increase in the chemoreceptor activity by four fold which subsequently diminished, and by a gradual four fold increase in ventilation. Termination of hypercapnia after 30 min was followed by a prompt return of chemoreceptor activity and by a slow return of ventilation to near control levels. Dopamine receptor blockade increased carotid chemoreceptor responsiveness to acute hypoxia but did not alter the response pattern during sustained hypoxia. After bilateral CSN section, ventilation decreased during maintained hypoxia. Thus, a stimulatory peripheral and inhibitory central effects of hypoxia could produce a biphasic ventilatory response to short-term hypoxia in the anesthetized cat with intact CSN but did not manifest it. The results suggest that the chemosensory input not only promptly stimulates ventilation but also prevents the subsequent depressant effect of hypoxia on the brain-stem respiratory mechanisms and hence presumably a biphasic ventilatory response in the anesthetized cat.

Animals↗
PubMed1987

Carotid body chemosensory function in prolonged normobaric hyperoxia in the cat.

The effects of normobaric hyperoxia on carotid body chemosensory function in the cat were studied. The hypothesis was that carotid body chemosensory function would be affected by chronic exposure to 100% O2 at sea level. It was based on the assumptions that carotid body tissue is exposed to high PO2 because of its high blood flow and that its O2 chemosensing mechanism is sensitive to O2 radical-induced reactions. Twelve cats were exposed to 100% O2 for 60-67 h, and 10 control cats were maintained in room air at sea level. They were anesthetized with pentobarbital sodium (Nembutal), and chemosensory afferents from a cut carotid sinus nerve were isolated and identified. The responses of single or a few clearly identifiable chemoreceptor afferents to isocapnic hypoxia and hypercapnia during hyperoxia and to the bolus injections of cyanide, nicotine, and dopamine were studied. We found that chronic hyperoxia severely blunted or eliminated the O2-sensitive response of the carotid chemoreceptors while augmenting the hypercapnic response. The response to cyanide but not to nicotine and dopamine were attenuated. Thus the hypoxic and hypercapnic responses that normally interact were separable. The lack of the cyanide response was consistent with the lack of the hypoxic response, suggesting a possible shared mechanism of carotid chemoreceptor response. Qualitatively normal responses to dopamine and nicotine indicated that the respective receptors were relatively intact after chronic exposure to hyperoxia and that the sensory nerves themselves were not affected by the prolonged O2 exposure.

Animals↗
PubMed1987

Differential effects of oligomycin on carotid chemoreceptor responses to O2 and CO2 in the cat.

Effects of oligomycin on carotid chemoreceptor responses to O2 and CO2 were investigated using an in situ perfusion technique. Cats were anesthetized, paralyzed, and artificially ventilated. To avoid a possible reaction between an oligomycin-ethanol mixture and blood, we administered oligomycin to the carotid body via cell- and protein-free perfusate. Except for the perfusion periods, the carotid body received its own natural blood supply. Responses to O2, CO2, sodium cyanide, and nicotine of the same carotid chemoreceptor afferents were studied before and after each perfusion. An appropriate low dose of oligomycin completely blocked carotid chemoreceptor response to O2 while preserving the CO2 response. At the same time cyanide response was attenuated leaving nicotine response intact. Additional doses of oligomycin attenuated carotid chemoreceptor response to CO2 as well. Perfusion with a blank solution containing ethanol did not change the carotid body chemoreceptor responses. These effects of oligomycin on carotid chemoreceptor responses to O2 and CO2 were reversible, and restoration of the response to CO2 preceded that to O2. In addition, oligomycin administered into the blood with close intra-arterial injection produced similar differential blockade of O2 and CO2 chemoreception, preserving the nicotine and dopamine effects. This study confirmed the previous findings and provided new evidence showing that 1) the responses of carotid chemoreceptor to O2 and CO2 were separable by oligomycin due to the inhibition of oxidative phosphorylation and 2) the responses to nicotine and dopamine were intact even after blockade of O2 response.

Animals↗
PubMed1986

Differences in the effects of hypercapnia and hypoxia on the swallowing reflex in cats.

The effects of changes in PaCO2 and PaO2 on the swallowing reflex were studied in anaesthetized, vagotomized, paralysed and artificially ventilated cats. The swallowing reflex was induced by electrical stimulation of the superior laryngeal nerve (SLN). This initially suppressed activity in the phrenic nerve (PN). The swallowing reflex was then identified by a characteristic brief burst of PN activity and a large amplitude burst of hypoglossal nerve (HN) activity. Steady-state responses to constant SLN stimulation for 60 s were measured at four carbon dioxide tensions (PaCO2 3.9, 5.1, 6.3 and 7.8 kPa) with hyperoxia (PaO2 greater than 51 kPa) and at four values of PaO2 (PaO2 56, 11.3, 6.9 and 4.8 kPa) at a fixed PaCO2 (PaCO2 4.2 kPa). Although both hypercapnia and hypoxia increased the spontaneous respiratory activity in PN and HN, the number of swallows elicited during SLN stimulation was not influenced by PaCO2, whereas a progressive decrease in the number of swallows with decreasing PaO2 was observed consistently. These results indicate that the swallowing reflex is independent of the background respiratory activity and that hypoxia depresses the swallowing reflex, whereas hypercapnia has no effect.

Animals↗
PubMed1985

Effects of increasing depth of anaesthesia on phrenic nerve and hypoglossal nerve activity during the swallowing reflex in cats.

The effects of increasing depths of anaesthesia on phrenic nerve (PN) activity and hypoglossal nerve (HN) activity during the swallowing reflex elicited by stimulation of the superior laryngeal nerve (SLN) were investigated in 10 cats. Swallowing induced by SLN stimulation always coincided with a characteristic brief burst of PN activity and a large amplitude burst of HN activity. These characteristic responses of PN and HN activities were not influenced by either bilateral vagotomy or neuromuscular blockade, indicating that the characteristic responses of PN and HN activities can be used as indicators of the swallowing reflex in vagotomized and paralysed animals. The results obtained in such animals showed that increasing depth of anaesthesia depressed progressively the swallowing reflex. Detailed analysis of HN activity revealed also that SLN stimulation elicited three different responses of HN activity which had different sensitivities to anaesthesia. However, the characteristic response observed during the swallowing reflex was the most sensitive to increasing depth of anaesthesia.

Anesthesia, Inhalation↗
PubMed1985

Effects of hypercapnia on renal nerve activity.

We investigated the response of renal nerve activity (RNA) to hypercapnia and assessed the contribution of the peripheral chemoreceptors to the response of RNA in anesthetized and artificially ventilated cats. RNA and arterial pressure were recorded at four levels of PETCO2 with hyperoxia in intact and in peripheral chemoreceptor denervated cats. In intact cats, RNA increased progressively with increasing PETCO2, while no consistent change in arterial pressure was observed. In peripheral chemoreceptor denervated cats, the response of RNA to increasing PETCO2 was totally abolished. These results suggest that the peripheral chemoreceptors play an important role in increasing RNA during hypercapnia.

Animals↗
PubMed1984

Comparison of changes in the hypoglossal and the phrenic nerve activity in response to increasing depth of anesthesia in cats.

The effects of increasing depths of anesthesia on the activities of the hypoglossal nerve (HN) and the phrenic nerve (PN) were investigated in artificially ventilated, vagotomized cats. An abrupt increase in inspired concentration of halothane from 1% to 4% immediately decreased both HN and PN activities, but HN activity decreased more and disappeared much earlier than did PN activity. Steady-state responses of HN and PN activities to changes in end-tidal concentration of halothane showed that halothane depressed both HN and PN activities in a dose-related manner but at different rates, suggesting that respiratory control of the tongue muscles and the diaphragm are in part mediated by different neural pathways. Differential suppression of PN and HN activities also was observed following an acute increase in anesthetic depth with thiopental and diazepam. In contrast, no such differential suppression was observed following ketamine administration. Thus, differential suppression of PN and HN may be associated not only with depth of anesthesia but also with the type of anesthetic used.

Anesthesia, Inhalation↗
PubMed1983

Effects of ketamine on renal nerve activity, arterial pressure and heart rate in rats.

We recorded renal nerve activity (RNA) together with arterial pressure (AP) and heart rate (HR) in 24 Wister rats anesthetized with nitrous oxide to investigate the effects of ketamine on the sympathetic nerve activity and the cardiovascular dynamics. The magnitude and time course of the responses to four graded doses of ketamine (1, 5, 10, 25 mg/kg) were studied in 19 rats. RNA responded biphasically, initially decreasing dose-dependently to minimal values of 89 +/- 4.4, 77 +/- 8.2, 54 +/- 5.2, and 17 +/- 3.7% of control for 1, 5, 10, and 25 mg/kg, respectively, and then increasing above control dose-independently. AP showed a biphasic response. HR first decreased dose-dependently but then increased slightly. In the remaining five rats, we compared the effects of ketamine 5 mg/kg on RNA, AP, and HR before surgical baroceptor denervation with those after the denervation. The denervation abruptly increased RNA, AP, and HR. Ketamine decreased RNA, AP, and HR in the denervated state and returned them to pre-ketamine values without overshoot. The finding that in the nerve intact state ketamine produced the characteristically biphasic response of RNA could be explained by the following mechanisms: (1) ketamine depresses the vasomotor center causing the initial decrease in RNA; (2) ketamine depresses the inhibitory effects of baroreflex causing the successive increase in RNA. The biphasic change in AP could be partly attributed to biphasic responses of RNA to ketamine.

Animals↗
PubMed1981

Ventricular systolic pressure-volume area as predictor of cardiac oxygen consumption.

We scrutinized the recently reported correlation between the canine left ventricular systolic pressure-volume area (PVA) and cardiac oxygen consumption rate per beat (Vo2) by use of an improved method of Vo2 assessment. PVA is the specific area in the pressure-volume (PV) plane bounded by the end-systolic and end-diastolic PV lines and the systolic segment of the PV loop. Different from the previous study in which Vo2-PVA data from isovolumic and ejecting contractions were pooled for analyses, we analyzed Vo2-PVA data from the two different modes separately to examine whether there was any difference of Vo2-PVA relationship between them. The results indicated that the linear regressions of Vo2 on PVA were virtually the same for isovolumic and ejecting contractions. The regression line was Vo2 (ml O2/beat) = a[PVA (mmHg x ml x beat-1)] + b, where a = 1.64 (+/- 0.12 SE) X 10(-5) (ml O2/beat)/(mmHg x ml x beat-1) and b = 0.015 +/- 0.002 ml O2/beat in 10 hearts. We conclude that PVA serves as a reliable predictor of Vo2 regardless of the mode of contraction in a given left ventricle with a stable inotropic background.

Animals↗
PubMed1981

Regression of cardiac oxygen consumption on ventricular pressure-volume area in dog.

Left ventricular systolic pressure-volume area (PVA) has been reported to be a reliable predictor of cardiac oxygen consumption rate per beat (VO2) in a given heart with a stable inotropic background. PVA is the specific area in the pressure-volume (PV) diagram, consisting of the area (EW) within the PV loop and the area (PE) bound by the end-systolic and end-diastolic PV lines and the relaxation segment of the PV loop. EW and PE correspond to the external mechanical work and the end-systolic elastic potential energy in the ventricular wall, respectively. We determined the optimal combination of EW and PE for the best prediction of VO2, using the linear multiple regression analysis. From EW, PE, and VO2, data of many isovolumic and ejecting contractions, the optimal coefficients of EW and PE were 1.67 +/- 0.43 (SD; 7 hearts) and 1.74 +/- 0.49 (10(-5) ml O2/mmHg . ml), virtually identical to each other, corroborating that PVA, i.e., a simple sum of EW and PE, can reliably predict VO2 of a given heart in a stable contractile state.

Animals↗
PubMed1981

Equal oxygen consumption rates of isovolumic and ejecting contractions with equal systolic pressure-volume areas in canine left ventricle.

Left ventricle systolic pressure-volume area (PVA) has been found to be highly linearly correlated with cardiac oxygen consumption rate per beat (VO2) in a given canine heart with a stable inotropic background. PVA is a specific area in the pressure-volume (P-V) diagram that is bounded by the end-systolic and end-diastolic P-V relationship lines and the systolic segment of the P-V loop, consisting of the sum of external mechanical work and what is considered the end-systolic elastic potential energy in the ventricular wall. In this study, we compared VO2's of steady state entirely isovolumic and variously ejecting contractions that were made to have equal PVA's in the canine left ventricle. We found that VO2's of these isovolumic and ejecting contractions with equal PVA's (isovolumic vs. ejecting = 1008 +/- 64 (SE) vs. 1022 +/- 62 mm Hg ml/beat, n = 32 pairs in 10 hearts) were equal to each other (0.0375 +/- 0.0021 vs. 0.0368 +/- 0.0021 ml O2/beat) regardless of the marked differences in stroke volume (0 vs. 9.8 +/- 0.6 ml), end-diastolic volume (20.3 +/- 0.8 vs. 23.7 +/- 0.9 ml), end-systolic volume (20.3 +/- 0.8 vs. 13.9 +/- 0.7 ml), peak pressure (123 +/- 5 vs. 88 +/- 5 mm Hg), stroke work (0 vs. 636 +/- 36 mm Hg ml/beat), and calculated peak total wall force (1588 +/- 77 vs. 1077 +/- 72 g). Therefore, we conclude that PVA can serve as a reliable predictor of VO2 in a given canine left ventricle with a stable inotropic background whether the contraction mode is isovolumic or ejecting.

Animals↗
PubMed1980

Critical evaluation of left ventricular systolic pressure volume areas as predictor of oxygen consumption rate.

Left ventricular systolic pressure volume area (PVA) has been reported to be a reliable predictor of cardiac oxygen consumption rate per beat (VO2) in a given heart with a stable inotropic background. PVA has been defined as the specific area in the pressure-volume (P-V) plane that is bounded by the end-systolic and end-diastolic P-V relationship lines and the systolic segment of the P-V loop trajectory. In the present experimental study, we separated PVA into two parts: EW and PE. EW is the area surrounded by the P=V loop, corresponding to the external mechanical work. PE is the area surrounded by the end-systolic and end-diastolic P-V lines and the relaxation segment of the P-V loop, corresponding to what is considered the end-systolic elastic potential energy in terms of a time-varying elastance model of the ventricle. We attempted to find an optimal weighting coefficient K of PE for the best correlation between VO2 and PVAW = EW + K . PE, changing K from 0 to infinity. Results in 7 canine excised cross-circulated hearts showed that PVAW best correlated with VO2 at K = 1.03 +/- 0.03 (SE). Since PVAW at K = 1 is identical with the original PVA, we concluded that PVA could serve as a reliable predictor of VO2. PVA is concluded to be physiologically significant in the coupling between cardiac mechanics and energetics.

Animals↗
PubMedDate not supplied

The cholinergic hypothesis revisited--an unfinished story.

Though exogenously delivered acetylcholine excites the carotid body, past evidence has been considered as unsupportive in assigning acetylcholine an excitatory role during hypoxia or hypercapnia. With ganglionic transmission used as the model, data is presented which aims at blocking the postsynaptic cholinergic receptors, at preventing the presynaptic release of acetylcholine, and at quantitating its release under stimulating conditions. The data support an excitatory role for acetylcholine during hypoxia.

Acetylcholine↗