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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of two anaesthetics, sodium pentobarbital and urethane, and the effects of anaesthesia-associated hypothermia on acid-base status and blood gases were studied in rats without assisted ventilation. 2. Manipulation of conscious rats produces a progressive increase in arterial lactate associated with slight hyperventilation. 3. Sodium pentobarbital anaesthesia produces mild respiratory acidosis accompanied by increase in lactate arterial values. Urethane anaesthesia leads to partially compensated metabolic acidosis. 4. Hypothermia reduces metabolic acidosis and hypercapnia induced by sodium pentobarbital anaesthesia. No difference between hypothermic and normothermic values was observed in urethane anaesthesia.
Gen Pharmacol 1992 Jul
PMID:Differential effects of hypothermia upon blood acid-base state and blood gases in sodium pentobarbital and urethane anaesthetised rats. 139 74

Experiments were conducted to test the hypothesis that one or more interrenal steroids are active in regulatory responses to respiratory acidosis in the toad, Bufo marinus. Toads were divided into four experimental groups. The first group received sham injections. The second group received 1-3 mg of aminoglutethimide (AG) every 8 hr. AG inhibits the conversion of cholesterol to pregnenolone, thus inhibiting all steroid hormone synthesis. The third group received AG + 5 micrograms of aldosterone on the same schedule. The fourth group received AG + 25 micrograms of corticosterone on the same schedule as the other groups. All four groups were subjected to hypercapnia using 5% CO2 to induce a respiratory acidosis. The sham-operated animals displayed the normal compensatory pattern of producing a metabolic alkalosis (elevated plasma HCO3-) after 24 hr. AG-treated toads failed to elevate plasma HCO3-. Administration of interrenal steroids produced compensation in varying degrees. Aldosterone produced a small compensation while corticosterone produced a compensation similar to that seen in sham-operated animals. Analysis of steroid titers in toad plasma during hypercapnia showed that Bufo marinus does not elevate aldosterone during respiratory acidosis, but that corticosterone is elevated. AG blocked the corticosterone elevation, however. AG also produced a hyponatremia that was corrected with aldosterone or corticosterone. Normocapnic controls showed that AG does not produce deleterious effects on pH or blood gases in toads in the absence of a respiratory acidosis. We conclude that corticosterone is important in acid-base regulatory responses to respiratory acidosis in this amphibian.
Gen Comp Endocrinol 1992 Apr
PMID:Acid-base-electrolyte balance responses of Bufo marinus to aminoglutethimide, corticosterone, and aldosterone during hypercapnia. 150 25

1. Cerebral blood flow (CBF) in the rat was monitored by a venous outflow technique with an extracorporeal circulation which allowed for continuous monitoring of flow over the several hours of the study. 2. Brief challenges with carbon dioxide (CO2) increased the CBF. 3. Nifedipine (1.00 mg/kg), a dihydropyridine calcium antagonist, attenuated the response of the animal to hypercapnia, while leaving the basal flow rate unchanged. 4. This study may have significant implications as to the effect of nifedipine on CBF. 5. Since similar results have been obtained with nifedipine in anoxia, this study suggests that the responses to anoxia and hypercapnia are interrelated and that the resulting hyperemia may be governed by the same mechanisms.
Gen Pharmacol 1991
PMID:Nifedipine reduces the increases in cerebral blood flow during hypercapnic episodes. 190 50

Morphine sulfate effects (30 mg, intramuscularly) on cerebral glucose utilization and subjective self-reports were examined in 12 polydrug abusers by positron emission tomography and [fluorine 18]fluorodeoxyglucose in a double-blind placebo-controlled crossover study. During testing, subjects sat with eyes covered, listening to white noise and "beep" prompts. Morphine significantly reduced glucose utilization by 10% in whole brain and by about 5% to 15% in telencephalic areas and the cerebellar cortex, assuming no contribution of hypercapnia. When the contribution of PaCO2 (45 minutes after morphine was administered) was partialled out, significant morphine-induced reductions persisted in whole brain and six cortical areas. Irrespective of morphine, left-greater-than-right asymmetry occurred in the temporal cortex, and an interaction between hemisphere and drug was noted in the postcentral gyrus. In most cases, effects on glucose utilization were not significantly related to measures of euphoria.
Arch Gen Psychiatry 1990 Jan
PMID:Morphine-induced metabolic changes in human brain. Studies with positron emission tomography and [fluorine 18]fluorodeoxyglucose. 240 75

The metabolic consequences of external hypercapnia (1% CO2) were assessed in rainbow trout (Salmo gairdneri) in the presence or absence of circulating levels of the beta adrenoceptor antagonist, propranolol. External hypercapnia caused a severe extracellular respiratory acidosis and a less pronounced reduction of hepatic intracellular pH (pHi). pHi was restored to prehypercapnic values after 48 hr of continuous hypercapnia due to elevation of bicarbonate levels. In the presence of propranolol, hypercapnia elicited a pronounced activation of pyruvate kinase (PyK) (measured at both low and high phosphoenolpyruvate (PEP) concentrations) and inactivation of both total glycogen phosphorylase (GPase) and glycogen phosphorylase a (GPase a). In the absence of propranolol, the changes in enzyme activities were significantly reduced (low PEP PyK activity) or totally absent (GPase inactivation). These results suggest that beta adrenoceptor-mediated phenomena offset disruptive effects of hypercapnia on PyK and GPase activities and may be important in the control of gluconeogenesis and glycogenolysis during this acid-base disturbance. The adrenergic effects were not related to modification of hepatic intracellular acid-base status. Hypercapnia induced a rapid depletion of liver glycogen and concomitant hyperglycemia. These effects were not prevented by pretreating fish with propranolol and appeared to be unrelated to changes in GPase a activity. These results suggest that factors other than adrenergic activation of GPase a are involved in the enhancement of liver glycogenolysis.
Gen Comp Endocrinol 1988 Mar
PMID:Metabolic consequences of hypercapnia in the rainbow trout, Salmo gairdneri: beta-adrenergic effects. 283 62

The possibility that endogenously released adenosine, a potent vasodilator, is involved in the increase in cerebral blood flow (CBF) response to hypercapnia has been investigated in an anesthetized, paralyzed rat model. The left retroglenoid vein was cannulated and cerebral venous blood flow measured with a drop counter. Animals were ventilated with a 40% oxygen, 60% nitrogen gas mixture. At 20 min intervals, at a constant rate of flow, the inspired gas mixture was altered to 10% carbon dioxide, 40% oxygen, 50% nitrogen for periods of between 30-90 sec. This brief hypercapnic challenge induced a rapid increase in CBF in the absence of any change in MABP. An involvement of adenosine in this response was demonstrated using an adenosine antagonist, caffeine, an uptake inhibitor, dipyridamole and an adenosine deaminase inhibitor, deoxycoformycin. Caffeine (10 and 20 mg/kg i.p.) 15 min prior to hypercapnic challenges significantly decreased the peak increases in CBF. Dipyridamole (0.1 mg/kg) and deoxycoformycin (0.1 microgram/kg) enhanced the peak increases in flow. These results are consistent with an important role for adenosine in coupling PCO2 to cerebral blood flow.
Gen Pharmacol 1987
PMID:An involvement of adenosine in cerebral blood flow regulation during hypercapnia. 349 49

1. Late cerebral arterial spasm was induced by repeated injections of autologous blood in a total amount of 14-33 ml into the basal cisterns of baboons to mimick subarachnoid hemorrhage (SAH). Regional cerebral blood flow (CBF), sagittal sinus pressure, cerebral arterial caliber from angiograms, and cerebral metabolic rate of oxygen (CMRO2) were measured before and after the experimental SAH to determine responses to hypercapnia and induced hypertension. The effect of the calcium antagonist, Nimodipine, on CBF autoregulation pre- and post-SAH was tested. 2. One week after the blood injections were started there was about 10-20% reduction, depending on territory measured, in the arterial diameter of the carotid and vertebral systems. This was associated with an 18% reduction in CBF and 9% decrease in the brain metabolism. 3. During hypercapnia before and after experimental SAH the flow increased with a mean of 3.7 and 1.8 ml, respectively, for each mm Hg elevation of PaCO2. In control animals, graded angiotensin-induced hypertension did not overtly affect CBF. Following SAH, the CBF autoregulation was impaired in 5 of 6 animals tested. 4. I.v. infusion of Nimodipine markedly curtailed the CBF autoregulation in pre-SAH animals and, to a somewhat slighter extent, also in post-SAH animals.
Gen Pharmacol 1983
PMID:Late cerebral arterial spasm: the cerebrovascular response to hypercapnia, induced hypertension and the effect of nimodipine on blood flow autoregulation in experimental subarachnoid hemorrhage in primates. 682 30

Acidosis increases resting cytosolic [Ca2+], (Cai) of myocardial preparations; however, neither the Ca2+ sources for the increase in Cai nor the effect of acidosis on mitochondrial free [Ca2+], (Cam) have been characterized. In this study cytosolic pH (pHi) was monitored in adult rat left ventricular myocytes loaded with the acetoxymethyl ester (AM form) of SNARF-1. A stable decrease in the pHi of 0.52 +/- 0.05 U (n = 16) was obtained by switching from a bicarbonate buffer equilibrated with 5% CO2 to a buffer equilibrated with 20% CO2. Electrical stimulation at either 0.5 or 1.5 Hz had no effect on pHi in 5% CO2, nor did it affect the magnitude of pHi decrease in response to hypercarbic acidosis. Cai was measured in myocytes loaded with indo-1/free acid and Cam was monitored in cells loaded with indo-1/AM after quenching cytosolic indo-1 fluorescence with MnCl2. In quiescent intact myocytes bathed in 1.5 mM [Ca2+], hypercarbia increased Cai from 130 +/- 5 to 221 +/- 13 nM. However, when acidosis was effected in electrically stimulated myocytes, diastolic Cai increased more than resting Cai in quiescent myocytes, and during pacing at 1.5 Hz diastolic Cai was higher (285 +/- 17 nM) than at 0.5 Hz (245 +/- 18 nM; P < 0.05). The magnitude of Cai increase in quiescent myocytes was not affected either by sarcoplasmic reticulum (SR) Ca2+ depletion with ryanodine or by SR Ca2+ depletion and concomitant superfusion with a Ca(2+)-free buffer. In unstimulated intact myocytes hypercarbia increased Cam from 95 +/- 12 to 147 +/- 19 nM and this response was not modified either by ryanodine and a Ca(2+)-free buffer or by 50 microM ruthenium red in order to block the mitochondrial uniporter. In mitochondrial suspensions loaded either with BCECF/AM or indo-1/AM, acidosis produced by lactic acid addition decreased both intra- and extramitochondrial pH and increased Cam. Studies of mitochondrial suspensions bathed in indo-1/free acid-containing solution showed an increase in extramitochondrial Ca2+ after the addition of lactic acid. Thus, in quiescent myocytes, cytoplasmic and intramitochondrial buffers, rather than transsarcolemmal Ca2+ influx or SR Ca2+ release, are the likely Ca2+ sources for the increase in Cai and Cam, respectively; additionally, Ca2+ efflux from the mitochondria may contribute to the raise in Cai. In contrast, in response to acidosis, diastolic Cai in electrically stimulated myocytes increases more than resting Cai in quiescent cells; this suggests that during pacing, net cell Ca2+ gain contributes to enhance diastolic Cai.
J Gen Physiol 1993 Sep
PMID:Effects of acidosis on resting cytosolic and mitochondrial Ca2+ in mammalian myocardium. 824 24

Experiments were performed on isolated, nonworking rat hearts perfused at constant pressure according to the Langendorff technique to evaluate the role of adenosine in hypercapnia-evoked coronary vasodilation. Hypercapnia/acidosis resulted in increases in heart rate and coronary flow rates in conjunction with a decrease in ventricular contractile tensions. The adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA, 10 microM) reduced the heart rate and enhanced CO2-evoked increases in coronary vascular flow. 5-Iodotubercidin (1 microM), an inhibitor of adenosine kinase, caused a reduction in heart rate and enhanced coronary flow rates during hypercapnic perfusion. Adenosine deaminase (1 U/ml) significantly attenuated CO2-evoked increases in coronary vascular flow. These results extend those of previous investigations implicating adenosine in the regulation of coronary flow during conditions of respiratory or metabolic acidosis.
Gen Pharmacol 1999 Nov
PMID:Further evidence for the role of adenosine in hypercapnia/acidosis-evoked coronary flow regulation. 1055 85

CO2 chemoreception may be related to modulation of inward rectifier K+ channels (Kir channels) in brainstem neurons. Kir4.1 is expressed predominantly in the brainstem and inhibited during hypercapnia. Although the homomeric Kir4.1 only responds to severe intracellular acidification, coexpression of Kir4.1 with Kir5.1 greatly enhances channel sensitivities to CO2 and pH. To understand the biophysical and molecular mechanisms underlying the modulation of these currents by CO2 and pH, heteromeric Kir4. 1-Kir5.1 were studied in inside-out patches. These Kir4.1-Kir5.1 currents showed a single channel conductance of 59 pS with open-state probability (P(open)) approximately 0.4 at pH 7.4. Channel activity reached the maximum at pH 8.5 and was completely suppressed at pH 6.5 with pKa 7.45. The effect of low pH on these currents was due to selective suppression of P(open) without evident effects on single channel conductance, leading to a decrease in the channel mean open time and an increase in the mean closed time. At pH 8.5, single-channel currents showed two sublevels of conductance at approximately 1/4 and 3/4 of the maximal openings. None of them was affected by lowering pH. The Kir4.1-Kir5.1 currents were modulated by phosphatidylinositol-4,5-bisphosphate (PIP2) that enhanced baseline P(open) and reduced channel sensitivity to intracellular protons. In the presence of 10 microM PIP2, the Kir4.1-Kir5.1 showed a pKa value of 7.22. The effect of PIP2, however, was not seen in homomeric Kir4.1 currents. The CO2/pH sensitivities were related to a lysine residue in the NH2 terminus of Kir4.1. Mutation of this residue (K67M, K67Q) completely eliminated the CO2 sensitivity of both homomeric Kir4.1 and heteromeric Kir4.1-Kir5.1. In excised patches, interestingly, the Kir4.1-Kir5.1 carrying K67M mutation remained sensitive to low pHi. Such pH sensitivity, however, disappeared in the presence of PIP2. The effect of PIP2 on shifting the titration curve of wild-type and mutant channels was totally abolished when Arg178 in Kir5.1 was mutated. Thus, these studies demonstrate a heteromeric Kir channel that can be modulated by both acidic and alkaline pH, show the modulation of pH sensitivity of Kir channels by PIP2, and provide information of the biophysical and molecular mechanisms underlying the Kir modulation by intracellular protons.
J Gen Physiol 2000 Jul 01
PMID:Biophysical and molecular mechanisms underlying the modulation of heteromeric Kir4.1-Kir5.1 channels by CO2 and pH. 1087 38


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