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

Malignant hyperthermia is a potentially fatal condition inducible by volatile anaesthetics and/or suxamethonium in genetically susceptible individuals. A disturbed calcium homeostasis in skeletal muscle (possibly in the ryanodin receptor) results in elevated myoplasmatic calcium. The latter causes muscle contraction and a hypermetabolic state, clinically observed as rigidity, fever, hypercarbia, metabolic acidosis and hyperkalemia. Arythmia ensues. Dantrolene inhibits the release of calcium and can halt the process if the diagnosis is made early. A fatal incident of probable malignant hyperthermia in a 13 year old boy is described and evaluated according to a multifactorial clinical grading scale. The value of the in vitro contracture test to diagnose malignant hyperthermia is discussed. Suggestions concerning the treatment of masseterspasm rigidity, an acute episode of malignant hyperthermia, and safe anaesthesia for susceptible patients are presented.
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PMID:[Malignant hyperthermia--still a current and dangerous problem]. 777 Aug 53

The objective of the study was to explore whether hypoglycemic brain damage is affected by super-imposed acidosis. To that end, animals with insulin-induced hypoglycemic coma, defined in terms of a negative DC potential shift, massive release of K+, or cellular uptake of Ca2+, were exposed to excessive hypercapnia (PaCO2 approximately 200 or approximately 300 mm Hg) during the last 25 min of the 30-min coma period. Animals were allowed to survive for 7 days before their brains were fixed by perfusion, and the cell damage was assessed by light microscopy. Other animals were analyzed with respect to changes in extracellular pH (pHe) or extracellular K+ or Ca2+ concentrations (K+e and Ca2+e, respectively). The total CO2 content (TCO2) was also measured to allow derivation of intracellular pH (pHi). The increase in PaCO2 to 190 +/- 15 and 312 +/- 23 mm Hg (means +/- SD) reduced the pHe from a predepolarization value of approximately 7.4 and a postdepolarization value (after the first 5 min of coma) of approximately 7.3 to 6.8 and 6.7, respectively. The corresponding mean pHi values were 6.7 and 6.5. The hypercapnia did not alter the K+e, which rose to 50-60 mM at the onset of hypoglycemic coma, but it increased the Ca2+e from approximately 0.05 to 0.10-0.16 mM. Normocapnic animals with induced hypoglycemic coma of 30-min duration showed the expected neuronal lesions in the neocortex, hippocampus, and caudoputamen. Hypercapnia clearly aggravated this damage, particularly in the caudoputamen, subiculum, and CA1 region of the hippocampus, and caused additional damage to cells in the CA3 region and piriform cortex. A rise in CO2 tension from approximately 200 to 300 mm Hg did not further aggravate the damage. The results thus demonstrate that relative moderate acidosis aggravates damage that is believed to be mostly neuronal, sparing glia cells and vascular tissue.
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PMID:The influence of acidosis on hypoglycemic brain damage. 779 41

Hypercapnia and hypoxia both relax airway smooth muscle, but the mechanisms responsible are poorly understood. Because hypercapnia and hypoxia can each decrease intracellular pH (pHi) and acidosis can inhibit Ca2+ channels, we hypothesized that decreased pHi mediates relaxation of trachealis muscle by each of these respiratory gases. To examine the relationship between pHi and tone, we measured isometric tension, bath pH, and fluorescence intensity (540 nm) in porcine tracheal smooth muscle strips loaded with 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein and excited alternately with 440- and 500-nm light. Strips equilibrated in Krebs-Henseleit solution bubbled with 95% O2-5% CO2 were contracted with carbachol and then relaxed with either 95% N2-5% CO2 or 93% O2-7% CO2. The ratio of fluorescence intensity at 500 nm to 440 nm was calibrated vs. pHi with use of nigericin. Baseline pHi was 7.19 +/- 0.03 (n = 13). Hypoxia decreased active tension by approximately 60% but did not change pHi. Hypercapnia induced decreases in tension that were associated with substantial decreases in pHi. Thus, decreased pHi does not mediate hypoxic relaxation, but the relaxation during physiologically relevant increases in CO2 concentration is associated with significant cellular acidification.
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PMID:Role of intracellular pH in relaxation of porcine tracheal smooth muscle by respiratory gases. 786 41

High CO2 stimulates dilator prostanoid (prostaglandin; PG) synthesis by piglet cerebral microvascular endothelial cells, but the mechanism of stimulation is unclear. We address the hypothesis that intracellular pH (pHi) and Ca2+ signaling are involved. When extracellular pH (pHe) and PCO2 were constant and pHi was rapidly reduced (propionate or nigericin), PG synthesis was stimulated. When pHe was lowered by reducing NaHCO3, pHi fell slowly, but PG synthesis was not altered. When pHe was decreased by increasing PCO2 or returned to 7.4 by increasing NaHCO3, with a constant PCO2 of 100 mmHg, pHi dropped quickly and PG synthesis was stimulated. When pHi was reduced slowly by changing CO2 slowly, or by stepwise addition of propionate, PG synthesis was increased regardless of pHe, suggesting that the rapid decline of pHi plays a central role in mediating the PG synthesis. Ca2+ signaling is a potential mechanism by which pHi increases PG synthesis. However, extracellular Ca2+ removal did not affect PG synthesis induced by propionate or hypercapnia. Furthermore, neither rapid nor slow decreases of pHi altered cytosolic free Ca2+ concentration. Therefore, Ca2+ signals do not appear to be involved in the CO2 stimulation of PG synthesis.
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PMID:Mechanisms of hypercapnia-stimulated PG production in piglet cerebral microvascular endothelial cells. 786 84

Microscopic fluorometry was used to examine the effects of CO2, acetate and low extracellular pH (pHo) on cytosolic Ca2+ ([Ca2+]i, fura-2) and on cytosolic pH (pHi, BCECF) in cultured glomus cells of the newborn rabbit carotid body. Applications of CO2 and acetate at a constant pHo of 7.4 rapidly produced a sustained increase in [Ca2+]i and a sustained decrease in pHi. A slightly lowered pHo of 7.0 slowly induced a small increase in [Ca2+]i and an exponential-like decrease in pHi. An approximately linear correlation was seen between the changed values of [Ca2+]i and pHi induced by the weak acidic stimuli. The speed of the initial pHi response to CO2 was faster than the response to low pHo. It is suggested that the induction of increased [Ca2+]i by hypercapnia and acidosis may be mediated by cytosolic acidification, in which exposure to CO2 causes a faster response than exposure to H+.
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PMID:Effects of CO2, acetate and lowering extracellular pH on cytosolic Ca2+ and pH in cultured glomus cells of the newborn rabbit carotid body. 793 5

Anesthetized, paralyzed and mechanically ventilated pigs were hypoventilated to extreme hypercapnia (PaCO2 approximately 20 kPa) at FiO2 0.5, and allotted to receive hypothermia (approximately 31.5 degrees C) and buffer infusion, (HB-group, n = 6) or to a hypothermic control group (H-group, n = 6). The HB-group had higher arterial pH (7.34 vs 7.09, P < 0.01) and plasma bicarbonate (58.8 vs 35.4 mmol.l-1, P < 0.01) than the controls, but lower mean pulmonary arterial pressure (MPAP), (16 vs 23 mmHg (2.1 vs 3.1 kPa), P < 0.01) and pulmonary vascular resistance (PVR), (512 vs 699 dyn.s.cm-5 (5120 vs 6990 microN.s.cm-5), P < 0.05). Mixed venous PO2 (PVO2) was lower in the HB-group (5.1 vs 6.8 kPa, P < 0.01), as well as serum potassium (2.8 vs 3.7 mmol.l-1, P < 0.01) and ionized calcium (1.01 vs 1.29 mmol.l-1, P < 0.01). Subsequently, the inspired oxygen fraction (FiO2) was decreased stepwise (0.3, 0.25, 0.21, 0.15, 0.10) at 30 min intervals. At FiO2 0.3, the HB-group had lower PVO2 (6.6 vs 7.8 kPa, P < 0.01), O2 half saturation tension (3.6 vs 4.2 kPa, P < 0.01), MPAP (17 vs 25 mmHg (2.3 vs 3.3 kPa, P < 0.01) and PVR (598 vs 793 dyn.s.cm-5 (5980 vs 7930 microN.s.cm-5, P < 0.05) compared with the controls, but higher arterial O2 saturation (95.3 vs. 88.6%, P < 0.01) and O2 content (17.7 vs 15.7 ml.100 ml-1, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of hypothermia with and without buffering in hypercapnia and hypercapnic hypoxemia. 802 72

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.
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PMID:Effects of acidosis on resting cytosolic and mitochondrial Ca2+ in mammalian myocardium. 824 24

We have investigated the effects of acidic stimuli upon [Ca2+]i in isolated carotid body type I cells from the neonatal rat using indo-1 (AM-loaded). Under normocapnic, non-hypoxic conditions (23 mM HCO3-, 5% CO2 in air, pHo = 7.4), the mean [Ca2+]i for single cells was 102 +/- 5.0 nM (SEM, n = 55) with 58% of cells showing sporadic [Ca2+]i fluctuations. A hypercapnic acidosis (increase in CO2 to 10%-20% at constant HCO3-, pHo 7.15-6.85), an isohydric hypercapnia (increase in CO2 to 10% at constant pHo = 7.4) and an isocapnic acidosis (pHo = 7.0, constant CO2) all increased [Ca2+]i in single cells and cell clusters. The averaged [Ca2+]i response to both hypercapnic acidosis and isohydric hypercapnia displayed a rapid rise followed by a secondary decline. The averaged [Ca2+]i response to isocapnic acidosis displayed a slower rise and little secondary decline. The rise of [Ca2+]i in response to all the above stimuli can be attributed to no single factor other than to a fall of pHi. The hypercapnia-induced rise of [Ca2+]i was almost completely abolished in Ca(2+)-free solution, suggesting a role for Ca2+ influx in triggering and/or sustaining the [Ca2+]i response. These results are consistent with a role for type I cell [Ca2+]i in mediating pH/PCO2 chemoreception.
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PMID:Effects of acidic stimuli on intracellular calcium in isolated type I cells of the neonatal rat carotid body. 827 80

The aqueous humors of 100 freshly enucleated rabbit eyes were assessed within 10 min postmortem by taking samples in the last stage of corneal dissection following the Dikstein-Maurice procedure. Aqueous levels of partial pressure of carbon dioxide (pCO2) averaged 58.2 +/- 8.5 mm Hg to give calculated tCO2 and bicarbonate levels of 34.9 +/- 2.2 mEq/l and 30.0 +/- 3.4 mM/l, respectively. The pH and ionized Ca2+ levels averaged 7.39 and 1.50 mM while partial pressure of oxygen (pO2) values were variable (31.5 +/- 23.6 mm Hg). The pH showed an inverse correlation to pCO2 values, and Ca2+ increased as pCO2 increased. O2 levels tended to decrease as CO2 increased. The results suggest that significant hypercapnia and hypoxia of the eye fluids can occur even within 10 min postmortem for an enucleated globe at room temperature.
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PMID:Postmortem evaluation of rabbit aqueous humor partial pressure of carbon dioxide, total carbon dioxide, bicarbonate, partial pressure of oxygen and ionized calcium levels. 832 20

Uremic acidosis accompanies chronic renal failure in hemodialysis patients because of a retention of nonvolatile acids. Standard bicarbonate (39 mEq/L) and acetate (38 mEq/L) dialysates do not completely correct the acidosis. The acid-base and biochemical effect of a high-bicarbonate (42 mEq/L) dialysate was evaluated in 38 patients during high-efficiency and high-flux dialysis over 12 wk. All patients were dialyzed on standard bicarbonate dialysate before the study and for 8 wk after the study. In order to monitor potential excessive alkalosis, predialysis and postdialysis arterial blood gases were measured in seven patients who initially had a normal predialysis pH. Serum chemistries revealed no significant changes in predialysis BUN, calcium, ionized calcium, or phosphorus during the 12-wk study. There was no change in postdialysis ionized calcium or phosphorus. Predialysis and postdialysis serum total CO2 (STCO2) increased over the 12-wk study (P < 0.0001). By week 12, 75% of the hemodialysis patients had an STCO2 > 23 mEq/L and no patient had an STCO2 > 30 mEq/L predialysis. After the 8-wk washout, all chemistries were no different from prestudy concentrations. Predialysis blood gases in seven patients with normal predialysis HCO3 revealed a significant increase (P < 0.009) in PCO2 and HCO3 over the 12-wk study; predialysis pH and PO2 did not change. There was no significant change in postdialysis blood gases. It was concluded that: (1) a high-bicarbonate dialysate corrects predialysis acidosis in 75% of hemodialysis patients without causing progressive alkalemia, hypoxia, or hypercarbia; and (2) predialysis BUN, calcium, ionized calcium, and phosphorus are unaffected by high-bicarbonate dialysate.
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PMID:Normalization of uremic acidosis in hemodialysis patients with a high bicarbonate dialysate. 813 52


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