Effects of respiratory acidosis and alkalosis on the distribution of cyanide into the rat brain.
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The aim of this study was to determine whether respiratory acidosis favors the cerebral distribution of cyanide, and conversely, if respiratory alkalosis limits its distribution. The pharmacokinetics of a nontoxic dose of cyanide were first studied in a group of 7 rats in order to determine the distribution phase. The pharmacokinetics were found to best fit a 3-compartment model with very rapid distribution (whole blood T(1/2)alpha = 21.6 +/- 3.3 s). Then the effects of the modulation of arterial pH on the distribution of a nontoxic dose of intravenously administered cyanide into the brains of rats were studied by means of the determination of the permeability-area product (PA). The modulation of arterial blood pH was performed by variation of arterial carbon dioxide tension (PaCO2) in 3 groups of 8 anesthetized mechanically ventilated rats. The mean arterial pH measured 20 min after the start of mechanical ventilation in the acidotic, physiologic, and alkalotic groups were 7.07 +/- 0.03, 7.41 +/- 0.01, and 7.58 +/- 0.01, respectively. The mean PAs in the acidotic, physiologic, and alkalotic groups, determined 30 s after the intravenous administration of cyanide, were 0.015 +/- 0.002, 0.011 +/- 0.001, and 0.008 +/- 0.001 s(-1), respectively (one-way ANOVA; p < 0.0087). At alkalotic pH the mean permeability-area product was 43% of that measured at acidotic pH. This effect of pH on the rapidity of cyanide distribution does not appear to be limited to specific areas of the brain. We conclude that modulation of arterial pH by altering PaCO2 may induce significant effects on the brain uptake of cyanide. (+info)
Effects of hypercapnia and hypocapnia on [Ca2+]i mobilization in human pulmonary artery endothelial cells.
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The hydrogen ion is an important factor in the alteration of vascular tone in pulmonary circulation. Endothelial cells modulate vascular tone by producing vasoactive substances such as prostacyclin (PGI2) through a process depending on intracellular Ca2+ concentration ([Ca2+]i). We studied the influence of CO2-related pH changes on [Ca2+]i and PGI2 production in human pulmonary artery endothelial cells (HPAECs). Hypercapnic acidosis appreciably increased [Ca2+]i from 112 +/- 24 to 157 +/- 38 nmol/l. Intracellular acidification at a normal extracellular pH increased [Ca2+]i comparable to that observed during hypercapnic acidosis. The hypercapnia-induced increase in [Ca2+]i was unchanged by the removal of Ca2+ from the extracellular medium or by the depletion of thapsigargin-sensitive intracellular Ca2+ stores. Hypercapnic acidosis may thus release Ca2+ from pH-sensitive but thapsigargin-insensitive intracellular Ca2+ stores. Hypocapnic alkalosis caused a fivefold increase in [Ca2+]i compared with hypercapnic acidosis. Intracellular alkalinization at a normal extracellular pH did not affect [Ca2+]i. The hypocapnia-evoked increase in [Ca2+]i was decreased from 242 +/- 56 to 50 +/- 32 nmol/l by the removal of extracellular Ca2+. The main mechanism affecting the hypocapnia-dependent [Ca2+]i increase was thought to be the augmented influx of extracellular Ca2+ mediated by extracellular alkalosis. Hypercapnic acidosis caused little change in PGI2 production, but hypocapnic alkalosis increased it markedly. In conclusion, both hypercapnic acidosis and hypocapnic alkalosis increase [Ca2+]i in HPAECs, but the mechanisms and pathophysiological significance of these increases may differ qualitatively. (+info)
Malignant hyperthermia in a patient with Graves' disease during subtotal thyroidectomy.
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We report the case of a 31-year-old man with Graves' disease who manifested malignant hyperthermia during subtotal thyroidectomy. His past medical history and family history were unremarkable. Before surgery, his condition was well controlled with propylthiouracil, beta-adrenergic blocker and iodine. During the operation, anesthesia was induced by intravenous injection of vecuronium and thiopental, followed by suxamethonium for endotracheal intubation. Anesthesia was maintained with nitrous oxide and sevoflurane. One hour after induction of anesthesia, his end tidal carbon dioxide concentration (ET(CO2)) increased from 40 to 50 mmHg, heart rate increased from 90 to 100 beats per min and body temperature began to rise at a rate of 0.3 degrees C per 15 min. Suspecting thyroid storm, propranolol 0.4 mg and methylprednisolone 1,500 mg were administered, which, however, had little effect. Despite the lack of muscular rigidity, the diagnosis of malignant hyperthermia was made based on respiratory acidosis. Sevoflurane was discontinued and dantrolene was given by intravenous bolus. Soon after the treatment, ET(CO2), heart rate and body temperature started to fall to normal levels. His laboratory findings showed abnormally elevated serum creatine phosphokinase and myoglobin but normal thyroid hormone levels. Since dantrolene is efficacious in thyrotoxic crisis and malignant hyperthermia, an immediate intravenous administration of dantrolene should be considered when a hypermetabolic state occurs during anesthesia in surgical treatment for a patient with Graves' disease. (+info)
Total weak acid concentration and effective dissociation constant of nonvolatile buffers in human plasma.
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The strong ion approach provides a quantitative physicochemical method for describing the mechanism for an acid-base disturbance. The approach requires species-specific values for the total concentration of plasma nonvolatile buffers (A(tot)) and the effective dissociation constant for plasma nonvolatile buffers (K(a)), but these values have not been determined for human plasma. Accordingly, the purpose of this study was to calculate accurate A(tot) and K(a) values using data obtained from in vitro strong ion titration and CO(2) tonometry. The calculated values for A(tot) (24.1 mmol/l) and K(a) (1.05 x 10(-7)) were significantly (P < 0.05) different from the experimentally determined values for horse plasma and differed from the empirically assumed values for human plasma (A(tot) = 19.0 meq/l and K(a) = 3.0 x 10(-7)). The derivatives of pH with respect to the three independent variables [strong ion difference (SID), PCO(2), and A(tot)] of the strong ion approach were calculated as follows: dpH/dSID(+) = [1 + 10(pK(a)-pH)](2)/(2.303 x [SPCO(2)10(pH-pK'(1)[1 + 10(pK(a)-pH](2) + A(tot)10(pK(a)-PH]]; dpH/dPCO(2) = S10(-pK'(1)/[2.303[A(tot)10(pH)(10(pH + 10(pK(a))(-2) - SID(+)10(-pH)]], dpH/dA(tot) = -1/[2.303[SPCO(2)10(pH-pK'(1) + SID(+)10(pK(a)-pH)]], where S is solubility of CO(2) in plasma. The derivatives provide a useful method for calculating the effect of independent changes in SID(+), PCO(2), and A(tot) on plasma pH. The calculated values for A(tot) and K(a) should facilitate application of the strong ion approach to acid-base disturbances in humans. (+info)
Acute respiratory and metabolic acidosis induced by excessive muscle contraction during spinal evoked stimulation.
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Spinal somatosensory evoked potentials (SSEPs) have been used to monitor spinal cord function during corrective scoliosis surgery. We report three cases in which direct epidural stimulation for measurement of SSEPs produced paraspinal muscle contraction, resulting in respiratory and metabolic acidosis. In two of the cases, SSEP-induced acidosis was observed even when only the first twitch of the train-of-four response was detectable after a second dose of muscle relaxant. In one of these two cases, the acidosis was abolished after a sufficient dose of vecuronium to ablate the twitch response. To prevent SSEP-induced respiratory and metabolic acidosis, we recommend that SSEPs should be measured only when profound neuromuscular blockade has been obtained. (+info)
Metabolic, but not respiratory, acidosis increases bone PGE(2) levels and calcium release.
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A decrease in blood pH may be due to either a reduction in bicarbonate concentration ([HCO(3)(-)]; metabolic acidosis) or to an increase in PCO(2) (respiratory acidosis). In mammals, metabolic, but not respiratory, acidosis increases urine calcium excretion without altering intestinal calcium absorption, indicating that the additional urinary calcium is derived from bone. In cultured bone, chronic metabolic, but not respiratory, acidosis increases net calcium efflux (J(Ca)), decreases osteoblastic collagen synthesis, and increases osteoclastic bone resorption. Metabolic acidosis increases bone PGE(2) production, which is correlated with J(Ca), and inhibition of PGE(2) production inhibits this acid-induced J(Ca). Given the marked differences in the osseous response to metabolic and respiratory acidosis, we hypothesized that incubation of neonatal mouse calvariae in medium simulating respiratory acidosis would not increase medium PGE(2) levels, as observed during metabolic acidosis. To test this hypothesis, we determined medium PGE(2) levels and J(Ca) from calvariae incubated at pH approximately 7.1 to model either metabolic (Met; [HCO(3)(-)] approximately 11 mM) or respiratory (Resp; PCO(2) approximately 83 Torr) acidosis, or at pH approximately 7.5 as a control (Ntl). We found that after 24-48 and 48-51 h in culture, periods when cell-mediated J(Ca) predominates, medium PGE(2) levels and J(Ca) were increased with Met, but not Resp, compared with Ntl, and there was a direct correlation between medium PGE(2) levels and J(Ca). Thus metabolic, but not respiratory, acidosis induces the release of bone PGE(2), which mediates J(Ca) from bone. (+info)
Pickwickian syndrome, 20 years later.
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The Pickwickian Syndrome stimulated new pathophysiological concepts in regard to control of ventilation. With the advent of sleep laboratories, the peculiar sleep apnea occurring in some of these patients has been explained on the basis of intermittent upper airway obstruction. Two patients with different manifestations of the Pickwickian Syndrome are presented. The suggestion is made that these two subsyndromes should have unique designations. The Auchincloss Syndrome is manifested by right heart failure and respiratory acidosis in obese patients who are alert and have no major abnormality of breathing pattern. The fundamental cause of this abnormality is the increased work of breathing caused by the obesity. The cost of breathing is so high that the ventilatory regulation is compromised and respiratory acidosis results. The Gastaut Syndrome is characterized principally by hypersomnia and sleep apnea. The fundamental defect is upper airway obstruction during sleep, resulting in increased work of breathing, which together with the increased work caused by obesity leads to respiratory acidosis and right ventricular failure. Hypersomnia, rather than heart failure or respiratory acidosis, is the major manifestation of this syndrome, and is the result of sleep loss. (+info)
Contribution of respiratory acidosis to diaphragmatic fatigue at exercise.
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The factors that may modulate ventilatory muscle fatigue during exercise are controversial. In this study the contribution of acidosis to exercise-induced diaphragmatic fatigue was investigated, using measurements of the twitch mouth pressure response (tw,Pmo) to cervical magnetic stimulation. After learning sessions, 14 healthy subjects performed two cycling tests (at 60% of maximal aerobic power for 16 min), one while breathing spontaneously (mean minute ventilation (V'E) 67.9 L x min(-1)) and the other while hypoventilating voluntarily (mean V'E 53.8 L x min(-1)). Exercise was voluntarily set at a moderate power to avoid a fatiguing effect of exercise per se. As compared with spontaneous breathing (SB), voluntary hypoventilation (VHV) significantly increased mean carbon dioxide tension in arterial blood (Pa,CO2) (51 mmHg versus 41 mmHg) and significantly decreased arterial pH (7.28 versus 7.34). After 10 min of SB test, tw,Pmo was unchanged compared to the baseline value (19.1 versus 18.5 cmH2O) whereas tw,Pmo fell significantly as compared to baseline (17.1 versus 18.5 cmH2O) and to SB (17.1 versus 19.1 cmH2O) after the VHV test. The results of this study suggest that exposure to hypercapnia may impair respiratory muscle function. This impairment could be more clinically relevant in patients with chronic obstructive lung disease. (+info)