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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The ventilatory responses to transient and steady-state hypoxia were measured in ten patients with hepatic cirrhosis and in ten healthy control subjects. Successive measurements of these responses were also obtained in six goats before and after the experimental production of liver failure. Changes in the effect of steady-state hypoxia on the ventilatory response to hypercapnia were evaluated by successive studies in another goat. 2. In spite of a respiratory alkalosis during liver failure, the response to transient hypoxia was greater in the patients than in the control subjects. This response was increased after the onset of liver failure in all the goats. 3. In healthy humans and goats the responses to transient and steady-state hypoxia were similar in magnitude. During liver failure there was a disparity between the size of these responses, since the ventilatory increment evoked by steady-state hypoxia was unchanged in spite of the increase in response to transient hypoxia. Steady-state hypoxia consistently enhanced the ventilatory response to hypercapnia in a healthy goat, but frequently depressed the response to hypercapnia during liver failure. 4. The findings suggest that liver failure heightens the sensitivity of the peripheral chemoreceptors to the hypoxic stimulus, but may increase the tendency of the medullary centres to become depressed in hypoxia.
Clin Sci Mol Med 1976 Jan
PMID:Effect of liver failure on the ventilatory response to hypoxia in man and the goat. 0 6

1. The ventilatory response to severe metabolic acidosis was studied by measuring arterial blood carbon dioxide tension and pH in sixty-seven patients with blood pH less than 7-10, none of whom had hypercapnia, pulmonary oedema, or chronic pulmonary insufficiency. The results were compared with those previously found in patients with uncomplicated diabetic ketoacidosis. 2. By that comparison, fifty-two of the sixty-seven patients with blood pH less than 7-10 were judged to have "appropriate hypocapnia", and fifteen had "submaximal hypocapnia". Thirteen of the latter fifteen had circulatory failture and/or acute hypoxia, and seven of nine in whom it was measured had plasma lactate greater than 9 mmol/1. 3. Hyperventilation was therefore usually well sustained in these patients with severe metabolic acidosis, except in most of those with acute tissue hypoxia. The latter may have had insufficient time to achieve maximum hyperventilation in response to their acidosis, or perhaps their submaximal hypercapnia presaged imminent failure of the hyperventilatory response.
Clin Sci Mol Med 1976 May
PMID:The ventilatory response in severe metabolic acidosis. 0 84

1. The acid-base state of arterial blood and cerebrospinal fluid, and the ventilatory response to CO2, were measured in twelve patients with liver disease. The CO2 response was also measured in eight goats before and after the experimental production of liver failure. Arterial PCO2 and pH, cerebral blood flow and the cerebral metabolic rate for oxygen were also measured in four of the goats while they breathed air and various CO2-enriched gas mixtures. 2. Liver failure was accompanied by a respiratory alkalosis in both the patients and in the goats. Decreased PCO2 and increased pH occurred in the cerebrospinal fluid and in the arterial blood of the patients. 3. The slope of the ventilatory response to CO2 was reduced when liver failure was severe, in patients and goats alike. In addition there was a reduction in the extrapolated PCO2 at zero ventilation, even when liver failure was mild. 4. Cerebral blood flow and metabolic rate were consistently reduced in the goats during liver failure. There was also less cerebral vasodilatation and a greater reduction in cerebral metabolism during experimental hypercapnia when these animals were in liver failure. 5. The decreases in the ventilatory and cerebral circulatory responsiveness to CO2 indicate that the brain is less well defended against hypercapnia in liver failure, and these changes are especially unfavourable as cerebral function deteriorates when the PCO2 is increased.
Clin Sci Mol Med 1975 Aug
PMID:Effect of liver failure on the response of ventilation and cerebral criculation to carbon dioxide in man and in the goat. 23 83

1. The concentration of metabolites in intercostal and quadriceps muscle, and pulmonary function, were studied in twelve patients with chronic obstructive lung disease and acute respiratory failure before, during and after standardized treatment at an intensive care unit. The findings were compared with those obtained in hospitalized patients of comparable age with non-pulmonary diseases. 2. On admission, when the patients had marked hypoxaemia, hypercapnia and acidosis, the concentrations of ATP and creatine phosphate were low in both intercostal and quadriceps muscle, particularly the latter. The lactate concentration was increased in relation to control values but glycogen did not differ significantly. 3. In response to therapy, the Pa,CO2 and the patient's acidosis decreased, the vital capacity increased and lung mechanics improved along with the clinical condition. At the same time there were significant increases in the concentrations of ATP, creatine phosphate and glycogen in intercostal and quadriceps muscles, to values similar to, and for glycogen in excess of, those found in control subjects. Lactate concentration fell significantly during treatment. 4. In view of the low initial muscle concentrations of ATP and creatine phosphate in the patients, it is suggested that dysfunction of the respiratory muscles may be an important component of respiratory failure. Moreover, the concentration of energy-rich compounds in muscle rose significantly as the patients responded to treatment, which emphasizes the importance of adequate nutritional therapy in this disorder.
Clin Sci Mol Med 1977 Apr
PMID:Muscle metabolism in patients with chronic obstructive lung disease and acute respiratory failure. 86 35

1. The blood-bathed organ technique was used to study the release of catecholamines, angiotensin II and prostaglandin-like (PL) substances into the circulation during hypercapnia and after haemorrhage in anaesthetized dogs. 2. Elevated blood concentrations of noradrenaline, angiotensin II and prostaglandin-like substances have been detected during both experimental conditions. 3. The rise of arterial blood pressure during hypercapnia and after haemorrhage was associated with elevated concentrations of angiotensin II in the blood and could be abolished by inhibition of the angiotensin I-converting enzyme with SQ 20881. 4. The compensation of arterial pressure during both stresses was significantly impaired by release of prostaglandin-like substances; it could be restored by inhibition of prostaglandin biosynthesis with indomethacin. 5. The results indicate that activation of the renin-angiotensin system represents the major humoral mechanism for the maintenance of arterial pressure during hypercapnic acidosis and after haemorrhage.
Clin Sci Mol Med Suppl 1976 Dec
PMID:Humoral response and blood pressure regulation during hypercapnia and haemorrhage in dogs. 107 98

The ability of different substrates to affect myocardial function is well established but the mechanism for this effect has yet to be determined. To explore this area further, the studies described below were designed to determine the effect of different metabolic substrates, glucose or pyruvate, on myocardial response to hypercapnia. To assess this response, both the mechanical performance and the intracellular pH (pHi) were continuously measured. Intracellular pH was measured using the changes in absorbance of the vital staining dye, neutral red (NR). Although the presence of either substrate did not affect the response to hypercapnia, the addition of pyruvate was accompanied by a significant change in pHi. Specifically, there was a monotonic decrease in pHi comparable to that observed when PCO2 is increased from 5% to 10% (delta OD = -0.018 +/- 0.002 CO2; delta OD = -0.020 +/- 0.002 PYR, respectively). The mechanical response was similar for both; developed tension (tau) decreased initially (97 +/- 6% v. 93 +/- 8%) and then recovered (115 +/- 4% v. 101% +/- 5%). However, the changes in the maximum rate of relaxation, i.e. minimum time derivative: (tau mn) were dependent on the cause of the decrease in pHi. With hypercapnia, tau mn initially decreased and this was followed by a recovery phase which was 147 +/- 8% of the initial value. With pyruvate, tau mn decreased to 81 +/- 5% of control and was followed by no recovery. Because of the difference in the changes in tau mn, the effects of theophylline [3, 5] on these responses were determined. There was no effect on the response to an increase in PCO2. However, with theophylline present, the addition of pyruvate was accompanied by an increase in pHi (delta OD = + 0.005 +/- 0.001). The mechanical response was consistent with this increase and was similar to that seen when PCO2 is decreased from 10% to 5%. Specifically, there was an increase in tau (122 +/- 7%) followed by a small decrease (113 +/- 4%). Tissue assays for lactate showed a significant increase with the introduction of pyruvate. However, this increase was not affected by the presence of theophylline despite the opposite response of pHi. The data suggest that pyruvate affects myocardial function by altering pHi, and this effect is not due to an increase in lactate. In addition, the data are consistent with the model that the heart is capable of accommodating changes in pHi with only transient effects on contractile function.
J Mol Cell Cardiol 1986 Jul
PMID:A study of the effects of substrates on intracellular pH in toad ventricular strips. 309 40

The purpose of the present study was to determine the effect of various types of acidosis on vessel diameter, intracellular pH (pHi), and calcium concentration ([Ca2+]i) in a cannulated preparation of the mesenteric arteriole of the rabbit. The effect of acidosis on vessel contraction was also studied in the wire-mounted preparation. In the cannulated preparation, pre-contracted by noradrenaline, hypercapnia caused vasoconstriction and increases in [Ca2+]i. In the wire-mounted preparation pre-contracted by either noradrenaline or high KCl, hypercapnia caused a transient vasoconstriction. In contrast, in the cannulated preparation pre-contracted by high KCl, hypercapnia caused a transient vasorelaxation and decreases in [Ca2+]i. Intracellular acidosis, induced by a NH4Cl prepulse, caused vasoconstriction and increases in [Ca2+]i even in the cannulated preparation pre-contracted by high KCl. The decrease in pHi during hypercapnia was similar to that observed after NH4Cl withdrawal. These data suggest that: (1) the effect of acidosis on vascular tone and [Ca2+]i is different depending upon the type of preparation and the mode of pre-activation, and (2) [Ca2+]i may, at least partly, regulate vascular contraction and relaxation during acidosis.
J Mol Cell Cardiol 1996 Aug
PMID:Effect of acidosis on contraction, intracellular pH and calcium in the rabbit mesenteric small artery. 887 81

Anesthetic agent, arterial pCO2 level, and opioid peptides have all been implicated in the pathophysiology of experimental stroke models. The effects of halothane, alpha-chloralose, and differing concentrations of arterial pCO2 on injury volume and CSF beta-endorphin levels were studied in a feline model of experimental focal cerebral ischemia. The type of anesthetic agent used had no effect on injury volume following 6 h of focal cerebral ischemia. Over a 6-h period, beta-endorphin levels significantly increased from 10.1 +/- 5.0 fmol/mL at zero time to 14.4 +/- 7.2 fmol/mL at 6 h under halothane anesthesia (p < 0.05), whereas they did not significantly change (10.1 +/- 6.7 to 7.8 +/- 4.7 fmol/mL) under alpha-chloralose anesthesia. In contrast, hypercapnia had no effect on beta-endorphin levels, but significantly increased injury volume from 30.6 +/- 5.7% of the ipsilateral hemisphere under normocapnic conditions to 37.1 +/- 5.9% under hypercapnic conditions (p < 0.05). These results suggest that hypercapnia increases injury volume in a feline model of focal cerebral ischemia, and pCO2 should be controlled in experimental focal cerebral ischemia models.
Mol Chem Neuropathol 1997 May
PMID:Effects of halothane, alpha-chloralose, and pCO2 on injury volume and CSF beta-endorphin levels in focal cerebral ischemia. 927 Oct 3

Respiratory muscle injury may result from excessive loading due to a decrease in respiratory muscle strength, an increase in the work of breathing, or an increase in the rate of ventilation. Other conditions such as hypoxemia, hypercapnia, aging, decreased nutrition, and immobilization may potentiate respiratory muscle injury. Respiratory muscle injury has been shown in animal models using direct muscle or phrenic nerve stimulation, acute inspiratory resistive loading, tracheal banding, corticosteroids, phrenic nerve section, and the mdx mouse. Although numerous examples of diaphragm injury have been shown in animal models, evidence in humans is sparse. Potential mechanisms which may contribute to respiratory muscle injury include high levels of intracellular calcium-activated degradative enzymes, non-uniformity of stresses and strains, plasma membrane disruptions, and activation of the inflammatory process.
Mol Cell Biochem 1998 Feb
PMID:Respiratory muscle injury in animal models and humans. 954 50

We assessed the seasonal variations in the effects of hypercarbia (3 or 5% inspired CO2) on cardiorespiratory responses in the bullfrog Rana catesbeiana at different temperatures (10, 20 and 30 degrees C). We measured breathing frequency, blood gases, acid-base status, hematocrit, heart rate, blood pressure and oxygen consumption. At 20 and 30 degrees C, the rate of oxygen consumption had a tendency to be lowest during winter and highest during summer. Hypercarbia-induced changes in breathing frequency were proportional to body temperature during summer and spring, but not during winter (20 and 30 degrees C). Moreover, during winter, the effects of CO2 on breathing frequency at 30 degrees C were smaller than during summer and spring. These facts indicate a decreased ventilatory sensitivity during winter. PaO2 and pHa showed no significant change during the year, but PaCO2 was almost twice as high during winter than in summer and spring, indicating increased plasma bicarbonate levels. The hematocrit values showed no significant changes induced by temperature, hypercarbia or season, indicating that the oxygen carrying capacity of blood is kept constant throughout the year. Decreased body temperature was accompanied by a reduction in heart rate during all four seasons, and a reduction in blood pressure during summer and spring. Blood pressure was higher during winter than during any other seasons whereas no seasonal change was observed in heart rate. This may indicate that peripheral resistance and/or stroke volume may be elevated during this season. Taken together, these results suggest that the decreased ventilatory sensitivity to hypercarbia during winter occurs while cardiovascular parameters are kept constant.
Comp Biochem Physiol A Mol Integr Physiol 1999 Oct
PMID:Seasonal changes in the cardiorespiratory responses to hypercarbia and temperature in the bullfrog, Rana catesbeiana. 1062 62


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