Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 6-year old female child received succinylcholine (1 mg.kg-1) and isoflurane (concentrations of 1.5-2 percent) and developed at the end of surgery a hypermetabolic syndrome suggestive of malignant hyperthermia (MH) with masseter muscle spasm, muscle rigidity, tachypnea, systolic hypertension (140 mm Hg), tachycardia (205 beats.min-1), hypercarbia (end expiratory CO2 71 mmHg), and an increase in body temperature (39.2 degrees C). The child responded well to therapy which included cooling, hyperventilation with pure oxygen and dantrolene administration. However, blood creatine kinase and myoglobin elevations were moderate (respectively 375 IU.L-1 and 114 micrograms.L-1) and an in vitro halothane and caffeine contracture test was negative. Differential diagnostic proposals are discussed and compared to the clinical incident.
 ...
PMID:Malignant hyperthermia suggestive hypermetabolic syndrome at emergence from anesthesia. 871 51

The roles of nitric oxide, adenosine and cortical arousal in the response to 7.5% CO2 inhalation were investigated by measuring cerebral blood flow bilaterally in the rat somatosensory cortices with laser-Doppler flow probes. Administration of N(omega)-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg, i.v.) significantly attenuated the response to hypercapnia (mean decrease of 47%). This effect was partially reversed by a subsequent administration of L-arginine. Caffeine (10 mg/kg, i.v.) also significantly reduced hypercapnic responses (mean decrease of 44%). Caffeine administration was also associated with a tendency for animals to exhibit electrocorticographic signs of arousal; often associated with a reduction in the attenuation of the flow response to CO2 inhalation. 8-(3-Chlorostyryl) caffeine (CSC, 1.0 mg/kg), a selective antagonist at adenosine A2a striatal receptors failed to attenuate CO2-evoked responses, whereas CGS 15943, a less selective A2a receptor antagonist, significantly reduced CO2 responses. These data from the rat suggest (1) that both nitric oxide and adenosine may contribute to pial arteriolar vasodilatation during hypercapnia, and (2) that CO2 inhalation acts as a potent stimulus for cortical arousal, with enhanced neuronal activity contributing to the vascular response. The effects of administration of adenosine antagonists, such as the methylxanthines antagonists caffeine and theophylline, on CBF responses to hypercapnia can potentially be negated by the ability of these agents to facilitate CO2-induced cortical arousal.
 ...
PMID:Hypercapnia-induced increases in cerebral blood flow: roles of adenosine, nitric oxide and cortical arousal. 920 26

The effects of chronic caffeine administration on ventilation and schedule-controlled behavior were studied in 12 adult rhesus monkeys. In seated subjects prepared with a head plethysmograph, ventilation was measured during exposure to air (normocapnia) and to elevated levels of CO2 (3%, 4% and 5%) mixed in air (hypercapnia). Acute administration of caffeine (10.0-30.0 mg/kg i.m.) produced marked, dose-dependent increases in ventilation during conditions of normocapnia and hypercapnia. However, daily administration of caffeine (10.0 mg/kg i.m.) for 8 consecutive days resulted in tolerance to its respiratory-stimulant effects that was surmountable with higher doses. Caffeine-tolerant subjects also were cross-tolerant to theophylline, an active metabolite of caffeine, and to rolipram and Ro 20-1724, selective phosphodiesterase inhibitors. When chronic administration was terminated and the acute effects of caffeine were redetermined, sensitivity returned to levels obtained before chronic administration within 9 days. Drug effects on behavior were studied in monkeys trained to respond under a fixed-interval schedule of stimulus termination. Acute administration of caffeine (1.0-30.0 mg/kg i.m.) produced significant rate-increasing effects on fixed-interval responding, but chronic administration resulted in tolerance that was insurmountable, such that no dose increased responding above control rates. Although the time course for development and loss of tolerance to the behavioral effects of caffeine corresponded closely with respiration, cross-tolerance did not extend to the behavioral effects of rolipram. Chronic caffeine administration had little effect on caffeine metabolism or clearance, which indicated that caffeine tolerance was pharmacodynamic. The results suggest that different neurochemical mechanisms mediate the effects of caffeine on respiration and behavior, and that inhibition of type IV phosphodiesterase plays a prominent role in caffeine-induced respiratory stimulation.
 ...
PMID:Effects of chronic caffeine administration on respiration and schedule-controlled behavior in rhesus monkeys. 933 24

To investigate cardiac stunning, we recorded intracellular [Ca(2+)], contractions, and electrical activity in isolated guinea pig ventricular myocytes exposed to simulated ischemia and reperfusion. After equilibration, ischemia was simulated by exposing myocytes to hypoxia, acidosis, hyperkalemia, hypercapnia, lactate accumulation, and substrate deprivation for 30 min at 37 degrees C. Reperfusion was simulated by exposure to Tyrode solution. Field-stimulated myocytes exhibited stunning upon reperfusion. By 10 min of reperfusion, contraction amplitude decreased to 43.0 +/- 5.5% of preischemic values (n = 15, P < 0.05), although action potential configuration and sarcoplasmic reticulum Ca(2+) stores, assessed with caffeine, were normal. Diastolic [Ca(2+)] and Ca(2+) transients (fura 2) were also normal in stunned myocytes. In voltage-clamped cells, peak L-type Ca(2+) current was reduced to 47.4 +/- 4.5% of preischemic values at 10 min of reperfusion (n = 21, P < 0.05). Contractions elicited by Ca(2+)-induced Ca(2+) release and the voltage-sensitive release mechanism were both depressed in reperfusion. Our observations suggest that stunning is associated with reduced L-type Ca(2+) current but that alterations in Ca(2+) homeostasis and release are not directly responsible for stunning.
 ...
PMID:Changes in excitation-contraction coupling in an isolated ventricular myocyte model of cardiac stunning. 1212 30

Malignant Hyperthermia (MH) has been a recognized complication of general anesthesia after the first case reports in the 1940's. Since then a great deal has been discovered about the genetics, pathophysiology and treatment of this once fatal syndrome. MH is the only clinical entity specifically related to and caused by anesthetic agents. MH once triggered during anesthesia results in a profound hyper metabolic state with rise in the core temperature, increased carbon dioxide production and oxygen consumption. Death will ensue if specific treatment is not started. The incidence of fulminant MH ranges from 1:62,000 to 1: 84,000 of general anesthesia cases if succinylcholine and inhalation agents are used. Massseter muscle spasm on induction of anesthesia, with an incidence of between 1:16,000 and 1:4,000, may be a predromal indication of the development of MH. Anesthetic agents, which may trigger MH in susceptible individuals, are the depolarizing muscle relaxant, succinyl choline and all the volatile anesthetic gasses. Nitrous oxide, intravenous induction agents, benzodiazepines, opioids, and the non-depolarizing relaxants do not trigger MH. MH susceptibility is associated with certain disorders, such as Duchene muscular dystrophy, and triggering agent should not be used in these patients. Inheritance is an autosomal dominant trait with variable penetrance. The pathogenesis of MH involves the loss of control of intracellular calcium ions in skeletal muscle with resultant protracted spasm and hyper metabolism. Clinically this will progress to hypercarbia, hypoxia, hyperthermia, hyperkalemia and death will result if specific treatment is not started. Management involves immediate discontinuation of the triggering anesthetics, hyperventilation with 100% oxygen and most importantly the definitive treatment with intravenous dantrolene.The importance of instigating the use of dantrolene in cases of MH cannot be overemphasized. MH is now treatable when once it would be fatal before the availability of dantrolene. Unless of an emergent nature, surgery should be canceled following the acute phase of MH. The patient should be admitted to intensive care for at least 24 hours and dantrolene continued as recurrence has been described. It is imperative that the patient and their family are counseled, Medalert bracelets provided and registration with the Malignant Hyperthermia Association of the United States (MHAUS), encouraged. The caffeine/halothane testing of muscle biopsies is currently the most definitive test for malignant hyperthermia susceptibility. The routine use in suspected cases or the immediate family of known cases remains a matter of contention.
 ...
PMID:Malignant hyperthermia. 1450 52

Panic disorder (PD) is a complex condition that is further complicated by its numerous inducers, which include hypercapnia, hypoxia, sodium lactate, caffeine and cholecystokinin. It seems unlikely that there are specific suffocation receptors for each of these inducers in the brain. The pulmonary neuroepithelial bodies (NEBs), which are situated at the bifurcation point of the small bronchi, act as storage cells for 5-hydroxytryptamine (5-HT) and sensors for suffocation. If we suppose that PD might represent an inflammation of the NEBs, bradykinin (BK) which augments the airway hyper-response to diverse indcers might cause these cells to release 5-HT along with peptides and panneuroendcrine markers from their dence-core secretory granules. It was revealed that BK with 5-HT could cross the blood-brain barrier (BBB). When 5-HT released from these cells along with BK cross the BBB, the release of 5-HT at the axonal terminals in the serotonergic neurons in the brain will be inhibited, since the 5-HT1 autoreceptor have a higher affinity for 5-HT than do the 5-HT2 receptors. The inhibition of 5-HT at the axonal terminal causes to suppress the periaqueductal gray matter, which inhibits flight reactions to impending danger, pain or asphyxia. In short, this serotonergic situation might bring about PD. According to this theory, the type of inducer that the PD patient is exposed to is unimportant as long as it stimulates the NEBs, and through the effect of 5-HT and BK, PD would be revaluated as a somatic disease that directly and reversibly affects the brain.
 ...
PMID:Novel hypothesis for the cause of panic disorder via the neuroepithelial bodies in the lung. 1582 15

Caffeine is an adenosine receptor antagonist commonly used as a respiratory stimulant to treat neonatal apneas of premature newborn. Neonatal caffeine treatment (NCT) has long-term effects on adenosine receptor expression and distribution; however, the potential effects of NCT on respiratory control development are unknown. To address this issue, rat pups received orally each day from postnatal d 3-12, 15 mg/kg of caffeine (NCT), water (vehicle), or were undisturbed during early life (control). Measurements of resting ventilation, apnea index, and ventilatory response to moderate hypercapnia (FiCO2 = 0.05) were made using whole-body plethysmography at postnatal d 20 (juvenile) and adulthood. At d 20, resting respiratory variables were not affected by the treatments. Juvenile NCT male rats showed a 22% higher minute ventilation response to hypercapnia than vehicle rats. However, oral gavage alone increased the frequency component of the response by 11%. In adult males, caffeine increased the resting respiratory frequency by 15%. In these animals, the tidal volume response to hypercapnia was increased by 15%, whereas the frequency response was decreased by 20%. In juvenile and adult females, no differences were observed between treatments. In juvenile rats of both sexes, gavage increased the apnea index by at least 200%. These results show that NCT and gavage influence respiratory control during early life and that these effects persist until adulthood. The underlying mechanisms are unclear, but may be related to persistent changes in adenosinergic neurotransmission because neonatal caffeine administration increases A1 adenosine receptor density in adult rats.
 ...
PMID:Long-term consequences of neonatal caffeine on ventilation, occurrence of apneas, and hypercapnic chemoreflex in male and female rats. 1654 22

Caffeine is commonly used to treat respiratory instabilities related to prematurity. However, the role of adenosinergic modulation and the potential long-term effects of neonatal caffeine treatment (NCT) on respiratory control are poorly understood. To address these shortcomings, we tested the following hypotheses: 1) adenosine A(1)- and A(2A)-receptor antagonists modulate respiratory activity at rest and during hypercapnia; 2) NCT has long-term consequences on adenosinergic modulation of respiratory control. Rat pups received by gavage either caffeine (15 mg/kg) or water (control) once a day from postnatal days 3 to 12. At day 20, rats received intraperitoneal injection with vehicle, DPCPX (A(1) antagonist, 4 mg/kg), or ZM-241385 (A(2A) antagonist, 1 mg/kg) before plethysmographic measurements of resting ventilation, hypercapnic ventilatory response (5% CO(2)), and occurrence of apneas in freely behaving rats. In controls, data show that A(2A), but not A(1), antagonist decreased resting ventilation by 31% (P = 0.003). A(1) antagonist increased the hypercapnic response by 60% (P < 0.001), whereas A(2A) antagonist increased the hypercapnic response by 42% (P = 0.033). In NCT rats, A(1) antagonist increased resting ventilation by 27% (P = 0.02), but the increase of the hypercapnic response was blunted compared with controls. A(1) antagonist enhanced the occurrence of spontaneous apneas in NCT rats only (P = 0.005). Finally, A(2A) antagonist injected in NCT rats had no effect on ventilation. These data show that hypercapnia activates adenosinergic pathways, which attenuate responsiveness (and/or sensitivity) to CO(2) via A(1) receptors. NCT elicits developmental plasticity of adenosinergic modulation, since neonatal caffeine persistently decreases ventilatory sensitivity to adenosine blockers.
 ...
PMID:Disruption of adenosinergic modulation of ventilation at rest and during hypercapnia by neonatal caffeine in young rats: role of adenosine A(1) and A(2A) receptors. 1713 26

Reduction of cerebral blood flow by caffeine has been shown in multiple studies. However, the effect of this substance on pathologically dilated cerebral vessels is not clearly defined. The aim of this study was to investigate the effect of caffeine on an already dilated cerebral circulation and specify if these vessels are still able to constrict as a consequence of caffeine stimulation. A second aim of this study was to compare results of cerebral vasomotor CO(2) reactivity testing with and without caffeine ingestion. Seventeen healthy adult volunteers had vasomotor reactivity tested before and thirty minutes after ingestion of 300 mg of caffeine. Each vasomotor reactivity test consisted of velocity measurements from both middle cerebral arteries using transcranial Doppler ultrasound during normocapnia, hypercapnia, and hypocapnia. Hemodynamic data and end-tidal CO(2) (etCO(2)) concentration were also recorded. The vasomotor reactivity (VMR) and CO(2) reactivity were calculated from a measured data pool. At a level of etCO(2)=40 mmHg the resting velocity in the middle cerebral artery (V(MCA)) dropped from 70.7+/-22.8 cm/sec to 60.7 +/- 15.4 cm/sec 30 minutes after caffeine stimulation (14.1% decrease, p<0.001). During hypercapnia of etCO(2)=50 mmHg there was also a significant decline of V(MCA) from 103.1+/-25.4 to 91.4+/-21.8 cm/sec (11.3%, p<0.001). There was not a statistically significant reduction of V(MCA) during hypocapnia. Calculated VMR and CO(2) reactivity before and after caffeine intake were not statistically significant. The presented data demonstrate a significant decrease in cerebral blood flow velocities after caffeine ingestion both in a normal cerebrovascular bed and under conditions of peripheral cerebrovascular vasodilatation. These findings support the important role of caffeine in regulation of CBF under different pathological conditions. Despite significant reactive vasodilatation in the brain microcirculation, caffeine is still able to act as a competitive antagonist of CO(2) on cerebral microvessels. The fact that caffeine may decrease CBF despite significant pathological vasodilatation offers the possibility of therapeutic manipulation in patients with traumatic vasoparalysis. For routine clinical testing of CO(2) reactivity it is not necessary to insist on pre-test dietary restrictions.
 ...
PMID:The effect of caffeine on dilated cerebral circulation and on diagnostic CO2 reactivity testing. 1734 75

Although functional MRI (fMRI) based on blood oxygenation level-dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, quantitative studies of the physiological effects of pharmacological agents using fMRI alone are difficult to interpret due to the complexities inherent in the BOLD response. Hypercapnia-calibrated BOLD methodology is potentially a more powerful physiological probe of brain function, providing measures of the changes in cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO(2)). In this study, we implemented a quantitative R(2)* approach for assessing the BOLD response to improve the stability of repeated measurements, in combination with the calibrated BOLD method, to examine the CBF and CMRO(2) responses to caffeine ingestion. Ten regular caffeine consumers were imaged before and after a 200-mg caffeine dose. A dual-echo arterial spin labeling technique was used to measure CBF and BOLD responses to visual stimulation, caffeine consumption and mild hypercapnia. For a region of interest defined by CBF activation to the visual stimulus, the results were: hypercapnia increased CBF (+46.6%, +/-11.3, mean and standard error), visual stimulation increased both CBF (+47.9%, +/-2.9) and CMRO(2) (+20.7%, +/-1.4), and caffeine decreased CBF (-34.5%, +/-2.6) with a non-significant change in CMRO(2) (+5.2%, +/-6.4). The coupling between CBF and CMRO(2) was significantly different in response to visual stimulation compared to caffeine consumption. A calibrated BOLD methodology using R(2) * is a promising approach for evaluating CBF and CMRO(2) changes in response to pharmacological interventions.
 ...
PMID:Caffeine-induced uncoupling of cerebral blood flow and oxygen metabolism: a calibrated BOLD fMRI study. 1819 83


<< Previous 1 2 3 4 Next >>