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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetazolamide (ACZ), a potent carbonic anhydrase inhibitor, is known to decrease submaximal exercise tolerance under normoxic and hypoxic conditions. These decrements in performance occur despite the maintenance of O2 consumption and CO2 removal. Because ACZ is a diuretic, it induces a moderate hypohydration that may have a role in reducing the ability to sustain exercise through cardiovascular and thermoregulatory impairment. To investigate this potential impairment, seven healthy males between 21 and 35 yr of age were studied in a double-blind crossover design (placebo vs. ACZ). ACZ was administered in three 250-mg oral doses 14, 8, and 2 h before exercise. Subjects exercised at 70% peak O2 uptake for 30 min on a cycle ergometer in a normoxic thermoneutral environment (25 degrees C, 40% relative humidity). Results indicate that exercise minute ventilation was greater but O2 uptake, CO2 output, and respiratory exchange ratio did not differ with ACZ. ACZ led to lower mean skin (0.7 degrees C), higher rectal (0.6 degrees C), and higher mean body temperatures (0.4 degrees C) after 30 min of exercise. Whole-body sweat loss was reduced 23%, and heat storage during the exercise bout was increased 55%. Stroke volume decreased 25%, and arteriovenous O2 difference increased 15%. A significant inverse relationship (r = -0.63) between heart rate and stroke volume was observed. It is concluded that previously reported decreases in the ability to sustain submaximal exercise with ACZ may be related to hypohydration-induced impairment of the cardiovascular and thermoregulatory systems.
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PMID:Acetazolamide alters temperature regulation during submaximal exercise. 226 61

Increases in regional cerebral blood flow have been described in a variety of cerebral pathologic states, including stroke and seizure disorders. The usefulness of technetium-99m-labeled cysteinate dimer as a marker in the measurement of regional cerebral blood flow was tested in five cynomolgus monkeys. To expand the range of blood flow to beyond the normal limits, 40 mg/kg i.v. of the carbonic anhydrase inhibitor acetazolamide was administered. Regional cerebral blood flow in all five monkeys was measured using radiolabeled microspheres (before and after acetazolamide) and the marker (after acetazolamide) in 60-70 samples from 12 brain regions. Acetazolamide significantly increased the mean +/- SEM regional cerebral blood flow measured using microspheres from 0.56 +/- 0.21 to 1.71 +/- 0.9 ml/min/g (p less than 0.01 for each region). A significant positive correlation was found between regional cerebral blood flow values calculated using microspheres and the marker after normalizing the values to those in the cerebellum (r = 0.773, p less than 0.0001). The mean +/- SEM regional cerebral blood flow determined using the marker in a single monkey (1.21 +/- 0.04 ml/min/g) did not differ significantly from that determined in the same monkey using microspheres (1.13 +/- 0.04 ml/min/g). These data support the potential use of this new brain perfusion imaging agent to assess regional cerebral blood flow over a clinically relevant range of blood flows.
Stroke 1990 Jul
PMID:Regional cerebral blood flow and distribution of [99mTc]ethyl cysteinate dimer in nonhuman primates. 236 7

Cerebral blood flow (CBF) was measured with 133xenon inhalation and single photon emission computed tomography in 33 cases of internal carotid artery occlusion, in the resting state and 25 minutes after acetazolamide (Diamox) administration. The patient population consisted of 24 males and nine females with a mean age of 57 years, who presented with transient ischemic attacks or stroke. Acetazolamide inhibits carbonic anhydrase, and CBF increases as a result of dilatation of cerebral arteries due to CO2 accumulation. The mean CBF was 46 ml/100/g/min on the affected hemisphere and 56 ml/100/g/min on the unaffected hemisphere. The mean CBF value obtained by the same method in 10 normal volunteers was 55 ml/100/g/min. Thus, in the patients, CBF decreased on the affected side. The average increase in CBF after acetazolamide administration was 9% on the affected side and 17% on the unaffected side. The average increase in 10 normal volunteers was 32%. The reduced cerebral arterial reactivity to acetazolamide administration was bilateral in the patient group, which suggests that the cerebral arteries were dilated in order to maintain normal CBF. Extra-intracranial (EC-IC) bypass surgery was performed in nine patients. Preoperatively, the mean CBF was 48 ml/100 g/min on the affected side and 57 ml/100 g/min on the unaffected side; the postoperative CBF was 48 ml/100 g/min on the affected side and 56 ml/100 g/min on the unaffected side. Thus, there was no notable change in CBF on either side after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Measurement of cerebral blood flow by single photon emission computed tomography in cases of internal carotid artery occlusion]. 247 52

The National Registry of Drug-induced Ocular Side Effects has accumulated 13 cases of possible major haemopoietic responses from topical ocular chloramphenicol. Over 75 cases of major haemopoietic events from carbonic anhydrase inhibitors are also reviewed. While numerous reports of local ocular effects secondary to timolol have been received by the Registry, the more significant adverse effects are the same systemic side effects seen with any beta-receptor blocking agent. Data in the Registry have shown that allopurinol may be possibly associated with cataract formation. Severe cardiovascular effects with elevated blood pressure and stroke are uncommon systemic adverse reactions following topical ophthalmic 10% phenylephrine, but these systemic effects have also been seen secondary to concentrations of 2.5%. Other drugs, such as adrenaline (epinephrine), ecothiopate (echothiophate), practolol, thiabendazole, and penicillamine are suspected of causing ocular pseudopemphigoid.
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PMID:Ocular toxicology update. 639 76

This study tests the hypothesis that the increase in blood PCO2 and associated respiratory acidosis after exhaustive exercise play an important role in stimulating ventilation during post-exercise recovery in fish. Injection of bovine carbonic anhydrase (10 mg kg-1) into the bloodstream of rainbow trout caused a persistent 40 % increase in the HCO3- dehydration capacity of the blood. The treatment was designed to increase CO2 excretion and therefore to reduce PCO2 build-up and acidosis after exercise. Aerobic and anaerobic swimming performance were not affected by carbonic anhydrase, and there were only very minor effects on arterial blood acid­base status in resting fish. However, carbonic anhydrase attenuated post-exercise increases in PaCO2 and decreases in pHa by about 50 % without altering arterial O2 variables, red cell swelling or the intracellular pH of the brain or muscle tissues. The effects on arterial pH (pHa) resulted largely from alleviation of the increase in PaCO2. In accordance with the original hypothesis, normal post-exercise hyperventilation was greatly attenuated, through reductions in both ventilatory stroke volume and frequency, and excess post-exercise O2 consumption was reduced. Post-exercise increases in plasma levels of adrenaline and noradrenaline were also reduced by the carbonic anhydrase treatment. Overall, there was a strong correlation between increases in relative ventilation and decreases in pHa after exhaustive exercise. The results provide functional significance for the phenomenon of PaCO2 elevation and associated respiratory acidosis after exercise and are consistent with other recent studies indicating an important secondary drive to ventilation in fish based on arterial acid­base status, in addition to the primary drive based on arterial O2 levels.
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PMID:CARBONIC ANHYDRASE INJECTION PROVIDES EVIDENCE FOR THE ROLE OF BLOOD ACID-BASE STATUS IN STIMULATING VENTILATION AFTER EXHAUSTIVE EXERCISE IN RAINBOW TROUT 931 87

The aim of the present study was to evaluate the effects of endothelin-l-elicited cardiovascular events on respiratory gas transfer in the freshwater rainbow trout (Oncorhynchus mykiss) and the marine dogfish (Squalus acanthias). In both species, endothelin-1 (666 pmol kg(-1)) caused a rapid (within 4 min) reduction (ca. 30-50 mmHg) in arterial blood partial pressure of O2. The effects of endothelin-1 on arterial blood partial pressure of CO2 were not synchronised with the changes in O2 partial pressure and the responses were markedly different in trout and dogfish. In trout, arterial CO2 partial pressure was increased transiently by approximately 1.0 mmHg but the onset of the response was delayed and occurred 12 min after endothelin-1 injection. In contrast, CO2 partial pressure remained more-or-less constant in dogfish after injection of endothelin-1 and was increased only slightly (approximately 0.1 mmHg) after 60 min. Pre-treatment of trout with bovine carbonic anhydrase (5 mg ml(-1)) eliminated the increase in CO2 partial pressure that was normally observed after endothelin-1 injection. In both species, endothelin-1 injection caused a decrease in arterial blood pH that mirrored the changes in CO2 partial pressure. Endothelin-1 injection was associated with transient (trout) or persistent (dogfish) hyperventilation as indicated by pronounced increases in breathing frequency and amplitude. In trout, arterial blood pressure remained constant or was decreased slightly and was accompanied by a transient increase in systemic resistance, and a temporary reduction in cardiac output. The decrease in cardiac output was caused solely by a reduction in cardiac frequency; cardiac stroke volume was unaffected. In dogfish, arterial blood pressure was lowered by approximately 10 mmHg at 6-10 min after endothelin-1 injection but then was rapidly restored to pre-injection levels. The decrease in arterial blood pressure reflected an increase in branchial vascular resistance (as determined using in situ perfused gill preparations) that was accompanied by simultaneous decreases in systemic resistance and cardiac output. Cardiac frequency and stroke volume were reduced by endothelin-1 injection and thus both variables contributed to the changes in cardiac output. We conclude that the net consequences of endothelin-1 on arterial blood gases result from the opposing effects of reduced gill functional surface area (caused by vasoconstriction) and an increase in blood residence time within the gill (caused by decreased cardiac output.
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PMID:The effects of endothelin-1 on the cardiorespiratory physiology of the freshwater trout (Oncorhynchus mykiss) and the marine dogfish (Squalus acanthias). 1176 71

The sulfonamides constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anticarbonic anhydrase, diuretic, hypoglycemic, and antithyroid activity among others. A large number of structurally novel sulfonamide derivatives have ultimately been reported to show substantial protease inhibitory properties. Of particular interest are some metalloprotease inhibitors belonging to this class, which by inhibiting several matrix metalloproteases (MMPs) show interesting antitumor properties. Some of these compounds are currently being evaluated in clinical trials. The large number of sulfonamide MMP inhibitors ultimately reported also lead to the design of effective tumor necrosis factor-alpha converting enzyme (TACE) inhibitors, potentially useful in the treatment of inflammatory states of various types. Since both MMPs and TACE contribute synergistically to the pathophysiology of many diseases, such as arthritis, bacterial meningitis, tumor invasion; the dual inhibition of these enzymes emerged as an interesting target for the drug design of anticancer/antiinflammatory drugs, and many such sulfonamide derivatives were recently reported. Human neutrophyl elastase (HNE) inhibitors of the sulfonamide type may also be useful in the treatment of inflammatory conditions, such as emphysema, cystic fibrosis, chronic bronchitis, ischemia reperfusion injury, and acute respiratory distress syndrome. Inhibition of some cysteine proteases, such as several caspase and cathepsin isozymes, may lead to the development of pharmacological agents effective for the management of several diseases, such as rheumatoid arthritis, inflammatory bowel disease, brain damage, and stroke. Another research line that progressed much in the last time regards different sulfonamides with remarkable antiviral activity. Some clinically used HIV protease inhibitors (such as amprenavir) possess sulfonamide moieties in their molecules, which are critical for the potency of these drugs, as shown by means of X-ray crystallography, whereas a very large number of other derivatives are constantly being synthesized and evaluated in order to obtain compounds with lower toxicity or augmented activity against viruses resistant to the such first generation drugs. Other viral proteases, such as those isolated from several types of herpes viruses may be inhibited by sulfonamide derivatives, leading thus to more effective classes of antiviral drugs.
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PMID:Protease inhibitors of the sulfonamide type: anticancer, antiinflammatory, and antiviral agents. 1278 86

Experiments were carried out to test the hypothesis that ventilatory and cardiovascular responses to hypercarbia (elevated water P(CO2)) in the tambaqui Colossoma macropomum are stimulated by externally oriented receptors that are sensitive to water CO(2) tension as opposed to water pH. Cardiorespiratory responses to acute hypercarbia were evaluated in both the absence and presence of internal hypercarbia (elevated blood P(CO2)), achieved by treating fish with the carbonic anhydrase inhibitor acetazolamide. Exposure to acute hypercarbia (15 min at each level, final water CO(2) tensions of 7.2, 15.5 and 26.3 mmHg) elicited significant increases in ventilation frequency (at 26.3 mmHg, a 42% increase over the normocarbic value) and amplitude (128%), together with a fall in heart rate (35%) and an increase in cardiac stroke volume (62%). Rapid washout of CO(2) from the water reversed these effects, and the timing of the changes in cardiorespiratory variables corresponded more closely to the fall in water P(CO2) (Pw(CO2)) than to that in blood P(CO2) (Pa(CO2)). Similar responses to acute hypercarbia (15 min, final Pw(CO2) of 13.6 mmHg) were observed in acetazolamide-treated (30 mg kg(-1)) tambaqui. Acetazolamide treatment itself, however, increased Pa(CO2) (from 4.81+/-0.58 to 13.83+/-0.91 mmHg, mean +/-S.E.M.; N=8) in the absence of significant change in ventilation, heart rate or cardiac stroke volume. The lack of response to changes in blood P(CO2) and/or pH were confirmed by comparing responses to the bolus injection of hypercarbic saline (5% or 10% CO(2); 2 ml kg(-1)) into the caudal vein with those to the injection of CO(2)-enriched water (1%, 3%, 5% or 10% CO(2); 50 ml kg(-1)) into the buccal cavity. Whereas injections of hypercarbic saline were ineffective in eliciting cardiorespiratory responses, changes in ventilation and cardiovascular parameters accompanied injection of CO(2)-laden water into the mouth. Similar injections of CO(2)-free water acidified to the corresponding pH of the hypercarbic water (pH 6.3, 5.6, 5.3 or 4.9, respectively) generally did not stimulate cardiorespiratory responses. These results are in agreement with the hypothesis that in tambaqui, externally oriented chemoreceptors that are predominantly activated by increases in water P(CO2), rather than by accompanying decreases in water pH, are linked to the initiation of cardiorespiratory responses to hypercarbia.
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PMID:Cardiorespiratory responses to hypercarbia in tambaqui Colossoma macropomum: chemoreceptor orientation and specificity. 1576 10

The human sweating response is subject to the influence of diverse classes of drugs. Some act centrally at the hypothalamus or at spinal thermoregulatory centres, while others act at sympathetic ganglia or at the eccrine-neuroeffector junction. Pharmacological disturbances of sweating have broad clinical implications. Drugs that induce hyperhidrosis, or sweating in excess of that needed to maintain thermoregulation, can cause patient discomfort and embarrassment, and include cholinesterase inhibitors, selective serotonin reuptake inhibitors, opioids and tricyclic antidepressants. Drugs that induce hypohidrosis, or deficient sweating, can increase the risk of heat exhaustion or heat stroke and include antimuscarinic anticholinergic agents, carbonic anhydrase inhibitors and tricyclic antidepressants. As acetylcholine is the principal neuroeccrine mediator, anhidrosis is one of the clinical hallmarks by which acute anticholinergic toxicity may be recognized. The symptom of dry mouth often accompanies the less apparent symptom of hypohidrosis because the muscarinic M(3) acetylcholine receptor type predominates at both sweat and salivary glands. Management options include dose reduction, drug substitution or discontinuation. When compelling medical indications require continuation of a drug causing hyperhidrosis, the addition of a pharmacological agent to suppress sweating can help to reduce symptoms. When hypohidrotic drugs must be continued, deficient sweating can be managed by avoiding situations of heat stress and cooling the skin with externally applied water. The availability of clinical tests for the assessment of sudomotor dysfunction in neurological disease has enhanced recognition of the complex effects of drugs on sweating. Advances in the understanding of drug-induced anhidrosis have also enlarged the therapeutic repertoire of effective treatments for hyperhidrosis.
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PMID:Drug-induced hyperhidrosis and hypohidrosis: incidence, prevention and management. 1821 88

Zonisamide (ZNS), a sulfonamide antiepileptic drug, is indicated as an adjunct therapy for partial seizure disorders with and without secondary generalization. ZNS has a favorable pharmacokinetic profile because of its rapid absorption and high bioavailability. Its activity is related to the blockade of voltage gated sodium and calcium channels, modulation of central dopaminergic, GABAergic, and serotonergic functions, as well as inhibition of carbonic anhydrase and monoamine oxidase B. ZNS has potential efficacy for an array of neuropsychiatric disorders including migraine and other headache syndromes, neuropathic pain, Parkinson's disease, essential tremor, stroke, obesity, anxiety, bipolar and binge-eating disorders.
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PMID:Therapeutic role of zonisamide in neuropsychiatric disorders. 1878 51


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