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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Intensive care medicine 22 (1996), S. 1191-1196 
    ISSN: 1432-1238
    Keywords: Key words Cardiac arrest ; Delayed hypoperfusion phase ; Cerebral oxygen extraction ; Endothelin ; Nitrate ; cGMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To determine the role of cerebral vasoconstriction in the delayed hypoperfusion phase in comatose patients after cardiac arrest. Design: Prospective study. Setting: Medical intensive care unit in a university hospital. Patients: 10 comatose patients (Glasgow Coma Score ≤6) successfully resuscitated from a cardiac arrest occurring outside the hospital. Measurements: We measured the pulsatility index (PI) and mean blood flow velocity (MFV) of the middle cerebral artery, the cerebral oxygen extraction ratio and jugular bulb levels of endothelin, nitrate, and cGMP during the first 24 h after cardiac arrest. Results: The PI decreased significantly from 1.86±1.02 to 1.05±0.22 (p=0.03). The MFV increased significantly from 29±10 to 62±25 cm/s (p=0.003). Cerebral oxygen extraction ratio decreased also from 0.39±0.13 to 0.24±0.11 (p=0.015). Endothelin levels were high but did not change during the study period. Nitrate levels varied widely and showed a slight but significant decrease from 37.1 μmol/l (median; 25th–75th percentiles: 26.8–61.6) to 31.3 μmol/l (22.1–39.6) (p=0.04). Cyclic guanosine monophosphate levels increased significantly from 2.95 nmol/l (median; 25th–75th percentiles: 2.48–5.43) to 7.5 nmol/l (6.2–14.0) (p=0.02). Conclusions: We found evidence of increased cerebrovascular resistance during the first 24 h after cardiac arrest with persistent high endothelin levels, gradually decreasing nitrate levels, and gradually increasing cGMP levels. This suggests that active cerebral vasoconstriction due to an imbalance between local vasodilators and vasoconstrictors plays a role in the delayed hypoperfusion phase.
    Type of Medium: Electronic Resource
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 45 (1993), S. 255-260 
    ISSN: 1432-1041
    Keywords: Ramipril ; Propranolol ; interaction ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacodynamic effects of ramipril, propranolol, and their combination, as well as the effect of propranolol on the pharmacokinetics of ramipril in 12 healthy men (age 24 (SD 6) y, weight 72 (7) kg). Propranolol and placebo, ramipril and placebo, or propranolol and ramipril were given orally for four days in a crossover, double-blind fashion. The pharmacokinetics of ramipril and ramiprilat were investigated on day 4. Effects on plasma renin activity, ACE activity, and heart rate and blood pressure both before and after a standardized exercise test were measured on days 1 and 4. On day 4 the combination reduced the mean arterial pressure by 2.8 mmHg compared with propranolol alone and by 3.7 mmHg compared with ramipril alone. Ramipril had no effect on the bradycardia induced by propranolol. Propranolol reduced exercise mean arterial pressure by 9 mmHg (day 4) and heart rate by 7 beats.min−1 (day 4) compared with ramipril; this was not affected by co-administration of ramipril. On day 4 the average plasma renin activity was not significantly higher than after the combination. ACE activity was not affected by propranolol. The pharmacokinetics of ramipril and ramiprilat were not influenced by propranolol. The combination of ramipril and propranolol has additive pharmacodynamic effects that may be useful in the treatment of hypertension.
    Type of Medium: Electronic Resource
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  • 13
    ISSN: 1432-1041
    Keywords: celiprolol ; renal failure ; pharmacokinetics ; enantioselective kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the ß1-selective adrenergic antagonist (R,S)-celiprolol has been studied after oral administration of 200 mg celiprolol-HCl to 8 healthy volunteers and 8 patients with various degrees of impaired renal function. No significant difference was found between the two enantiomers in the control group or in the patients. In healthy volunteers an average of 9.8% of the dose of R-(+)-celiprolol and 9.5% of S-(-)-celiprolol was recovered unchanged in the urine. Renal impairment reduced the urinary excretion of both enantiomers to the same extent according to the severity of the uraemia, producing higher AUCs. Nevertheless, the terminal half-lives of the R- and S-enantiomers were not significantly different between the groups. Dosage reduction in patients with renal impairment does not seem to be necessary.
    Type of Medium: Electronic Resource
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