Microvascular responses to topical or intravascular saralasin were determined in the cremaster muscle arterioles of adult spontaneously hypertensive rats (SHR, n = 19) and Wistar-Kyoto (WKY, n = 16) normotensive rats. Animals were anesthetized with chloralose and urethane, and they breathed room air spontaneously. Mean arterial pressure was obtained from a catheter in a carotid artery, and microvascular diameters were determined by video microscopy. Plasma renin activity was measured in animals that were treated identically except that saralasin was not administered. For all animals, mean arterial pressure averaged 126 +/- 4 mm Hg in SHR and 82 +/- 4 mm Hg (p less than 0.001) in WKY rats. Topical saralasin, 10(-6)M, was applied to the cremaster muscles of SHR (n = 9) or WKY (n = 8) rats while internal diameters of first-through fourth-order arterioles (A1, A2, A3, A4) were measured. Topical saralasin did not alter arteriolar diameters (A1 through A4) in WKY rats, but A3 and A4 vessels dilated significantly (29% +/- 5% and 38% +/- 7% respectively; p less than 0.01) in SHR. Fourth-order diameters were measured in other SHR (n = 10) and WKY (n = 8) rats while saralasin was administered intraarterially (300 micrograms bolus into the hypogastric artery) or intravenously (10 micrograms/kg/min for 30 minutes). Intraarterial or intravenous saralasin caused significant dilation (32% +/- 12% and 20% +/- 4%, respectively; p less than 0.01) of A4 arterioles in SHR, but no dilation occurred in the arterioles of WKY rats. Arteriolar responses were significantly different (p less than 0.001) in SHR vs WKY rats for both the topical and the intravascular administration of saralasin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

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Clinical investigation of a new intravenous anesthetic--etoxadrol hydrochloride (CL-1848; U-37862A).

Twenty-eight patients were anesthetized with etoxadrol as primary agent. The anesthesia produced was characterized by profound analgesia and amnesia, while pharyngeal and laryngeal reflexes, as well as swallowing and lid reflexes, remained active. Systolic, diastolic, and pulse pressure were slightly increased, with associated tachycardia and tachypnea. A dose of 0.75 mg/kg produced anesthesia for an average of 26 (14 to 53) minutes. Alternating nystagmus was present for several hours and associated with dreams and/or visions that were pleasing to most patients. Six patients, however, had unpleasant dreams for up to 24 hours. One patient given an excessive dose (4.65 mg/kg) was cataleptic, amnesic, and analgesic for 6 days. The occurrence of unpleasant dreams and aberrations in over 20% of the patients suggests that the drug probably has little usefulness in anesthesia. However, the extreme safety of the drug (an LD50 equal to some 20 to 40 times the ED50) and the prolonged analgesia justified clinical testing. There was no evidence of metabolic or systemic organ system change from any of the clinical laboratory studies.

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Pharmacokinetics: the scientific basis for drug selection.

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Anesthesia, Epidural↗

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Limitations of the cyanide electrode for use in plasma and whole blood.

Although the cyanide ion-specific electrode has been used for the measurement of cyanide in biologic fluids, its validity has not been documented under these conditions. Therefore, we analyzed 60 paired samples of blood and plasma in a blinded fashion and compared the cyanide ion concentrations obtained from the ion-specific electrode with those obtained from a standard chemical assay. There was poor correlation between results in plasma samples (r = .52, n = 26) and no correlation in whole blood (r = .02, n = 34). Until refinements of the electrode technique are made, this method cannot be recommended for the measurement of cyanide in biologic fluids.

Animals↗

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