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J Splawinski

Publications and source records attributed to J Splawinski.

3 recordsLinked to original sources

Reproducibility of isoproterenol tilt-table tests in patients with syncope.

To assess the reproducibility of head-up tilt-table testing 46 patients each underwent 2 isoproterenol tilt-table tests 1 to 6 weeks apart. Of 20 patients with an initially asymptomatic negative test result, 17 (85%) had a second negative test result. Of 20 patients whose initial test ended in syncope, 18 had a second test ending in syncope (n = 12) or presyncope (n = 6). Five of 6 patients whose first test ended in presyncope had a second test that ended in presyncope, and 1 had a second test that was asymptomatic. Finally, a total of 14 patients had at least 1 test (either the first or second) ending in presyncope, and 11 of these (79%) had another test ending in presyncope or syncope. The dose-dependence of isoproterenol was irreproducible. The reproducibility of the duration of head-up tilt necessary to elicit symptoms of presyncope or syncope was determined in the 23 patients who had these symptoms on both tests. Symptoms developed monoexponentially with duration of head-up tilt with half-times of 1.4 to 2.6 minutes, but these times did not correlate significantly between tests. In a selected subgroup of 12 patients who developed syncope in the first test and either presyncope or syncope in the second test during administration of isoproterenol (5 micrograms/min), the time of onset of presyncope correlated well (r = 0.73, p = 0.007) as did that of syncope (r = 0.86, p = 0.012). Finally, hemodynamic changes during symptoms were compared between the 2 tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

A new anti-inflammatory derivative of imidazole which is less ulcerogenic than indomethacin in rats.

The mechanism of the anti-inflammatory activity and ulcerogenicity of (2-dimethylamino-1(2)-methyl) ethyl ester of the 1-(2-carboxyethyl)-2-(p-chlorophenyl)-4,5-bis-(p-methoxyphenyl)-imidazole (A-162-ester) was compared with that of indomethacin in rats and enzymatic preparations derived from other species. A-162-ester was found to be deesterified in plasma to A-162. A-162-ester was about 3 times less anti-inflammatory and about 17 times less ulcerogenic than indomethacin. A-162-ester, when given orally, decreased prostaglandin I2 (PGI2) biosynthesis by gastric mucosa. The IC50 was close to the ulcerogenic ED50. Indomethacin--in the same test--was 37 times more potent than A-162-ester and the PGI2 inhibition and ulcerogenic dose-response curves for indomethacin were parallel. In other in vitro systems of prostaglandin (PG) biosynthesis, the inhibitory activity of A-162 was comparable to that of indomethacin. It is concluded that the ulcerogenicity of indomethacin results from a high affinity of this drug to gastric mucosal wall PG-synthetase which leads to decreased PGI3 formation at this site. The relatively low ulcerogenicity of A-162-ester most probable results from a lower affinity of this drug to the same site.

Animals

Endogenous mechanisms which regulate prostacyclin release.

When infused intravenously into anaesthetized cats angiotensin II (1--4 micrograms/kg) released into the circulation an unstable substance that caused de-aggregation of platelet clumps, relaxed a strip of bovine coronary artery, and its release was blocked by aspirin and indomethacin. Because of these characteristics this substance is likely to be prostacyclin. Catecholamines and phenylephrine did not induce the release of prostacyclin. It is suggested that a chemical modification of the molecule of angiotensin II may render a peptide with little hypertensive properties which will be an activator of prostacyclin biosynthesis.

Angiotensin II