Steady state and time-dependent slowing of conduction in canine hearts. Effects of potassium and lidocaine.
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Biomedical subjects
Publications and source records attributed to C M Chen.
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Adenosine kinase was partially purified from wheat germ. This enzyme preparation, which was devoid of adenine phosphoribosyltransferase and nearly free of adenosine deaminase but contained adenylate kinase, rapidly phosphorylated adenosine and a cytokinin, N(6)-(delta(2)-isopentenyl)adenosine. Electrophoretic analysis indicated that only N(6)-(delta(2)-isopentenyl)adenosine-monophosphate was formed from the cytokinin while about 55% AMP, 45% ADP, and a trace of ATP were formed from adenosine. The biosynthesized nucleoside monophosphates were quantitatively hydrolyzed to the corresponding nucleosides by 5'-nucleotidase and the isopentenyl side chain of the phosphorylated cytokinin was not cleaved. The enzyme did not catalyze phosphorylation of inosine.The phosphorylation of the cytokinin and adenosine required ATP and Mg(2+). The pH optimum was from 6.8 to 7.2 for both the cytokinin and adenosine. At pH 7 and 37 C the Km and V(max) for the cytokinin were 31 mum and 8.3 nmoles per mg protein per minute, and the values for adenosine were 8.7 mum and 46 nmoles per mg protein per minute. Crude enzyme preparations from tobacco callus tissue and wheat germ phosphorylated N(6)-(delta(2)-isopentenyl)adenosine. These preparations also phosphorylated N(6)-(delta(2)-isopentenyl)adenine when 5-phosphorylribose-1-pyrophosphate was present.
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Seven 1,5-dioxaspiro[2.5]octanes were synthesized and tested in the mouse P388 lymphocytic leukemia screen and the mouse Ehrlich ascites screen. These compounds possess the "epoxypyran" structure which has been believed to be the active portion of the trichothecene class of sesquiterpene tumor inhibitors. Three of the compounds were found to have marginal to moderate activity in the Ehrlich ascites screen (inhibition 74.1-86.3%) and low activity in the P388 screen (T/C = 126-131). A carbocyclic analogue, 1-oxaspiro[2.5]octane (9), was moderately active in both screens (inhibition 78.8%, T/C = 140). In the Ehrlich ascites screen, T-2 toxin (2) was about 25 times more potent than 9. None of the spirooctanes studied caused any skin irritation in 10-mg doses on the skin of rabbits, whereas 2 caused extensive necrosis at 0.1-mg doses.
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We studied the effects of quinidine and lidocaine on the steady-state relationship between membrane potential and the maximum rate of rise of the action potential, (dV/dt)max, and on the recovery kinetics of (dV/dt)max in guinea pig papillary muscles. The steady-state relationships were determined in fibers stimulated at 0.2/sec and depolarized with KCl. Recovery kinetics were determined at various resting membrane potentials by assessing (dV/dt)max in progressively earlier premature action potentials. Lidocaine caused a dose-dependent decrease in (dV/dt)max, shifted the curve defining the steady-state relationship along the voltage axis in the direction of more negative potentials, and slowed the recovery kinetics of (dV/dt)max. Quinidine caused a dose-dependent decrease in (dV/dt)max but did not alter the shape of the curves defining either the steady-state relationship or the recovery kinetics of (dV/dt)max. Both drugs depressed membrane responsiveness as determined in premature action potentials originating from incompletely repolarized fibers. Our study indicates that the mechanisms whereby quinidine and lidocaine influence (dV/dt)max are different. It is possible that this difference may underlie some of the differences in the clinical effects of these two drugs.
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Between May and September 1973, 68 cases of scrub typhus in Chinese military personnel on the Pescadores Islands were studied. The common symptoms and signs were fever, chills, headache, eschar, myalgia, and lymph node enlargement. Most eschars were located in the axilla, waist, groin and genitals, and neck. These lesions were painless and not noticed by the patients themselves. Regional lymph node enlargement at the site of eschar drainage was common. Relative bradycardia with fever was observed in 40%, a skin rash in 35% of the patients. Leucopenia was noted more frequently in the febrile than in the convalescent stage, but more than half of the patients had a normal count. Lymphocytosis was prominent, especially during the convalescent period. An acceleration of ESR was noted. Instead of depression of the erythroid series in the marrow which was reported previously, 47% of examined patients were found to have erythroid hyperplasia. Two patients showed marked hypocellularity of the marrow in the acute febrile stage; later on became normocellular. Albuminuria was present in 15 and BUN increased in 12 patients. Elevation of serum bilirubin and SGOT was also noted. Biologic false positive VDRL tests were observed in nine patients. In 30 tests elevation of Proteus OX-K titres between 1:160 and 1:640 was noted. A geometric mean OX-K titre rise in the patients is presented; the mean titre reached a peak in the third week of illness, and then fell off. Most of the patients were treated with tetracycline 500 mg every six hours for about nine days. The fever usually subsided within 36 hours. Complications or mortality were not encountered.
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