THE EFFECT OF LARGE DOSES OF 1,3-INDANDIONES AND 4-HYDROXYCOUMARINS ON OXYGEN CONSUMPTION OF ANESTHETIZED CATS AND RABBITS

¹ Nobel Institute for Neurophysiology, Karolinska Institutet, Stockholm, and the Department of Organic Chemistry, Royal Institute of Technology, Stockholm, Sweden
² Nobel Institute for Neurophysiology, Karolinska Instilutet, Stockholm, and the Department of Organic Chemistry, Royal Institute of Technology, Stockholm, Sweden

A number of indandiones and 4-hydroxycoumarins have been studied in deeply-anesthetized cats and rabbits.

Large doses of 2-benzoyl-and 2-phenyl-1,3-indandiones and of bishydroxycoumanin, Warfarin, Cumachlor, Marcoumar and Tromexan injected intravenously produced a rapid rise in oxygen consumption. Rate and amplitude of respiration was increased to a corresponding degree. The rise in oxygen consumption was uninfluenced by d-tubocurarine. Functional hepatectomy produced by removing the liver from circulation, and adrenalectomy, did not affect the results.

The body temperature rose slowly although cutaneous blood vessels were usually dilated and muscle tonus decreased. The depth of narcosis was unaffected or slightly increased.

Blood pressure was usually decreased, though changes in both directions sometimes occurred immediately after injection.

The effects on oxygen consumption were uninfluenced by vitamin K₁. Vitamin K₃ potentiated the effects markedly.

Immediately after death from lethal doses of phenyl-indandione and bishydroxycoumanin a rapid onset of rigor mortis was observed. This was also seen in an animal treated with both bishydroxycoumanin and vitamin K₃.

The action of the anticoagulants on basal metabolism are on the whole very similar to those of 2,4-dinitrophenol (DNP), vulpinie acid, usnic acid and humulone.

No direct correlation appears to exist between the hemorrhagic and hypermetabolic activities of the anticoagulants tested.