Abstract-Using the 31P-topical nuclear magnetic resonance method (TMR), an attempt was made to determine the myocardial high-energy phosphate compounds (HEP) contents under in situ conditions in closed-chest animals, and the effects of opening the thorax on the myocardial energy metabolism were studied comparing the cardiotoxic effects of 5-fluorouracil (5-FU) in closed-chest and open-chest animals.It was found that the depletion of myocardial HEP produced by 5-FU was much more marked in open-chest animals than in closed-chest ones, indicating the necessity of conducting the experiments in closed-chest animals for the proper evaluation of the cardiotoxicity of certain types of compounds. Therefore, the cardiotoxicity of a prodrug of 5-FU was assessed in closed-chest animals, and it was found to be less cardiotoxic than 5-FU.

1Drug effects were studied on the cerebral circulation by measuring the sagittal sinus outflow in the anaesthetized dog following the method of Michenfelder and by monitoring cerebral oxygen consumption. Systemic aortic pressure, heart rate and spinal fluid pressure were also studied. 2 Since dilatation of cerebral vessels was observed in nearly all the preparations after inhalation of C02, it was thought that gross extracerebral contamination was virtually eliminated in this preparation. A close correlation was observed between the oxygen consumption of the brain as a whole and the sagittal sinus outflow (r= 0.93, P< 0.001); therefore it became feasible to differentiate the direct effects of drugs on cerebral blood vessels from indirect ones attributable to changes in the cerebral oxidative metabolism. 3 Sodium pentobarbitone (5 mg kg-1, i.v.), reduced the cerebral venous outflow and caused a decrease in the oxygen consumption. Pentylenetetrazol (30 mg kg -i.v.) and bemegride (5 mg kg-1 i.v.) produced an increase in the blood flow and a corresponding increase in the cerebral oxygen consumption. Thus, it was concluded these substances had no direct effects on the cerebral blood vessels. 4 Acetazolamide (10mgkg-1, i.v.), a carbonic anhydrase inhibitor, produced a marked and sustained vasodilatation after a latent period of 0.5-1 min. There was no increase in the cerebral oxygen consumption. A similar pattern was seen after CO2 had been inhaled. Methylergometrine and dihydroergotamine (20 jig kg-1 i.v.) induced a prolonged vasoconstriction of the cerebral vascular bed without any changes in the oxygen consumption of the brain. Therefore this method can discriminate between indirect or direct effects of drugs on cerebral vascular outflow.

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Abstract-The effects of thiamine tetrahydrofurfuryl disulfide (TTFD) on the gradual increase in the coronary blood flow (CBF) inherent in the canine heart-lung preparation were studied.