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Treatment of Hemorrhagic Shock with a New Vasodilator (Phosphorothioic Acid).

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Rept. for Jan 69-Jan 72,

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The present study was initiated to evaluate S-2-5-aminopentylaminoethyl phosphorothioic acid WR-2823 in the post-hemorrhage treatment of acute hypovolemic shock. Twenty-two adult mongrel dogs, 12 adult beagle dogs, and 14 Rhesus monkeys were anesthetized with sodium pentobarbital 30 mgkg, iv. Thirteen unanesthetized crossbred sheep were also used. Changes in arterial and venous blood pressures, EKG, and heart rate were continuously recorded and determinations of pH, pO2, and pCO2 content vol were made hourly. Cortical electric activity EEG was also monitored in the sheep and was used as an indicator of brain oxygenation. All animals were bled to a mean arterial pressure of from 45 to 50 mm Hg which was maintained at that level for 3 to 3-12 hours. During this time, dogs and monkeys were allowed to recover shed blood from the blood reservoir or to lose blood into the reservoir as dictated by the tone of their cardiovascular systems. The dogs showed a progressive decrease in arterial pH during the first 3 hours. The O2 content of the venous blood fell and arterial CO2 also decreased during this period. Control dogs and monkeys continued to deteriorate and at 8 hours had all taken back more shed blood than the treated group had. Treated dogs showed slow but progressive recovery of arterial pH, CO2, and venous O2 to pre-hemorrhage levels. At 8 hours pH stabilized at approximately 7.4 plus or minus 0.05 and venous O2 and arterial CO2 approached normal. Seven of 11 mongrel dogs, 4 of 6 beagle dogs, 7 of 7 monkeys, and 6 of 6 sheep treated with WR-2823 survived, whereas only one control animal was alive at 24 hours.

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  • Pharmacology

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