CONTROL OF BLOOD-PRESSURE, HEART-RATE AND HEMATOCRIT DURING HIGH-DOSEINTRAVENOUS PARAOXON EXPOSURE IN MINI PIGS

A therapeutic regimen was established to keep blood pressure, heart ra te and haematocrit within the normal range during high-dose paraoxon ( PX) exposure (ca, 150 x LD50) in mini pigs in order to achieve surviva l, Previous experiments showed that mini pigs exposed to high-dose PX died shortly after PX infusion due to hypertension, tachycardia and in creased haematocrit if no antihypertensive and fluid therapy was initi ated. Therefore, antihypertensive and fluid therapy with magnesium (Mg SO4) and Ringer's solution was established to keep the blood pressure, heart rate and haematocrit within a preestablished normal range. Anae sthesized mini pigs received intravenously PX (54 mg kg(-1) body wt.) dissolved in alcohol, The control group received alcohol in correspond ing amounts. When the blood pressure and heart rate increased, MgSO4 w as given intravenously until measured values reached the normal range. When the haematocrit increased, fluids were given intravenously until the haematocrit reached the normal range. The measured values in the PX group were compared with the measured values of the control group u sing the 'rank order test', As intended, no statistically significant differences between blood pressure, heart rate or haematocrit were fou nd after therapy, but the PX group required statistically significantl y more MgSO4 and fluids than the control group to keep the blood press ure, heart rate and haematocrit within the normal range. We assume tha t the increased need of antihypertensive therapy is due to a phaeochro mocytoma-like pattern caused by an excessive release of catecholamines from the adrenal medulla, which is under sympathotonic control and ac tivated by acetylcholine, Paraoxon is known to cause endogenous acetyl choline poisoning. The high fluid requirements in the PX group are mos t probably caused by extravasation of fluids due to the damage indicte d on biological membranes by organophosphorus compounds. An activation of secretory glands probably also contributes to the increase in haem atocrit through consumption of fluids. In conclusion, the survival of mini pigs exposed to high-dose PX can be achieved by tight control of blood pressure, heart rate and haematocrit using MgSO4 and fluids. (C) 1998 John Wiley & Sons, Ltd.