Control of blood pressure, heart rate and haematocrit during high-dose intravenous paraoxon exposure in mini pigs.
A therapeutic regimen was established to keep blood pressure, heart rate and haematocrit within the normal range during high-dose paraoxon (PX) exposure (ca. 150 x LD50) in mini pigs in order to achieve survival. Previous experiments showed that mini pigs exposed to high-dose PX died shortly after PX infusion due to hypertension, tachycardia and increased haematocrit if no antihypertensive and fluid therapy was initiated. Therefore, antihypertensive and fluid therapy with magnesium (MgSO4) and Ringer's solution was established to keep the blood pressure, heart rate and haematocrit within a pre-established normal range. Anaesthesized mini pigs received intravenously PX (54 mg kg(-1) body wt.) dissolved in alcohol. The control group received alcohol in corresponding amounts. When the blood pressure and heart rate increased, MgSO4 was 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 using the 'rank order test'. As intended, no statistically significant differences between blood pressure, heart rate or haematocrit were found after therapy, but the PX group required statistically significantly more MgSO4 and fluids than the control group to keep the blood pressure, heart rate and haematocrit within the normal range. We assume that the increased need of antihypertensive therapy is due to a phaeochromocytoma-like pattern caused by an excessive release of catecholamines from the adrenal medulla, which is under sympathotonic control and activated by acetylcholine. Paraoxon is known to cause endogenous acetylcholine poisoning. The high fluid requirements in the PX group are most probably caused by extravasation of fluids due to the damage inflicted on biological membranes by organophosphorus compounds. An activation of secretory glands probably also contributes to the increase in haematocrit 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.
Department of Pharmacology, University of Heidelberg at Mannheim, Germany.
G
G
Petroianu
L M
LM
Toomes
A
A
Petroianu
W
W
Bergler
R
R
Rüfer
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D002802:Cholinesterases / Q000097:blood; D005440:Fluid Therapy; D006339:Heart Rate / Q000187:drug effects*; D006400:Hematocrit; D006973:Hypertension / Q000517:prevention & control; D007275:Injections, Intravenous; D007552:Isotonic Solutions / Q000627:therapeutic use; D008278:Magnesium Sulfate / Q000627:therapeutic use; D062025:Organophosphate Poisoning; D009943:Organophosphorus Compounds / Q000008:administration & dosage; D010261:Paraoxon / Q000008:administration & dosage / Q000506:poisoning*; D011897:Random Allocation; D000077331:Ringer's Solution; D013552:Swine; D013556:Swine, Miniature; D013610:Tachycardia / Q000517:prevention & control; D018675:Toxicity Tests
D000959:Antihypertensive Agents; D007552:Isotonic Solutions; D009943:Organophosphorus Compounds; D008278:Magnesium Sulfate; D000077331:Ringer's Solution; D002802:Cholinesterases; D010261:Paraoxon