Acute effects of the heavy metal antidotes DMPS and DMSA on circulation, respiration, and blood homoeostasis in dogs.
The heavy metal antidotes sodium-2,3-dimercaptopropane-1-sulfonate (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) were investigated in anaesthetized dogs for their effects on a variety of physiological variables and parameters. In addition, the influence of both dithiols on oxygen consumption and ferrihaemoglobin production was studied in blood and red blood cells in vitro. DMPS (15 and 75 mg/kg i.v.) did not affect respiration, central venous pressure, left ventricular pressure or cardiac output and showed only marginal, statistically non-significant effects on aortic and effective perfusion pressure. In contrast to the slight, non-significant changes due to DMPS (15 mg/kg i.v.), an equimolar dose of DMSA (12 mg/kg i.v.) led to a slight transient decrease in femoral blood pressure with strong reflex tachycardia and increase in blood flow. The higher DMPS dose (75 mg/kg i.v.), however, caused marked decreases in femoral blood pressure and blood flow, strong changes in blood gases and pH, and lactacidosis. Most of the physiological variables and parameters did not return to the initial level by 60 min. The R-spike of the electrocardiogram decreased, and the T-wave increased. Experiments on the denervated hind leg indicate that DMPS may be a direct vasodilator. The fall of blood pressure due to DMPS was markedly reduced when 30% ferrihaemoglobin had been formed by 4-dimethylaminophenol.HCl (DMAP). The highest DMPS dose (150 mg/kg i.v.) provoked circulatory failure and respiratory arrest. Artificial ventilation with room air restored spontaneous respiration, but one of three animals did not survive this dose for more than 90 min. DMPS and DMSA reacted with oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)
Klimmek
R
R
Walther-Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität, München, Germany.
Krettek
C
C
Werner
H W
HW
D000818:Animals; D001775:Blood Circulation / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006706:Homeostasis / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D008670:Metals / Q000633:toxicity*; D008706:Methemoglobin / Q000096:biosynthesis / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011041:Poisoning / Q000188:drug therapy; D012119:Respiration / Q000187:drug effects*; D004113:Succimer / Q000494:pharmacology*; D014494:Unithiol / Q000494:pharmacology*
D008670:Metals; D014494:Unithiol; D008706:Methemoglobin; D004113:Succimer