TREATMENTS WITH LEAD EXPEDITE HYPERTHERMIA-INDUCED THROMBOEMBOLISM INMOUSE PIAL MICROVESSELS

Three trials were carried out to study the influence of acute and chro nic treatments with lead on hyperthermia-induced thromboembolic activi ty in pial microvessels of adult male mice. Each trial consisted of fo ur groups, 10 mice (similar to 33 g) per group. Three groups were inje cted with lead acetate dissolved in a 5% glucose solution (vehicle) at doses of 0.1, 0.5 and l.0 mg/kg and the control group received only t he vehicle. Acute treatments were by a single injection made 1 h (i.p. ) in one trial and 24 h (i.p.) in another; prior to the a hyperthermic exposure at 45 degrees C. In the third trial, a single injection was given daily (s.c.) for 7 days. Mice were anesthetized by urethane (1-2 mg/kg, i.p.), the trachea was intubated, a craniotomy was performed a nd the mouse was placed on the microscope stage of an intravital micro scopy set-up. Core body and brain surface temperatures were raised fir st to 37 degrees C, the animal was stabilized for 30 min then only the brain surface temperature was raised to 45 degrees C by heating the i rrigating artificial cerebrospinal fluid. The hyperthermic exposure la sted for 45 min. In all trials, lead at the three doses given (low, me dium and high) significantly reduced (p < 0.001) the time of initial t hromboembolic activity seen. Lead exerted its influence as quickly as in 1 h, even with the low dose administered. Neither the acute nor chr onic treatments affected the degree of arteriolar constriction observe d or caused venular diameter change. Arteriolar patency rate at the en d of experiment was higher for control than for all lead-treated group s. Data evidenced the rapidity of the adverse influence of lead on the susceptibility to thrombosis, in vivo. The enhanced initiation of thr ombotic activity may be attributed to facilitated damage to the microv ascular endothelium caused by lead, when challenged by hyperthermia.