Treatments with Lead Expedite Hyperthermia-Induced Thromboembolism in Mouse Pial Microvessels

Abstract

Three trials were carried out to study the influence of acute and chronic treatments with lead on hyperthermia-induced thromboembolic activity in pial microvessels of adult male mice. Each trial consisted of four groups, 10 mice (∼33 g) per group. Three groups were injected with lead acetate dissolved in a 5% glucose solution (vehicle) at doses of 0.1, 0.5 and 1.0mg/kg and the control group received only the 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°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 and the mouse was placed on the microscope stage of an intravital microscopy set-up. Core body and brain surface temperatures were raised first to 37°C, the animal was stabilized for 30 min then only the brain surface temperature was raised to 45°C by heating the irrigating artificial cerebrospinal fluid. The hyperthermic exposure lasted for 45 min. In all trials, lead at the three doses given (low, medium and high) significantly reduced (p > 0.001) the time of initial thromboembolic activity seen. Lead exerted its influence as quickly as in 1 h, even with the low dose administered. Neither the acute nor chronic treatments affected the degree of arteriolar constriction observed or caused venular diameter change. Arteriolar patency rate at the end of experiment was higher for control than for all lead-treated groups. Data evidenced the rapidity of the adverse influence of lead on the susceptibility to thrombosis, in vivo. The enhanced initiation of thrombotic activity may be attributed to facilitated damage to the microvascular endothelium caused by lead, when challenged by hyperthermia.

Key Words:

• Cerebral
• embolism
• hyperthermia
• lead
• microcirculation
• mouse pial
• thrombosis