HEMODYNAMIC AND ELECTROPHYSIOLOGICAL ACUTE TOXIC EFFECTS OF MERCURY IN ANESTHETIZED RATS AND IN LANGENDORFF PERFUSED RAT HEARTS

The acute toxic effects of HgCl2 on the cardiovascular system were stu died in Langendorff-perfused rat hearts and in anaesthetized rats. Iso volumic systolic pressure (ISP), atrial and ventricular rates, and atr ioventricular conduction (PR-interval) were studied in the hearts perf used with bicarbonate buffer Krebs solution, at 31 degrees C, under a constant pressure of 75 mmHg. Eight hearts were studied at a fixed rat e (200 bpm) under control conditions and at different HgCl2 concentrat ions (0.1, 1 and 10 mu M). In these preparations the left ventricular function curves showed that Hg2+ reduces ISP development in a concentr ation-dependent manner whilst the myocardial response to increasing di astolic pressure is preserved. Ten additional spontaneously beating he arts were studied also under control conditions and at several HgCl2 c oncentrations (0.5, 1, 2 and 10 mu M). ISP and ECG were recorded. Agai n, ISP decreased after Hg2+ treatment, but all HgCl2 concentrations pr oduced effects of the same magnitude. The reduction of heart rate that also occurs during Hg2+ treatment is the possible explanation for the different effects of Hg2+ on the ISP obtained from the driven and spo ntaneously beating preparations. Hg2+ also decreased the atrial and ve ntricular rate driven by atria and increased the PR-interval. Several arrhythmias were induced, such as extrasystoles, A-V blocks, brady- an d tachyarrhythmias and ventricular fibrillation without a clear relati onship with Hg2+ concentrations. The possibility of an increased activ ity of autonomic neurotransmitters was also investigated. Cholinergic activity was evaluated in 14 preparations and adrenergic activity in e ight by blocking their effects with atropine (0.2 mu g ml(-1)) and pro pranolol (0.1 mu g ml(-1)), respectively. Atropine reduced Hg2+ effect s on ISP, heart rate and PR-interval while propranolol enhanced the ch olinergic effects. In the anaesthetized rats the changes in mean arter ial blood pressure (MBP), heart rate (HR), and atrioventricular conduc tion (PR-interval) were recorded and followed for 120 min. In five rat s acute poisoning was achieved using a high dose of HgCl2 (50 mg kg(-1 )). MBP and HR decreased and PR-interval increased. Arrhythmias develo ped followed by ventricular fibrillation and all the animals died afte r 1 min. In nine other rats a lower dosage (5 mg kg(-1)) was used. MBP and HR decreased progressively and the PR-interval increased after 40 min. Using the same protocol, six other rats were pretreated with pro pranolol (2 mg kg(-1)), and seven with atropine (1 mg kg(-1)). Propran olol delayed the reduction in MBP caused by HgCl2. HR decreased after propranolol injection but did not change thereafter. The PR-interval, however, increased significantly within the first minute after HgCl2 i njection. Atropine blocked the changes in MBP, HR and PR interval prod uced by HgCl2 during 120 min of observation. Another group treated wit h 0.5 mg kg(-1) was also studied but no changes of the parameters anal ysed were observed. The results suggest that, in addition to the reduc tion of mechanical activity, Hg2+ affects heart rate and atrioventricu lar conduction, has arrhythmogenic effects, decreases arterial blood p ressure and increases autonomic neurotransmitter activity. (C) 1995 Th e Italian Pharmacological Society