Haemodynamic and electrophysiological acute toxic effects of mercury in anaesthetized rats and in langendorff perfused rat hearts.
The acute toxic effects of HgCl2 on the cardiovascular system were studied in Langendorff-perfused rat hearts and in anaesthetized rats. Isovolumic systolic pressure (ISP), atrial and ventricular rates, and atrioventricular conduction (PR-interval) were studied in the hearts perfused with bicarbonate buffer Krebs solution, at 31 degrees C, under a constant pressure of 75 mmHg. Eight hearts were studied at a fixed rate (200 bpm) under control conditions and at different HgCl2 concentrations (0.1, 1 and 10 microM). In these preparations the left ventricular function curves showed that Hg2+ reduces ISP development in a concentration-dependent manner whilst the myocardial response to increasing diastolic pressure is preserved. Ten additional spontaneously beating hearts were studied also under control conditions and at several HgCl2 concentrations (0.5, 1, 2 and 10 microM). ISP and ECG were recorded. Again, ISP decreased after Hg2+ treatment, but all HgCl2 concentrations produced 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 spontaneously beating preparations. Hg2+ also decreased the atrial and ventricular rate driven by atria and increased the PR-interval. Several arrhythmias were induced, such as extrasystoles, A-V blocks, brady- and tachyarrhythmias and ventricular fibrillation without a clear relationship with Hg2+ concentrations. The possibility of an increased activity of autonomic neurotransmitters was also investigated. Cholinergic activity was evaluated in 14 preparations and adrenergic activity in eight by blocking their effects with atropine (0.2 micrograms ml-1) and propranolol (0.1 microgram ml-1), respectively. Atropine reduced Hg2+ effects on ISP, heart rate and PR-interval while propranolol enhanced the cholinergic effects. In the anaesthetized rats the changes in mean arterial blood pressure (MBP), heart rate (HR), and atrioventricular conduction (PR-interval) were recorded and followed for 120 min. In five rats acute poisoning was achieved using a high dose of HgCl2 (50 mg kg-1). MBP and HR decreased and PR-interval increased. Arrhythmias developed followed by ventricular fibrillation and all the animals died after 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 propranolol (2 mg kg-1), and seven with atropine (1 mg kg-1). Propranolol 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 injection. Atropine blocked the changes in MBP, HR and PR interval produced by HgCl2 during 120 min of observation. Another group treated with 0.5 mg kg-1 was also studied but no changes of the parameters analysed were observed. The results suggest that, in addition to the reduction of mechanical activity, Hg2+ affects heart rate and atrioventricular conduction, has arrhythmogenic effects, decreases arterial blood pressure and increases autonomic neurotransmitter activity.
Massaroni
L
L
Department of Physiological Sciences, Federal University of Espirito Santo, Porto Alegre, Brazil.
Rossoni
L V
LV
Amaral
S M
SM
Stefanon
I
I
Oliveira
E M
EM
Vassallo
D V
DV
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000009:adverse effects*; D001283:Atrioventricular Node / Q000187:drug effects*; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004202:Disinfectants / Q000009:adverse effects*; D004594:Electrophysiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006439:Hemodynamics; D008297:Male; D008627:Mercuric Chloride / Q000009:adverse effects*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D015425:Myocardial Reperfusion; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000319:Adrenergic beta-Antagonists; D000891:Anti-Infective Agents, Local; D004202:Disinfectants; D018727:Muscarinic Antagonists; D008627:Mercuric Chloride; D001285:Atropine; D011433:Propranolol