CARDIOTOXICITY OF CHLORODIBROMOMETHANE AND TRICHLOROMETHANE IN RATS AND ISOLATED RAT CARDIAC MYOCYTES

The cardiovascular effects were investigated after acute and subacute treatment with chlorodibromomethane (CDBM; 0.4 to 3.2 mmol/kg p.o.), t richloromethane (TCM; 0.31 and 1.25 mmol/kg p.o.) and mixtures of CDBM and TCM (acute, 0.8 mmol CDBM/kg + 1.25 mmol TCM/kg p.o.; subacute, 0 .4 mmol CDBM/kg + 0.31 mmol TCM/kg p.o.) in conscious and urethane ana esthetized male Wistar rats (n = 6-10 per treatment). Furthermore it w as observed whether cardiovascular responses were modified in CDBM or TCM treated rats after administration of exogenous catecholamines (epi nephrine, 1 mu g/kg; norepinephrine, 2 mu g/kg) and underpinned with i n vitro alterations of Ca2+ dynamics in cardiac myocytes. The present findings demonstrated that single and subacute oral administration of CDBM or TCM and mixtures of CDBM and TCM resulted in arrhythmogenic an d negative chronotropic and dromotropic effects in conscious and ureth ane anaesthetized rats. The atrioventricular conduction time and the i ntraventricular extension time were extended. A slight shortening of t he repolarization velocity was observed. The myocardial contractility was depressed and the heart was sensitized to the arrhythmogenic effec ts of epinephrine. After catecholamine injection the adrenergic cardio vascular responses in urethane anesthetized rats were modified: increa sed hypertensive epinephrine and norepinephrine action as well as augm entation of negative chronotropic and negative dromotropic cardiac eff ects of catecholamines were observed. The positive inotropic adrenergi c response was diminished. The present in vivo findings, myocardial de pression after acute CDBM treatment, as determined by different indice s of contractility, correlate well with the observed inhibitory action s of CDBM on Ca2+ dynamics in isolated cardiac myocytes. All cardiovas cular alterations found after CDBM or TCM treatment were not intensifi ed after treatment with mixtures of CDBM and TCM. The effects observed were distinctly stronger after TCM (1.25 and 0.31 mmol/kg) treatment compared to CDBM (0.8 and 0.4 mmol/kg) treatment.