Satyajeet S Rathi1, Yan-Jun Xu, Naranjan S Dhalla. 1. Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre, and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba.
Abstract
BACKGROUND: Tumour necrosis factor alphs (TNF-alpha), a proinflammatory cytokine, is synthesized in the heart under pathologic conditions; however, it is not clear whether this cytokine results in heart dysfunction or serves as a cardioprotective agent. OBJECTIVE: To examine whether TNF-alpha in low concentrations exerts a cardioprotective effect on the heart and prevents the occurrence of intracellular calcium overload. ANIMALS AND METHODS: The effect of TNF-alpha was studied in vivo on hemodynamic parameters in anesthetized rats. The cardioprotective action of TNF-alpha was tested against ischemia-reperfusion-induced changes in cardiac performance in the isolated perfused rat hearts. The effect of TNF-alpha on intracellular free calcium was evaluated in freshly isolated adult rat cardiomyocytes by Fura 2 technique. RESULTS: An intravenous injection of TNF-alpha (200 mug/kg) in rats produced a transient but significant depressant effect on cardiac function and an increase in heart rate. TNF-alpha (25 mug/mL) did not affect cardiac function in the isolated heart; however, it attenuated the ischemia-reperfusion-induced changes in the left ventricular pressures (developed pressure, end diastolic pressure, +dP/dt and -dP/dt). In the isolated cardiomyocytes, TNF-alpha did not produce any change in the level of intracellular free calcium, but this agent (10 to 100 ng/mL) significantly decreased the potassium chloride (30 mM) -induced increase in free calcium. CONCLUSIONS: The inhibitory effect of low concentrations of TNF-alpha on calcium influx may reduce the occurrence of intracellular calcium overload, and this may be responsible for improving left ventricular dysfunction due to ischemia-reperfusion injury in the heart.
BACKGROUND:Tumour necrosis factor alphs (TNF-alpha), a proinflammatory cytokine, is synthesized in the heart under pathologic conditions; however, it is not clear whether this cytokine results in heart dysfunction or serves as a cardioprotective agent. OBJECTIVE: To examine whether TNF-alpha in low concentrations exerts a cardioprotective effect on the heart and prevents the occurrence of intracellular calcium overload. ANIMALS AND METHODS: The effect of TNF-alpha was studied in vivo on hemodynamic parameters in anesthetized rats. The cardioprotective action of TNF-alpha was tested against ischemia-reperfusion-induced changes in cardiac performance in the isolated perfused rat hearts. The effect of TNF-alpha on intracellular free calcium was evaluated in freshly isolated adult rat cardiomyocytes by Fura 2 technique. RESULTS: An intravenous injection of TNF-alpha (200 mug/kg) in rats produced a transient but significant depressant effect on cardiac function and an increase in heart rate. TNF-alpha (25 mug/mL) did not affect cardiac function in the isolated heart; however, it attenuated the ischemia-reperfusion-induced changes in the left ventricular pressures (developed pressure, end diastolic pressure, +dP/dt and -dP/dt). In the isolated cardiomyocytes, TNF-alpha did not produce any change in the level of intracellular free calcium, but this agent (10 to 100 ng/mL) significantly decreased the potassium chloride (30 mM) -induced increase in free calcium. CONCLUSIONS: The inhibitory effect of low concentrations of TNF-alpha on calcium influx may reduce the occurrence of intracellular calcium overload, and this may be responsible for improving left ventricular dysfunction due to ischemia-reperfusion injury in the heart.
Authors: C Natanson; P W Eichenholz; R L Danner; P Q Eichacker; W D Hoffman; G C Kuo; S M Banks; T J MacVittie; J E Parrillo Journal: J Exp Med Date: 1989-03-01 Impact factor: 14.307