Combined blockade of ET and TXA2 receptors with bosentan and SQ 30,741 did not improve the postischaemic recovery of coronary flow, contractile performance, or cardiac energy metabolism.
Does combined blockade of ET and TXA2 receptors improve postischaemic recovery of coronary flow, contractile performance, and cardiac energy metabolism in isolated perfused rat hearts?
Combined blockade of ET and TXA2 receptors does not protect against postischemic contractile dysfunction or energy metabolism impairment in isolated rat hearts.
Endothelin-1 (ET-1) may play a role in myocardial ischaemia/reperfusion injury because both the release and vasoconstrictor effect of ET-1 are increased after ischaemia. Since the increased vasoconstrictor effect of ET-1 can be mediated by ET-1-induced release of thromboxane A(2) (TXA(2)), the aim of this study was to test whether combined blockade of ET and TXA(2) receptors protects the coronary flow, contractile performance, and cardiac energy metabolism during ischaemia and reperfusion. 2. Bosentan (antagonist for ET(A) and ET(B) receptors, 1 microM based on concentration-response curves of ET-1), SQ 30,741 (antagonist of TXA(2) receptors, 0.1 microM), or the combination thereof was administered to isolated perfused rat hearts undergoing 15 min of global ischaemia and 60 min of reperfusion. 3. Neither bosentan or SQ 30,741 alone, nor the combination thereof, improved the incomplete postischaemic recovery of coronary flow, left ventricular developed pressure, phosphocreatine, or ATP. However, they attenuated ischaemia-induced acidosis but this did not translate into a measurable effect on haemodynamic or metabolic variables. 4. Thus, combined blockade of ET and TXA(2) receptors does not protect the coronary flow, contractile performance, and cardiac energy metabolism during ischaemia and reperfusion in isolated perfused rat hearts. This finding suggests that neither ET-1 nor ET-1-induced release of TXA(2) play a major role in the postischaemic recovery of the cardiac contractile function and energy metabolism.
Hornstein et al. (2001) studied Myocardial ischaemia/reperfusion injury. Bosentan and/or SQ 30,741 vs. Control was evaluated on Postischaemic recovery of coronary flow, left ventricular developed pressure, phosphocreatine, or ATP. Combined blockade of ET and TXA2 receptors with bosentan and SQ 30,741 did not improve the postischaemic recovery of coronary flow, contractile performance, or cardiac energy metabolism.