Abstract 19797: TXA-2--Induced Contractile Response of Human Coronary Arterioles Is Diminished Post Cardioplegia
Objectives: Cardiopelgic arrest and reperfusion (CP-rep) is associated with microvascular dysfunction. We investigated the contractile response to TXA-2, the blockade of TXA-2 receptors and the inhibition of phospholipase-C (PLC) in the human coronary microvasculature before and after CP-rep. We also examined the protein expression of thromboxane A-2 (TXA-2) receptors, TXA-2 synthase, and PLC.
Methods: Right atrial tissues were harvested before and after CP-rep from an atrial segment exposed to hyperkalemic cold blood cardioplegia followed by 10-minutes of reperfusion from patients (n = 10) undergoing cardiac surgery. Coronary arterioles (90–160 μm in diameter) were dissected from the harvested tissue and placed in an organ bath containing Krebs solution. Microvascular constriction was assessed by videomicroscopy in response to the TXA-2 analog U46619, with and without the highly selective TXA-2 receptor antagonist, SQ 29548 or the specific PLC inhibitor, U73122. The protein expression of TXA-2 receptors, TXA-2 synthase and PLCγ-1 were also examined by immunoblot.
Results: The post-CP-rep contractile response of coronary arterioles to TXA-2 analog U46619 (10−5M) was significantly impaired compared with pre-CP-rep (38 ± 9% vs. 62 ± 8 %, P=0.041). The presence of TXA-2 antagonist SQ 29548 (10−6 M) prevented the contractile response to U46619 (pre-CP-rep: 10 ± 2 % vs. 62 ± 8 %, P = 0.001; post-CP-rep: 12 ± 3% vs. 38 ± 9%%, P =0.004). Pretreatment with the PLC inhibitor U73122 (10−5M) significantly inhibited U46619-induced contractile response (pre-CP-rep: 11 ± 2 % vs. 62 ± 8 % post-CP-rep: 16 ± 3 % vs. 38 ± 9% P<0.05, respectively). There were no significant differences in the sodium nitroprusside (10−5M) -induced vasodilatation between pre and post-CP-rep. The total protein levels of TXA-2 receptors, TXA-2 synthase and PLCγ-1 were not altered post-CP-rep.
Conclusions: CP-rep decreases the contractile response of human coronary arterioles to TXA-2 soon after termination of cardiopulmonary bypass. The contractile response to the TXA-2 analog U46619 is via activation of TXA-2 receptors and PLC. These results provide novel mechanisms for TXA-2-induced contraction in vasomotor dysfunction soon after cardiac surgery.
- © 2010 by American Heart Association, Inc.