title: Impaired contractile response of human peripheral arterioles to thromboxane A-2 after cardiopulmonary bypass.
abstract: BACKGROUND
  We studied the contractile response of human peripheral microvasculature to thromboxane A-2 (TXA-2) before and after cardiopulmonary bypass (CPB), with and without the blockade of TXA-2 receptors, or the inhibition of phospholipase C (PLC), phospholipase A-2 (PLA-2) or protein kinase C (PKC)-α. We also examined the protein/gene expression and localization of TXA-2 receptors, TXA-2 synthase, PLC, and other TXA-2-related proteins.
  
  
  METHODS
  Skeletal muscle arterioles (90-180 μm in diameter) were harvested pre- and post-CPB from patients (n = 28) undergoing cardiac surgery.
  
  
  RESULTS
  The post-CPB contractile response of skeletal muscle arterioles to TXA-2 analog U-46619 was impaired compared with pre-CPB (P < .05). The presence of TXA-2 receptor antagonist SQ-29548 (10(-6)mol/L) prevented the contractile response to U-46619 (P < .05). Pretreatment with the PLC inhibitor U-73122 (10(-6)mol/L) significantly inhibited the U-46619-induced contractile response (P < .01). Administration of the PLA-2 inhibitor quinacrine (10(-6)mol/L) or PKC-α inhibitor safingol (2 × 10(-5)mol/L), however, failed to affect U-46619-induced contraction. Total protein levels and gene expression of TXA-2 receptors, and TXA-2 synthase of skeletal muscle, were not altered post-CPB. Confocal microscopy showed no differences in the expression of PLCβ-3 in the microcirculation. PLCβ-3 was localized to both smooth muscle and endothelium.
  
  
  CONCLUSIONS
  CPB decreases the contractile response of human peripheral arterioles to TXA-2 soon after cardiac surgery. This response may be in part responsible for the decrease in vascular tone, and accompanying hypotension sometimes observed after cardiac operations utilizing CPB.
authors.affiliation: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Liu
authors.forename: Arun K
authors.initials: AK
authors.lastname: Singh
authors.forename: Nikola
authors.initials: N
authors.lastname: Dobrilovic
authors.forename: William C
authors.initials: WC
authors.lastname: Feng
authors.forename: Louis M
authors.initials: LM
authors.lastname: Chu
authors.forename: Michael P
authors.initials: MP
authors.lastname: Robich
authors.forename: Kamal R
authors.initials: KR
authors.lastname: Khabbaz
authors.forename: Frank W
authors.initials: FW
authors.lastname: Sellke
mesh_terms: D000368:Aged; D001160:Arterioles / Q000187:drug effects* / Q000503:physiopathology*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply; D013928:Thromboxane A2 / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D014662:Vasoconstrictor Agents; D013928:Thromboxane A2