title: Differential effects on the mesenteric microcirculatory response to vasopressin and phenylephrine after cardiopulmonary bypass.
abstract: OBJECTIVE
  Mesenteric ischemia is a rare but potentially devastating complication of cardiac surgery with cardiopulmonary bypass. We hypothesized that alterations in mitogen-activated protein kinase pathways contribute to mesenteric microcirculatory dysfunction resulting from cardiopulmonary bypass.
  
  
  METHODS
  Pigs underwent cardiopulmonary bypass (n = 6) for 90 minutes and postbypass reperfusion for 180 minutes. Sham operations (n = 6) were performed on controls. Mesenteric tissue was harvested before bypass and after postbypass reperfusion. Microvascular contraction to phenylephrine and vasopressin was examined by videomicroscopy. Contractile responses with inhibition of the extracellular regulated kinase 1/2 (ERK1/2) pathway by PD98059 (30 micromol/L) and p38 kinase inhibition by SB203580 (1 micromol/L) also were determined. Activated forms of ERK1/2 and p38 kinase were measured by Western blot. ERK1/2 and p38 activity were localized in mesenteric tissue by immunohistochemistry.
  
  
  RESULTS
  Contractile responses to phenylephrine were increased at 180 minutes after cardiopulmonary bypass (+49.7% +/- 5.5%, P < .01), whereas contraction to vasopressin was unchanged. ERK1/2 pathway inhibition reduced contractile responses to phenylephrine at baseline and 180 minutes after bypass (both P < .01) but had no effect on contraction to vasopressin. p38 Kinase inhibition decreased the contractile responses to vasopressin at baseline and 180 minutes after bypass (both P < .01) but did not alter the contractile response to phenylephrine. Activated ERK1/2 levels were increased by more than 40% at 180 minutes after bypass (P < .01). Protein levels of activated p38 kinase were not changed. The increased ERK1/2 activity was associated with mesenteric arterioles by immunohistochemistry.
  
  
  CONCLUSIONS
  A differential pattern of mesenteric vasomotor regulation exists after cardiopulmonary bypass that may contribute to the risk of mesenteric ischemia after cardiac surgery.
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass 02215, USA.
authors.forename: Tanveer A
authors.initials: TA
authors.lastname: Khan
authors.forename: Cesario
authors.initials: C
authors.lastname: Bianchi
authors.forename: Marc
authors.initials: M
authors.lastname: Ruel
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.forename: Frank W
authors.initials: FW
authors.lastname: Sellke
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002315:Cardiopulmonary Bypass; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008833:Microcirculation / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology*; D011336:Probability; D011897:Random Allocation; D012680:Sensitivity and Specificity; D013152:Splanchnic Circulation / Q000187:drug effects*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects; D014667:Vasopressins / Q000494:pharmacology*
chemical_list: D014667:Vasopressins; D010656:Phenylephrine; D019950:Mitogen-Activated Protein Kinase 1