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Assessment of Vascular Tone Responsiveness using Isolated Mesenteric Arteries with a Focus on Modulation by Perivascular Adipose Tissues
Published on: June 3, 2019
Differential effects on the mesenteric microcirculatory response to vasopressin and phenylephrine after
Tanveer A Khan1, Cesario Bianchi, Marc Ruel
1Division of Cardiothoracic Surgery, Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass 02215, USA.
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.
Insights
Cardiopulmonary bypass alters mesenteric blood vessel function, increasing phenylephrine response via extracellular regulated kinase 1/2 (ERK1/2) and vasopressin response via p38 kinase. This may increase mesenteric ischemia risk after cardiac surgery.
Area of Science:
- Physiology
- Vascular Biology
- Cardiac Surgery
Background:
- Mesenteric ischemia is a serious complication following cardiac surgery with cardiopulmonary bypass.
- Mitogen-activated protein kinase (MAPK) pathways are implicated in microcirculatory dysfunction.
Purpose of the Study:
- To investigate the role of MAPK pathways, specifically extracellular regulated kinase 1/2 (ERK1/2) and p38 kinase, in mesenteric microcirculatory dysfunction after cardiopulmonary bypass.
- To determine how cardiopulmonary bypass affects mesenteric vasomotor regulation.
Main Methods:
- Pigs underwent cardiopulmonary bypass or sham operations.
- Mesenteric microvascular contractile responses to phenylephrine and vasopressin were assessed.
- The effects of ERK1/2 and p38 kinase inhibitors (PD98059 and SB203580) on contractile responses were evaluated.
- Activated ERK1/2 and p38 kinase levels and localization were measured using Western blot and immunohistochemistry.
Main Results:
- Cardiopulmonary bypass increased mesenteric contractile responses to phenylephrine but not vasopressin.
- ERK1/2 inhibition attenuated phenylephrine-induced contraction, while p38 kinase inhibition affected vasopressin-induced contraction.
- Activated ERK1/2 levels significantly increased post-bypass, localized to mesenteric arterioles.
- Activated p38 kinase levels remained unchanged.
Conclusions:
- A distinct pattern of mesenteric vasomotor regulation occurs after cardiopulmonary bypass, involving differential MAPK pathway activation.
- These alterations in vascular control may contribute to the heightened risk of mesenteric ischemia in patients undergoing cardiac surgery.
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