Endothelial dysfunction in the pulmanory circulation after cardiopulmonary bybass : with special reference to the reactivity to acetylcholine
Author: Angdin, Monika
Date: 2001-05-04
Location: Thoraxklinikerna, plan U1, Karolinska Sjukhuset
Time: 9.00
Department: Institutionen för kirurgisk vetenskap / Department of Surgical Science
Abstract
The endothelium is important as a physical barrier between the
bloodstream and the body tissues. It also plays an important role in the
control of vasomotor tone, coagulation, and for the interaction between
the vessel wall, leukocytes and platelets. One of the most important
regulators released from the endothelium is nitric oxide (NO). It is
released from endothelial cells after conversion of L- arginine to NO and
L-citrulline. Acetylcholine stimulates this reaction through activation
of the enzyme nitric-oxide synthase. Nitric oxide regulates vasomotor
tone through stimulation of guanylate cyclase in the vascular smooth
muscle cell. The rise in c-GMP leads to vascular smooth muscle relaxation
and a reduced vascular resistance. Ischemia-reperfusion attenuates this
endothelial function.
During cardiopulmonary bypass (CPB) there is no blood flow through the pulmonary artery followed by reperfusion. An attenuated reaction to acetylcholine in the pulmonary circulation after CPB in children had earlier been reported. In the studies presented here, the aim was to investigate in adult patients the time course of this endothelial dysfunction after heart surgery with CPB (study I and II), to compare acetylcholine reactivity in the pulmonary circulation after surgery in coronary artery bypass grafting (CABG) patients operated with or without CPB (study III), and to test if the post-bypass endothelial dysfunction could be reduced or prevented by treatment with L-arginine, the precursor of NO, during surgery (study IV) or by pre-treatment with antioxidants; vitamin E and C combined with allopurinol and acetylcysteine (study V).
Altogether 109 adult patients scheduled for elective heart surgery were included in the studies. Acetylcholine-reactivity in the pulmonary circulation was tested with measurements of the pulmonary vascular resistance, before and during an infusion of acetylcholine, using a Swan-Ganz catheter. In study 1, the acetylcholine-reactivity in the pulmonary circulation was decreased at 1-2 and 4 hours after CPB At 8 and 24 hours after CPB it had returned back to the pre-bypass level. In study 11, the response to acetylcholine immediately after weaning from CPB did not differ from the response before bypass and deteriorated first 1-2 hours later, indicating reperfusion injury. The acetylcholine-reactivity was better maintained in CABG patients operated without CPB compared to patients operated with CPB (Study 111). In contrast to experimental studies, L-arginine, tested in both a high and a low dose, was without effect. The acetylcholine-reactivity was identical to that seen in the placebo patients (study IV). However, patients pre-treated with antioxidants had a better preserved endothelial function after CPB compared to patients treated with placebo (Study V).
In conclusion a reversible endothelial dysfunction in the pulmonary circulation, in terms of vasodilation in response to acetylcholine, was demonstrated after CPB The time course indicated reperfusion injury. L-arginine was without effect but pre-treatment with antioxidants had a protective effect. Patients operated without CPB, with maintained flow through the pulmonary artery during surgery, had a better response to acetylcholine.
During cardiopulmonary bypass (CPB) there is no blood flow through the pulmonary artery followed by reperfusion. An attenuated reaction to acetylcholine in the pulmonary circulation after CPB in children had earlier been reported. In the studies presented here, the aim was to investigate in adult patients the time course of this endothelial dysfunction after heart surgery with CPB (study I and II), to compare acetylcholine reactivity in the pulmonary circulation after surgery in coronary artery bypass grafting (CABG) patients operated with or without CPB (study III), and to test if the post-bypass endothelial dysfunction could be reduced or prevented by treatment with L-arginine, the precursor of NO, during surgery (study IV) or by pre-treatment with antioxidants; vitamin E and C combined with allopurinol and acetylcysteine (study V).
Altogether 109 adult patients scheduled for elective heart surgery were included in the studies. Acetylcholine-reactivity in the pulmonary circulation was tested with measurements of the pulmonary vascular resistance, before and during an infusion of acetylcholine, using a Swan-Ganz catheter. In study 1, the acetylcholine-reactivity in the pulmonary circulation was decreased at 1-2 and 4 hours after CPB At 8 and 24 hours after CPB it had returned back to the pre-bypass level. In study 11, the response to acetylcholine immediately after weaning from CPB did not differ from the response before bypass and deteriorated first 1-2 hours later, indicating reperfusion injury. The acetylcholine-reactivity was better maintained in CABG patients operated without CPB compared to patients operated with CPB (Study 111). In contrast to experimental studies, L-arginine, tested in both a high and a low dose, was without effect. The acetylcholine-reactivity was identical to that seen in the placebo patients (study IV). However, patients pre-treated with antioxidants had a better preserved endothelial function after CPB compared to patients treated with placebo (Study V).
In conclusion a reversible endothelial dysfunction in the pulmonary circulation, in terms of vasodilation in response to acetylcholine, was demonstrated after CPB The time course indicated reperfusion injury. L-arginine was without effect but pre-treatment with antioxidants had a protective effect. Patients operated without CPB, with maintained flow through the pulmonary artery during surgery, had a better response to acetylcholine.
List of papers:
I. Angdin M, Settergren G (1997). "Acetylcholine reactivity in the pulmonary artery during cardiac surgery in patients with ischemic or valvular heart disease. " J Cardiothorac Vasc Anesth 11(4)
::
458-62
Pubmed
II. Angdin M, Settergren G, Astudillo R, Liska J (1998). "Altered reactivity to acetylcholine in the pulmonary circulation after cardiopulmonary bypass is part of reperfusion injury. " J Clin Anesth 10(2): 126-32
Pubmed
III. Angdin M, Settergren G, Vaage J (2001). "Better preserved pulmonary endothelial function after off-pump coronary artery bypass surgery." (Submitted)
IV. Angdin M, Settergren G, Liska J, Astudillo R (2001). "No effect of L-arginine supplementation on pulmonary endothelial dysfunction after cardiopulmonary bypass" Acta Anaesthesiol Scand 45(4): 441-8 (In Print)
Pubmed
V. Angdin M, Settergren G, Vaage J (2001). "Protective effect of antioxidants on endothelial function in the pulmonary circulation after cardiopulmonary bypass." (Manuscript)
I. Angdin M, Settergren G (1997). "Acetylcholine reactivity in the pulmonary artery during cardiac surgery in patients with ischemic or valvular heart disease. " J Cardiothorac Vasc Anesth 11(4)
::
458-62
Pubmed
II. Angdin M, Settergren G, Astudillo R, Liska J (1998). "Altered reactivity to acetylcholine in the pulmonary circulation after cardiopulmonary bypass is part of reperfusion injury. " J Clin Anesth 10(2): 126-32
Pubmed
III. Angdin M, Settergren G, Vaage J (2001). "Better preserved pulmonary endothelial function after off-pump coronary artery bypass surgery." (Submitted)
IV. Angdin M, Settergren G, Liska J, Astudillo R (2001). "No effect of L-arginine supplementation on pulmonary endothelial dysfunction after cardiopulmonary bypass" Acta Anaesthesiol Scand 45(4): 441-8 (In Print)
Pubmed
V. Angdin M, Settergren G, Vaage J (2001). "Protective effect of antioxidants on endothelial function in the pulmonary circulation after cardiopulmonary bypass." (Manuscript)
Issue date: 2001-04-13
Publication year: 2001
ISBN: 91-628-4721-X
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