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Comparative effects of angiotensin receptor blockade and ACE inhibition on the fibrinolytic and inflammatory responses to cardiopulmonary bypass.

Billings FT, Balaguer JM, C Y, Wright P, Petracek MR, Byrne JG, Brown NJ, Pretorius M - Clin. Pharmacol. Ther. (2012)

Bottom Line: ACE inhibition increased intraoperative bradykinin and tissue-type plasminogen activator (t-PA ) concentrations as compared to AR B.Both ACE inhibition and AR B decreased the need for plasma transfusion relative to placebo, but only ACE inhibition decreased the duration of hospital stay.ACE inhibitors and ARBs may be safely continued until the day of surgery.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Vanderbilt University Medical School, Nashville, Tennessee, USA.

ABSTRACT
The effects of angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 receptor blockade (ARB) on fibrinolysis and inflammation after cardiopulmonary bypass (CPB) are uncertain. This study tested the hypothesis that ACE inhibition enhances fibrinolysis and inflammation to a greater extent than ARB in patients undergoing CPB. One week to 5 days before surgery, patients were randomized to ramipril 5 mg/day, candesartan 16 mg/day, or placebo. ACE inhibition increased intraoperative bradykinin and tissue-type plasminogen activator (t-PA ) concentrations as compared to AR B. Both ACE inhibition and AR B decreased the need for plasma transfusion relative to placebo, but only ACE inhibition decreased the duration of hospital stay. Neither ACE inhibition nor AR B significantly affected concentrations of plasminogen activator inhibitor-1 (PAI -1), interleukin (IL )-6, IL -8, or IL -10. ACE inhibition enhanced intraoperative fibrinolysis without increasing the likelihood of red-cell transfusion. By contrast, neither ACE inhibition nor ARB affected the inflammatory response. ACE inhibitors and ARBs may be safely continued until the day of surgery.

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Effects of study drug on markers of inflammation. A) Interleukin (IL)-6. B) IL-8. C) IL-10. Preop indicates preoperative, post indicates post-bypass, and POD indicates postoperative day.
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Figure 3: Effects of study drug on markers of inflammation. A) Interleukin (IL)-6. B) IL-8. C) IL-10. Preop indicates preoperative, post indicates post-bypass, and POD indicates postoperative day.

Mentions: Preoperative t-PA antigen, PAI-1 antigen, and the PAI-1:t-PA molar ratio were not significantly different among treatment groups (all P-values > 0.44).Although study drug did not significantly affect t-PA antigen concentrations over time (P=0.28 for effect of study drug over time, Figure 2A)we observed a trend for the interaction between study drug and t-PA over time. Because of this interaction trend and the fact that the fibrinolytic response following CPB surgery is characterized by an initial hyperfibrinolytic intraoperative phase and a subsequent hypofibrinolytic postoperative phase, we investigated the effect of study drug on intraoperative and postoperative t-PA antigen concentrations separately, using the Wilcoxon rank-sum test. Ramipril significantly increased the t-PA antigen concentrations and decreased the PAI-1:t-PA antigen molar ratio compared to candesartan measured at the conclusion of surgery (post-bypass). Study drug did not affectPAI-1 antigen concentrations (P=0.84 for effect of study drug, Figure 2B).Preoperative IL-6, IL-8, and IL-10 concentrations were similar among treatment groups (all P-values >0.57). There was no effect of study drug on IL-6, IL-8 or IL-10 concentrations over time (P=0.69, P=0.97, P=0.46 respectively for effect of study drug, Figure 3A, B and C).


Comparative effects of angiotensin receptor blockade and ACE inhibition on the fibrinolytic and inflammatory responses to cardiopulmonary bypass.

Billings FT, Balaguer JM, C Y, Wright P, Petracek MR, Byrne JG, Brown NJ, Pretorius M - Clin. Pharmacol. Ther. (2012)

Effects of study drug on markers of inflammation. A) Interleukin (IL)-6. B) IL-8. C) IL-10. Preop indicates preoperative, post indicates post-bypass, and POD indicates postoperative day.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3822756&req=5

Figure 3: Effects of study drug on markers of inflammation. A) Interleukin (IL)-6. B) IL-8. C) IL-10. Preop indicates preoperative, post indicates post-bypass, and POD indicates postoperative day.
Mentions: Preoperative t-PA antigen, PAI-1 antigen, and the PAI-1:t-PA molar ratio were not significantly different among treatment groups (all P-values > 0.44).Although study drug did not significantly affect t-PA antigen concentrations over time (P=0.28 for effect of study drug over time, Figure 2A)we observed a trend for the interaction between study drug and t-PA over time. Because of this interaction trend and the fact that the fibrinolytic response following CPB surgery is characterized by an initial hyperfibrinolytic intraoperative phase and a subsequent hypofibrinolytic postoperative phase, we investigated the effect of study drug on intraoperative and postoperative t-PA antigen concentrations separately, using the Wilcoxon rank-sum test. Ramipril significantly increased the t-PA antigen concentrations and decreased the PAI-1:t-PA antigen molar ratio compared to candesartan measured at the conclusion of surgery (post-bypass). Study drug did not affectPAI-1 antigen concentrations (P=0.84 for effect of study drug, Figure 2B).Preoperative IL-6, IL-8, and IL-10 concentrations were similar among treatment groups (all P-values >0.57). There was no effect of study drug on IL-6, IL-8 or IL-10 concentrations over time (P=0.69, P=0.97, P=0.46 respectively for effect of study drug, Figure 3A, B and C).

Bottom Line: ACE inhibition increased intraoperative bradykinin and tissue-type plasminogen activator (t-PA ) concentrations as compared to AR B.Both ACE inhibition and AR B decreased the need for plasma transfusion relative to placebo, but only ACE inhibition decreased the duration of hospital stay.ACE inhibitors and ARBs may be safely continued until the day of surgery.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Vanderbilt University Medical School, Nashville, Tennessee, USA.

ABSTRACT
The effects of angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 receptor blockade (ARB) on fibrinolysis and inflammation after cardiopulmonary bypass (CPB) are uncertain. This study tested the hypothesis that ACE inhibition enhances fibrinolysis and inflammation to a greater extent than ARB in patients undergoing CPB. One week to 5 days before surgery, patients were randomized to ramipril 5 mg/day, candesartan 16 mg/day, or placebo. ACE inhibition increased intraoperative bradykinin and tissue-type plasminogen activator (t-PA ) concentrations as compared to AR B. Both ACE inhibition and AR B decreased the need for plasma transfusion relative to placebo, but only ACE inhibition decreased the duration of hospital stay. Neither ACE inhibition nor AR B significantly affected concentrations of plasminogen activator inhibitor-1 (PAI -1), interleukin (IL )-6, IL -8, or IL -10. ACE inhibition enhanced intraoperative fibrinolysis without increasing the likelihood of red-cell transfusion. By contrast, neither ACE inhibition nor ARB affected the inflammatory response. ACE inhibitors and ARBs may be safely continued until the day of surgery.

Show MeSH
Related in: MedlinePlus