Limits...
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.Neither ACE inhibition nor AR B significantly affected concentrations of plasminogen activator inhibitor-1 (PAI -1), interleukin (IL )-6, IL -8, or IL -10.

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

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

License
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).


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

License
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.Neither ACE inhibition nor AR B significantly affected concentrations of plasminogen activator inhibitor-1 (PAI -1), interleukin (IL )-6, IL -8, or IL -10.

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