Endothelin-1 during and after cardiopulmonary bypass: Association to graft sensitivity and postoperative recovery

Bond, Brian R.; Dorman, B. Hugh; Clair, Mark J.; Walker, C.Allyson; Pinosky, Mark L.; Reeves, Scott; Walton, Scott; Kratz, John M.; Zellner, James L.; Crumbley, Arthur J.; Multani, Marlina M.; Spinale, Francis G.

doi:10.1067/mtc.2001.114936

Cited by 41 publications

(57 citation statements)

References 31 publications

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“…For instance, endothelin-1 (ET-1) levels have been shown to correlate with the duration of CPB and postoperative complications. 53,54 Unfortunately, strategies towards controlling only the ET-1 pathway were also unsuccessful in the international TACTICS trial. 36 Therefore, future preventive or therapeutic strategies in PH and RV failure should consider combining therapies that would target multiple sites of action as previously reported.…”

Section: Discussionmentioning

confidence: 99%

A multicentre randomized-controlled trial of inhaled milrinone in high-risk cardiac surgical patients

Denault

Bussières

Arellano

et al. 2016

Can J Anesth/J Can Anesth

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Purpose Inhaled milrinone (iMil) has been used for the treatment of pulmonary hypertension (PH) but its efficacy, safety, and prophylactic effects in facilitating separation from cardiopulmonary bypass (CPB) and preventing right ventricular (RV) dysfunction have not yet been evaluated in a clinical trial. The purpose of this study was to investigate if iMil administered before CPB would be superior to placebo in facilitating separation from CPB.Methods High-risk cardiac surgical patients with PH were randomized to receive iMil or placebo after the induction of anesthesia and before CPB. Hemodynamic parameters and RV function were evaluated by means of pulmonary artery catheterization and transesophageal echocardiography. The groups were compared for the primary outcome of the level of difficulty in weaning from CPB. Among the secondary outcomes examined were the reduction in the severity of PH, the incidence of RV failure, and mortality. Results Of the 124 patients randomized, the mean (standard deviation [SD]) EuroSCORE II was 8.0 (2.6), and the baseline mean (SD) systolic pulmonary artery pressure (SPAP) was 53 (9) mmHg. The use of iMil was associated with increases in cardiac output (P = 0.03) and a reduction in SPAP (P = 0.04) with no systemic hypotension. Nevertheless, there was no difference in the combined incidence of difficult or complex separation from CPB between the iMil and control groups (30% vs 28%, respectively; absolute difference, 2%; 95% confidence interval [CI], -14 to 18; P = 0.78). There was also no difference in RV failure between the iMil and control groups (15% vs 14%, respectively; difference, 1%; 95% CI, -13 to 12; P = 0.94). Mortality was increased in patients with RV failure vs those without (22% vs 2%, respectively; P \ 0.001). Conclusion In high-risk cardiac surgery patients with PH, the prophylactic use of iMil was associated with favourable hemodynamic effects that did not translate into improvement of clinically relevant endpoints. This trial was registered at ClinicalTrials.gov; identifier: NCT00819377. RésuméObjectif La milrinone inhalée est utilisée pour traiter l'hypertension pulmonaire (HP) mais son efficacité, son innocuité et ses effets prophylactiques pour faciliter le sevrage de la circulation extracorporelle (CEC) et prévenir la dysfonction ventriculaire droite (VD) n'ont pas encore été évalués dans le cadre d'une étude clinique. L'objectif de cette étude était d'examiner si la milrinone inhalée avant la CEC serait supérieure à un placebo pour faciliter le sevrage de la CEC. Méthode Des patients de chirurgie cardiaque à risque élevé et souffrant d'HP ont été randomisés à recevoir de la milrinone inhalée ou un placebo après l'induction de l'anesthésie et avant la CEC. Les paramètres hémodynamiques et la fonction VD ont été évalués à l'aide d'un cathéter de l'artère pulmonaire et d'une échocardiographie transoesophagienne. Les groupes ont été comparés selon notre critère d'évaluation principal, soit le niveau de difficulté du sevrage de la CEC. Parmi les critères...

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Section: Discussionmentioning

confidence: 99%

A multicentre randomized-controlled trial of inhaled milrinone in high-risk cardiac surgical patients

Denault

Bussières

Arellano

et al. 2016

Can J Anesth/J Can Anesth

View full text Add to dashboard Cite

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“…Higher plasma ET-1 levels are associated with longer intensive care unit stay (Dorman et al, 2000). Furthermore, there is a positive correlation between conduit sensitivity to ET-1 and a prolonged need for vasodilator support with nitroglycerin (Bond et al, 2001). These observations provide evidence that increased ET-1 levels may negatively impact outcome in CABG patients.…”

Section: Abbreviationsmentioning

confidence: 99%

Vascular Dysfunction of Venous Bypass Conduits Is Mediated by Reactive Oxygen Species in Diabetes: Role of Endothelin-1

Ergul

Johansen

Strømhaug

et al. 2004

J Pharmacol Exp Ther

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“…Transient left ventricular (LV) dysfunction occurs after CA 1 and is associated with increased levels of bioactive peptides, including the vasoactive peptide, endothelin-1 (ET-1). [2][3][4] Moreover, elevated ET-1 levels in patients during and after cardiac surgery requiring CA may contribute to a complex postoperative course. 3 Although the effects of ET-1 on LV pump function after CA are likely to be multifactorial, ET-1 has been demonstrated to modulate myocyte contractile function, [5][6][7] which in turn can influence LV function.…”

mentioning

confidence: 99%

Protein Kinase C Isoform Activation and Endothelin-1 Mediated Defects in Myocyte Contractility After Cardioplegic Arrest and Reperfusion

et al. 2006

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Background-Endothelin-1 (ET-1) is released after hyperkalemic cardioplegic arrest (CA) and reperfusion and may contribute to contractile dysfunction. ET-1 receptor transduction causes activation of protein kinase C (PKC) isoforms, which can cause differential intracellular events. The goal of this study was to determine which PKC isoforms contribute to myocyte contractile dysfunction with ET-1 and CA. Methods and Results-Percent shortening (PERSHORT) and the time to 50% relaxation (T50) were measured in porcine (n ϭ22) left ventricular myocytes, randomized (minimum: 30 cells/group) to normothermia: (cell media for 2 hours/37°C), and CA: (2 hours/4°C, 24 mEq K ϩ solution followed by reperfusion in cell media), ET-1/CA: (100 pM ET-1 during CA). Studies were performed in the presence and absence of PKC inhibitors (500 nM) against the classical (Beta-I, Beta-II, Gamma) and novel (Epsilon, Eta) isoforms (myocytes from a minimum of 3 pigs per inhibitor). CA reduced PERSHORT by Ϸ35% from normothermia (PϽ0.05), which was further reduced with ET-1. PKC-Beta-II or PKC-Gamma inhibition increased PERSHORT from ET-1/CA as well as CA only (PϽ0.05). CA prolonged T50 by Ϸ19% from normothermia (PϽ0.05) and was further prolonged with ET-1. Inhibition of the classical PKC isoforms reduced T50 from ET-1/CA (PϽ0.05). Inhibition of novel PKC isoforms did not yield similar effects on either PERSHORT or T50 with ET-1/CA. Conclusions-Inhibition of the classical PKC isoforms relieved the negative inotropic and lusitropic effects of ET-1 after CA. These findings provide mechanistic support for developing targeted inhibitory strategies with respect to ET-1 signaling and myocyte contractile dysfunction with cardioplegic arrest and reperfusion.

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Endothelin-1 during and after cardiopulmonary bypass: Association to graft sensitivity and postoperative recovery

Cited by 41 publications

References 31 publications

A multicentre randomized-controlled trial of inhaled milrinone in high-risk cardiac surgical patients

A multicentre randomized-controlled trial of inhaled milrinone in high-risk cardiac surgical patients

Vascular Dysfunction of Venous Bypass Conduits Is Mediated by Reactive Oxygen Species in Diabetes: Role of Endothelin-1

Protein Kinase C Isoform Activation and Endothelin-1 Mediated Defects in Myocyte Contractility After Cardioplegic Arrest and Reperfusion

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