Acute Bradykinin Receptor Blockade During Hemorrhagic Shock in Mice Prevents the Worsening Hypotensive Effect of Angiotensin-Converting Enzyme Inhibitor. Issue 9 (September 2016)

• Record Type: Journal Article
• Authors: Charbonneau, Hélène; Buléon, Marie; Minville, Vincent; Faguer, Stanislas; Girolami, Jean-Pierre; Bascands, Jean-Loup; Tack, Ivan; Mayeur, Nicolas
• Is Part Of: Critical care medicine. Volume 44:Issue 9(2016)
• Publication Date: 2016-09
• Subjects: angiotensin-converting enzyme inhibitor -- arterial hypotension -- blood lactate -- bradykinin receptor -- hemorrhagic shock -- icatibant; Critical care medicine -- Periodicals; Soins intensifs -- Périodiques; 616.028
• DOI: 10.1097/CCM.0000000000001646
• Languages: English
• ISSNs: 0090-3493

Abstract

Abstract : Objectives: Angiotensin-converting enzyme inhibitors are associated with deleterious hypotension during anesthesia and shock. Because the pharmacologic effects of angiotensin-converting enzyme inhibitors are partly mediated by increased bradykinin B2 receptor activation, this study aimed to determine the impact of acute B2 receptor blockade during hemorrhagic shock in angiotensin-converting enzyme inhibitor–treated mice. Design: In vivo study. Setting: University research unit. Subjects: C57/Bl6 mice. Interventions: The hemodynamic effect of B2 receptor blockade using icatibant (B2 receptor antagonist) was studied using a pressure-targeted hemorrhagic shock and a volume-targeted hemorrhagic shock. Animals were anesthetized with ketamine and xylazine (250 mg/kg and 10 mg/kg, respectively), intubated using intratracheal cannula, and ventilated (9 mL/kg, 150 min –1 ). Five groups were studied: 1) sham-operated animals, 2) control shocked mice, 3) shocked mice treated with ramipril for 7 days (angiotensin-converting enzyme inhibitors) before hemorrhagic shock, 4) shocked mice treated with angiotensin-converting enzyme inhibitors and a single bolus of icatibant (HOE-140) immediately before anesthesia (angiotensin-converting enzyme inhibitors + icatibant), and 5) shocked mice treated with a single bolus of icatibant. One hour after volume-targeted hemorrhagic shock, blood lactate was measured to evaluate organ failure. Measurements and Main Results: During pressure-targeted hemorrhagic shock, the mean blood volume withdrawn was significantly lower in the angiotensin-converting enzyme inhibitor group than in the other groups ( p < 0.001). During volume-targeted hemorrhagic shock, icatibant prevented blood pressure lowering in the angiotensin-converting enzyme inhibitor group ( p < 0.001). Blood lactate was significantly higher in the angiotensin-converting enzyme inhibitor group than in the other groups, particularly the HOE groups. Conclusions: During hemorrhagic shock, acute B2 receptor blockade significantly attenuates the deleterious hemodynamic effect of angiotensin-converting enzyme inhibitor treatment in mice. This beneficial effect of B2 receptor blockade is rapidly reached and sustained with a single bolus of icatibant. This benefit could be of interest in angiotensin-converting enzyme inhibitor–treated patients during both emergency anesthesia and resuscitation.