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Captopril improves postresuscitation hemodynamics protective against pulmonary embolism by activating the ACE2/Ang-(1-7)/Mas axis

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Abstract

Acute pulmonary embolism (APE) has a very high mortality rate, especially at cardiac arrest and even after the return of spontaneous circulation (ROSC). This study investigated the protective effect of the angiotensin-converting enzyme (ACE) inhibitor captopril on postresuscitation hemodynamics, in a porcine model of cardiac arrest established by APE. Twenty-nine Beijing Landrace pigs were infused with an autologous thrombus leading to cardiac arrest and subjected to standard cardiopulmonary resuscitation and thrombolysis. Ten resuscitated pigs were randomly and equally apportioned to receive either captopril (22.22 mg/kg) infusion or the same volume saline, 30 min after ROSC. Hemodynamic changes and ACE-Ang II-angiotensin II type 1 receptor (AT1R) and ACE2/Ang-(1-7)/Mas receptor axis levels were determined. APE was associated with a decline in mean arterial pressure and a dramatic increase in pulmonary artery pressure and mean right ventricular pressure. After ROSC, captopril infusion was associated with significantly lower mean right ventricular pressure and systemic and pulmonary vascular resistance, faster heart rate, and higher Ang-(1-7) levels, ACE2/ACE, and Ang-(1-7)/Ang II, compared with the saline infusion. The ACE2/Ang-(1-7)/Mas pathway correlated negatively with external vascular lung water and pulmonary vascular permeability and positively with the right cardiac index. In conclusion, in a pig model of APE leading to cardiac arrest, captopril infusion was associated with less mean right ventricular pressure overload after resuscitation, compared with saline infusion. The reduction in systemic and pulmonary vascular resistance associated with captopril may be by inhibiting the ACE-Ang II-AT1R axis and activating the ACE2/Ang-(1-7)/Mas axis.

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Abbreviations

ACE:

Angiotensin-converting enzyme

Ang:

Angiotensin

APE:

Acute pulmonary embolism

AT1R:

Angiotensin II type 1 receptor

MAP:

Mean arterial pressure

PAP:

Pulmonary artery pressure

RAS:

Renin-angiotensin system

ROSC:

Return of spontaneous circulation

SVR:

Systemic vascular resistance

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Acknowledgments

The authors would like to thank Chun-Sheng Li for his dedication to make this work possible, Lian-Xing Zhao, Nan Tong, Le An, and Yun Yang for their excellent technical assistance, and Qi-Tong Liu for the CT interpretation.

Funding

This study was funded by the National Natural Science Foundation of China (No. 81372025) and the 2015 Annual Special Cultivation and Development Project for Technology Innovation Base of Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation (No. Z151100001615056).

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Authors and Affiliations

  1. Department of Emergency Medicine, Beijing Chaoyang Hospital, Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Capital Medical University, Workers Stadium Road No. 8, Chaoyang District, 100020, Beijing, China

    Hong-Li Xiao, Chun-Sheng Li, Lian-Xing Zhao, Jun Yang, Nan Tong & Le An

  2. Department of Radiology, Beijing Chaoyang Hospital, Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Capital Medical University, Beijing, China

    Qi-Tong Liu

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  1. Hong-Li Xiao
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Correspondence to Chun-Sheng Li.

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Figure S1

Stereogram of massive APE. (GIF 85 kb)

High Resolution Image (TIF 900 kb)

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Xiao, HL., Li, CS., Zhao, LX. et al. Captopril improves postresuscitation hemodynamics protective against pulmonary embolism by activating the ACE2/Ang-(1-7)/Mas axis. Naunyn-Schmiedeberg's Arch Pharmacol 389, 1159–1169 (2016). https://doi.org/10.1007/s00210-016-1278-7

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