title: Captopril improves postresuscitation hemodynamics protective against pulmonary embolism by activating the ACE2/Ang-(1-7)/Mas axis.
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.
authors.affiliation: 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.
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Xiao
authors.affiliation: 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. lcscyyy@163.com.
authors.forename: Chun-Sheng
authors.initials: CS
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Lian-Xing
authors.initials: LX
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Nan
authors.initials: N
authors.lastname: Tong
authors.affiliation: 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.
authors.forename: Le
authors.initials: L
authors.lastname: An
authors.affiliation: Department of Radiology, Beijing Chaoyang Hospital, Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Capital Medical University, Beijing, China.
authors.forename: Qi-Tong
authors.initials: QT
authors.lastname: Liu
mesh_terms: D000803:Angiotensin I / Q000378:metabolism*; D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D002199:Capillary Permeability / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D016887:Cardiopulmonary Resuscitation; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005260:Female; D006323:Heart Arrest / Q000097:blood / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy*; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D011654:Pulmonary Edema / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control; D011655:Pulmonary Embolism / Q000097:blood / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D034421:Sus scrofa; D015912:Thrombolytic Therapy; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D016278:Ventricular Function, Right / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000803:Angiotensin I; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)
keywords: ACE2/Ang-(1-7)-Mas axis; Acute pulmonary embolism; Captopril; Cardiac arrest; Restoring spontaneous circulation