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

Autor: Jun Yang, Le An, Nan Tong, Hong-Li Xiao, Lian-Xing Zhao, Qi-Tong Liu, Chunsheng Li
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Captopril
Time Factors
Sus scrofa
Angiotensin-Converting Enzyme Inhibitors
030204 cardiovascular system & hematology
Proto-Oncogene Mas
Receptors
G-Protein-Coupled
Renin-Angiotensin System
0302 clinical medicine
Thrombolytic Therapy
General Medicine
Pulmonary edema
medicine.anatomical_structure
Anesthesia
cardiovascular system
Cardiology
Ventricular pressure
Female
Angiotensin-Converting Enzyme 2
hormones
hormone substitutes
and hormone antagonists
Signal Transduction
medicine.drug
Mean arterial pressure
medicine.medical_specialty
Pulmonary Edema
Peptidyl-Dipeptidase A
Pulmonary Artery
Return of spontaneous circulation
Capillary Permeability
03 medical and health sciences
Proto-Oncogene Proteins
medicine.artery
Internal medicine
Ventricular Pressure
medicine
Animals
Arterial Pressure
Pharmacology
business.industry
Hemodynamics
medicine.disease
Cardiopulmonary Resuscitation
Peptide Fragments
Heart Arrest
Enzyme Activation
Disease Models
Animal
030104 developmental biology
Blood pressure
Pulmonary artery
Ventricular Function
Right
Vascular resistance
Vascular Resistance
Angiotensin I
Pulmonary Embolism
business
Biomarkers
Zdroj: Naunyn-Schmiedeberg's Archives of Pharmacology. 389:1159-1169
ISSN: 1432-1912
0028-1298
Popis: 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.
Databáze: OpenAIRE
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