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 |
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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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