Imbalance of angiotensin-converting enzymes affects myocardial apoptosis during cardiac arrest induced by acute pulmonary embolism in a porcine model.

Acute pulmonary embolism (APE) with cardiac arrest (CA) is associated with a high mortality rate. Even upon return of the spontaneous circulation (ROSC), APE­CA survivors are prone to myocardial cell apoptosis, a key cellular mechanism that induces heart failure. A recent study by our group discovered a post­resuscitation imbalance in the serum angiotensin­converting enzyme (ACE)2/ACE axis of the renin­angiotensin system (RAS), as well as regressive cardiac function in a porcine model of APE­CA. However, it has remained elusive how this imbalance in the ACE2/ACE axis affects myocardial cell apoptosis. In the present study, western blot and immunohistochemical analyses demonstrated that the RAS was only activated in the left myocardium, as evidenced by a decreased ACE2/ACE ratio following APE­CA and ROSC, but not the right myocardium. Ultrastructural analysis confirmed myocardial apoptosis in the left and right myocardium. Furthermore, B­cell lymphoma 2 (Bcl­2)­associated X protein (Bax) and caspase­3 levels were elevated and Bcl­2 levels were decreased in the left myocardium following APE­CA and ROSC. Treatment with the ACE inhibitor captopril for 30 min after initiation of ROSC prevented the increase in Bax and the decrease in Bcl­2 in the left myocardium compared with that in saline­treated pigs. Captopril also inhibited the activation of extracellular signal­regulated kinase (ERK)1/2 in the left myocardium. The results of the present study suggest that an imbalance in the ACE2/ACE axis has an important role in myocardial apoptosis following APE­CA, which may be attributed to decreased ERK1/2 activation. In addition, it was indicated that captopril prevents apoptosis in the left myocardium after ROSC.

[CT observation of retromaxillary posterior ethmoid].

Objective:To investigate the morphologic characteristics of the retromaxillary posterior ethmoid.Method:A total of 103 outpatients encountered in our hospital during March 2012 and December 2012,who completed paranasal sinus CT examination,were included in this study.Patients had no sinus trauma,surgery or tumor history.Their paranasal sinus CT scans were analyzed from scheduled axial and coronal plane.The incidence and imaging features of the retromaxillary posterior ethmoid were observed.Result:The retromaxillary posterior ethmoid(RMPE)was the posterior ethmoid cell that expanded along the lamina papyracea toward the infraorbital region.RMPE was located behind the posterior wall of the maxillary sinus and under the orbital floor.The occurrence rate of the RMPE was 74.3%.The ethmomaxillary septum is the bony septum the between the maxillary sinus and posterior ethmoid.Anatomical confirmation of RMPE is based mainly on the presence of the ethmomaxillary septum.RMPE is located at the back of ethmomaxillary septum.The sagittal angulation of the ethmomaxillary septum ranged from 22 to 87 degrees,with an average of(50.34±12.10)degrees.Conclusion:The ethmomaxillary septum is important for anatomic recognition of the RMPE.Accurate identification of the RMPE before ESS can help improve the removal of the posterior ethmoid sinus.

Association between ACE2/ACE balance and pneumocyte apoptosis in a porcine model of acute pulmonary thromboembolism with cardiac arrest.

Acute pulmonary embolism (APE) is frequently reported in patients with cardiac arrest (CA) in emergency care. Pneumocyte apoptosis is commonly observed in the lungs following an APE. An important pathological mechanism evoking apoptosis during a lipopolysaccharide­induced acute lung injury is the angiotensin­converting enzyme 2 (ACE2)/ACE imbalance. The present study uses a porcine model to examine the anti­apoptotic effects of captopril on APE­CA and the return of spontaneous circulation (ROSC). Pigs were randomly assigned into four groups: Control, APE­CA, ROSC­saline, and ROSC­captopril. Surviving pigs were euthanized at 6 h and lungs were isolated for analysis using several biochemical assays. Compared with the control group, the ACE2/ACE ratio was lower in the APE­CA and ROSC pigs. In addition, APE­CA pigs had higher Bcl­2­associated X protein (Bax) and cleaved caspase­3 levels, and lower B­cell lymphoma­2 (Bcl­2) level compared to control pigs. Captopril treatment reduced lung apoptosis, as demonstrated by lower TUNEL­positive cells, higher Bcl­2, and lower cleaved caspase­3 protein levels in the lung. Notably, the ACE2/ACE ratio was positively correlated with Bcl­2 protein levels and Bcl­2/Bax ratio. In conclusion, captopril has a protective effect against lung apoptosis following ROSC and that maintaining the balance of the ACE2/ACE axis is important for inhibiting pulmonary apoptosis during APE.

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

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.