The effect of isosorbide dinitrate on cardiac function after cardiopulmonary resuscitation in a porcine model / 中华急诊医学杂志

Objective To assess the effect of isosorbide dinitrate on the improvement of cardiac function after cardiopulmonary resuscitation (CPR) by regulating myocardial cells apoptosis..Methods Total of 30 domestic pigs were divided into three groups randomly (random mumber) after anesthetization:the sham group (n=6),the control group (n=12),and the isosorbide dinitrate group (n=12).Cardiac arrest of ventricular fibrillation was induced by programed electrical stimulation in the control and isosorbide dinitrate groups.Isosorbide dinitrate was infused at the rate of 2 μg/(kg·min) in the isosorbide dinitrate group.Coronary perfusion pressure (CPP) and cardiac output (CO) were recorded at baseline,2,6,12 and 24 h after restoration of spontaneous circulation (ROSC).Myocardial enzyme and heart fatty acid binding protein (H-FABP) was tested at the same time points.At 24 h after ROSC,the animals were sacrificed to obtain the myocardium for pathological section and Western blot.The expression of Bcl-2,Bax and activated Caspase-3 were tested and apoptosis was tested by TUNEL and apoptosis index was calculated.Results Right atrial pressure (RAP) increased after ROSC and decreased in the isosorbide dinitrate group compared with the control group (P＜0.05).CPP at 12,24 h after ROSC and CO at 24 h after ROSC in the isosorbide dinitrate group increased significantly compared with the control group (both P＜0.05).HE staining revealed that the injury of myocardial cells was ameliorated in the isosorbide dinitrate group.Apoptosis index of the isosorbide dinitrate group significantly decreased than the control group [(37.8±15.5)％ vs (13.1±0.5)％,P＜0.05].The expression of Bax and activated Caspase-3 decreased while Bcl-2 and Bcl-2/Bax increased after ROSC in the isosorbide dinitrate group compared with the control group (all P＜0.05).Conclusions Isosorbide dinitrate could improve the isehemia/reperfusion injury and cardiac function after ROSC by inhibiting apoptosis regulated with Caspase-3 pathway.

A Novel Porcine Model of Septic Shock Induced by Acute Respiratory Distress Syndrome due to Methicillin-resistant / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Sepsis is one of the main causes of mortality in critically ill patients following progression to septic shock. To investigate the pathophysiologic changes of sepsis, we developed a novel porcine model of septic shock induced by acute respiratory distress syndrome (ARDS) due to methicillin-resistant Staphylococcus aureus(MRSA) pneumonia.</p><p><b>METHODS</b>Twenty-six male Landraces (Lvyuanweiye, Beijing, China) weighing 30 ± 2 kg were divided into four groups: sham group (SH; n = 5); cotton smoke inhalation group (SM; n = 6); MRSA pneumonia group (MR; n = 6); and septic shock group with cotton smoke inhalation + MRSA pneumonia (SS; n = 9). Extensive hemodynamics, oxygen dynamics, and lung function were monitored for 24 h following the injury or until death. Tissues were collected, and histopathology evaluations were carried out.</p><p><b>RESULTS</b>Blood cultures from 6 of 9 animals in the SS group were positive for MRSA. Two hours following the injury, decreased mean arterial blood pressure (60-70 mmHg) and cardiac index (<2 L.min-1.m-2) were observed in the animals in the SS group, while systemic vascular resistance index was increased. The hemodynamic characteristics of septic shock were only observed in the SS group but not significant in the other groups. The PO2/FiO2in the SM and SS groups decreased to 300 and 100, respectively. In the SS group, extravascular lung water index increased to 20 ml/kg, whereas thoracopulmonary compliance decreased to 10 ml/H2O after injury. Deterioration of pulmonary function in the SS group was more serious than the SM and MR groups. Severe lung injury in the SS group was confirmed by the histopathology evaluations. The lung injury confirmed by high-resolution thin-section computed tomography and histopathology in the SS group was more serious than those of other groups.</p><p><b>CONCLUSIONS</b>In the present study, we developed a novel porcine model of septic shock induced by ARDS due to severe MRSA pneumonia with characteristic hyperdynamic and hypodynamic phases in 24 h, which mimicked the hemodynamic changing of septic shock in human.</p>

Effects of Shenfu Injection () on cerebral metabolism in a porcine model of cardiac arrest / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of Shenfu Injection (, SFI) on cerebral metabolism in a porcine model of cardiac arrest (CA).</p><p><b>METHODS</b>Thirty Wuzhishan minipigs were randomly assigned to the control group (n=6), epinephrine group (EP group, n=12) and Sfigroup (n=12). After 8 min of untreated ventricular fifibrillation (VF), pigs in the EP group or Sfigroup were administered with either EP (0.02 mg/kg) or Sfi(1.0 mL/kg), respectively. After successful resuscitation, cerebrospinal fluid (CSF) levels of glucose, pyruvate, lactate, glutamate and glycerol were measured at 1, 6, 12 and 24 h after recover from spontaneous circulation (ROSC). In addition, neurologic defificit score (NDS) was calculated at 24 h after ROSC. Surviving pigs were killed at 24 h after ROSC, and the brain tissue was obtained for ultra-microstructure examination.</p><p><b>RESULTS</b>Compared with the EP group, CSF glucose and pyruvate levels were higher (all P<0.01), and lactate levels were lower in the Sfigroup (P<0.01). Meanwhile, CSF glutamate and glycerol levels in the Sfigroup were lower in comparison to the EP group (all P<0.05). In addition, Sfidecreased NDS at 24 h after ROSC (P<0.01), and alleviated the histopathological damage of the brain.</p><p><b>CONCLUSIONS</b>Sficould alleviate brain injury after CA, which may be associated with improving cerebral metabolism.</p>

Comparison of Cerebral Metabolism between Pig Ventricular Fibrillation and Asphyxial Cardiac Arrest Models / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Morbidity and mortality after resuscitation largely depend on the recovery of brain function. Ventricular fibrillation cardiac arrest (VFCA) and asphyxial cardiac arrest (ACA) are the two most prevalent causes of sudden cardiac death. Up to now, most studies have focused on VFCA. However, results from the two models have been largely variable. So, it is necessary to characterize the features of postresuscitation cerebral metabolism of both models.</p><p><b>METHODS</b>Forty-four Wuzhishan miniature inbred pigs were randomly divided into three groups: 18 for VFCA group, ACA group, respectively, and other 8 for sham-operated group (SHAM). VFCA was induced by programmed electric stimulation, and ACA was induced by endotracheal tube clamping. After 8 min without treatment, standard cardiopulmonary resuscitation (CPR) was initiated. Following neurological deficit scores (NDS) were evaluated at 24 h after achievement of spontaneous circulation, cerebral metabolism showed as the maximum standardized uptake value (SUVmax) was measured by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography. Levels of serum markers of brain injury, neuron specific enolase (NSE), and S100β were quantified with an enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>Compared with VFCA group, fewer ACA animals achieved restoration of spontaneous circulation (61.1% vs. 94.4%, P < 0.01) and survived 24-h after resuscitation (38.9% vs. 77.8%, P < 0.01) with worse neurological outcome (NDS: 244.3 ± 15.3 vs. 168.8 ± 9.71, P < 0.01). The CPR duration of ACA group was longer than that of VFCA group (8.1 ± 1.2 min vs. 4.5 ± 1.1 min, P < 0.01). Cerebral energy metabolism showed as SUVmax in ACA was lower than in VFCA (P < 0.05 or P < 0.01). Higher serum biomarkers of brain damage (NSE, S100β) were found in ACA than VFCA after resuscitation (P < 0.01).</p><p><b>CONCLUSIONS</b>Compared with VFCA, ACA causes more severe cerebral metabolism injuries with less successful resuscitation and worse neurological outcome.</p>

Renal Doppler and Novel Biomarkers to Assess Acute Kidney Injury in a Swine Model of Ventricular Fibrillation Cardiac Arrest / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Majority of the research on cardiac arrest (CA) have focused on post-CA brain injury and myocardial dysfunction, the renal dysfunction and acute kidney injury (AKI) in other critical illnesses after CA have not been well described. This study was designed to assess AKI with renal Doppler and novel AKI biomarkers in a swine model of ventricular fibrillation cardiac arrest (VFCA).</p><p><b>METHODS</b>Thirty healthy piglets were divided into VFCA group (n = 22) and Sham group (n = 8) in a blinded manner. Mean arterial pressure, heart rate, and cardiac output were recorded continuously. Cardiac arrest (CA) was induced by programmed electric stimulation in the VFCA group, and then cardiopulmonary resuscitation was performed. Twenty piglets returned of spontaneous circulation (ROSC) and received intensive care. Blood and urine samples were collected for AKI biomarkers testing, and Color Doppler flow imaging was performed at baseline, 6 h, 12 h, and 24 h, respectively after ROSC. At ROSC 24 h, the animals were sacrificed and a semi-quantitative evaluation of pathologic kidney injury was performed.</p><p><b>RESULTS</b>In the VFCA group, corrected resistive index (cRI) increased from 0.47 ± 0.03 to 0.64 ± 0.06, and pulsatility index (PI) decreased from 0.82 ± 0.03 to 0.68 ± 0.04 after ROSC. Cystatin C (CysC) in both serum and urine samples increased at ROSC 6 h, but neutrophil gelatinase-associated lipocalin (NGAL) in serum increased to 5.34 ± 1.68 ng/ml at ROSC 6 h, and then decreased to 3.16 ± 0.69 ng/ml at ROSC 24 h while CysC increasing constantly. According to the renal histopathology, 18 of 20 animals suffered from kidney injury. The grade of renal injury was highly correlated with RI, cRI, NGAL, and CysC. Linear regression equation was established: Grade of renal injury = 0.002 × serum CysC + 6.489 × PI + 4.544 × cRI - 8.358 (r2 = 0.698, F = 18.506, P < 0.001).</p><p><b>CONCLUSIONS</b>AKI is common in post-CA syndrome. Renal Doppler and novel AKI biomarkers in serum and urine are of significant importance as early predictors of post-CA AKI.</p>

Neuroprotective effect of Shenfu Injection () following cardiac arrest in pig correlates with improved mitochondrial function and cerebral glucose uptake / 中国结合医学杂志

<p><b>OBJECTIVE</b>To test whether Shenfu Injection (, SFI) might attenuate the impact of cerebral energy dysfunction after resuscitation in a pig model of cardiac arrest (CA).</p><p><b>METHODS</b>Thirty-four Wuzhishan miniature inbred pigs were randomly divided into three groups: the SFI group (n=12), the saline group (SA group, n=12), and the sham-operated group (sham group, n=10). Following successful return of spontaneous circulation (ROSC) from 8-min untreated ventricular fibrillation, animals received a continuous infusion of either SFI (0.2 mL/min) or saline for 6 h. Cerebral performance category score was evaluated at 24 and 48 h after ROSC, followed by positron emission tomography and computed tomography scans of cerebral glucose uptake. Surviving pigs were euthanized 48 h after ROSC, and the brains were removed for detecting mitochondrial function.</p><p><b>RESULTS</b>Compared with the SA group, SFI treatment produced a better neurologic outcome 48 h after ROSC (P<0.05). However, there was no significant difference of survival rate between the SA and SFI groups (83.3% vs. 81.8%, P>0.05). After ROSC, the SA group showed a decrease in the maximum standardized uptake value of different regions in the brain tissue, where SFI treatment can ameliorate these decreases (P<0.01 or P<0.05). Improved mitochondrial respiratory properties and higher mitochondrial membrane potential were also found following SFI treatment compared with the SA group at 48 h after ROSC (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>SFI treatment after resuscitation has significant neuroprotective effects against disruption of cerebral energy metabolism from CA by improving glucose uptake and by normalizing mitochondrial function.</p>