Lu Xie

Naloxone and epinephrine are equally effective for cardiopulmonary resuscitation in a rat asphyxia model

Background:  It is not known whether naloxone is as efficacious as epinephrine during cardiopulmonary resuscitation (CPR). The aim of the study was to compare the effects of naloxone and epinephrine on the outcomes of CPR following asphyxial cardiac arrest in rats.

What is the optimal dose of epinephrine during cardiopulmonary resuscitation in a rat model

OBJECTIVE Because different species may require different doses of drug to produce the same physiologic response, we were provoked to evaluate the dose-response of epinephrine during cardiopulmonary resuscitation (CPR) and identify what is the optimal dose of epinephrine in a rat cardiac arrest model. METHODS Rat cardiac arrest was induced via asphyxia, and then the effects of different doses of epinephrine (0.04, 0.2, and 0.4 mg/kg IV, respectively) and saline on the outcome of CPR were compared (n = 10/each group). The primary outcome measure was restoration of spontaneous circulation (ROSC), and the secondary was the change of spontaneous respiration and hemodynamics after ROSC. RESULTS Rates of ROSC were 9 of 10, 8 of 10, 7 of 10, and 1 of 10 in the low-dose, medium-dose, and high-dose epinephrine groups and saline group, respectively. The rates of withdrawal from the ventilator within 60 minutes in the low-dose (7 of 9) and medium-dose epinephrine groups (7 of 8) were higher than in the high-dose epinephrine group (1 of 7, P < .05). Mean arterial pressures were comparable, but the heart rate in the high-dose epinephrine group was the lowest among epinephrine groups after ROSC. These differences in part of time points reached statistical significance (P < .05). CONCLUSION Different doses of epinephrine produced the similar rate of ROSC, but high-dose epinephrine inhibited the recovery of spontaneous ventilation and caused relative bradycardia after CPR in an asphyxial rat model. Therefore, low and medium doses of epinephrine were more optimal for CPR in a rat asphyxial cardiac arrest model.

PD98059 Protects Brain against Cells Death Resulting from ROS/ERK Activation in a Cardiac Arrest Rat Model.

The clinical and experimental postcardiac arrest treatment has not reached therapeutic success. The present study investigated the effect of PD98059 (PD) in rats subjected to cardiac arrest (CA)/cardiopulmonary resuscitation (CPR). Experimental rats were divided randomly into 3 groups: sham, CA, and PD. The rats except for sham group were subjected to CA for 5 min followed by CPR operation. Once spontaneous circulation was restored, saline and PD were injected in CA and PD groups, respectively. The survival rates and neurologic deficit scores (NDS) were observed, and the following indices of brain tissue were evaluated: ROS, MDA, SOD, p-ERK1/2/ERK1/2, caspase-3, Bax, Bcl-2, TUNEL positive cells, and double fluorescent staining of p-ERK/TUNEL. Our results indicated that PD treatment significantly reduced apoptotic neurons and improved the survival rates and NDS. Moreover, PD markedly downregulated the ROS, MDA, p-ERK, and caspase-3, Bax and upregulated SOD and Bcl-2 levels. Double staining p-ERK/TUNEL in choroid plexus and cortex showed that cell death is dependent on ERK activation. The findings in present study demonstrated that PD provides neuroprotection via antioxidant activity and antiapoptosis in rats subjected to CA/CPR.

Edaravone improves survival and neurological outcomes after CPR in a ventricular fibrillation model of rats

OBJECTIVE Overproduction of free radicals is a main factor contributing to cerebral injury after cardiac arrest (CA)/cardiopulmonary resuscitation (CPR). We sought to evaluate the impact of edaravone on the survival and neurological outcomes after CA/CPR in rats. METHODS Rats were subjected to CA following CPR. For survival study, the rats with restoration of spontaneous circulation (ROSC) were randomly allocated to one of the two groups (edaravone and saline group, n=20/each group) to received Edaravone (3 mg/kg) or normal saline. Another 10 rats without experiencing CA and CPR served as the sham group. Survival was observed for 72 hours and the neurological deficit score (NDS) was calculated at 12, 24, 48, and 72 hours after ROSC. For the neurological biochemical analysis study, rats were subjected to the same experimental procedures. Then, edaravone group (n=24), saline group (n=24) and sham group (n=16) were further divided into 4 subgroups according to the different time intervals (12, 24, 48, and 72 hours following ROSC). Brain tissues were harvested at relative time intervals for evaluation of oxidative stress, TUNEL staining and apoptotic gene expression. RESULTS Edaravone improved postresuscitative survival time and neurological deficit, decreased brain malonylaldehyde level, increased superoxide dismutase activities, decreased proapoptotic gene expression of capase-8, capase-3, and Bax, and increased antiapoptotic Bcl-2 expression at 12, 24, 48, and 72 hours after ROSC. CONCLUSIONS Edaravone improves survival and neurological outcomes following CPR via antioxidative and antiapoptotic effects in rats.

The benefits of respective and combined use of green tea polyphenols and ERK inhibitor on the survival and neurologic outcomes in cardiac arrest rats induced by ventricular fibrillation.

BACKGROUND Cerebral injury is a main factor contributing to a high mortality after cardiac arrest (CA)/cardiopulmonary resuscitation (CPR). OBJECTIVE We sought to evaluate the effect of green tea polyphenols (GTPs) and ERK1/2 inhibitor PD98059 (PD) on the survival and neurologic outcomes after CA/CPR in rats. METHODS First, rats were subjected to CA after CPR. The rats that restored spontaneous circulation were blindly allocated to the saline group (saline, IV, n = 12), the GTP group (GTPs, 10 mg/kg, IV, n = 12), the PD group (PD, 0.3 mg/kg, IV, n = 12), and the GTPs + PD group (GTPs, 10 mg/kg; PD, 0.3 mg/kg, IV, n = 12). Another 12 rats without experiencing CA and CPR were served as a sham group. Survival and the neurologic deficit score were observed for 72 hours after restoration of spontaneous circulation. Second, same experimental procedures were performed, and in 1 of 5 groups, animals were divided into 4 subgroups further according to the different time points (12, 24, 48, and 72 hours after restoration of spontaneous circulation [ROSC], n = 6/group). Brain tissues were harvested at relative time points for the morphologic evaluation as well as reactive oxygen species (ROS), malonylaldehyde, and superoxide dismutase (SOD) measurement. RESULTS Green tea polyphenols, PD, and a combination of GTPs and PD used after ROSC alleviated the morphologic changes of the cerebrum. These 3 treatments also decreased the productions of ROS and malonylaldehyde, increased SOD activities in cerebral tissues, and improved the neurologic deficit and survival rates at 12, 24, 48, and 72 hours after ROSC. CONCLUSIONS Administration of GTPs and PD after ROSC can alleviate cerebral injury, improve the survival and neurologic outcomes via reduction of ROS, and increase of SOD activity in a rat CA/CPR model.

Dose-response of vasopressin in a rat model of asphyxial cardiac arrest.

The advantage of vasopressin over epinephrine in the treatment of cardiac arrest (CA) is still being debated, and it is not clear whether a high dose of vasopressin is beneficial or detrimental during or after cardiopulmonary resuscitation (CPR) in a rat model of CA. In this study, asphyxial CA was induced in 40 male Sprague-Dawley rats. After 10 minutes of asphyxia, CPR was initiated; and the effects of different doses of vasopressin (low dose, 0.4 U/kg; medium dose, 0.8 U/kg; and high dose, 2.4 U/kg; intravenous; n = 10 in each group) and a saline control (isotonic sodium chloride solution, 1 mL, intravenous) were compared. Outcome measures included the rate of restoration of spontaneous circulation (ROSC) and changes of hemodynamic and respiratory variables after ROSC. The rates of ROSC were 1 of 10 in the saline group and 8 of 10 in each of the 3 vasopressin groups. There were no differences in mean aortic pressure or changes of respiratory function after CPR among the vasopressin groups. However, the heart rate was lower in the high-dose vasopressin group than in the low- and medium-dose groups. These findings indicate that different doses of vasopressin result in a similar outcome of CPR, with no additional benefits afforded by a high dose of vasopressin during or after CPR, in a rat model of asphyxial CA. The mechanism and physiologic significance of the relative bradycardia that occurred in the high-dose vasopressin group are currently unknown and require further investigation.

Elevated Serum Potassium Concentration Alleviates Cerebral Ischemia-Reperfusion Injury via Mitochondrial Preservation

Background/Aims: The anti-apoptotic effect of an increase in the extracellular concentration of potassium ([K+]) has been confirmed in vitro. However, it is not yet known whether elevated serum [K+] exerts a cerebroprotective effect in vivo. In this study, we aimed to explore the effect of elevated serum [K+] in a rat model of middle cerebral artery occlusion and reperfusion (MCAO/R). Methods: Rats subjected to 90-min MCAO received 2.5% KCL, 1.25% KCL, or a normal saline solution at a dose of 3.2 mL/kg at the onset of reperfusion. Rats that were subjected to vascular exposure and ligation without MCAO were defined as the Sham group. Serum [K+] was determined using a blood gas analyzer at 1 min after medicine administration. At 24 h post-reperfusion, rat brains were harvested and processed for 2% 2,3,5-triphenyltetrazolium chloride staining, terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling staining, detection of caspase-3 and cleaved-caspase-3 by western blotting, detection of reactive oxygen species (ROS) by dihydroethidium staining, and observation of mitochondrial structure by electron microscopy. In addition, malondialdehyde (MDA), adenosine triphosphate (ATP), total superoxide dismutase (T-SOD), cytochrome C oxidase (COX) activity, and mitochondrial permeability transition pore (MPTP) opening were measured using detection kits. Results: The results showed that elevated serum [K+] decreased cerebral injury and apoptosis, reduced ROS and MDA levels and MPTP opening, increased ATP levels and cytochrome C oxidase activity, and improved mitochondrial ultrastructural changes, although there was no significant difference in T-SOD activity. Conclusion: These findings suggested that elevated serum [K+] could alleviate cerebral ischemia-reperfusion injury and the mechanism may be associated with the preservation of mitochondrial function.

Tea polyphenols alleviate oxidant injury following CPR in an asphyxia rat model

Background Cerebral ischemia/reperfusion injury following cardiac arrest and cardiopulmonary resuscitation (CPR) have been demonstrated. Oxidant injury plays a critical role in the process. We have reported that tea polyphenols from green tea improved the survival time and neurological deficit score of CPR in an asphyxia rat model. However, whether it acts via preventing the oxidising reaction by its phenolic hydroxyl group combined of oxygen free radicals and lipid peroxides in this model remains unknown. Therefore, we hypothesised that tea polyphenols would counteract the oxidant injury. Methods Male Sprague–Dawley rats, weighing 200–400 g, were induced cardiac arrest by clamping the trachyeal tubes. At the end of 8 min of clamping, mechanical chest compression at a rate of 180/min was performed. Ventilation was started with room air at 70 breaths per min and tidal volume adjusted to 6 ml. Epinephrine was administered at 1 min of CPR. Animals were randomly treated with either saline (n=52, Sal-gro) or 10mg/kg tea polyphenols (n=24, TP-gro) following ROSC. Animals in the sham control group (n=15, Con-gro) were only treated with anesthesia, and underwent surgical operation. Each group was divided into 3 groups according to the 12h, 24h, 48h points with five rats respectively. The changes of Superoxide Dismutase (SOD), Malondialdehyde (MDA) in serum were assayed. Results There were no significant differences in regard to hemodynamics among three groups before asphyxia. Time from the initiation of asphyxia to cardiac arrest and the duration of CPR were not significant among the groups. However, SOD of serum at 12h, 24h, 48 h following ROSC was significantly higher in TP-gro than in sal-group (p<0.05), the level of serum MDA at each point following ROSC was significantly lower in TP-gro than in that of sal-gro (p<0.05). Conclusion Tea ployphenols alleviated oxidant injury following CPR in an asphyxial rat model.