Lack of a neuroprotective effect from N-acetylcysteine after cardiac arrest and resuscitation in a canine model.

Objective: Oxygen free radicals cause brain injury following resuscitation from cardiac arrest. In preclinical trials, some free radical scavenging drugs reduce oxidative neuronal damage after ischemia and reperfusion, but these drugs are generally not yet available for clinical testing or use. N-Acetylcysteine (NAC), a commonly used antidote in acetaminophen poisoning, is also a potent free radical scavenger that can ameliorate oxidative injury following ischemia and reperfusion in neuronal cell culture. We hypothesized that treatment with NAC would improve neurological outcome after cardiac arrest and resuscitation. Methods: In 16 adult female beagles, 10 min of ventricular fibrillation was followed by 3 min of open-chest CPR, and defibrillation. Immediately following return of spontaneous circulation, animals randomly received either 150 mg/kg NAC (3% solution) (n=8) or an equivalent volume of normal saline (n=8). Twenty-three hours later, neurological deficit was scored (0=normal, 100=brain death). Results: All animals were successfully resuscitated, and there were no apparent adverse effects to the administration of NAC in post resuscitative animals. There was, however, no significant difference in neurological deficit in the animals receiving NAC (40±12.9, mean±SD) compared to control animals (44±6.5, P=0.73). Conclusion: No neuroprotective effect was found from the administration of NAC at currently used clinical dosages, to dogs subjected to 10 min of global cerebral ischemia from cardiac arrest and resuscitation.     

Effects of naloxone on the adrenomedullary response during and after cardiopulmonary resuscitation in dogs

To determine the effects of naloxone, an opiate antagonist, on the adrenomedullary response to cardiac arrest, plasma epinephrine and norepinephrine levels were measured before, during, and after cardiac arrest in dogs. Ventricular fibrillation was induced in 12 dogs anesthetized with pentobarital sodium (30 mg/kg) and standard American Heart Association cardiopulmonary resuscitation (CPR) was begun using a mechanical device. At 6.5 minutes of CPR, naloxone (10 mg/kg) or 0.9% saline (10 ml) was given intravenously. At 12 minutes of CPR, the cardiac ventricles were electrically defibrillated. Plasma epinephrine and norepinephrine levels were measured before ventricular fibrillation; at 2.5, 4.5, 9.5, and 11.5, minutes of CPR; and at 5, 10, 15, and 20 minutes after resuscitation. Epinephrine and norepinephrine increased from prearrest levels of 3.66 +/- 0.67 (+/- SE) and 24.02 +/- 3.67 ng/ml to 66.67 +/- 9.65 and 74.00 +/- 9.91 ng/ml, respectively, at 4.5 minutes of CPR. After resuscitation, norepinephrine levels remained slightly elevated, while epinephrine fell to prearrest levels. Naloxone did not cause a significant change in either epinephrine or norepinephrine from 6.5 minutes of CPR (time of treatment) through 20 minutes postresuscitation. In addition, naloxone had no effect on either the end-diastolic pressure difference during CPR or resuscitation outcome. We conclude that cardiac arrest causes significant increases in plasma epinephrine and norepinephrine levels, which remain elevated for the duration of the arrest, and that naloxone has no effect on these levels.     

Thrombolysis using plasminogen activator and heparin reduces cerebral no-reflow after resuscitation from cardiac arrest: An experimental study in the cat

Objective Successful resuscitation of the brain requires complete microcirculatory reperfusion, which, however, may be impaired by activation of blood coagulation after cardiac arrest. The study addresses the question of whether postischemic thrombolysis is effective in reducing cerebral noreflow phenomenon.Design 14 adult normothermic cats were submitted to 15-min cardiac arrest, followed by cardiopulmonary resuscitation (CPR) and 30 min of spontaneous recirculation. The CPR protocol included closed-chest cardiac massage, administration of epinephrine 0.2 mg/kg, bicarbonate 2mEq/kg per 30 min, and electrical defibrillation shocks.Interventions During CPR, animals in the treatment group (n=6) received intravenous bolus injections of 100 U/kg heparin and 1 mg/kg recombinant tissue type plasminogen activator (rt-PA), followed by an infusion of rt-PA 1mg/kg per 30 min.Measurements and results Microcirculatory reperfusion of the brain was visualized by labeling the circulating blood with 300 mg/kg of 15% fluorescein isothiocyanate albumin at the end of the recirculation period. Areas of cerebral noreflow — defined as the absence of microvascular filling — were identified by fluorescence microscopy at eight standard coronal levels of forebrain, and expressed as the percentage of total sectional area. One animal in the treatment group was excluded from further analysis because of intracerebral hemorrhage due to brain injury during trepanation. Autopsy revealed the absence of intracranial, intrathoracic, or intra-abdominal bleeding in all the other animals. In untreated animals (n=8), no-reflow affected 28±13% of total forebrain sectional areas, and only 1 out of 8 animals showed homogeneous reperfusion (i.e., no-reflow <15% of total forebrain sectional areas). Thrombolytic therapy (n=5) significantly reduced no-reflow to 7±5% of total forebrain sectional areas and all treated animals showed homogeneous reperfusion at the microcirculatory level.Conclusions The present data demonstrate that thrombolytic therapy improves microcirculatory reperfusion of the cat brain when administered during reperfusion after cardiac arrest.Presented in part at the 1994 Annual Meeting of the American Society of Anesthesiologists, 18 October 1994, Washington, DC, and at the 39th Annual Meeting of the German Association of Thrombosis and Hemostasis, 17 February 1995, Berlin, Germany     

Aortic-carotid artery pressure differences and cephalic perfusion pressure during cardiopulmonary resuscitation in humans.

OBJECTIVE: Animal studies have shown an aortic-carotid artery pressure difference during cardiopulmonary resuscitation (CPR), which compromises cerebral perfusion. This pressure difference is most marked with prolonged CPR and can be abolished with administration of high doses of epinephrine. To better understand the mechanism of cerebral blood flow during CPR in humans, we determined the aortic-carotid artery pressure difference, the cephalic perfusion pressure (the carotid artery-jugular vein pressure difference), and thoracic inlet venous "valving" (the central venous-jugular vein pressure difference), while administering standard doses of epinephrine. DESIGN: Prospective study with randomization as to which side the carotid artery was catheterized. SETTING: The resuscitation room of a large urban hospital's emergency department. PATIENTS: Fifteen adults in normothermic, nontraumatic prehospital cardiac arrest treated according to Advanced Cardiac Life Support guidelines, including administration of 1 mg epinephrine iv every 5 mins. INTERVENTIONS: The descending aorta, cervical common carotid artery, internal jugular vein, and central venous system were catheterized. Pressures were recorded during standard CPR for 5 mins after administration of 1 mg epinephrine iv. MEASUREMENTS AND MAIN RESULTS: Most patients received CPR for greater than 20 mins before the first epinephrine dose and for greater than 45 mins before pressure recording as described above. There was no significant difference between aortic and carotid artery compression and relaxation phase pressures. The mean +/- SD compression central venous-jugular vein pressure difference was 22.1 +/- 15.0 mm Hg, and the mean cephalic perfusion pressure was 20.8 +/- 19.5 mm Hg. CONCLUSIONS: There is no clinically important aortic-carotid artery pressure difference during human CPR using the standard dose of epinephrine, even with prolonged CPR. Despite carotid artery patency and thoracic inlet venous valving, the cephalic perfusion pressure is low during CPR in humans.     

Effects of epinephrine in a pig model of hypothermic cardiac arrest and closed-chest cardiopulmonary resuscitation combined with active rewarming

OBJECTIVE: The aim of the current study was to assess the effects of epinephrine in a pig model of hypothermic cardiac arrest followed by closed-chest cardiopulmonary resuscitation combined with active rewarming, simulating the clinical management of an arrested hypothermic patient in a hospital without cardiopulmonary bypass facilities. DESIGN: Prospective, randomized animal study. SETTING: University research laboratory. SUBJECTS: Twelve 12- to 16-week-old domestic pigs. INTERVENTIONS: Pigs were surface cooled to a body core temperature of 28 degrees C. After 4 min of untreated cardiac arrest, manual closed-chest CPR and thoracic lavage with 40 degrees C warmed fluid were started. After 3 min of external chest compression animals were randomly assigned to receive epinephrine (45, 45 and 200 microg/kg) or saline placebo in 5-min intervals. MEASUREMENTS AND MAIN RESULTS: Coronary perfusion pressure was about 15 mmHg in placebo group pigs. Coronary perfusion pressure was significantly higher after epinephrine, but restoration of spontaneous circulation was not more frequent (one of six epinephrine versus three of six saline placebo pigs, P=0.34). After 45 microg/kg epinephrine the arterial PO(2) was significantly lower when compared to the saline placebo. The third 200 microg/kg epinephrine dose resulted in a significantly enhanced mixed venous hypercarbic acidosis. CONCLUSIONS: After a short 4-min period of hypothermic cardiac arrest, epinephrine may not be necessary to maintain coronary perfusion pressure around the threshold usually correlating with successful defibrillation, even during prolonged closed-chest CPR combined with active rewarming. The enhanced mixed venous hypercarbic acidosis in epinephrine-treated animals may support the argument against repeated or high dose epinephrine administration during hypothermic CPR.     

Arterial blood gases during cardiac arrest: markers of blood flow in a canine model.

Measures of CO2 have been shown to correlate with coronary perfusion pressure and cardiac output during cardiac arrest. We evaluated arterial pH (pHa) relative to blood flow during cardiac arrest in a canine electromechanical dissociation (EMD) model of cardiac arrest using different resuscitation techniques. Following 15 min of cardiac arrest, 24 mongrel dogs received epinephrine with continued CPR or closed-chest cardiopulmonary bypass. Central arterial blood gases, end-tidal carbon dioxide (PetCO2), coronary perfusion pressure and cardiac output were measured. During CPR, prior to epinephrine or bypass, there was no correlation of pHa, PACO2 and PetCO2, with cardiac output or coronary perfusion pressure. Immediately after instituting the resuscitation techniques, both pHa and PaCO2 showed a significant correlation with cardiac output (pHa; R = -0.78, P less than 0.001 and PaCO2; R = 0.87, P less than 0.001) and with coronary perfusion pressure (pHa; R = -0.75, P less than 0.001 and PaCO2; R = 0.75, P less than 0.001). Eventual survivors (n = 15) had an early significant decrease in pHa, base excess and a significant increase in PaCO2 which was not present in non-survivors (n = 9). Neither pHa nor PaCO2 correlate with blood flow under low flow conditions of CPR. However, with effective circulatory assistance, pHa and PaCO2 reflect systemic blood flow and reperfusion washout.     

Periodic acceleration (pGz) CPR in a swine model of asphyxia induced cardiac arrest. Short-term hemodynamic comparisons

BACKGROUND: Asphyxia is one of the most common causes of pediatric cardiac arrest, and becoming a more frequently recognized cause in adults. Periodic acceleration (pGz) is a novel method of cardiopulmonary resuscitation (CPR). pGz is achieved by rapid motion of the supine body headward-footward that generates adequate perfusion and ventilation during cardiac arrest. In a swine ventricular fibrillation cardiac arrest model, pGz produced a higher return of spontaneous circulation (ROSC), superior neurological outcome, less echocardiography evidence of post resuscitation myocardial stunning, and decreased indices of tissue injury. In contrast to standard chest compression CPR, pGz does not produce rib fractures. We investigated the feasibility of pGz in severe asphyxia cardiac arrest and assessed whether beneficial effects seen in the VF model of cardiac arrest could be realized. METHODS AND RESULTS: Sixteen swine weight 4+/-1 kg were anesthetized, tracheally intubated, and instrumented to measure, hemodynamics and echocardiography. Asphyxia was induced by occlusion of the tracheal tube. After loss of aortic pulsations (median time 10 min) animals were observed for three additional minutes following which all were in cardiac arrest. The animals were then randomized to receive 10 min of pGz or standard chest compression ventilation performed with a commercial device (Thumper). A single dose of epinephrine (adrenaline) and sodium bicarbonate were given and defibrillation attempted if appropriate for a maximum of 10 min. Both groups received fractional inspired O2 concentration of 100% during CPR and after resuscitation. Four animals in each group (50%) had an initial ROSC, however only two of the four initial survivors remained alive 3h after ROSC. There were no significant differences in blood pressure, coronary perfusion pressure during CPR and after early ROSC between groups. pGz treated animals had significantly lower pulmonary artery pressure; 20+/-4 mmHg compared to Thumper 46+/-5 mmHg, 30 min after ROSC (p<0.01). Surviving animals in both groups had severe myocardial dysfunction at 30 min after ROSC. At necropsy, 25% of the Thumper treated animals had rib fractures, while none occurred in the pGz group. CONCLUSIONS: In a lethal model of asphyxia cardiac arrest, pGz is equivalent to standard CPR, with respect to acute outcomes and resuscitation survival rates but is associated with significantly lower pulmonary artery pressures and does not produce traumatic rib fractures.     

Comparison of epinephrine and norepinephrine in the treatment of asphyxial or fibrillatory cardiac arrest in a porcine model

Many animal experiments have shown that alpha-receptor stimulation is a prerequisite for the improvement of myocardial perfusion during CPR. As there are no recent reports on the effectiveness of norepinephrine in the treatment of cardiac arrest, we investigated the effectiveness of epinephrine and norepinephrine after asphyxial or ventricular fibrillation cardiac arrest using a porcine model. After 3 min of asphyxial cardiac arrest, seven animals each received either 45 micrograms/kg epinephrine, 45 micrograms/kg norepinephrine, or placebo (controls). All drugs were given blind. All seven animals given epinephrine could be resuscitated after 174 +/- 53 sec, whereas six of seven given norepinephrine could be resuscitated after 473 +/- 116 sec. None of the seven given the placebo could be resuscitated. After 4 min of ventricular fibrillation cardiac arrest, none of the seven animals that received defibrillating countershocks at 4 min without either mechanical measures or drug therapy, and none of the seven that received CPR and countershocks but no drugs, could be resuscitated. In the group that received CPR plus 45 micrograms/kg epinephrine, defibrillation and restoration of spontaneous circulation were achieved in six of seven animals in 667 +/- 216 sec. In the group that received CPR plus 45 micrograms/kg norepinephrine, defibrillation and restoration of spontaneous circulation were achieved in all seven animals in the significantly shorter time of 86 +/- 18 sec. In this porcine model, norepinephrine appeared superior to the same dose of epinephrine in the treatment of ventricular fibrillation, with respect to resuscitation time.     

Endogenous and exogenous plasma catecholamine levels in cardiac arrest in swine

The use of epinephrine in cardiac arrest remains an area of continuing controversy. This study was undertaken to characterize the effect of endogenous and exogenous epinephrine on plasma epinephrine levels, and the relationship between plasma epinephrine and norepinephrine and mean arterial pressure and diastolic arterial pressure. Nineteen young swine were anesthetized with ketamine and alpha-chloralose and instrumented with arterial and central venous lines. Ventricular fibrillation was induced by pacemaker. At 5 min post arrest cardiopulmonary resuscitation (CPR) was begun with a mechanical resuscitator. Animals were randomized to receive either saline placebo (n = 9), 0.01 mg/kg epinephrine (n = 5) or 0.1 mg/kg epinephrine (n = 5) via the central venous line. Plasma was drawn for high pressure liquid chromatographic analysis of catecholamines every 2 min. The resuscitation was carried on for 30 min after the arrest. Plasma epinephrine levels differed significantly between treated subjects and controls, as did mean arterial pressure and diastolic arterial pressure. There was a correlation between both mean arterial pressure and diastolic arterial pressure with plasma epinephrine and log epinephrine, but no correlation with plasma norepinephrine. The two doses of epinephrine did not differ in the degree to which they elevated the mean arterial pressure and diastolic pressure. We conclude that the endogenous catecholamine response to cardiac arrest while producing norepinephrine and epinephrine levels many times greater than those in the resting animal, is not sufficient to maintain blood pressure. There is a strong correlation between blood pressure and the log of the plasma epinephrine concentration, but epinephrine concentration alone does not solely account for changes in blood pressure during arrest.     

加压素与肾上腺素在小鼠心肺复苏中的疗效比较

目的 比较加压素与肾上腺素在小鼠心肺复苏中的疗效.方法 30只雄性昆明小鼠经食道快速起搏心窒诱发室颤、建立心搏骤停模型,起搏开始后4 min将小鼠随机分成3组(n=10/组):对照组(Sal-gro)、加压素组(Vas-gro)、肾上腺素组(Epi-gro),分别经动脉注射药物(生理盐水、加压素0.4 U/kg和肾上腺素0.04mg/kg)1次,开始胸外心脏按压及机械通气,观察自主循环恢复情况,10min无效则放弃复苏.自主循环恢复的小鼠连续监测心电和血压60 min,观察血压、心率、呼吸恢复情况及生存时间.结果 加压素与肾上腺素组小鼠的自主循环恢复率均显著高于对照组(9/10,10/10和3/10,P＜0.05,P＜0.01).加压素与肾上腺素组组间比较差异无统计学意义(P＞0.05).肾上腺素组小鼠在自主循环恢复后全部出现自主呼吸,而加压素组小鼠只有4只出现自主呼吸(P＜0.05).肾上腺素组小鼠的生存时间明显长于加压素组和对照组小鼠(P＜0.05,P＜0.05).结论 加压素和肾上腺素均可显著提高心搏骤停小鼠的自主循环恢复率,但0.04 mg/kg的肾上腺素对自主循环恢复后小鼠呼吸功能及生存时间的影响明显优于0.4 U/k的加压素,其机制尚不清楚,还有待进一步研究.     

不同剂量肾上腺素对大鼠心肺复苏的影响

[目的]探讨不同剂量肾上腺素对大鼠心肺复苏的影响.[方法]选用清洁级雄性SpragueDawley（SD）大鼠32只分为两组,采用呼气末夹闭气管窒息致大鼠心脏骤停,夹闭5 min后开始心肺复苏,给予不同剂量肾上腺素（0.02 mg/kg,小剂量组;0.2 mg/kg,大剂量组）,记录心率、血压的变化,自主循环恢复（ROSC）的时间,1 h和6 h存活率.[结果]造模后约1～2 min所有大鼠均出现心脏骤停,小剂量组与大剂量组复苏成功率分别为69%和74%,ROSC时间分别为（155±78）s、（85±25）s,1 h存活率分别为89%和86%,6 h存活率分别为44%和57%.两组复苏成功率,6 h存活率相比较差异无显著性（P〉0.05）;而1 h存活率,ROSC时间相比较差异有显著性（P〈0.05）.[结论]0.2 mg/kg肾上腺素用于大鼠心肺复苏较0.02 mg/kg可明显减少心脏按压时间,缩短ROSC时间,但对提高复苏成功率和6 h存活率无明显差异,反而会降低1 h存活率.     

Compared to angiotensin II, epinephrine is associated with high myocardial blood flow following return of spontaneous circulation after cardiac arrest

INTRODUCTION: Epinephrine (adrenaline) and vasopressin are used currently to improve myocardial blood flow (MBF) during cardiac arrest. Angiotensin II has also been shown to improve MBF during CPR. We explored the effects of angiotensin II or epinephrine alone, and the combination of angiotensin with epinephrine, on myocardial and cerebral blood flows in a swine model of cardiac arrest. METHODS: Swine were instrumented for regional blood flow measurements. Ventricular fibrillation was induced and CPR begun. Angiotensin II 50 mcg/kg (ANG), epinephrine 0.02 mg/kg (EPI) or the combination (ANG+EPI) was administered. Blood flow was measured during baseline normal sinus rhythm (NSR), before (CPR) and after drug administration (CPR+DRUG), and post reperfusion return of spontaneous circulation (ROSC). RESULTS: All groups had a significant increase in MBF during CPR following drug administration (P<0.05). [table: see text] There was a trend toward higher flows in the EPI groups. The group receiving both EPI and ANG did not have higher blood flows than the EPI or ANG alone groups. Both groups that received EPI had markedly elevated MBF following ROSC compared with angiotensin II (P<0.05). CONCLUSIONS: The combination of ANG and EPI did not improve MBF during cardiac arrest. Epinephrine may increase MBF compared with angiotensin II post-reperfusion.     

山莨菪碱对心脏停搏大鼠复苏中微循环的影响

目的 观察复苏早期给予山莨菪碱(Ani)对心脏停搏(CA)大鼠肠系膜微循环和肠壁组织血流量变化的影响.方法 采用电击法制备大鼠CA模型,将实验动物随机分为4组,每组15只.待大鼠CA后4 min行呼吸机辅助呼吸、胸外按压.静脉补液复苏.对照组仅给予生理盐水;肾上腺素组(Epi组)注射Epi200 μg/kg;Epi+低剂量Ani组(低剂量Ani组)注射Epi 200 μg/kg+Ani 5 mg/kg;Epi+高剂量Ani组(高剂量Ani组)注射Epi 200 μg/kg+Ani 10 mg/kg.观察大鼠肠系膜微动、静脉血管再通率和再通血管管径及肠壁血流量.结果 微动、静脉再通率:高剂量Ani组(66.6%,60.0%)>低剂量Ani组(60.0%,53.3%)>对照组(40.0%,40.0%)>Epi组(26.7%,20.0%),Epi组与两个Ani组间差异均有统计学意义(P均<0.05).微动、静脉血管管径:自主循环恢复(ROSC)30 rain和60 min时高剂量Ani组>低剂量Ani组>对照组>Epi组.其中30 min时高、低剂量Ani组与Epi组比较差异有统计学意义(P均<0.05);60 min时低剂量Ani组微静脉血管管径与Epi组比较差异无统计学意义;高、低剂量Ani组间比较差异均无统计学意义.高、低剂量Ani组大鼠ROSC 15 min肠壁组织血液灌注量明显高于对照组和Epi组.随时问延长明显增高.持续至ROSC 60 min.结论 复苏早期给予Ani干预可改善组织微循环状态,从而提高ROSC率和复苏成功率.     

窒息家兔心肺复苏疗效与血浆内皮素变化的关系

目的探讨窒息家兔心肺复苏(cardiopulmonaryresuscitation,CPR)疗效与血浆内皮素(endothelin,ET)变化的关系。方法对62只家兔均在呼气末夹闭气管8min,造成窒息性心脏停搏模型后,开始人工胸外心脏按压及机械通气,期间不用任何药物,复苏5min内恢复自主循环(restorationof spontaneouscirculation,ROSC)的家兔定义为常规CPR成功;对5min内未能ROSC者再随机分为两组,分别给予肾上腺素(0.2mg kg)和加压素(0.8U kg)静脉注射,并继续行常规CPR。分别在窒息前和CPR15、60、120min采血测血浆ET浓度。结果常规CPR的家兔ROSC率为24.16%(1562),加用肾上腺素和加压素后总的ROSC率提高到48.39%(3062)。对常规CPR失败的家兔而言,肾上腺素疗效明显优于加压素(ROSC率分别为54.16%和8.70%,P=0.001)。但复苏成功组和复苏失败组家兔血浆ET的比较,差异无显著性。结论对窒息性心脏停搏的家兔CPR时应用肾上腺素或加压素可提高ROSC率,但肾上腺素疗效明显优于加压素。窒息家兔CPR疗效与血浆内皮素变化无明显相关关系。     

Cardiovascular response to epinephrine varies with increasing duration of cardiac arrest

OBJECTIVE: Epinephrine (adrenaline) is widely used as a primary adjuvant for improving perfusion pressure and resuscitation rates during cardiopulmonary resuscitation (CPR). Epinephrine is also associated with significant myocardial dysfunction in the post-resuscitation period. We tested the hypothesis that the cardiac effects of epinephrine vary according to the duration of cardiac arrest. METHODS AND MATERIALS: Cardiac arrest (CA) was induced in Sprague-Dawley rats with an IV bolus of KCl (40 microg/g). Three series of experiments were performed with CPR begun after 2, 4, or 6 min of cardiac arrest. Epinephrine (0.01 mg/kg) IV or placebo was given immediately in the 2 and 4 min CA groups. In the 6 min group, CPR was started after 6 min CA and epinephrine was given at 15 min if no return of spontaneous circulation (ROSC) occurred. Time to ROSC was recorded in all groups. Cardiac function was determined with trans-thoracic echocardiography at baseline, 5, 30 and 60 min after ROSC. RESULTS: After 2 min CA, 8/8 (100%) placebo animals and 8/8 (100%) epinephrine animals attained ROSC. Cardiac index was significantly increased during the first 60 min in the epinephrine group compared with the placebo group (p<0.01). After 4 min of cardiac arrest, 14/29 (48%) placebo animals and 14/16 (88%) epinephrine animals attained ROSC (p<0.01). Cardiac index after ROSC returned to baseline in both groups, although tended to be lower in the epinephrine group. After 6 min CA, 10/31 (32%) animals attained ROSC without epinephrine and 17/21 (81%) animals with epinephrine (p<0.01). Post-ROSC depression of cardiac index was greatest in the epinephrine group (p<0.05). CONCLUSIONS: As the duration of cardiac arrest increases, a paradoxical myocardial epinephrine response develops, in which epinephrine becomes increasingly more important to attain ROSC, but is increasingly associated with post-ROSC myocardial depression.     

Non-selective cyclooxygenase inhibition before periodic acceleration (pGz) cardiopulmonary resuscitation (CPR) in a porcine model of ventricular fibrillation

Whole body periodic acceleration (pGz) along the spinal axis is a novel method of cardiopulmonary resuscitation (CPR). Oscillatory motion of the supine body in a horizontal fashion provides ventilation and blood flow to vital organs during cardiac arrest and pulsatile shear stress to the vascular endothelium. We previously showed in pigs that pGz–CPR affords better overall survival, post resuscitation myocardial function, and neurological outcomes compared to conventional chest compression CPR. pGz through pulsatile shear stress on the vascular endothelium elicits acute production of prostaglandins and endothelial-derived nitric oxide (eNO) in whole animal models and in vitro preparations. The salutary effects associated with pGz–CPR compared to chest compression CPR are in part related to endothelial-derived nitric oxide. Both eNO and prostaglandins are cardioprotective in ischemia reperfusion models. To differentiate between the roles of these mediators, indomethacin a non-selective cyclooxygenase inhibitor (COX) was used as a tool to investigate prostaglandin effects during pGz–CPR by acute outcomes of survival, cardioprotection and regional blood flows (RBF). Two groups of anesthetized, intubated pigs weighing 25–36 kg were studied. Prior to electrical induction of ventricular fibrillation (VF) animals received equal volumes of either saline placebo Control (CONT) (n = 9) or indomethacin (INDO), (n = 8), (2 mg/kg). After 3 min of unsupported VF, both groups received 15 min of pGz–CPR followed by pharmacologic and electrical attempts for resuscitation. Return of circulation (ROSC) to 3 h occurred in (78%) in CONT and (63%) in INDO pretreated animals. There was no statistically significant difference in hemodynamics between groups at baseline or during the protocol. At baseline, INDO caused a decrease in brain RBF. Two hours after ROSC, INDO blunted the hyperemia response to brain and heart. Echocardiographic evidence of myocardial dysfunction was most notable for the INDO group in the wall motion score index (WMSI). After 3 h of ROSC there was a 4-fold difference in both creatine phosphokinase (CPK) and Troponin I concentration between INDO and CONT. Therefore, non-specific acute inhibition of COX in part blunts the salutary effects of pGz–CPR. These data suggest that prostaglandins in part are involved in the cardio protection induced by pGz during CPR.     

Standard and Higher Doses of Atropine in a Canine Model of Pulse less Electrical Activity

Objective: To determine whether standard or increased doses of atropine improve the return of spontaneous circulation (ROSC) rate in a canine model of pulseless electrical activity (PEA).
Methods: A prospective, controlled, blinded laboratory investigation was performed using an asphyxial canine cardiac arrest model. After the production of asphyxial PEA, 75 dogs remained in untreated PEA for 10 minutes and then were randomized to receive placebo (group 1) or one of four doses of atropine (group 2, 0.04 mg/kg; group 3, 0.1 mg/kg; group 4, 0.2 mg/kg; group 5, 0.4 mg/kg). All the animals received mechanical external CPR and epinephrine (0.02 mg/kg every 3 minutes) throughout resuscitation.
Results: The ROSC rates were not significantly different between the groups (group 1, 73%; group 2, 67%; group 3. 40%; group 4, 47%; group 5, 27%; p = 0.06). The heart rates and hemodynamics during resuscitation were not significantly different between the groups.
Conclusion: In this canine model of asphyxial PEA cardiac arrest, standard-dose atropine did not improve ROSC rates, compared with placebo. Increasing doses of atropine tended to decrease ROSC rates, compared with placebo and standard-dose atropine.     

Sudden cardiac death: directing the scope of resuscitation towards the heart and brain

BACKGROUND: The fundamental goal of cardiopulmonary resuscitation (CPR) is recovery of the heart and the brain. This is best achieved by (1) immediate CPR for coronary and cerebral perfusion, (2) correction of the cause of cardiac arrest, and (3) controlled cardioplegic cardiac reperfusion. Failure of such an integrated therapy may cause permanent brain damage despite cardiac resuscitation. METHODS: This strategy was applied at four centers to 34 sudden cardiac death patients (a) after acute myocardial infarction (n = 20), (b) "intraoperatively" following successful discontinuation of cardiopulmonary bypass (n = 4), and (c) "postoperatively" in the surgical ICU (n = 10). In each witnessed arrest the patient failed to respond to conventional CPR with ACLS interventions, including defibrillation. The cardiac arrest interval was 72 +/- 43 min (20-150 min). Compression and drugs maintained a BP > 60 mmHg to avoid cerebral hypoperfusion. Operating room (OR) transfer was delayed until the blood pressure was monitored. In four patients femoral bypass maintained perfusion while an angiographic diagnosis was made. RESULTS: Management principles included no repeat defibrillation attempts after 10 min of unsuccessful CPR, catheter-monitored peak BP > 60 mmHg during diagnosis and transit to the operating room, left ventricular venting during cardiopulmonary bypass and 20 min global and graft substrate enriched blood cardioplegic reperfusion. Survival was 79.4% with two neurological complications (5.8%). CONCLUSIONS: Recovery without adverse neurological outcomes is possible in a large number of cardiac arrest victims following prolonged manual CPR. Therapy is directed toward maintaining a monitored peak BP above 60 mmHg, determining the nature of the cardiac cause, and correcting it with controlled reperfusion to preserve function.     

延迟使用升压素与肾上腺素在窒息家兔心肺复苏中的疗效比较

目的 观察心肺复苏时延迟使用升压素或肾上腺素对自主循环恢复率的影响，比较两者对窒息性心跳停搏家兔心肺复苏的疗效。方法 62只家兔均在呼气末夹闭气管8min，造成窒息性心脏停搏模型后，开始人工胸外心脏按压及机械通气，期间不用任何药物，复苏5min内恢复自主循环的家兔定义为常规心肺复苏成功，对5min内复苏不成功者，再随机分为两组，分别给予升压素（0．8IU／kg）或肾上腺素（0．2mg／kg）静脉注射，并继续常规心肺复苏：结果 常规心肺复苏的自主循环恢复率为24．19％（15／62），加用升压素和肾上腺素后总的自主循环恢复率提高到48．39％（30／62）。其中升压素组23只家兔中2只复苏成功（8．70％），肾上腺素组24只家兔中13只复苏成功（54．16％），肾上腺素组复苏成功率明显高于升压素组（P=0．001）。结论 对窒息性心脏停搏的家兔心肺复苏时应用升压素或肾上腺素可提高自主循环恢复率。肾上腺素在提高窒息家兔冠脉灌注压及复苏成功率方面明显优于升压素。     

大剂量肾上腺素对心肺复苏大鼠心肌超微结构的影响

目的：观察用大剂量肾上腺素对心肺复苏大鼠心肌超微结构的影响，为心肺复苏时正确合理使用肾上腺素提供依据。方法：Ｗｉｓｔａｒ大鼠５０只随机分为５组：正常对照组（Ａ组）、模型对照组（Ｂ组）、标准剂量肾上腺素组（Ｃ组）、大剂量肾上腺素组（Ｄ组）和超大剂量肾上腺素组（Ｅ组）。用窒息使大鼠心脏停搏作为动物模型，进行心肺复苏，电镜观察心肌超微结构的变化。结果：Ａ组和Ｂ组心肌细胞超微结构正常，无明显区别。Ｃ组在复苏１０分钟时心肌超微结构无明显变化；复苏３０分钟时，心肌细胞肌丝排列不整齐，线粒体轻度扩张。Ｄ组复苏１０分钟时心肌超微结构无明显变化；复苏３０分钟时，心肌细胞部分损害，损害程度比Ｃ组复苏３０分钟时严重。Ｅ组复苏１０分钟时心肌超微结构略有部分改变；复苏３０分钟时，其损害比Ｄ组更加严重。结论：在复苏早期使用标准剂量肾上腺素和大剂量肾上腺素对心肌细胞超微结构无明显影响。在复苏晚期使用大剂量肾上腺素或超大剂量肾上腺素对心肌细胞超微结构有明显破坏。忽略其它复苏措施，单靠加大肾上腺素剂量有危险，应合理使用肾上腺素。