Postresuscitation Myocardial Dysfunction Research Articles

Impaired β-adrenergic receptor signalling in post-resuscitation myocardial dysfunction

ObjectivePost-resuscitation myocardial dysfunction is a major cause of fatality in patients receiving successful cardiopulmonary resuscitation. The mechanism of post-resuscitation myocardial dysfunction is largely unknown, although is generally considered related to ischaemia occurring during cardiac arrest and resuscitation and/or reperfusion injury after restoration of circulation. A key mechanism responsible for reduced contractile reserves in chronic heart failure is impaired β-adrenergic receptor signalling. Thus, we hypothesised that β-adrenergic receptor signalling is markedly abnormal in the post-resuscitation period following cardiopulmonary resuscitation. MethodsMale landrace domestic pigs were randomised into a sham group (anaesthetised and instrumented, no ventricular fibrillation) or cardiopulmonary resuscitation (CPR) group (ventricular fibrillation) (n=8 per group). Haemodynamic and echocardiographic data were recorded. β-Adrenergic receptor signalling was assessed at 6h after the operation by measuring myocardial adenylate cyclase activity, β-adrenergic receptor density and β-adrenergic receptor kinase expression. ResultsLeft ventricular function in the CPR group was significantly decreased at 6h after restoration of spontaneous circulation. Basal and isoproterenol-stimulated adenylate cyclase activity was blunted in the CPR group compared with the sham group. Total β-AR density was significantly decreased in CPR group compared with the sham group. Myocardial β-adrenergic receptor kinase expression was 2.03-fold greater in the CPR group than in the sham group. Conclusionsβ-Adrenergic receptor signalling is markedly impaired in the post-resuscitation period, which may be a mechanism of post-resuscitation myocardial dysfunction.

Abstract 201: Specific Metabolic Pathways Involved in Outcome of Cardiopulmonary Resuscitation: A Pilot Plasma Metabolomic Study in a Rat Model of Cardiac Arrest and CPR

Introduction. The mechanisms responsible for postresuscitation myocardial and cerebral dysfunction are not well understood. We hypothesized that untargeted plasma metabolomic analyses would be a feasible approach to identify perturbations in circulating metabolites and thus potential mechanisms accounting for outcome of cardiac arrest (CA). Methods. Six male rats, 440 ± 50 g, were used. Ventricular fibrillation was induced in 3 rats and was untreated for 6 mins. CPR, including mechanical chest compressions, ventilations and epinephrine, was then initiated and continued for additional 6 mins prior to defibrillation. Two hrs following resuscitation, animals were sacrificed and plasma collected. The other 3 rats were not subjected to cardiac arrest and served as controls. Plasma metabolome was examined by liquid chromatography-tandem mass spectrometry. Differences in chromatogram profiles were then analyzed using SIEVE v1.3 analysis software. Chromatographic peaks, with accurate masses, retention time and tandem mass fragmentation patterns were then identified using mass-spectral libraries of metabolites. Results. A total of 523 chromatographic peaks showed significant differences after CA. Changes in metabolites participating in purine/pyrimidine metabolism, glycolisis, TCA cycle, pentose phosphate pathways, cholesterols and derivatives, lipids, and fatty acid oxidation, were observed. Changes in long-chain acylcarnitine and corticosterone/cortisol levels were also found, suggesting oxidative damages and deregulation of hypothalamic-pituitary-adrenal axis, respectively. More importantly, numerous metabolites along the kynurenine pathway from tryptophan oxidation, typically related to neurological degeneration, were identified (Figure). Conclusions. In this pilot study, plasma metabolomics allowed for identification of specific metabolic pathways, i.e. tryptophan pathway, that ultimately may contribute to CA outcome.

Abstract 57: Erythropoietin Selectively Preserves Electron Transport Complex IV Activity During Resuscitation from Cardiac Arrest

Introduction: We have previously documented in a rat model of VF and closed-chest resuscitation that administration of erythropoietin (EPO) preserves left ventricular distensibility - yielding hemodynamically more effective CPR - and attenuates post-resuscitation myocardial dysfunction. Hypothesis: Given that similar functional myocardial benefits can be elicited by preservation of mitochondrial bioenergetic function, we hypothesized that EPO could mediate the aforementioned myocardial effects in part by preserving activity of electron transport complexes I, III, IV and V (FoF1 ATPase). Methods: VF was electrically induced in 10 Sprague-Dawley male rats and left untreated for 8 minutes before attempting resuscitation by closed-chest resuscitation and delivery of electrical shocks. Rats were randomized to receive 5,000 U/kg of EPO (n=5) or NaCl 0.9% vehicle (n=5) into the right atrium immediately before starting closed-chest resuscitation, with the investigators blind to the assignment. All rats were resuscitated and survived 120 minutes, time at which hearts were removed storing the left ventricles at -80°C. Mitochondria were isolated from frozen tissue and activity of electron transport complexes I, I & III, IV and V measured spectrophotometrically via dichloro indophenol reduction, cytochrome c reduction, cytochrome c oxidation, and phosphate estimation, respectively. Results: Only complex IV activity was significantly higher in EPO compared with NaCl 0.9% treated rats with the levels in EPO rats comparable to the reference levels (Table). Conclusions: EPO ameliorated reductions in complex IV activity prompted by cardiac arrest and resuscitation, an effect that could mediate the favorable myocardial effect of EPO observed during resuscitation from cardiac arrest.

Cholecystokinin octapeptide induces hypothermia and improves outcomes in a rat model of cardiopulmonary resuscitation*

To investigate the effects of cholecystokinin octapeptide on thermoregulation, postresuscitation myocardial function, neurologic outcome, and duration of survival in a rat model of cardiopulmonary resuscitation. : Prospective, randomized, placebo-controlled experimental study. University-affiliated animal research laboratory. Ten male Sprague-Dawley rats. Ventricular fibrillation was induced and untreated for 6 mins. Defibrillation was attempted after 8 mins of cardiopulmonary resuscitation. Animal temperature was adjusted to 37.0 °C with the aid of a heating lamp. At 30 mins after resuscitation, animals were randomized to receive an intravenous injection of either cholecystokinin octapeptide (200 μg/kg in 0.3 mL saline) or vehicle placebo (0.3 mL saline). The ambient temperature settings and that of the distance of the heating lamp from the animal remained the same in both groups throughout the entire experiment. Body temperature, hemodynamic measurements, and postresuscitation myocardial function, including cardiac output, left ventricular ejection fraction, and myocardial performance index, were measured together with neurologic deficit scores and duration of survival. After injection of cholecystokinin octapeptide, blood temperature decreased progressively from 37.0 °C to 34.8 °C 5 hrs after resuscitation and returned to 37.0 °C at 9 hrs after injection. In the control group, blood temperature was sustained at 37.0 °C ± 0.2 °C during the same period of observation. Myocardial and neurologic function and duration of survival were significantly better in the cholecystokinin octapeptide-treated animals when compared to the control group. : In a rat model of cardiopulmonary resuscitation, cholecystokinin octapeptide induced mild hypothermia, attenuated postresuscitation myocardial dysfunction, and improved neurologic outcome and duration of survival.

AS06 Mechanisms involved in post resuscitation myocardial dysfunction in a rat model of cardiac arrest and resuscitation

AS06 Mechanisms involved in post resuscitation myocardial dysfunction in a rat model of cardiac arrest and resuscitation

Ultrastructural evidence of mitochondrial abnormalities in postresuscitation myocardial dysfunction

ObjectivesThough there is evidence to implicate that the mitochondrion may play an important role in the development of postresuscitation myocardial dysfunction, limited data are available regarding the ultrastructural alterations of the mitochondria, mitochondrial energy-producing ability, and their relationship to postresuscitation myocardial dysfunction. This study was designed to determine whether mitochondrial abnormalities contribute to the development of postresuscitation myocardial dysfunction. MethodsFifteen anesthetized male Sprague-Dawley rats were randomized to: (1) global myocardial ischemia/reperfusion, in which 8min of ventricular fibrillation was induced and successful defibrillation was achieved after 6min of cardiopulmonary resuscitation (CPR); (2) global myocardial ischemia, in which ventricular fibrillation and CPR were performed without defibrillation attempt; and (3) sham control. ResultsMyocardial function was significantly impaired after resuscitation. Mitochondria were massively swollen in global ischemic hearts and mildly swollen in the resuscitated hearts. Concomitantly, ATP levels abruptly declined during global ischemia and partially recovered after resuscitation. Furthermore, mitochondrial abnormalities were supported by the incapability of utilizing energy substrates manifested by the accumulations of intramyocellular lipid droplets and glycogen deposits. ConclusionsIn this model of cardiac arrest and CPR, the presence of ultrastructural mitochondrial abnormalities, further evidenced by the incapability of utilizing energy substrates and impairment of energy-production, might, in part, contribute to the development of postresuscitation myocardial dysfunction.

Management of postcardiac arrest myocardial dysfunction

Recent recognition of the importance of postresuscitation care has stimulated interest and new reports concerning therapies for postcardiac arrest myocardial dysfunction. Such cardiac dysfunction after successful resuscitation can be severe and even lethal; however, it is also transient emphasizing the importance of early supportive therapies. The most important strategies for dealing with postresuscitation myocardial dysfunction include a community-formalized effort by individual communities to shorten the time from arrest to restoration of spontaneous circulation, use of therapeutic hypothermia for myocardial preservation, not just cerebral, and early coronary angiography and intervention for all survivors with a high suspicion of a cardiac cause for their arrest. Exciting specific therapies targeted for one or another of the ischemia/reperfusion myocardial injuries associated with cardiac arrest include manipulation of the nitric oxide production in the myocardium, treatment of myocardial microcirculatory dysfunction post resuscitation, inhibition of Na+/H+ exchange, and treatment of calcium flux abnormalities. Every community should be striving to provide more timely restoration of pulse and circulation, whereas every medical center receiving patients resuscitated from out-of-hospital cardiac arrest should be providing therapeutic hypothermia for both central nervous system and myocardial preservation. The ability and commitment to provide '24/7' early coronary angiography and percutaneous intervention for all resuscitated victims of sudden cardiac death with a likely cardiac cause for their arrest is also key.

Emulsified isoflurane postconditioning improves early post-resuscitation myocardial dysfunction in the rat

s and Programme: EUROANAESTHESIA 2011: The European Anaesthesiology Congress: Intensive Care Medicine

Shen-Fu Injection Attenuates Postresuscitation Myocardial Dysfunction in a Porcine Model of Cardiac Arrest

To investigate the effect of Shen-Fu injection (SFI) for the management of postresuscitation myocardial dysfunction in a porcine model of cardiac arrest. Ventricular fibrillation was induced electrically in anesthetized domestic swine. After 4 min of untreated ventricular fibrillation, cardiopulmonary resuscitation was initiated. Sixteen successfully resuscitated pigs were randomized to receive a continuous infusion of either SFI (0.24 mg/min) or saline placebo for 6 h, beginning 15 min after return of spontaneous circulation (ROSC). The SFI treatment produced better left ventricular +dP/dtmax, -dP/dtmax, cardiac output, and ejection fraction after ROSC. The SFI treatment also produced lower serum cardiac troponin I, lactate levels, and left ventricle malondialdehyde content after ROSC, whereas left ventricle superoxide dismutase, Na-K-ATPase, and Ca-ATPase activity were significantly increased in the SFI group when compared with saline group. The cardioprotective effect of SFI was further confirmed by myocardial ultrastructure examination. Shen-Fu injection can attenuate postresuscitation myocardial dysfunction through beneficial effects on energy metabolism and remarkable antioxidant capacity.

Effect of therapeutic hypothermia vs δ-opioid receptor agonist on post resuscitation myocardial function in a rat model of CPR

AimThis study is to compare the effect of the δ-opioid receptor agonist, d-Ala2-d-Leu5 enkephalin (DADLE) with normothermic control and therapeutic hypothermia on post resuscitation myocardial function and 72-h survival in a rat model of cardiac arrest and resuscitation. MethodsVentricular fibrillation (VF) was induced in 15 male Sprague–Dawley rats. After 8min of untreated VF, cardiopulmonary resuscitation was performed for 8min before defibrillation. Animals were randomized to three groups of five: (a) normothermia; (b) hypothermia (32°C); and (c) normothermia with DADLE intravenous infusion (1mg/kgh−1). Hypothermia and drug infusion were started after successful defibrillation. Myocardial functions, including cardiac output (CO), left ventricular ejection fraction (LVEF), and myocardial performance index (MPI) were measured echocardiographically together with duration of survival. ResultsThe 72-h survival was significantly greater in the hypothermic group than in both DADLE and normothermic group (p=0.02). However, the survival time of the DADLE treated animals was significantly longer than that of the normothermia group (51.8±18.9 vs 18.8±10.1h, p<0.01). DADLE group showed significantly better CO (PR 60min, p=0.049), better LVEF (PR 60min, p=0.044; PR 240min, p<0.001) and lower MPI (PR 60min, p=0.043; PR 240min, p=0.045) than normothermic group. Hypothermia group also showed significantly better CO (PR 60min, p=0.044; PR 240min, p=0.007), better LVEF (PR 60min, p=0.001; PR 240min, p<0.001) and lower MPI (PR 60min, p=0.003; PR 240min, p=0.012) than the normothermic group. ConclusionsDADLE attenuated post resuscitation myocardial dysfunction and increased short term survival time. However, the 72-h survival in the DADLE group was less than that in the hypothermia group.

The effects of epinephrine on outcomes of normothermic and therapeutic hypothermic cardiopulmonary resuscitation*

To investigate the effects of epinephrine when administered during either normothermic or therapeutic hypothermic cardiopulmonary resuscitation on postresuscitation myocardial and cerebral function and survival. Prospective, randomized, placebo-controlled experimental study. University-affiliated animal research laboratory. Thirty-two healthy male Sprague-Dawley rats. Ventricular fibrillation was induced and untreated for 8 mins. The animals were then randomly assigned to one of four groups: normothermic placebo control; normothermic epinephrine; hypothermic placebo control; and hypothermic epinephrine. Hypothermia was initiated coincident with the start of cardiopulmonary resuscitation. The blood temperature was reduced and maintained at 32 ± 0.2°C and continued for 4 hrs after resuscitation. Normothermic animals were maintained at 37 ± 0.2°C. Either placebo or epinephrine (20 μg/kg) was administered 5 mins after the start of cardiopulmonary resuscitation and 3 mins before defibrillation. Postresuscitation cardiac output, ejection fraction, and myocardial performance index were measured hourly for 4 hrs after resuscitation; neurologic deficit scores were measured daily for 7 days, and durations of survival were observed for up to 3 mos. Except for three normothermic control animals, all animals were resuscitated. When epinephrine was administered during normothermic cardiopulmonary resuscitation, postresuscitation myocardial function was severely impaired when compared with the normothermic control group. However, postresuscitation myocardial function was significantly better in animals treated with epinephrine during hypothermic cardiopulmonary resuscitation when compared with hypothermic controls. This was associated with significantly fewer postresuscitation ventricular arrhythmias, less ST-segment elevation, better postresuscitation neurologic deficit scores, and longer duration of survival. Epinephrine, when administered during normothermic cardiopulmonary resuscitation, significantly increases the severity of postresuscitation myocardial dysfunction and decreases the duration of survival. These detrimental effects of epinephrine, however, no longer exist when it is administered during therapeutic hypothermic cardiopulmonary resuscitation.

Part 6: Electrical Therapies

The recommendations for electrical therapies described in this section are designed to improve survival from SCA and life-threatening arrhythmias. Whenever defibrillation is attempted, rescuers must coordinate high-quality CPR with defibrillation to minimize interruptions in chest compressions and to ensure immediate resumption of chest compressions after shock delivery. The high first-shock efficacy of newer biphasic defibrillators led to the recommendation of single shocks plus immediate CPR instead of 3-shock sequences that were recommended prior to 2005 to treat VF. Further data are needed to refine recommendations for energy levels for defibrillation and cardioversion using biphasic waveforms.

Post-resuscitation myocardial microcirculatory dysfunction is ameliorated with eptifibatide

BackgroundThe post-cardiac arrest syndrome includes a decline in myocardial microcirculation function. Inhibition of the platelet IIb/IIIa glycoprotein receptor has improved myocardial microvascular function post-percutaneous coronary intervention. Therefore, we evaluated such inhibition with eptifibatide for its effect on myocardial microcirculation function post-cardiac arrest and resuscitation. MethodsFour groups of swine were studied in a prospective, randomized, blinded, placebo-controlled protocol including; eptifibatide administered during CPR (Group 1, n=5), after resuscitation (Group 2, n=4), during and after resuscitation (Group 3, n=5), or placebo (Group 4, n=10). CPR was initiated following 12min of untreated VF. Those successfully resuscitated were studied during a 4-h post-resuscitation period. Coronary flow reserve, a measure of microcirculation function (in the absence of coronary obstruction), as well as parameters of left ventricular systolic and diastolic function, were measured pre-arrest and serially post-resuscitation. ResultsCoronary flow reserve was preserved during the post-resuscitation period, indicating normal microcirculatory function in the eptifibatide-treated animals, but not in the placebo-treated group. However, LV function declined equally in both groups during the first 4h after cardiac arrest. ConclusionInhibition of platelet IIb/IIIa glycoprotein receptors with eptifibatide post-resuscitation prevented myocardial microcirculation dysfunction. Left ventricular dysfunction post-resuscitation was not improved with eptifibatide, and perhaps transiently worse at 30min post-resuscitation. Post-cardiac arrest ventricular dysfunction may require a multi-modality treatment strategy for successful prevention or amelioration.

Comparison of the efficacy of nifekalant and amiodarone in a porcine model of cardiac arrest

Objective To compare the efficacy of nifekalant and amiodarone in the treatment of cardiac arrest in a porcine model. Methods After 4 min of untreated ventricular fibrillation, animals were randomly treated with nifekalant (2 mg kg −1), amiodarone (5 mg kg −1) or saline placebo ( n = 12 pigs per group). Precordial compression and ventilation were initiated after drug administration and defibrillation was attempted 2 min later. Hemodynamics were continuously measured for 6 h after successful resuscitation. Results Compared with saline, nifekalant and amiodarone equally decreased the number of electric shocks, defibrillation energy, epinephrine dose, and duration of cardiopulmonary resuscitation required for successful resuscitation ( P < 0.01). The incidence of restoration of spontaneous circulation (ROSC) and the 24-h survival rate were higher in both antiarrhythmic drug groups ( P < 0.05) vs. the saline group. Furthermore, post-resuscitation myocardial dysfunction at 4–6 h after successful resuscitation was improved in animals given antiarrhythmic drugs as compared with the saline group ( P < 0.05). There were no differences between nifekalant and amiodarone for any of these parameters. Conclusion The effect of nifekalant was similar to that of amiodarone for improving defibrillation efficacy and for the treatment of cardiac arrest. Administration of either nifekalant or amiodarone before defibrillation increased the ROSC and 24-h survival rates and improved post-resuscitation cardiac function in this porcine model.

Apoptosis is not involved in the mechanism of myocardial dysfunction after resuscitation in a rat model of cardiac arrest and cardiopulmonary resuscitation

To investigate the presence of apoptosis after the global myocardial ischemia of cardiopulmonary resuscitation and the regional myocardial ischemia after left anterior descending coronary artery occlusion and relate it to the severity of postresuscitation myocardial dysfunction. Prospective animal study. University-affiliated animal research laboratory. Male Sprague-Dawley rats. Fifteen male Sprague-Dawley rats weighing 450-550 g were randomized to: (1) 8 mins of untreated cardiac arrest followed by 6 mins of cardiopulmonary resuscitation; (2)left anterior descending coronary artery occlusion for 45 mins followed by 4 hrs of reperfusion; and (3) left anterior descending coronary artery sham group. Cardiac functions, including ejection fraction, analog differentiation of left ventricular pressure at 40 mm Hg, and rate of maximal left ventricular pressure decline were continuously measured for 4 hrs. The hearts were then harvested for the terminal transferase-mediated 2'-deoxyuridine, 5'-triphosphate nick end-labeling assay analysis. Myocardial function was significantly impaired after resuscitation from cardiac arrest and reperfusion from left anterior descending coronary artery occlusion(p < .01). There was no difference in the percentage of apoptotic cells between the cardiopulmonary resuscitation animals and sham-operated animals. Fewer apoptotic cells were observed in cardiac arrest/cardiopulmonary resuscitation animals in comparison to left anterior descending coronary artery occlusion animals (p < .05), even though myocardial function was more severely impaired after resuscitation (p < .01). Myocardial function was significantly impaired after cardiac arrest/cardiopulmonary resuscitation and ischemia/reperfusion. However, apoptosis was not involved in the mechanism of postresuscitation myocardial dysfunction in this setting.

Infliximab attenuates early myocardial dysfunction after resuscitation in a swine cardiac arrest model

Left ventricular dysfunction after successful cardiopulmonary resuscitation contributes to early death after resuscitation. Proinflammatory cytokines are known to decrease myocardial function, and tumor necrosis factor-alpha has been shown to increase after successful resuscitation. We hypothesized that blocking the effects of tumor necrosis factor-alpha with infliximab would prevent or minimize postresuscitation cardiac dysfunction. Randomized, placebo-controlled comparative study. Large animal research laboratory. Twenty-eight anesthetized and instrumented domestic male swine (Yorkshire and Yorkshire/Hampshire mix; weight, 35-45 kg). Infusion of infliximab (5 mg/kg) or normal saline after resuscitation from ventricular fibrillation cardiac arrest. Hemodynamic variables, indices of left ventricular function, and tumor necrosis factor-alpha were measured before and after 8 mins of cardiac arrest during the early postresuscitation period (3 hrs). Within 5 mins of restoration of spontaneous circulation, 14 animals received infliximab, 5 mg/kg, infused over 30 mins. Fourteen animals received an infusion of normal saline. Inotropes and vasopressors were not administered to either group after resuscitation. Tumor necrosis factor-alpha increased after restoration of circulation and remained elevated throughout the observation period. Differences between groups were not significant. Interleukin-1beta concentration did not change significantly during the observation period in either study group. Mean arterial pressure and stroke work were significantly greater in the infliximab group within 30 mins of resuscitation, and these differences were sustained throughout the 3-hr postresuscitation period. The effect of tumor necrosis factor-alpha blockade was evident only in animals with a significant increase (doubling) in plasma tumor necrosis factor-alpha at 30 mins after arrest. Tumor necrosis factor-alpha plays a role in cardiac dysfunction after arrest and infliximab may attenuate or prevent postresuscitation myocardial dysfunction when administered immediately after resuscitation.

Opioid receptor agonist reduces myocardial ischemic injury when administered during early phase of myocardial ischemia

Aim of the study Postresuscitation myocardial dysfunction is one of the leading causes of early death after initial success of resuscitation, the mechanisms of postresuscitation myocardial dysfunction remain controversial. We hypothesize that ischemia injury, rather than reperfusion injury is the major cause of postresuscitation myocardial dysfunction. We proposed to investigate the separate effects of ischemia and reperfusion injury on postresuscitation myocardial dysfunction. Methods Thirty-three Langendorff-perfused isolated rat hearts were subjected to 15 min of global ischemia followed by 120 min of reperfusion. Pentazocine was utilized as a myocardial protective agent, either before ischemia or during reperfusion. All hearts were randomized into 3 groups: (1) “ischemia protection”, in which pentazocine was infused 10 min prior to global ischemia, (2) “reperfusion protection”, in which pentazocine was infused during 2 h of reperfusion and (3) “control”, with no pentazocine infusion. Left ventricular (LV) functions were measured by the maximal rate of LV pressure rise (d P/d t max) and decline (−d P/d t max), the maximal LV diastolic pressure (LVDP). The incidences of postischemic arrhythmias were measured. Results When pentazocine was administered before onset of ischemia, the LV systolic and diastolic functions were significantly greater, and the postischemic arrhythmias were significantly less in comparison to those with reperfusion protection ( p < 0.05) and the control group ( p < 0.05). Conclusions In this model, the severity of postischemic myocardial dysfunction was less when the heart was protected during ischemia. Ischemia injury may therefore be the major cause of postresuscitation myocardial dysfunction.

Hypocalcemia following resuscitation from cardiac arrest revisited

Objective Hypocalcemia associated with cardiac arrest has been reported. However, mechanistic hypotheses for the decrease in ionized calcium (iCa) vary and its importance unknown. The objective of this study was to assess the relationships of iCa, pH, base excess (BE), and lactate in two porcine cardiac arrest models, and to determine the effect of exogenous calcium administration on post-resuscitation hemodynamics. Methods Swine were instrumented and VF was induced either electrically (EVF, n = 65) or spontaneously, ischemically induced (IVF) with balloon occlusion of the LAD ( n = 37). Animals were resuscitated after 7 min of VF. BE, iCa, and pH, were determined prearrest and at 15, 30, 60, 90, 120 min after ROSC. Lactate was also measured in 26 animals in the EVF group. Twelve EVF animals were randomized to receive 1 g of CaCl 2 infused over 20 min after ROSC or normal saline. Results iCa, BE, and pH declined significantly over the 60 min following ROSC, regardless of VF type, with the lowest levels observed at the nadir of left ventricular stroke work post-resuscitation. Lactate was strongly correlated with BE ( r = −0.89, p < 0.0001) and iCa ( r = −0.40, p < 0.0001). In a multivariate generalized linear mixed model, iCa was 0.005 mg/dL higher for every one unit increase in BE (95% CI 0.003–0.007, p < 0.0001), while controlling for type of induced VF. While there was a univariate correlation between iCa and BE, when BE was included in the regression analysis with lactate, only lactate showed a statistically significant relationship with iCa ( p = 0.02). Post-resuscitation CaCl 2 infusion improved post-ROSC hemodynamics when compared to saline infusion (LV stroke work control 8 ± 5 g m vs 23 ± 4, p = 0.014, at 30 min) with no significant difference in tau between groups. Conclusions Ionized hypocalcemia occurs following ROSC. CaCl 2 improves post-ROSC hemodynamics suggesting that hypocalcemia may play a role in early post-resuscitation myocardial dysfunction.

CARDIOPROTECTIVE EFFECT OF THERAPEUTIC HYPOTHERMIA FOR POSTRESUSCITATION MYOCARDIAL DYSFUNCTION

Mild-to-moderate therapeutic hypothermia after resuscitation from cardiac arrest is neuroprotective, but its effect on postresuscitation myocardial dysfunction is not clear. We hypothesized that therapeutic hypothermia is cardioprotective in postresuscitation. Male adult Wistar rats underwent asphyxia-induced cardiac arrest and manual resuscitation with epinephrine. Therapeutic hypothermia is induced immediately after successful resuscitation and the return of spontaneous circulation (ROSC). One hour after ROSC, the rats achieved a target temperature of 30 degrees C to 31 degrees C, which was maintained for 1.5 h and then transitioned to the passive rewarming process in the hypothermia group. A temperature between 36.5 degrees C and 37.5 degrees C was maintained in the normothermia group. Echocardiography revealed that hypothermia resulted in significantly better systolic function of fractional shortening in 60 and 120 min after ROSC (both P < 0.05). The benefit of cardioprotection was also confirmed by the general linear mixed-models analysis of dP/dt, which revealed significantly better systolic function in positive dP/dtR(40) and diastolic function in maximal negative dP/dt (both P < 0.001). The 4-h and 3-day survival analyses both revealed better outcomes in the hypothermia groups in the log-rank test (P < 0.001 for the 4-h analysis, and P < 0.05 for the 3-day analysis). Serum level of heart-type, fatty acid-binding protein at 4 h after resuscitation as the myocardium damage marker was also significantly lower in the hypothermia group (52.4 ng/mL vs 186.5 ng/mL in the normothermia group; P < 0.05). Western blotting of myocardium showed that myocardial Akt and ERK1/2 were more activated in the hypothermia group 2 h after spontaneous circulation returned. In conclusion, postresuscitation mild-to-moderate therapeutic hypothermic is cardioprotective in the asphyxia-induced cardiac arrest animal model. It stabilizes hemodynamics, improves short-term survival, and decreases myocardial damage. The cardioprotective effect is associated with Akt and ERK1/2 activation in signal transduction.

Comparison of the effects of aminoguanidine and NG-nitro-L-arginine methyl ester on resuscitation from cardiac arrest in rabbits

Objective To observe the changes of nitric oxide (NO) levels in plasma during cardiopul-monary resuscitation (CPR) and to compare the effects of aminoguanidine (AG) and NG-nitro-L-arginine methyl ester (L-NAME) on CPR. Method This was a prospective, randomized animal study performed at the Function Laboratory of Lanzhou University. Cardiac arrest was electrically induced and was left untreated for 5 min. After performing chest compression for 1 min, 40 domestic rabbits were divided into four groups (n = 10) to receive ei-ther 20 mg/kg AG, 25 mg/kg L-NAME, 0.02 mg/kg epinephrine or 2 ml saline placebo before defibrillation. Successfully resuscitated rabbits were observed for a further 4 h. Hernodynamics variables and cardiac functions were monitored with appropriate instrumentation. Arterial blood NO levels were examined at baseline, at the end of 1 min chest compression and at 15, 30, 60 and 120 min after survival. Repeated measures analysis of variance was used to determine statistical significance between groups. Results During chest compression, the mean + stan-dard deviation coronary perfusion pressure was higher in the AG group (40±10 mmHg) than in the L-NAME group (34±8 mmHg; P =0.001) and was higher in both groups with the control group (20±5 mmHg; both P =0.000). Left ventricular + dp/dtmax and- dp/dtmax were higher in the AG group than in the L-NAME group. In the surviving rabbits, the left ventricular + dp/dtmax and - dp/dtmax were higher in the AG and L-NAME groups than in the epinephrine and control groups and were higher in the AG group (4783±912, 4409±827 mmHg/s)than in the b-NAME group (3554±847, 3398±764 mmHg/s; P = 0.001 and 0.023, respectively). Conclu-sions Both AG and L-NAME increased the coronary perfusion pressure, and improved left ventricular systolic and diastolic function during CPR and prevented post-resuscitation myocardial dysfunction. However, AG was signifi-canfly superior to L-NAME. Key words: Cardiac arrest; Cardiopulmonary resuscitation; Nitric oxide; Aminnguanidine; NG; -nitro-L-arginine methyl ester