Postresuscitation Myocardial Dysfunction Research Articles

The relationship between sarcoplasmic reticulum Ca(2+) modulation proteins and postresuscitation myocardial dysfunction

To investigate the relationship between sarcoplasmic reticulum Ca²⁺ modulation proteins and postresuscitation myocardial dysfunction. Thirty-eight SPF male Sprague-Dawley (SD) rats were randomly divided into control group (n=12) and cardiac arrest (CA) group (n=26). CA was induced by intravenous bolus of potassium chloride (40 μg/g), and cardiopulmonary resuscitation (CPR) was conducted 8 minutes later. No CA was induced in control group except catheter placement for monitoring cardiopulmonary parameters after anesthesia. Invasive hemodynamic parameters were monitored for 1 hour after CPR. Echocardiogram was performed to evaluate cardiac function. Myocardial samples were harvested 5 minutes and 1 hour after restoration of spontaneous circulation (ROSC), and sarcoplasmic reticulum Ca²⁺ ATPase (SERCA2a), phosphorylated phospholamban (p-PLB) and rynodine receptor (RyR) were determined by Western Blot. ROSC rate of CA group was 92.3% (24/26), and mean recovery time was (68 ± 39) seconds. Cardiac function was significantly impaired in CA group at 1 hour after resuscitation, and ejection fraction, fraction shortening (FS), the maximal rate of left ventricular pressure increase/decline (± dp/dt max) were significantly decreased compared with those in control group [ejection fraction: 0.548 ± 0.060 vs. 0.809 ± 0.043, F=71.692, P=0.000; FS: (34.4 ± 4.4)% vs. (46.0 ± 3.5)%, F=55.443, P=0.000; + dp/dt max (mmHg/s): 4 718 ± 43 vs. 7 098 ± 394, P<0.01; - dp/dt max (mmHg/s): -3 824 ± 612 vs. -6 187 ± 473, P<0.01]. Compared with control group, the expression levels of p-PLB (gray value) was significantly decreased at 5 minutes and 60 minutes (5 minutes: 0.64 ± 0.15 vs. 1.29 ± 0.13, P<0.01; 60 minutes: 0.95 ± 0.08 vs. 1.30 ± 0.09, P<0.05) after resuscitation in CA group, while the level of sarcoplasmic SERCA2a (gray value) and RyR (gray value) showed no significant differences (SERCA2a 5 minutes: 1.01 ± 0.18 vs. 1.24 ± 0.07, 60 minutes: 1.03 ± 0.14 vs. 1.25 ± 0.06; RyR 5 minutes: 0.96 ± 0.13 vs. 0.97 ± 0.13, 60 minutes: 0.88 ± 0.14 vs. 0.99 ± 0.11, all P>0.05). The impairment of the p-PLB is closely related to postresuscitation myocardial dysfunction.

The value of spontaneous gasping associated with duration of cardiac arrest in predicting post-resuscitation myocardial dysfunction in a rat model

Objective To analyze the timing and frequency of spontaneous gasping during cardiopulmonary resuscitation in a rat model,and evaluate its value bearing some relation to duration of cardiac arrest （CA ） in predicting the severity of post-resuscitation myocardial dysfunction.Methods Twenty-seven healthy Sprague-Dawley rats were randomly （random number）divided into 3 groups according to different durations of CA：CA 4 min （n=9）,CA 6 min （n=9）and CA 8 min （n=9）.CA of rats was electrically induced and untreated for 4,6 or 8 min respectively in the corresponding groups,and then cardiopulmonary resuscitation （CPR）was initiated and continued for 8 min in all animals.The emergence timing and frequency of spontaneous gasping during cardiopulmonary resuscitation and resuscitation outcomes were documented.Myocardial function such as cardiac output,ejection fraction and Tei index was measured by echocardiography prior to CA and at 1 h,2 h and 4 h post-resuscitation.Results The earliest appearance of gasping with highest frequency was observed in the CA 4 min group during CPR.Gasping appeared later with decreased frequency observed following longer duration of CA.There were statistically significant differences in the timing and frequency of gasping among the 3 groups.In the CA 4 min group with frequent gasping,all animals were successfully resuscitated with 8-min CPR with the least number of defibrillation,which was significantly better than that in the CA 8 min group.During the evaluation of post-resuscitation myocardial function,cardiac output,ejection fraction and myocardial work index （Tei index） were better in the CA 4 min group with frequent gasping,worse in the CA 6 min group and worst in the CA 8 min group, showing statistically significant differences in cardiac function among the 3 groups. Conclusions The spontaneous gasping appeared sooner with higher frequency during cardiopulmonary resuscitation indicated shorter duration of CA,and predicted better success of resuscitation and post-resuscitation myocardial function. Key words: Cardiac arrest; Cardiopulmonary resuscitation; Gasping; Myocardial dysfunction

Ranolazine ameliorates postresuscitation electrical instability and myocardial dysfunction and improves survival with good neurologic recovery in a rat model of cardiac arrest.

During ischemia, enhancement of the "late Na+ current" (I(NaL)) contributes to intracellular Ca2+ overload. Dysregulation of intracellular Ca2+ homeostasis plays a critical role in the pathophysiology of cardiac arrest and cardiopulmonary resuscitation (CPR), leading to ventricular arrhythmias and left ventricle (LV) dysfunction. The purpose of this study was to investigate the effects of the I(NaL) blocker ranolazine on outcome of CPR in a rat model. We hypothesized that ranolazine might reduce postresuscitation arrhythmias and improve survival and recovery. Eighteen rats were assigned to receive intravenous ranolazine 10 mg/kg or vehicle. Ventricular fibrillation was induced and untreated for 8 minutes. CPR then was performed for 8 minutes. ECG and arterial and right atrial pressures were monitored up to 3 hours after CPR. After resuscitation, LV function was monitored by echocardiography, and 72-hour survival with neurologic recovery was evaluated. Plasma was obtained for biomarkers of heart and brain injury. All animals in the ranolazine group were resuscitated and survived up to 72 hours, whereas 72% in the vehicle group were resuscitated but 54% survived. The period of postresuscitation arrhythmia with hemodynamic instability was shorter in the ranolazine group compared to vehicle group (P < .02). Seventy-two hours after resuscitation, LV systolic and diastolic functions were better in the ranolazine group compared to vehicle (P < .05). Full neurologic recovery was observed in all ranolazine animals, whereas neurologic impairment persisted in the vehicle group (P < .02). In this model, ranolazine pretreatment reduced postresuscitation electrical and hemodynamic instability and improved 72-hour postresuscitation LV function and survival with good neurologic recovery.

Epinephrine for Cardiac Arrest

Epinephrine for Cardiac Arrest: Are We Doing More Harm Than Good? Vijay Krishnamoorthy;Monica Vavilala;Michael Fettiplace;Guy Weinberg; Anesthesiology

Dysfonction myocardique post-arrêt cardiaque

Post-resuscitation myocardial dysfunction (PRMD) is a frequent complication, which worsens hemodynamic status and may be lethal by itself. Early identification and treatment of this cardiac complication is one of the key-targets of support during hospitalization of these patients. Easy to identify using echocardiography, PRMD usually begins early after the resuscitation, and is completely reversible within 48 to 72 hours. Its presentation associates myocardial systolic and diastolic dysfunctions, even in the absence of coronary cause. However, detection and treatment of myocardial ischemia should be systematically performed when a coronary cause of cardiac arrest is suspected. To date, the most recommended treatment for systolic dysfunction remains dobutamine since no other pharmacological agents demonstrated its superiority in this setting. In the most severe cases, a mechanical circulatory assistance should be considered providing that neurological prognosis is not compromised.

Sarcoplasmic Phospholamban Protein Is Involved in the Mechanisms of Postresuscitation Myocardial Dysfunction and the Cardioprotective Effect of Nitrite during Resuscitation

ObjectivesSarcoplasmic reticulum (SR) Ca2+-handling proteins play an important role in myocardial dysfunction after acute ischemia/reperfusion injury. We hypothesized that nitrite would improve postresuscitation myocardial dysfunction by increasing nitric oxide (NO) generation and that the mechanism of this protection is related to the modulation of SR Ca2+-handling proteins.MethodsWe conducted a randomized prospective animal study using male Sprague-Dawley rats. Cardiac arrest was induced by intravenous bolus of potassium chloride (40 µg/g). Nitrite (1.2 nmol/g) or placebo was administered when chest compression was started. No cardiac arrest was induced in the sham group. Hemodynamic parameters were monitored invasively for 90 minutes after the return of spontaneous circulation (ROSC). Echocardiogram was performed to evaluate cardiac function. Myocardial samples were harvested 5 minutes and 1 hour after ROSC.ResultsMyocardial function was significantly impaired in the nitrite and placebo groups after resuscitation, whereas cardiac function (i.e., ejection fraction and fractional shortening) was significantly greater in the nitrite group than in the placebo group. Nitrite administration increased the level of nitric oxide in the myocardium 5 min after resuscitation compared to the other two groups. The levels of phosphorylated phospholamban (PLB) were decreased after resuscitation, and nitrite increased the phosphorylation of phospholamban compared to the placebo. No significant differences were found in the expression of sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) and ryanodine receptors (RyRs).Conclusionspostresuscitation myocardial dysfunction is associated with the impairment of PLB phosphorylation. Nitrite administered during resuscitation improves postresuscitation myocardial dysfunction by preserving phosphorylated PLB protein during resuscitation.

Combination of Epinephrine with Esmolol Attenuates Post-Resuscitation Myocardial Dysfunction in a Porcine Model of Cardiac Arrest

BackgroundRecent experimental and clinical studies have indicated that the β-adrenergic effect of epinephrine significantly increases the severity of post resuscitation myocardial dysfunction. The aim of the study was to investigate whether the short-acting β1-selective adrenergic blocking agent, esmolol, would attenuate post resuscitation myocardial dysfunction in a porcine model of cardiac arrest.Methods and ResultsAfter 8 min of untreated ventricular fibrillation and 2 min of basic life support, 24 pigs were randomized to three groups (n = 8 per group), which received central venous injection of either epinephrine combined with esmolol (EE group), epinephrine (EP group), or saline (SA group). Hemodynamic status and blood samples were obtained at 0, 30, 60, 120, 240 and 360 min after return of spontaneous circulation (ROSC). Surviving pigs were euthanatized at 24 h after ROSC, and the hearts were removed for analysis by electron microscopy, Western blotting, quantitative real-time polymerase chain reaction, and terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling (TUNEL) assay. Compared with the EP and SA groups, EE group had a better outcome in hemodynamic function, (improved dp/dt maxima and minima and cardiac output) (P<0.05), and improved oxygen metabolism (oxygen delivery and oxygen consumption) (P<0.05), which suggesting that EE can protect myocardial tissue from injury and improve post-resuscitation myocardial dysfunction. The protective effect of EE also correlated with reducing cardiomyocyte apoptosis, evidenced by reducing TUNEL-positive cells, increasing anti-apoptotic Bcl-2/Bax ratio and suppression of caspase-3 activity in myocardium.ConclusionsEsmolol, a short-acting β1-selective adrenergic blocking agent, given during CPR has significant effects on attenuating post resuscitation myocardial dysfunction. The current study provides a potential pharmacologic target for post resuscitation myocardial dysfunction.

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Introduction: The detrimental effects of epinephrine are closely related to its β- and a1- action, which significantly increases the severity of post-resuscitation (PR) myocardial dysfunction. In the present study, we investigated the effects of β- and β- plus α1- adrenergic blocking agents on post-resuscitation myocardial dysfunction and myocardial injury biomarkers. Methods: Twenty-four male Sprague-Dawley rats weighing between 450 - 550g were randomized into 4 groups: 1) placebo; 2) epinephrine; 3) epinephrine with β- blocker (propranolol) and; 4) epinephrine with β- plus α1- blockers (propranolol and prazosin). Ventricular fibrillation (VF) was electrically induced. CPR was initiated after 8 mins of untreated VF and continued for 8 mins. Defibrillation was then attempted. Ejection fraction (EF) and myocardial performance index (MPI) were measured at baseline and at hourly intervals for 4 hrs after resuscitation. Troponin I (Tn I) and N-terminal pro-brain natriuretic peptide (NT-pro BNP) were measured at baseline and at 1 and 4 hrs after resuscitation by the ELISA kits. Results: The β- and β- plus α1- blockers significantly reduced the severity of PR myocardial dysfunction. EF and MPI were 60.23 ± 1.23 and 1.01 ± 0.06 in the β- blocker group and 63.63 ± 1.51 and 0.89 ± 0.03 in the β- plus α1- blockers treated group compared to 39.90 ± 2.60 and 1.34 ± 0.10 in the epinephrine treated group and 44.58 ± 4.57 and 1.25 ± 0.10 in the placebo group at PR 4 hrs (p<0.05). The β- and β- plus α1- blockers pretreatment also reduced the releases of Tn I and NT-pro BNP compared with the placebo and epinephrine groups at PR 4 hrs (2.4 ± 1.0 and 1.8 ± 0.6 vs. 8.2 ± 5.2 and 9.5 ± 6.9 ng/L, p<0.05; 153.7 ± 44.9 and 151.7 ± 24.3 vs. 241.8 ± 16.9 and 298.9 ± 118.5 ng/L, p<0.05). The β- and β- plus α1-blockers significantly improved the duration of survival (67.8 ± 10.2 and 72.0 ± 0 vs. 34.4 ± 34.6 and 22.8 ± 26.4 hrs, p<0.05). Conclusions: The β- and β- plus α1-blockers reduced the severity of PR myocardial dysfunction and attenuated release of myocardial injury biomarkers with improved duration of survival in a rat model of CPR.

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Introduction: Post-resuscitation myocardial dysfunction is one of leading causes of death after resuscitation from cardiac arrest. It is generally considered as a reversible myocardial stunning. However, its mechanism and especially whether there is myocardial tissue damage after global ischemia of cardiac arrest remain unclear. In the present study, we investigated the relationship between the severity of post-resuscitation myocardial dysfunction and myocardial injury biomarkers. Methods: Thirty-six male Sprague-Dawley rats weighing between 450-550g were randomized into 6 groups: 1) placebo; 2) epinephrine; 3) epinephrine with α1- blocker; 4) epinephrine with α2- blocker; 5) epinephrine with β- blocker and; 6) epinephrine with β- and α1- blocker. Ventricular fibrillation (VF) was electrically induced. CPR was initiated after 8 mins of untreated VF and continued for 8 mins. Defibrillation was then attempted. Ejection fraction (EF) and myocardial performance index (MPI) were measured by echocardiography at baseline and hourly interval for 4 hrs after resuscitation. The serum concentrations of Troponin I (Tn I) and N-terminal pro-brain natriuretic peptide (NT-pro BNP) were measured at baseline, 1 and 4 hrs after resuscitation by the ELISA kits. Results: All animals except for one in the placebo group were resuscitated. The post-resuscitation myocardial function measured by EF and MPI were significantly impaired after resuscitation in all animals. The most severe impairment was observed in epinephrine with α2- blocker and epinephrine treated animals. The impairment of myocardial mechanical function was parallel with myocardial injury biomarkers measured by Tn I and NT-pro BNP (EF and Tn I: r = -0.639, p < 0.01, EF and NT-pro BNP: r = -0.729, p < 0.01 and MPI and Tn I: r =-0.604, p < 0.01, MPI and NT-pro BNP: r = -0.649, p < 0.01, respectively). Conclusions: The severity of post-resuscitation myocardial dysfunction was closely related to myocardial injury biomarkers which indicate that post-resuscitation myocardial dysfunction is associated with myocardial tissue injury.

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Introduction: Although randomized controlled trials have explored the use of epinephrine for out-of-hospital cardiac arrest patients, there remains a lack of research on the benefit and proper dose of epinephrine for in-hospital cardiac arrest patients. Past research has indicated that epinephrine might increase return of spontaneous circulation (ROSC), but has not been shown to significantly improve long-term outcomes. Further, it has been linked to post-resuscitation myocardial dysfunction and reduced cerebral microcirculation, which might be a contributing factor to anoxic brain injury. Therefore, conservative use of epinephrine for in-hospital cardiac arrest patients might increase the survival rate. Methods: I conducted a retrospective chart review to see whether the use of epinephrine affects 24 hour survival after in-hospital cardiac arrest. Clinical, demographic, and treatment data were collected and analyzed for 85 in-hospital cardiac arrest patients. Of these 85 patients, 70 had a non-VF cardiac arrest due to pulseless electrical activity (PEA) or asystole. The non-VF arrest group was divided into three groups: short-duration arrest group (defined by downtime of less than 10 minutes), intermediate-duration arrest group (defined by downtime of 10 to 20 minutes), and long-duration arrest group (defined by downtime of more than 20 minutes). Results: In the non-VF arrest group, 60 percent of patients (42/70) survived 24 hours after cardiopulmonary resuscitation (CPR) initiation. 76 percent of patients (32/42) who survived 24 hours received a low dose of epinephrine (0mg -2mg) as compared to 21 percent (6/28) in the non-survivor group (p–value= 0.0029). In the intermediate-duration arrest group, 71 percent of patients (10/14) who survived 24 hours received a low dose of epinephrine (0mg-2mg) as compared to 10 percent (1/10) in the non-survivor group (p–value=0.0045). In the long-duration arrest group, 50 percent of patients (5/10) who survived 24 hours received a low dose of epinephrine (0mg-2mg) as compared to 19 percent (3/16) in the non-survivor group (p–value=0.1892). Further, 63 percent of patients (15/24) who survived 24 hours in prolonged cardiac arrest (defined by downtime of more than 10 minutes) received a low dose of epinephrine as compared to 15 percent (4/26) in the non-survivor group (p–value=0.0011). Conclusions: The results suggest that the conservative use of epinephrine might be beneficial for in-hospital cardiac arrest patients due to PEA or asystole. Further studies are needed to verify this intriguing preliminary data with more subjects.

Abstract 291: Intestinal Microcirculatory Alterations in a Rat Model of Cardiac Arrest and Resuscitation

Introduction: Abnormalities in intestinal microvascular blood flow are of increasing interest during the post-resuscitation phase following cardiac arrest because of the critical role attributed to the intestine in the pathogenesis of systemic inflammatory response, which potentially further aggravate post-resuscitation myocardial and cerebral dysfunction. The present study investigated post-resuscitation mesenteric microcirculatory dysfunctions in a rat model of cardiac arrest and resuscitation. Methods: Eight Sprague-Dawley rats were divided into two groups: 1) VF8+PC8 group: 8 mins of untreated VF followed by 8 mins of CPR and defibrillation (n=5); 2) sham control: animals only underwent surgical procedure (n=3). A laparotomy was performed to expose a segment of the jejunum. Twenty-second clips of the mesenteric microcirculation were captured with the sidestream dark field (SDF) video microscope at three locations at baseline and at 1, 2, 4, 6, 8 hours after the return of spontaneous circulation (ROSC). Mesenteric microcirculatory blood flow was quantified off-line by determining the microcirculatory flow index (MFI). Results: MFIs were significantly reduced 1 hour after ROSC and gradually recovered until it reached a peak at the 6th hour. This was followed by a remarkable decrease at the 8th hour. Compared with control group, MFIs reductions in the VF8+PC8 group were statistically significant (p&lt;0.01) at all time points except for 6 hours after ROSC. Conclusion: There was a significant reduction in mesenteric microcirculatory blood flow following successful resuscitation from cardiac arrest.

Abstract 9: Remote Ischemic Pre- and Post-Conditioning Produce Similar Improvement of Myocardial and Cerebral Function in a Rat Model of Cardiac Arrest and Resuscitation

Introduction: Remote ischemic pre-conditioning (RPC) has been demonstrated to provide powerful protection of the heart and the brain against ischemia reperfusion injury. However, it is not a practical use in the clinical settings of cardiac arrest and resuscitation. We investigated the effects of remote ischemic post-conditioning (RpostC) on post-resuscitation myocardial and cerebral function in a rat model of cardiac arrest. Hypothesis: RpostC is as effective as RPC in reducing post-resuscitation myocardial and cerebral dysfunction in a rat model of cardiac arrest. Methods: Twenty-one male Spague Dawley rats were randomized into three groups: 1) RPC, initiated 40 mins before induction of ventricular fibrillation (VF); 2) RpostC, initiated 5 mins after successful resuscitation; 3) Control. Remote ischemic conditioning was induced by four cycles of 5 mins of limb ischemia, followed by 5 mins of reperfusion. VF was induced and untreated for 6 mins while defibrillation was attempted after 8 mins of CPR. The animals were then monitored for 4 hours and observed for an additional 68 hours. Results: Equally improved post-resuscitation myocardial and neurological function were observed in the RPC and the RpostC groups, which were significantly better than the Control group (Table). Conclusion: In a rat model of cardiac arrest and resuscitation, remote ischemic pre- and post-conditioning produced similar improvement of myocardial and cerebral function.

Abstract 354: Nitrate Improves Postresuscitation Myocardial Dysfunction by Preserving Myocardial Nitric Oxide and Phospholamban Protein

Objectives: Sarcoplasmic reticulum (SR) Ca 2+ handling proteins have been shown to play an important role in myocardial dysfunction after acute ischemic/reperfusion injury. We assessed the hypothesis that nitrite would improve postresuscitation myocardial dysfunction by increasing NO generation, and the mechanism is related to the modulation of SR Ca 2+ handling proteins. Methods: We performed a randomized prospective animal study using male Sprague-Dawley rats. Cardiac arrest was induced by intravenous bolus of potassium chloride (40 μg/g). Nitrite (1.2nmol/g) or placebo was administered when chest compression was started. No cardiac arrest was induced in sham group. Hemodynamic parameters were monitored invasively for one hour after ROSC. Echocardiogram was performed to evaluate cardiac function. Myocardial sample was harvested 5 minutes and 1 hour after ROSC respectively. The expression of sarcoplasmic reticulum Ca 2+ ATPase (SERCA2a), phospholamban (PLB) and rynodine receptors (RyRs) were analyzed by Western blot analysis. Myocardial NO five minutes after ROSC were measured using Nitric Oxide Assay Kit. Results: Myocardial function measured as the maximal rate of LV pressure increase (dP/dtmax), the maximal rate of LV pressure decline (-dP/dtmax), ejection fraction, fractional shortening was significantly impaired in nitrite and placebo groups after resuscitation, and cardiac function in nitrite group was significantly greater than placebo group. Nitrite administration increased the level of nitric oxide in myocardium 5 min after resuscitation when compared to the other two groups. The levels of phosphorylated phospholamban were decreased after resuscitation, and nitrite preserved the phosphorylation of phospholamban in myocardium after resuscitation when compared to placebo group. No significant differences were found in the expressions of myocardial sarcoplasmic reticulum Ca 2+ ATPase and rynodine receptors after resuscitation. Conclusions: Nitrite administered during resuscitation improves postresusctation myocardial dysfunction as an exogenous donor of nitric oxide, and the modulation of phosphorylated phospholamban, an important SR Ca 2+ uptake protein, is involved in the mechanism.

Weaning from mechanical ventilation

Cytidine diphosphate choline (CDP-choline) is a cholinergic agent that can both stimulate the cholinergic pathway and increase blood pressure. We aimed to investigate the effects of CDP-choline on the outcome of cardiac arrest in comparison with epinephrine.This was a randomized prospective animal study. Cardiac arrest was induced by asphyxia in 45 rats. After 7 minutes of asphyxia, resuscitation was attempted. The rats were allocated to different groups treated with 2 mL/kg saline, 100 μg/kg epinephrine, or 250 mg/kg CDP-choline. The hemodynamic parameters were monitored for 2 hours after resuscitation, and cardiac function was evaluated by echocardiography 2 hours after resuscitation. The hearts were harvested at the end of monitoring for histologic evaluation.Epinephrine and CDP-choline improved the rate of return of spontaneous circulation and blood pressure during cardiopulmonary resuscitation; however, postresuscitation cardiac function in the CDP-choline and placebo groups was better than in the epinephrine group. Compared with the epinephrine group, less myocardial and mitochondrial injury was observed by electron microscopy in the CDP-choline and placebo groups; the level of superoxide dismutase and malondialdehyde indicated less peroxidative injury in the CDP-choline and placebo groups. Cytidine diphosphate choline and placebo also preserved connexin 43 when compared with epinephrine.When administered during resuscitation, CDP-choline increased the rate of return of spontaneous circulation similarly to epinephrine. In addition, it did not increase the severity of myocardial injury and postresuscitation myocardial dysfunction, whereas epinephrine appeared to be harmful.

Preservation of myocardial contractile function by aminoguanidine, a nitric oxide synthase inhibitors, in a rat model of hemorrhagic shock

Myocardial contractile dysfunction plays a major role in the outcome of trauma patients. Nitric oxide (NO) has been shown to increase following haemorrhagic shock. Peroxynitrite which is produced by the reaction of NO with reactive oxygen species leads to nitrosative stress mediated organ injury and myocardial contractile dysfunction. Aminoguanidine is a selective inhibitor of inducible nitric oxide synthase (iNOS). The aim of this study was to determine the protective effects of inhibiting the production of NO using aminoguanidine (AG) on myocardial contractility, following hemorrhagic shock and resuscitation in rats. Male Sprague-Dawley rats were assigned to 3 experimental groups (n = 6 per group):1) Normotensive rats (N), 2) Hemorrhagic shock rats (HS), and 3) Hemorrhagic shock rats treated with AG 60 mg/kg AG intra-arterially (HS-AG). Rats were hemorrhaged over 60 minutes to reach a mean arterial blood pressure of 40 mmHg. Rats were treated with 1 ml of 60 mg/Kg AG intra-arterially after 60 minutes haemorrhagic shock,. Resuscitation was performed in vivo by the reinfusion of the shed blood for 30 minutes to restore normo-tension. Hearts were harvested and ex vivo perfused in the Langendorff System and myocardial function was determined by measuring the left ventricular end diastolic pressure (LVEDP) and left ventricular systolic pressure (LVSP). Left ventricular generated pressure (LVGP) and + dP/dt max was calculated. Hemorrhagic shock rats treated with AG exhibited a significant increase in left ventricular generated pressure LVGP (137.1 ± 9.4 mmHg) and + dP/dtmax (589.6 ± 110.7 mmHg/sec) compared with the untreated group (44.43 ± 20.18 mmHg, 289.8 ± 25.0 mmHg/sec). Treatment with AG protects the myocardium from post-resuscitation myocardial dysfunction.

Differences of postresuscitation myocardial dysfunction in ventricular fibrillation versus asphyxiation

PurposeThis study aims to characterize postresuscitation myocardial dysfunction in 2 porcine models of cardiac arrest (CA): ventricular fibrillation cardiac arrest (VFCA) and asphyxiation cardiac arrest (ACA). MethodsThirty-two pigs were randomized into 2 groups. The VFCA group (n = 16) were subject to programed electrical stimulation, and the ACA group (n = 16) underwent endotracheal tube clamping to induce CA. Once induced, CA remained untreated for 8 minutes. Two minutes after initiation of cardiopulmonary resuscitation (CPR), defibrillation was attempted until return of spontaneous circulation (ROSC) was achieved or animals died. ResultsReturn of spontaneous circulation was 100% successful in VFCA and 50% successful in ACA. Cardiopulmonary resuscitation duration in VFCA was about half as short as in ACA. The survival time of VFCA was significantly longer than that of ACA. Ventricular fibrillation cardiac arrest had better mean arterial pressure, cardiac output, and left ventricular ± dp/dtmax after ROSC than ACA. Echocardiography revealed significantly lower left ventricular ejection fraction in ACA than in VFCA. Myocardial perfusion imaging using single-photon emission computed tomography demonstrated that myocardial injuries after ACA were more severe and widespread than after VFCA. Under a transmission electron microscope, the overall heart morphologic structure and the mitochondrial crista structure were less severely injured in the VFCA group than in the ACA group. Moreover, the percentage of apoptotic cardiomyocytes was higher in ACA than in VFCA. ConclusionsCompared with VFCA, ACA causes more severe cardiac dysfunction associated with less successful resuscitation and shorter survival time.

The role of inflammation in postresuscitation myocardial dysfunction

The role of inflammation in postresuscitation myocardial dysfunction

GW24-e1015 Nitrate improves postresuscitation myocardial dysfunction and the involvement of nitric oxide and phospholamban protein

ObjectivesThe abnormality of Sarcoplasmic reticulum (SR) Ca2+ handling proteins was shown to be essential in myocardial dysfunction after acute reperfusion injury, which might be attenuated by NO therapy. Cardiac arrest...

High-dose erythropoietin during cardiac resuscitation lessens postresuscitation myocardial stunning in swine

We investigated the metabolic and functional myocardial effects of erythropoietin (EPO) administered during resuscitation from cardiac arrest using an open-chest pig model of ventricular fibrillation and resuscitation by extracorporeal circulation, after having reported in rats a reversal of postresuscitation myocardial dysfunction associated with activation of mitochondrial protective pathways. Ventricular fibrillation was induced in 16 male domestic pigs and left untreated for 8 minutes, after which extracorporeal circulation was started and maintained for 10 additional minutes, adjusting the extracorporeal flow to provide a coronary perfusion pressure of 10 mmHg. Defibrillation was accomplished and the extracorporeal flow was adjusted to secure a mean aortic pressure of 40 mmHg or greater during spontaneous circulation for up to 120 minutes. Pigs were randomized 1:1 to receive EPO (1200 U/kg) or 0.9% NaCl before starting extracorporeal circulation. Severe postresuscitation myocardial dysfunction developed in both groups. However, recovery of myocardial function-comparing baseline with 120 minutes postresuscitation-was better in pigs treated with EPO than NaCl, as shown for left ventricular ejection fraction (from 45 ± 8% to 36 ± 9% in EPO, not significant; and from 46 ± 8% to 26 ± 8% in NaCl, P < 0.001) and for peak systolic pressure/end-systolic volume (from 2.7 ± 0.8 mmHg/mL to 2.4 ± 0.7 mmHg/mL in EPO, not significant; and from 3.0 ± 1.1 mmHg/mL to 1.8 ± 0.6 mmHg/mL, P < 0.001 in NaCl). The EPO effect was associated with significantly higher myocardial O2 consumption (12 ± 6 mL/min/unit of tissue vs 6 ± 2 mL/min/unit of tissue, P < 0.017) without effects on myocardial lactate consumption. Thus, EPO administered during resuscitation from ventricular fibrillation lessened postresuscitation myocardial stunning-an effect that could be useful clinically to help promote postresuscitation hemodynamic stability.

Management of postcardiac arrest myocardial dysfunction

Postresuscitation myocardial dysfunction (PRMD) is a frequent complication, which worsens the hemodynamic status and can be lethal. Early identification and treatment of this cardiac complication is one of the key therapeutic goals during hospitalization of these patients. PRMD is easy to characterize using echocardiography. It usually begins within minutes after the resuscitation and is completely reversible within 48-72 h. It takes the form of myocardial systolic and diastolic dysfunction, even in the absence of a coronary cause. Detection and treatment of myocardial ischemia should be considered when a coronary cause of cardiac arrest is suspected. The most frequently used treatment for systolic dysfunction remains dobutamine, as no other pharmacological agents have been shown to be superior in this setting. In the most severe cases, mechanical circulatory assistance may be indicated. Reversibility of PRMD justifies an aggressive management strategy, including detection of myocardial ischemia, inotropic support, and in the most severe cases, mechanical circulatory assistance. Hemodynamic dysfunction should not influence the decision to continue treatment because it is often reversible - the neurological status is much more likely to determine the ultimate outcome.