Adverse postresuscitation myocardial effects elicited by buffer-induced alkalemia ameliorated by NHE-1 inhibition in a rat model of ventricular fibrillation

2016 ◽  
Vol 121 (5) ◽  
pp. 1160-1168 ◽  
Author(s):  
Lorissa Lamoureux ◽  
Jeejabai Radhakrishnan ◽  
Thomas G. Mason ◽  
Jeffrey A. Kraut ◽  
Raúl J. Gazmuri
Keyword(s):  
Ventricular Fibrillation ◽  
Myocardial Function ◽  
Myocardial Dysfunction ◽  
Spontaneous Circulation ◽  
Male Rats ◽  
Intracellular Acidosis ◽  
Acid Base ◽  
Bicarbonate Buffer ◽  
Return Of Spontaneous Circulation ◽  
Blood Ph

Major myocardial abnormalities occur during cardiac arrest and resuscitation including intracellular acidosis—partly caused by CO2 accumulation—and activation of the Na+-H+ exchanger isoform-1 (NHE-1). We hypothesized that a favorable interaction may result from NHE-1 inhibition during cardiac resuscitation followed by administration of a CO2-consuming buffer upon return of spontaneous circulation (ROSC). Ventricular fibrillation was electrically induced in 24 male rats and left untreated for 8 min followed by defibrillation after 8 min of cardiopulmonary resuscitation (CPR). Rats were randomized 1:1:1 to the NHE-1 inhibitor zoniporide or vehicle during CPR and disodium carbonate/sodium bicarbonate buffer or normal saline (30 ml/kg) after ROSC. Survival at 240 min declined from 100% with Zoniporide/Saline to 50% with Zoniporide/Buffer and 25% with Vehicle/Buffer ( P = 0.004), explained by worsening postresuscitation myocardial dysfunction. Marked alkalemia occurred after buffer administration along with lactatemia that was maximal after Vehicle/Buffer, attenuated by Zoniporide/Buffer, and minimal with Zoniporide/Saline [13.3 ± 4.8 (SD), 9.2 ± 4.6, and 2.7 ± 1.0 mmol/l; P ≤ 0.001]. We attributed the intense postresuscitation lactatemia to enhanced glycolysis consequent to severe buffer-induced alkalemia transmitted intracellularly by an active NHE-1. We attributed the worsened postresuscitation myocardial dysfunction also to severe alkalemia intensifying Na+ entry via NHE-1 with consequent Ca2+ overload injuring mitochondria, evidenced by increased plasma cytochrome c. Both buffer-induced effects were ameliorated by zoniporide. Accordingly, buffer-induced alkalemia after ROSC worsened myocardial function and survival, likely through enhancing NHE-1 activity. Zoniporide attenuated these effects and uncovered a complex postresuscitation acid-base physiology whereby blood pH drives NHE-1 activity and compromises mitochondrial function and integrity along with myocardial function and survival.

Abstract 332: Controlling the Heart Rate After Resuscitation Decreases Duration of Survival in a Rat Model of Cardiac Arrest

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Zhangle Hu ◽  
Jin Yang ◽  
Qinyue Guo ◽  
Xiaobo Wu ◽  
Jennifer Bradley ◽  
...  
Keyword(s):  
Heart Rate ◽  
Ventricular Fibrillation ◽  
Femoral Artery ◽  
Myocardial Function ◽  
Myocardial Dysfunction ◽  
Spontaneous Circulation ◽  
Myocardial Oxygen Demand ◽  
High Heart Rate ◽  
Successful Resuscitation ◽  
Return Of Spontaneous Circulation

Introduction: A high heart rate (HR) after return of spontaneous circulation (ROSC) due to increased sympathetic drive is a compensatory mechanism of postresuscitation myocardial dysfunction. However, it increases myocardial oxygen demand and impairs oxygen supply, and may increase the severity of myocardial ischemia. Hypothesis: Reduction of HR would improve postresuscitation myocardial dysfunction. Methods: Thirty-two male Sprague-Dawley rats weighing 450-550g were randomized into 2 groups: 1) Saline group: Ventricular fibrillation was induced and untreated for 6 min followed by 8 min of CPR. Rats received 0.9% NaCl solution administered from the femoral artery at 1h after return of spontaneous circulation (ROSC). 2) Drug group: Ventricular fibrillation was induced and untreated for 6 min followed by 8 min of CPR. Rats received Ivabradine (0.5ml/kg) solution administered from the femoral artery at 1h after ROSC. All catheters including the endotracheal tube were removed at PR 5h and animals were returned to their cages and closely monitored for the duration of survival. Results: For both groups, postresuscitation myocardial function as expressed by CO, EF, MPI was impaired compared to baseline values. However, the IVA group was significantly inferior to the SAL group with myocardial function index from PR 120’ to PR 300 (*p<0.01) (Figure 1).A significantly shortened duration of survival was observed in the IVA group compared to the SAL group (p<0.01) (Figure 2). Conclusions: Lowering HR significantly reduces myocardial function the duration of survival following successful resuscitation.

Abstract 104: N-Acetyl Cysteine Improves Post Reperfusion Myocardial Dysfunction in a Rat Model of Cardiac Arrest and Return of Spontaneous Circulation

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Fenglian He
Keyword(s):  
Cardiac Arrest ◽  
Ventricular Fibrillation ◽  
Rat Model ◽  
Myocardial Function ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Spontaneous Circulation ◽  
Control Group ◽  
Successful Resuscitation ◽  
Return Of Spontaneous Circulation

N-acetylcysteine improves post reperfusion myocardial dysfunction in a Rat Model of Cardiac Arrest and return of spontaneous circulation Introduction: Studies have demonstrated that N-acetylcysteine (NAC) can attenuate regional myocardial ischemia/reperfusion injury and improved myocardial dysfunction. However, it is not clear whether NAC could protect post reperfusion myocardial dysfunction (PRMD) after cardiac arrest (CA) and return of spontaneous circulation (ROSC). In this study, we investigated the effect of NAC on post reperfusion myocardial dysfunction in a rat model of CA and ROSC. Hypothesis: NAC reduces the severity of PRMD in a rat model of CA and ROSC. Method: Ten healthy male Sprague-Dawley rats weighting 450g–550g were utilized, and randomly divided into two groups: 1) control group; 2) NAC group (150mg/kg). Ventricular fibrillation (VF) was induced. After 8 mins of VF, CPR was initiated for 8 mins, and defibrillation was then attempted. Myocardial function was measured by echocardiography at baseline, 2, 4 and 6 hours after successful resuscitation. Result: Except one in the control group, all animals were resuscitated. Myocardial function of post-resuscitation was significantly decreased in all animals. However, myocardial function gradually improved in animals treated with NAC when compared with those in control groups (Figure). Conclusion: In a rat model of cardiac arrest, NAC improves post-resuscitation myocardial dysfunction Figure The post-resuscitation myocardial dysfunction. BL, baseline; VF, ventricular fibrillation; CO, cardiac output; EF, ejection fraction; MPI, myocardial performance index; CPR, cardiopulmonary resuscitation; C group,control group; N group, NAC intervention group; * p < 0.05.vs. the C group.

scholarly journals Comparison of Resuscitation Outcomes Between 2‐ or 3‐Stacked Defibrillation Strategies With Minimally Interrupted Chest Compression and the Single Defibrillation Strategy: A Swine Cardiac Arrest Model

2021 ◽  
Vol 10 (18) ◽  
Author(s):  
Soyeong Kim ◽  
Woo Jin Jung ◽  
Young Il Roh ◽  
Tae Youn Kim ◽  
Sung Oh Hwang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Ventricular Fibrillation ◽  
Chest Compression ◽  
Neurological Deficit ◽  
Life Support ◽  
Spontaneous Circulation ◽  
Shock Group ◽  
Return Of Spontaneous Circulation ◽  
Single Shock ◽  
Neurological Deficit Score

Background There is controversy over whether the number and mode of electrical shock are optimal for successful defibrillation. Methods and Results Fifty‐four pigs were randomly assigned to 3 groups. After inducing ventricular fibrillation and a 2‐minute downtime, basic life support was initiated with a 30:2 compression/ventilation ratio for 8 minutes. Subsequently, 20 minutes of advanced life support, including asynchronous ventilation, every 10 chest compressions with 15 L/min of oxygen, was delivered. Animals of the single shock group received a single shock, animals of the 2‐stacked shock group received 2 consecutive shocks, and animals of the 3‐stacked shock group received 3 consecutive shocks. Animals with the return of spontaneous circulation underwent post–cardiac arrest care for 12 hours. The rates of successful defibrillation, return of spontaneous circulation, 24‐hour survival, and 48‐hour survival and neurological deficit score were compared between the groups. Hemodynamic parameters, arterial blood gas profiles, troponin I, and cardiac output were not different between the groups. There was a significant difference in chest compression fraction between the single and 3‐stacked shock groups ( P <0.001), although there was no difference between the single and 2‐stacked shock groups ( P =0.022) or the 2‐stacked and 3‐stacked shock groups ( P =0.040). The rates of successful defibrillation, return of spontaneous circulation, 24‐hour survival, and 48‐hour survival were higher in the 2‐ and 3‐stacked shock groups than in the single shock group ( P =0.021, P =0.015, and P =0.021, respectively). Neurological deficit score at 48 hours was not different between the groups. Conclusions A stacked shock strategy was superior to a single shock strategy for successful defibrillation and better resuscitation outcomes in treating ventricular fibrillation.

scholarly journals Targeted Delivery of Electrical Shocks and Epinephrine, Guided by Ventricular Fibrillation Amplitude Spectral Area, Reduces Electrical and Adrenergic Myocardial Burden, Improving Survival in Swine

2021 ◽  
Author(s):  
Salvatore R. Aiello ◽  
Jenna B. Mendelson ◽  
Alvin Baetiong ◽  
Jeejabai Radhakrishnan ◽  
Raúl J. Gazmuri
Keyword(s):  
Ventricular Fibrillation ◽  
Targeted Delivery ◽  
Myocardial Dysfunction ◽  
Spontaneous Circulation ◽  
Left Ventricular ◽  
Rank Test ◽  
Swine Model ◽  
Spectral Area ◽  
Electrical Shocks ◽  
Outcome Improvement

Background We previously reported that resuscitation delivering electrical shocks guided by real‐time ventricular fibrillation amplitude spectral area (AMSA) enabled return of spontaneous circulation (ROSC) with fewer shocks, resulting in less myocardial dysfunction. We now hypothesized that AMSA could also guide delivery of epinephrine, expecting further outcome improvement consequent to less electrical and adrenergic burdens. Methods and Results A swine model of ventricular fibrillation was used to compare after 10 minutes of untreated ventricular fibrillation a guidelines‐driven (n=8) resuscitation protocol, delivering shocks every 2 minutes and epinephrine every 4 minutes, with an AMSA‐driven shocks (n=8) protocol, delivering epinephrine every 4 minutes, and with an AMSA‐driven shocks and epinephrine (ADSE; n=8) protocol. For guidelines‐driven, AMSA‐driven shocks, and ADSE protocols, the time to ROSC (mean±SD) was 569±164, 410±111, and 400±80 seconds ( P =0.045); the number of shocks (mean±SD) was 5±2, 3±1, and 3±2 ( P =0.024) with ADSE fewer than guidelines‐driven ( P =0.03); and the doses of epinephrine (median [interquartile range]) were 2.0 (1.3–3.0), 1.0 (1.0–2.8), and 1.0 (0.3–3.0) ( P =0.419). The ROSC rate was similar, yet survival after ROSC favored AMSA‐driven protocols (guidelines‐driven, 3/6; AMSA‐driven shocks, 6/6; and ADSE, 7/7; P =0.019 by log‐rank test). Left ventricular function and survival after ROSC correlated inversely with electrical burden (ie, cumulative unsuccessful shocks, J/kg; P =0.020 and P =0.046) and adrenergic burden (ie, total epinephrine doses, mg/kg; P =0.042 and P =0.002). Conclusions Despite similar ROSC rates achieved with all 3 protocols, AMSA‐driven shocks and ADSE resulted in less postresuscitation myocardial dysfunction and better survival, attributed to attaining ROSC with less electrical and adrenergic myocardial burdens.

Abstract 11100: Effect of Different Oxygen Concentrations on Post Resuscitation Myocardial Oxidative Stress and Myocardial Function in a Rat Model of CPR

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Shen Zhao ◽  
Jie Qian ◽  
Jiangang Wang ◽  
Ping Gong ◽  
Zhengfei Yang ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Myocardial Function ◽  
Myocardial Dysfunction ◽  
Prostaglandin F2α ◽  
Blood Gases ◽  
Spontaneous Circulation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Sprague Dawley ◽  
Myocardial Oxidative Stress ◽  
Inspired Oxygen

Background: Lipid peroxidation induced by oxygen free radicals plays a prominent role in myocardial injury after global ischemia. The present study investigated whether ventilation with lower concentration of inspired oxygen would decrease the severity of myocardial lipid peroxidation and post resuscitation myocardial dysfunction. Methods: Ventricular fibrillation was induced and untreated for 8 mins in 46 male Sprague-Dawley rats. Defibrillation was attempted after 8 mins of CPR. The animals were randomized into 3 groups: mechanical ventilation with 100% O2, 50% O2 or 21% O2 during CPR and one hr following return of spontaneous circulation. Normoxic ventilation was maintained thereafter. The level of 8-iso-Prostaglandin F2α (8-iso-PGF2α) in myocardium was evaluated using the enzyme-linked immunosorbent assay (ELISA). Blood gases, post resuscitation myocardial function and the duration of survival were monitored in all animals. Results: Compared with the 100% and 21% groups, the 50% group showed a lower 8-iso-PGF2α level at 4 hrs post resuscitation (Table). Significantly greater oxygen extraction rate, lower lactate, better myocardial ejection fraction and myocardial performance index were observed in the 50% group (Table). A significantly shorter duration of survival was observed in the 21% group when compared with the other two groups (Table). There was a trend in the 50% group towards an increased duration of survival when compared with the 100% group. Conclusions: In a rat cardiac arrest model, ventilation with 50% inspired oxygen during early post-ischemic reperfusion contributed to a decreased lipid peroxidation, a better oxygenation, myocardial function and duration of survival.

Abstract 10770: Curcumin Mitigates the Severity of Post-Resuscitation Myocardial Dysfunction Caused by Epinephrine in a Rat Cardiac Arrest Model

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Zhengfei Yang ◽  
Jiangang Wang ◽  
Lu Yin ◽  
Shen Zhao ◽  
Ziren Tang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Placebo Group ◽  
Ventricular Fibrillation ◽  
Myocardial Function ◽  
Myocardial Dysfunction ◽  
Sprague Dawley ◽  
Successful Resuscitation ◽  
Sprague Dawley Rats ◽  
Group 3 ◽  
Group 2

Introduction: Epinephrine significantly increases the severity of post-resuscitation myocardial dysfunction (PRMD) and reduces the duration of survival. The cardioprotective effect of curcumin against catecholamine-induced cardiotoxicity has been established. In the present study, we investigated the effects of curcumin on PRMD caused by epinephrine in a rat model of cardiac arrest. Hypothesis: Curcumin reduces the severity of PRMD caused by epinephrine. Methods: Twenty-four male Sprague-Dawley rats weighing between 450-550g were randomized into three groups: 1) Placebo group; 2) Epinephrine (20ug/kg) group; 3) Curcumin (100 mg/kg) pretreatment + epinephrine (20ug/kg) group. Ventricular fibrillation (VF) was then induced. After 8 mins of VF, CPR was initiated for 8 mins, and defibrillation was then attempted. Myocardial function was measured by echocardiography at baseline and hourly for 4 hours following successful resuscitation. Results: All animals except for two in the placebo group were resuscitated. Post-resuscitation myocardial function was significantly impaired in all animals. Significantly worse myocardial function was observed in the Epinephrine group in comparison with the two other groups (Figure). However, myocardial function was significantly better in the animals treated with curcumin when compared with those in the two other groups (Figure). Conclusion: In a rat cardiac arrest model, curcumin reduced the severity of PRMD caused by epinephrine.

Abstract 140: Effects of ω-3 Polyunsaturated Fatty Acids on Systemic Inflammation and Post-resuscitation Myocardial Function in a Rat Model of Cardiac Arrest and Cardiopulmonary Resuscitation

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Cheng Cheng ◽  
Hui Li ◽  
Tao Jin ◽  
Lian Liang ◽  
Guozhen Zhang ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cardiac Arrest ◽  
Polyunsaturated Fatty Acids ◽  
Systemic Inflammation ◽  
Rat Model ◽  
Myocardial Function ◽  
Myocardial Dysfunction ◽  
Spontaneous Circulation ◽  
Sprague Dawley ◽  
Tnf Α

Introduction: Massive systemic inflammation is a primary cause of myocardial dysfunction following cardiac arrest (CA) and resuscitation (CPR). We investigated the effects of ω-3 polyunsaturated fatty acids (ω-3 PUFA) on systemic inflammation and myocardial function after CA and CPR. Hypothesis: Administration of ω-3 PUFA at the start of CPR will alleviate post CPR inflammation and improve cardiac function in a rat model of CA and CPR. Methods: 18 male Sprague-Dawley rats weighing between 450g-550g were randomized into three groups: Sham, Control, and ω-3 PUFA. Ventricular fibrillation (VF) was induced and untreated for 6 min. 4J defibrillation was attempted after 8 min of CPR. Saline placebo or ω-3 PUFA (5mL/kg) was infused at the start of CPR and continued for 4h. Ejection fraction (EF), cardiac output (CO) and myocardial performance index (MPI) were measured by echocardiography at baseline, 1, 3 and 6h after return of spontaneous circulation (ROSC). Inflammatory cytokines (IL-6 and TNF-α) and cardiac biomarker (cTnI) levels in plasma were detected at baseline and 6 hrs after ROSC. Results: A decrease in EF and CO and an increase in MPI occurred after resuscitation. Significant improvement was noted in ω-3 PUFA compared to control animals (p<0.05) (Fig. 1). ELISA analysis showed increased plasma IL-6, TNF-α, and cTnI in post-resuscitated rats. Administration of ω-3 PUFA attenuated the rise in these plasma biomarkers (p<0.05) (Fig. 2). Conclusion: Administration of ω-3 PUFA attenuates post-resuscitation systemic inflammation and improves myocardial function in a rat model of CA and CPR.

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