Post-cardiac arrest myocardial dysfunction is improved with cyclosporine treatment at onset of resuscitation but not in the reperfusion phase

Tsai, Min‐Shan; Hsu, Chiung-Yuan; Su, Ya; Wang, Tzung‐Dau; Chang, Wei‐Tien; Chen, Wen‐Jone

doi:10.1016/s0300-9572(11)70150-2

Cited by 27 publications

(28 citation statements)

References 34 publications

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“…The tissues were then dehydrated in acetone, embedded in resin and sectioned into 60 nm thick slices. These ultrathin LV sections were placed on uncoated 200-mesh copper grids, stained with 4% uranyl acetate and 0.2% lead citrate in 0.1 N NaOH, and examined in a Hitachi 7650 TEM (Hitachi, Tokyo, Japan) [21]. The mitochondria were imaged at 30,000×.…”

Section: Methodsmentioning

confidence: 99%

Panax QuinquefoliumSaponin Attenuates Cardiomyocyte Apoptosis and Opening of the Mitochondrial Permeability Transition Pore in a Rat Model of Ischemia/Reperfusion

Liu

Tao

et al. 2014

Cell Physiol Biochem

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Aims: Opening of the mitochondrial permeability transition pore (mPTP) is a critical event during ischemia/reperfusion (I/R) injury. Recently, we showed that Panax quinquefolium saponin (PQS) alleviates apoptosis of cardiomyocytes by suppressing excessive endoplasmic reticulum stress (ERS) during I/R injury. Here, we hypothesized that this anti-apoptotic effect might be mediated through inhibition of mPTP and the mitochondrial apoptotic pathway. Methods: Ninety-six healthy male Sprague-Dawley rats were randomly divided into sham, I/R, I/R+PQS (200 mg/kg/d), Cyclosporine A (CsA, 10 mg/kg), I/R+CsA (10 mg/kg), and I/R+PQS+CsA. I/R was modeled in rats by ligating the left anterior descending artery (LAD) for 30 min followed by 120 min of reperfusion. To evaluate the cardioprotective function of PQS, we measured hemodynamics, serum content of creatine kinase-MB (CK-MB), myocardial infarct size, and myocardial apoptotic index (AI). We investigated the underlying mechanism by examining changes in the mitochondrial ultrastructure and membrane potential (ΔΨm), dynamics of mPTP opening, expression of cleaved caspase-3, cleaved caspase-9 in the myocardium, Bcl-2 and Bax in the mitochondria versus cytosol, and translocation of cytochrome c. Results: Administration of PQS to I/R rats significantly reduced serum CK-MB level, infarct size and AI. In addition, PQS protected the mitochondrial structure, markedly inhibited mPTP opening and ΔΨm depolarization, led to upregulation of Bcl-2 and downregulation of Bax in the mitochondria compared to the cytosol, and suppressed the expression of cleaved caspase-9 and cleaved caspase-3, as well as I/R induced translocation of cytochrome c to the cytoplasm. Conclusion: Our results show that PQS can alleviate apoptosis of cardiomyocytes during I/R injury, possibly due to repressed mitochondrial apoptotic pathway associated with the opening of mPTP induced by myocardial I/R injury.

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Section: Methodsmentioning

confidence: 99%

Panax QuinquefoliumSaponin Attenuates Cardiomyocyte Apoptosis and Opening of the Mitochondrial Permeability Transition Pore in a Rat Model of Ischemia/Reperfusion

Liu

Tao

et al. 2014

Cell Physiol Biochem

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“…45 This may also be the reason why some previously conducted studies were unable to find an improvement in neurological deficit score or cerebral cellular and molecular pathways when the anaesthetic was given after achievement of ROSC in a pig model of cardiac arrest for only 8 min. 37,46 Whether noble gases differ in this context and provide neurologic and myocardial protection when given later is the subject of ongoing research.…”

Section: Discusssionmentioning

confidence: 99%

Anaesthetic Postconditioning at the Initiation of CPR Improves Myocardial and Mitochondrial Function in a Pig Model of Prolonged Untreated Ventricular Fibrillation

et al. 2014

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Background Anaesthetic postconditioning (APoC) attenuates myocardial injury following coronary ischaemia/reperfusion. We hypothesised that APoC at the initiation of cardiopulmonary resuscitation (CPR) will improve post resuscitation myocardial function along with improved mitochondrial function in a pig model of prolonged untreated ventricular fibrillation. Methods In 32 pigs isoflurane anaesthesia was discontinued prior to induction of ventricular fibrillation that was left untreated for 15 min. At the initiation of CPR, 15 animals were randomised to controls (CON), and 17 to APoC with 2 Vol% sevoflurane during the first 3 min CPR. Pigs were defibrillated after 4 min of CPR. After return of spontaneous circulation (ROSC), isoflurane was restarted at 0.8-1.5 Vol% in both groups. Systolic and diastolic blood pressures were measured continuously. Of the animals that achieved ROSC, 8 CON and 8 APoC animals were randomised to have their left ventricular ejection fraction (LVEF%) assessed by echocardiography at 4 hrs. Seven CON and 9 APoC were randomised to euthanasia 15 min after ROSC to isolate mitochondria from the left ventricle for bioenergetic studies. Results ROSC was achieved in 10/15 CON and 15/17 APoC animals. APoC improved haemodynamics during CPR and post-CPR LVEF%. Mitochondrial ATP synthesis, coupling of oxidative phosphorylation and calcium retention capacity were improved in cardiac mitochondria isolated after APoC. Conclusions In a porcine model of prolonged untreated cardiac arrest, APoC with inhaled sevoflurane at the initiation of CPR, is associated with preserved mitochondrial function and improved post resuscitation myocardial dysfunction.

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“…to minimize the possible suffering and distress caused to the animals during the procedures; prepared as previously described [6]. Anesthetic monitoring included testing of rear foot reflexes before any incision or intubation, and continuous observation of respiratory patterns, heart rates, and responsiveness to manipulations and rear foot reflexes throughout the procedure.…”

Section: Methodsmentioning

confidence: 99%

“…Further neuroprotective intervention for post-cardiac arrest syndrome is infeasible during profound shock and hypotension. Managing post-cardiac arrest myocardial dysfunction can potentially improve cardiovascular failure and survival outcomes [6–8]. …”

Section: Introductionmentioning

confidence: 99%

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Urocortin Treatment Improves Acute Hemodynamic Instability and Reduces Myocardial Damage in Post-Cardiac Arrest Myocardial Dysfunction

et al. 2016

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AimsHemodynamic instability occurs following cardiac arrest and is associated with high mortality during the post-cardiac period. Urocortin is a novel peptide and a member of the corticotrophin-releasing factor family. Urocortin has the potential to improve acute cardiac dysfunction, as well as to reduce the myocardial damage sustained after ischemia reperfusion injury. The effects of urocortin in post-cardiac arrest myocardial dysfunction remain unclear.Methods and ResultsWe developed a preclinical cardiac arrest model and investigated the effects of urocortin. After cardiac arrest induced by 6.5 min asphyxia, male Wistar rats were resuscitated and randomized to either the urocortin treatment group or the control group. Urocortin (10 μg/kg) was administrated intravenously upon onset of resuscitation in the experimental group. The rate of return of spontaneous circulation (ROSC) was similar between the urocortin group (76%) and the control group (72%) after resuscitation. The left ventricular systolic (dP/dt40) and diastolic (maximal negative dP/dt) functions, and cardiac output, were ameliorated within 4 h after ROSC in the urocortin-treated group compared to the control group (P<0.01). The neurological function of surviving animals was better at 6 h after ROSC in the urocortin-treated group (p = 0.023). The 72-h survival rate was greater in the urocortin-treated group compared to the control group (p = 0.044 by log-rank test). Cardiomyocyte apoptosis was lower in the urocortin-treated group (39.9±8.6 vs. 17.5±4.6% of TUNEL positive nuclei, P<0.05) with significantly increased Akt, ERK and STAT-3 activation and phosphorylation in the myocardium (P<0.05).ConclusionsUrocortin treatment can improve acute hemodynamic instability as well as reducing myocardial damage in post-cardiac arrest myocardial dysfunction.

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Post-cardiac arrest myocardial dysfunction is improved with cyclosporine treatment at onset of resuscitation but not in the reperfusion phase

Cited by 27 publications

References 34 publications

Panax QuinquefoliumSaponin Attenuates Cardiomyocyte Apoptosis and Opening of the Mitochondrial Permeability Transition Pore in a Rat Model of Ischemia/Reperfusion

Panax QuinquefoliumSaponin Attenuates Cardiomyocyte Apoptosis and Opening of the Mitochondrial Permeability Transition Pore in a Rat Model of Ischemia/Reperfusion

Anaesthetic Postconditioning at the Initiation of CPR Improves Myocardial and Mitochondrial Function in a Pig Model of Prolonged Untreated Ventricular Fibrillation

Urocortin Treatment Improves Acute Hemodynamic Instability and Reduces Myocardial Damage in Post-Cardiac Arrest Myocardial Dysfunction

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