Postresuscitation Myocardial Stunning Research Articles

Inhibition of nitric oxide synthases, but not inducible nitric oxide synthase, selectively worsens left ventricular function after successful resuscitation from cardiac arrest in swine.

Nitric oxide (NO) is a critical regulator of vascular tone and signal transduction in the cardiovascular system. NO is synthesized by three unique enzymes (nitric oxide synthases [NOS]): endothelial and neuronal NOS, both constitutively expressed, and inducible NOS (iNOS), which is induced by proinflammatory stimuli and subsequently produces a burst of NO. NO has been implicated as both an injurious and a beneficial mediator after cardiac arrest and resuscitation. A previous study in swine found that iNOS expression is absent in the myocardium prior to cardiac arrest and that it increases after 10 minutes of untreated ventricular fibrillation (VF), decreases somewhat during the early postresuscitation period, and then steadily increases up to 6 hours postresuscitation. Because this time course of iNOS expression mirrors that of postresuscitation myocardial dysfunction, this study was designed to test the hypothesis that selective inhibition of iNOS improves postresuscitation outcomes in swine. Thirty-two domestic swine of either sex were randomly assigned to receive one of the following treatments 15 minutes after return of spontaneous circulation (ROSC): (1) N(G) -nitro-l-arginine methyl ester (l-NAME), a global NO inhibitor; (2) aminoguanidine (AG), a selective iNOS inhibitor; or (3) saline as control. After 10 minutes of untreated VF, swine received a standard resuscitation protocol. Twenty-four-hour survival, neurological status, left ventricular (LV) function, and hemodynamic measurements were obtained. Return of spontaneous circulation occurred in 28 of 32 animals (88%). Only successfully resuscitated animals were assigned to treatment groups and completed the study. There were no differences in survival or neurological outcomes between groups. There were also no differences in LV function or hemodynamic variables found between the control group and the AG group. Global inhibition of NOS with l-NAME post-ROSC increased aortic pressure and transiently decreased pulse pressure. Treatment with l-NAME also increased LV end diastolic pressure and decreased cardiac output within 30 minutes post-ROSC, which was sustained throughout the 4-hour measurements, compared to both the control and the AG groups. In addition, LV ejection fraction recovered to baseline measurements in both the control and AG groups, but failed to recover in the l-NAME group. Global inhibition of NOS after cardiac arrest and resuscitation markedly worsens hemodynamic variables. Selective inhibition of iNOS after cardiac arrest and resuscitation does not prevent postresuscitation myocardial stunning. There were no significant differences in neurological outcome or survival between treatment groups.

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.

Establishing the Diagnosis of Inverted Stress Cardiomyopathy in a Patient with Cardiac Arrest during General Anesthesia: A Potential Role of Myocardial Strain?

In cardiac arrest survivors, postresuscitation myocardial stunning usually presents as either global left ventricular dysfunction or regional dyssynergy including the various forms of stress cardiomyopathy, in which rare variants may be difficult to diagnose. We present a patient with cardiac arrest during general anesthesia, in whom speckle tracking-derived myocardial strain helped to distinguish between the inverted variant of stress cardiomyopathy and global postresuscitation myocardial stunning.

Post-cardiac arrest syndrome: Mechanisms and evaluation of adrenal insufficiency

Cardiac arrest is one of the leading causes of death and represents maximal stress in humans. After restoration of spontaneous circulation, post-cardiac arrest syndrome is the predominant disorder in survivors. Besides the post-arrest brain injury, the post-resuscitation myocardial stunning, and the systemic ischemia/reperfusion response, this syndrome is characterized by adrenal insufficiency, a disorder that often remains undiagnosed. The pathophysiology of adrenal insufficiency has not been elucidated. We performed a comprehensive search of three medical databases in order to describe the major pathophysiological disturbances which are responsible for the occurrence of the disorder. Based on the available evidence, this article will help physicians to better evaluate and understand the hidden yet deadly post-cardiac arrest adrenal insufficiency.

Pathophysiology and pathogenesis of post-resuscitation myocardial stunning

The prognosis for cardiac arrest victims remains dismal, as only 17% survives to hospital discharge. Post-resuscitation myocardial stunning is the mechanical dysfunction that persists after the restoration of spontaneous circulation. Our knowledge regarding myocardial stunning has grown dramatically over the years, and several hypotheses have been proposed in order to explain its pathophysiology; however, the interrelationships among various mechanisms remain unclear. This review deals primarily with the basic aspects of the pathophysiology of post-resuscitation myocardial stunning. Given the large number of relevant studies and the fragmented information, an effort was made to summarize current knowledge in order to present a comprehensive pathophysiological mechanism. In this review, the pathophysiological disturbances occurring from the onset of cardiac arrest until the restoration of spontaneous circulation are addressed. Then, the pathophysiology of myocardial stunning during the post-resuscitation period is critically reviewed in 4 parts, the immediate, the early, the intermediate, and the recovery post-arrest phase. This article covers a huge gap in the existing literature regarding the pathophysiology of post-resuscitation period and provides a better understanding of the pathophysiology and pathogenesis of post-resuscitation myocardial stunning.

Myocardial microcirculatory dysfunction after prolonged ventricular fibrillation and resuscitation

The etiology of postresuscitation myocardial stunning is unknown but is thought to be related to either ischemia occurring during cardiac arrest and resuscitation efforts and/or reperfusion injury after restoration of circulation. A potential common pathway for postischemia/reperfusion end-organ dysfunction is microvascular injury. We hypothesized that myocardial microcirculatory function is markedly abnormal in the postresuscitation period. In vivo study of myocardial microvascular function. University animal laboratory. Five swine (25 +/- 2 kg). Measurements before and after cardiac arrest and resuscitation. Baseline data were not different among the five subjects. Left ventricular ejection fraction was significantly lower at all postresuscitation time periods (p < .05), reaching a nadir of 19% at 1 hr postresuscitation. Cardiac output declined following fibrillation and resuscitation and was significantly lower than baseline at 1 and 4 hrs postresuscitation (p < .05). Prearrest coronary flow reserve, a ratio of normal to maximal intracoronary flow velocity, was 3.4 ("normal" ratio is 2:4), but was below normal (<2) throughout the 4-hr post resuscitation period (p < .05). This in vivo study showed that normal myocardial microcirculatory function is quickly lost after prolonged ventricular fibrillation and resuscitation. As early as 30 min postresuscitation the myocardial microcirculatory function is less than 50% of its prearrest baseline level. This dysfunction persists for at least 4 hrs. During the postresuscitation period, both left ventricular ejection fraction and cardiac output decline from their prearrest levels. No cause and effect relationship was proven, but a parallel decline in left ventricular function and coronary flow reserve is evident.

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

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

The Resuscitation Outcome: Revisit the Story of the Stony Heart

Postresuscitation syndrome is a state of myocardial dysfunction after the restoration of circulation by successful resuscitation. Despite several advances in the field of resuscitation, the management of out-of-hospital cardiac arrest is still suboptimal. The high fatality rate shortly after successful resuscitation is mainly related to postresuscitation myocardial dysfunction. Postresuscitation myocardial stunning is reversible, while stony heart is irreversible due to prolonged unsuccessful resuscitation. This article reviews most of the published articles concerning the causes, mechanism, pathophysiology, and the updated trials for management of postresuscitation myocardial dysfunction. Further studies are warranted to highlight postresuscitation disease and its hemodynamic sequences and then to intervene according to the different phases of cardiac arrest. By modifying the conventional modalities of resuscitation together with new promising agents, the rescuers will be able to salvage the jeopardized postresuscitation myocardium and prevent its progression to the dismal stony heart. Community awareness and staff education are crucial to shorten resuscitation time and improve short-term and long-term outcomes. There is an urgent need to revise the guidelines for cardiopulmonary resuscitation in community setting, but how? It is a matter of where and when it is of enough value to be efficacious and cost-effective.

Postresuscitation Myocardial Stunning and its Outcome

What is the successful cardiopulmonary resuscitation? It is the few minutes postcardiopulmonary arrest that can answer. Twenty to 40 percent of patients who sustained cardiac arrest are initially resuscitated, but only 10% survive to hospital discharge, and more than 60% of victims succumb within 24 hours. This high fatality rate in the early hours and days after successful resuscitation is mainly related to the acute, intense, and reversible form of postresuscitation myocardial dysfunction (stunning) together with the ventricular tachyarrhythmia. It is a reversible process, provided that we are aware of the pertinent pathophysiology and then intervene accordingly. Herein I reviewed most of the published relevant articles concerning the causes, underlying mechanism, and the updated trials for management of postresuscitation myocardial stunning. I do agree that not only the restoration of the circulation but also long-term outcome should be the aim of resuscitation, and I readdress the role of epinephrine, dobutamine, biphasic defibrillator, with the new promising agent (ie, potassium channel opener), Delta-opioid receptor agonist, unloading intracellular calcium, antioxidants, and therapeutic hypothermia to halt this period of stunning. This will improve the outcome of the resuscitation efforts.

Treatment of post resuscitation myocardial dysfunction: aortic counterpulsation versus dobutamine

Background: Post resuscitation myocardial stunning is well described and recognized as a significant contributor to poor long-term outcome following cardiac arrest. Optimal strategies for treatment have not been determined. Methods: Ten domestic swine (49±3 kg) underwent 15 min of untreated ventricular fibrillation before being successfully resuscitated. Left ventricular systolic and diastolic function was measured at pre-arrest baseline, at 30 min and at 6 h post resuscitation. Five animals were treated immediately after resuscitation with intra-aortic balloon counterpulsation (IABP) and five were given dobutamine (5 mcg/kg per min). Results: No baseline differences were found. At 30 min post resuscitation pulmonary capillary wedge pressure and LVEDP were significantly higher (16±3 vs. 7±1 and 20±2 vs. 11±1 mmHg) while LV isovolumic relaxation (‘Tau’) was significantly longer (34±2 vs. 20±2 ms) in the IABP treated versus the dobutamine treated animals. Likewise, at 6 h post resuscitation LV ejection fraction was significantly less (21±6 vs. 39±4%), and LVEDP significantly higher (18 vs. 10 mmHg) in the IABP group. Heart rate was not different between the groups at any time post resuscitation. Conclusion: Dobutamine was superior to IABP for treatment of post resuscitation left ventricular systolic and diastolic dysfunction. The hypothesized advantage of IABP for treatment of post resuscitation myocardial stunning without excessively raising the heart rate like dobutamine was not realized.

Myocardial dysfunction after resuscitation from cardiac arrest: An example of global myocardial stunning

Objectives. This study investigated the effect of prolonged cardiac arrest and subsequent cardiopulmonary resuscitation on left ventricular systolic and diastolic function.Background. Cardiac arrest from ventricular fibrillation results in cessation of forward blood flow, including myocardial blood flow. During cardiopulmonary resuscitation, myocardial blood flow remains suboptimal. Once the heart is defibrillated and successful resuscitation achieved, reversible myocardial dysfunction, or “stunning,” may occur. The magnitude and time course of myocardial stunning from cardiac arrest is unknown.Methods. Twenty-eight domestic swine (26 ± 1 kg) were studied with both invasive and noninvasive measurements of ventricular function before and after 10 or 15 min of untreated cardiac arrest. Contrast left ventriculograms, ventricular pressures, cardiac output, isovolumetric relaxation time (tau) and transthoracic Doppler-echocardiographic studies were obtained.Results. Twenty-three of 28 animals were successfully resuscitated and postresuscitation data obtained. Left ventricular ejection fraction showed a significant reduction 30 min after resuscitation (p < 0.05). Regional wall motion analysis revealed diffuse, global left ventricular systolic dysfunction. Left ventricular end-diastolic pressure increased significantly in the postresuscitation period (p < 0.05). Isovolumetric relaxation time (tau) was significantly increased over baseline by 2 h after resuscitation (p < 0.05). Similar findings were noted with the Doppler-echocardiographic analysis, including a reduction in fractional shortening (p <0.05), a reduction in mitral valve deceleration time (p < 0.05) and an increase in left ventricular isovolumetric relaxation time in 5 h after resuscitation (p < 0.05). By 24 h, these invasive and noninvasive variables of systolic and diastolic left ventricular function had begun to improve. At 48 h, all measures of left ventricular function had returned to baseline levels.Conclusions. Myocardial systolic and diastolic dysfunction is severe after 10 to 15 min of untreated cardiac arrest and successful resuscitation. Full recovery of this postresuscitation myocardial stunning is seen by 48 h in this experimental model of ventricular fibrillation cardiac arrest.