Tempol prevents isoprenaline-induced takotsubo syndrome via the reactive oxygen species/mitochondrial/anti-apoptosis /p38 MAPK pathway.

Takotsubo Syndrome (TS) is a kind of acute cardiac syndrome with a complex pathophysiological mechanism that remains to be elucidated. The relationship between TS and reactive oxygen species has received increasing attention over in recent years. Therefore, the relationship between TS and reactive oxygen species was investigated in vivo and in vitro. Isoprenaline (ISO) was used to induce TS and tempol (quercetin) was selected as a scavenger to eliminate reactive oxygen species in animal experiments, and echocardiography was used to determine the incidence of TS. The H9C2 cells were cultured with different reagents to investigate the detailed mechanism; Reactive oxygen species levels and mitochondrial function were evaluated. Cell apoptosis rate was analyzed by TUNEL staining and the proteins involved in the signaling pathways were examined by Western blotting. It was found that a high dose of tempol almost eliminated TS and protected the cardiac function. Moreover, tempol also decreased the reactive oxygen species levels and reduced lipid droplet deposition in myocardial tissue. In terms of the cultured cells, tempol preconditioning decreased reactive oxygen species production as well as lipid droplet deposition, and protected the mitochondrial function by reducing mitochondrial swelling, thereby maintaining the mitochondrial membrane potential (ΔΨm) at a level that was higher than that of controls. Furthermore, tempol could reduce cells apoptosis after ISO treatment and decrease the protein level of p38, which is a member of the MAPK family, which and thus plays an important role in regulating cells apoptosis. This antiapoptotic effect of tempol was similar to that of a control reagent, SB203580, which is a specific inhibitor of phospha-p38 (p-p38). This study demonstrated, for the first time, a sudden increase in reactive oxygen species and effects of the downstream cascades play core roles in the development of TS.

Takotsubo Syndrome-Scientific Basis for Current Treatment Strategies.

Takotsubo syndrome (TS) is characterized by severe reversible left ventricular (LV) wall motion abnormality in the absence of explanatory coronary lesion. Despite an increasing number of patients diagnosed with TS worldwide, there are no randomized clinical trials. In mild cases, no treatment or a short course of limited anticoagulation therapy may be sufficient. Positive inotropic and vasodilating agents should be avoided. In severe cases with refractory cardiogenic shock, early treatment with mechanical support using venoarterial extracorporeal membrane oxygenation or a LV assist device should be considered.

Therapy of stress (takotsubo) cardiomyopathy: present shortcomings and future perspectives.

Several therapeutic options are available for the treatment of the acute phase of stress cardiomyopathy, pharmacological (ß-blockers, diuretics, anticoagulants, antiarrhythmics, noncatecholamine inotropics [levosimendan]), and nonpharmacological (intra-aortic balloon pumping, extracorporeal membrane oxygenation), according to the wide possible clinical presentation and course of the disease. However, there is a gap in evidence, and very few data come from randomized and adequately powered studies. Some evidence supports the use of ß-blockers, in particular with a short half-life, in the case of left ventricular outflow tract obstruction, and angiotensin-converting enzyme inhibitors in secondary prevention. Future perspectives include the study of genetic basis of stress cardiomyopathy, role of miRNA and neurovegetative modulation. Randomized studies, however, are surely warranted.

Actualización práctica en síndrome de Takotsubo / Practical update of Tsaktubo syndrome

El síndrome de Takotsubo, apical balloning o síndrome del «corazón roto», es una entidad de diagnóstico creciente que mimetiza clínicamente un síndrome coronario agudo. Englobado en el grupo de las miocardiopatías de estrés, se caracteriza por la ausencia de lesiones coronarias potencialmente responsables del cuadro y una paradójica alteración en la motilidad ventricular de carácter transitorio, que suele interesar varios territorios coronarios. Se observa generalmente en mujeres posmenopáusicas y se describe con frecuencia la presencia de una situación estresante, tanto física como emocional. Con una incidencia aproximada del 1,2% de aquellos síndromes coronarios agudos sometidos a cateterismo, a pesar de conllevar generalmente un buen pronóstico, ocasionalmente presenta en la fase aguda complicaciones, generalmente insuficiencia cardiaca, que pueden conducir incluso al fallecimiento de los enfermos. En la presente revisión nos planteamos repasar la última información disponible y presentarla de un modo práctico y útil al clínico (AU)

Takotsubo syndrome, apical ballooning or «broken heart» syndrome, is a growing diagnostic entity which clinically mimics an acute coronary syndrome. Included into the stress cardiomyopathy group of cardiopathies, this condition is characterized by the absence of potentially responsible coronary lesions, while displaying a transient abnormal ventricular motion, usually affecting various coronary territories. It is generally observed in postmenopausal women and frequently seen in the presence of a stressful situation, both physical and emotional. With a prevalence of 1.2% among patients undergoing a cardiac catheterization with a suspected diagnosis of acute coronary syndromes, Takotsubo syndrome usually has a good prognosis. However, complications can occur in the acute phase, generally heart failure, which can even lead to death. In this review we discuss the latest available information on this disease and present it in a practical and useful way for the attending physician (AU)

Liver Transplantation Using Dexmedetomidine in a Patient with a History of Takotsubo Cardiomyopathy.

Takotsubo cardiomyopathy has been described in patients undergoing liver transplantation. However, the ideal anesthetic management of patients with a history of takotsubo cardiomyopathy remains unclear, especially in patients undergoing liver transplantation. We describe the use of dexmedetomidine in a patient with a history of takotsubo cardiomyopathy undergoing living-donor liver transplantation.

Estrogen resisted stress-induced cardiomyopathy through increasing the activity of ß2AR-Gαs signal pathway in female rats.

BACKGROUND: Stress-induced cardiomyopathy (SCM) is characterized by transient left ventricular systolic dysfunction. Over 90% of SCM patients are postmenopausal women, suggesting that the incidence of SCM is associated with low level of estrogen. Previous studies have shown that high levels of epinephrine (EPI) triggered SCM by switching ß2-adrenoceptor (ß2AR) coupling from Gαs to Gαi signaling pathway. This study examined whether estrogen protected myocardium against SCM through modulating the ß2AR-G proteins signal pathway. METHODS AND RESULTS: Female Sprague-Dawley (SD) rats were divided into sham operation (Sham) and ovariectomized (OVX) groups. Six weeks after ovariectomy, the plasma levels of EPI and norepinephrine significantly increased. Then they were injected with EPI to make SCM models. Lack of estrogen resulted in more serious cardiac dysfunction and higher cardiac troponin I (cTnI) concentration in acute EPI surge. Pretreatment with ICI118,551 abolished the discrepancy induced by ovariectomy. Pretreatment with clenbuterol aggravated the difference of left ventricular hemodynamics between Sham and OVX rats. Blocking Gαi abolished the cardiomyocyte contractile inhibition by high levels of EPI. Estrogen deficiency decreased the concentration of cAMP and the phosphorylation of PKA in OVX+EPI group. After EPI injection for 20 min, acute estrogen supplementation could increase the concentration of cAMP and the phosphorylation of PKA in OVX rats suffered EPI-induced injury. CONCLUSIONS: Our results showed that estrogen improved the inhibitory effects of myocardial contraction induced by high levels of EPI. Estrogen protected myocardium against SCM via increasing the activity of ß2AR-Gαs signal pathway and decreasing the concentration of catecholamine in plasma.

[Cardiogenic shock due to atypical Tako-Tsubo cardiomyopathy in a young woman with pheochromocytoma]. / Atypische Tako-Tsubo-Kardiomyopathie bei einer jungen Patientin mit Phäochromozytom.

HISTORY AND CLINICAL FINDINGS: A 42-year old female patient was admitted in cardiogenic shock with pulmonary edema requiring prehospital intubation and mechanical ventilation. INVESTIGATIONS: | Emergency cardiac catheterization because of suspected acute coronary syndrome excluded coronary artery disease. Ventriculography and echocardiography suggested an inverse Tako-Tsubo cardiomyopathy with akinesia of the basal left ventricular myocardium and only apical preserved wall motion. TREATMENT AND COURSE: Under intensive care therapy with mechanical ventilation, inotropic support, infusion of saline and intraaortal balloon pumping, left ventricular function improved. After discontinuation of mechanical ventilation and discharge from ICU, the patient repeatedly suffered from panic attacks. She was therefore transferred to a psychosomatic center. There she exhibited repeated hypertensive crisis. Ultrasound of the kidney showed an adrenal mass. Together with elevated plasma catecholamines, the diagnosis of pheochromocytoma was suspected. This could be proved by magnetic resonance imaging. After surgical removement of the adrenal mass, the patient was free of symptoms.

Pharmacologic preventive strategies for takotsubo stress cardiomyopathy. What does evidence tell us? / Estrategias farmacológicas de prevención contra la miocardiopatía de takotsubo. ¿Qué nos aportan las pruebas?

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Takotsubo cardiomyopathy after systemic consolidation therapy with high-dose intravenous cytarabine in a patient with acute myeloid leukemia.

BACKGROUND: Takotsubo cardiomyopathy (TC) is characterized by the abrupt onset of cardiac dysfunction, with transient apical and midventricular hypo-/akinesia with a compensatory hypercontractility of the remaining segments. The clinical presentation appears to be similar to acute myocardial infarction (AMI). However, the myocardial dysfunction is reversible. CASE REPORT: We report on the case of a 58-year-old man with acute myeloid leukemia (AML) who was admitted to our hospital to receive the second course of consolidation chemotherapy with intravenous cytarabine. Subsequently, the patient developed severe dyspnea at rest, with cardiogenic shock after the central venous catheter was removed. Echocardiography revealed severe dyskinesia of the mid and apical portions of both ventricles, accompanied by a highly reduced left ventricular function (LVF). 5 months later, 12-lead electrocardiography (ECG) did not show any evidence of repolar-ization disorders and echocardiographic evaluation revealed a normal LVF. We suppose that the underlying mechanism was TC. CONCLUSIONS: TC can occur in patients with AML under systemic chemotherapy, which possibly represents a triggering factor for TC development. Cardiogenic shock is a serious life-threatening complication of TC. Nevertheless, the prognosis of TC is favorable and a complete recovery of the LVF is possible.

Cardioprotective effects of isoflurane in a rat model of stress-induced cardiomyopathy (takotsubo).

BACKGROUND: Stress-induced cardiomyopathy (SIC) is a common syndrome with substantial morbidity and mortality. SIC is common in intensive care units' patients. No therapeutic intervention for SIC has been evaluated in randomized clinical trial so far. Our aim was to investigate whether isoflurane is cardioprotective in an experimental SIC model. METHODS: We induced SIC-like cardiac dysfunction in rats with intraperitoneal injection of isoprenaline (50 mg/kg) and performed this study in two parts. First, we pre-treated rats with isoflurane (1.5%, n=12), pentobarbital (50 mg/kg, n=12) and ketamine (80 mg/kg, n=12) and compared to controls (n=12). We used glyburide, an ATP-dependent potassium channel blocker (n=6), to test whether isoflurane-protection is mediated through KATPm. In a second set of experiments, we treated rats with two different doses of isoflurane i.e. 0.75% (n=12) and 1.5% (n=12) before induction of SIC and compared to controls. We assessed left ventricular function and morphology in all rats by transthoracic echocardiography. We also measured peak body temperature, blood gases, acid-base homeostasis, blood pressure and heart rate. RESULTS: The extent of apical akinesia was lowest and cardiac function was best in the isoflurane treated rats. The protective effects were not attenuated by glibenclamide. Higher dose of isoflurane was more cardioprotective than the lower dose. This was persistent after the adjustment for changes in hemodynamics and blood biochemistry induced by anesthesia. CONCLUSIONS: Isoflurane prevented SIC-like cardiac dysfunction in rats. This protection was not mediated via KATPm. Our study provides an experimental foundation for future clinical trials in SIC.

Early endovascular treatment of aneurysmal subarachnoid hemorrhage complicated by neurogenic pulmonary edema and Takotsubo-like cardiomyopathy.

Aneurysmal subarachnoid hemorrhage (SAH) may be associated with acute cardiopulmonary complications, like neurogenic pulmonary edema (NPE) and Takotsubo-like cardiomyopathy (TCM). These dysfunctions seem to result from a neurogenically induced overstimulation of the sympathetic nervous system through the brain-heart connection and often complicate poor grade aneurysmal SAH. The optimal treatment modality and timing of intervention in this clinical setting have not been established yet. Early endovascular therapy seems to be the fitting treatment in this particular group of patients, in which surgical clipping is often contraindicated due to the added risk of craniotomy. Herein we describe the case of a woman admitted to the emergency department with aneurysmal SAH complicated by NPE-TCM, in which early endovascular coiling was successfully performed. Our case, characterized by a favorable outcome, further supports the evidence that early endovascular treatment should be preferred in this peculiar clinical scenario.