Nitrosative Stress as a Modulator of Inflammatory Change in a Model of Takotsubo Syndrome

Surikow, Sven Y; Nguyen, Thanh Ha; Stafford, Irene; Chapman, Matthew; Chacko, Sujith Thomas; Singh, Kuljit; Licari, Giovanni; Raman, Betty; Kelly, Darren J.; Zhang, Yuan; Waddingham, Mark T.; Ngo, D.; Bate, A.; Chua, Su Jen; Frenneaux, Michael; Horowitz, John D.

doi:10.1016/j.jacbts.2017.10.002

Cited by 48 publications

(55 citation statements)

References 51 publications

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“…This higher rate can be explained by the fact that the rats in this experiment are all postmenopausal female, and these almost identical features suggest that myocardial stunning resulting from emotional stress may share a common mechanism, which is believed to be mediated by catecholamines [17]. Recent studies [27,28] suggest that the pathophysiology of SCM may lie in changes in β-adrenergic receptor (AR) signaling. Additionally, biased agonism of epinephrine for β2AR-Gs at low concentrations and for Gi at high concentrations consolidates the acute apical cardiodepressive reaction observed in SCM, with an apical-basal gradient in β2ARs explaining the differential regional responses.…”

Section: Discussionmentioning

confidence: 74%

Speckle tracking echocardiography in early detection of myocardial injury in a rat model with stress cardiomyopathy

et al. 2019

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Aim: Studies on the usefulness of speckle tracking echocardiography (STE) in the evaluation of the left ventricle in rats with stress cardiomyopathy (SCM) are limited. Our aim was to investigate whether strain values by STE and cardiac troponin I (cTnI) could predict early myocardial injury in rats with SCM. Material and methods: SCM was induced in Sprague-Dawley female rats using immobilization (IMO) stress. Biomarkers and echocardiographic parameters were evaluated and compared among groups (group 1 -30 minutes after IMO stress, group 2 -24 hours after IMO stress, and control group). We defined myocardial injury as a left ventricular ejection fraction <50%. Possible predictors of early myocardial injury were determined by univariate logistic regression, and independent predictors of early myocardial injury were investigated with multivariable logistic regression. Results: A total of 44 rats with a mean weight of 426±33 g were evaluated. Group 1 had the highest plasma epinephrine and norepinephrine levels (p<0.001) and the highest heart rate (p<0.001). In univariate logistic regression, cTnI (OR=2.61 [1.02-10.25], p=0.043) and global longitudinal strain (GLS) (OR=2.13 [1.12-6.26], p=0.022) were predictive of early myocardial injury. When GLS and cTnI were included in a multivariate analysis, only GLS remained an independent predictor of early myocardial injury (OR=2.67 [1.14-14.76], p=0.027). Conclusions: STE is useful for the quantitative detection of subtle myocardial abnormalities in rats with SCM. GLS may provide a reliable and non-invasive method to predict early myocardial injury.

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Section: Discussionmentioning

confidence: 74%

Speckle tracking echocardiography in early detection of myocardial injury in a rat model with stress cardiomyopathy

et al. 2019

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“…The resultant oxidative stress may contribute to the generator of peroxynitrite, which appears pivotal to inflammatory activation in TTS. 12,29 Irrespective of mechanisms, the immediate consequence of impaired BNP effect, and consequent failure to suppress inflammation, may include aggravation of myocardial inflammation, which is prominent in both clinically based studies 30,31 and animal models of TTS. 12,13 In TTS, neutrophil infiltration of the myocardium occurs particularly during the first few days and thereafter is much less prominent.…”

Section: Discussionmentioning

confidence: 99%

Prolonged suppression of the anti‐oxidant/anti‐inflammatory effects of BNP post‐Takotsubo syndrome

et al. 2020

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Aims Takotsubo syndrome (TTS) episodes are primarily initiated by 'pulse' release of catecholamines inducing neutrophil infiltration and myocardial inflammation in susceptible individuals (largely ageing women). Evidence of myocardial inflammation and associated energetic impairment persists for ≥ 3 months post-acute TTS episodes, suggesting the existence of additional 'perpetuating' mechanisms. The effects of B-type natriuretic peptide (BNP) in suppressing superoxide (O 2 À) release from neutrophils are transiently impaired in acute heart failure. We also evaluated the extent and duration of BNP-induced suppression of O 2 À release post-TTS. Methods and results TTS patients were studied acutely (n = 34) and 3 months thereafter (n = 13) and compared with control subjects (n = 25). O 2 À generation from neutrophils, triggered by N-formyl-methionyl-leucyl-phenylalanine and phorbol myristate acetate, and its suppression by BNP, were measured in vitro. Determinants of variability in BNP effect were sought via univariate and multivariate analyses. Relative to control subjects, in TTS patients, BNP suppression of both phorbol myristate acetate and N-formyl-methionylleucyl-phenylalanine-induced O 2 À release was impaired acutely (P < 0.05 for both); this did not improve over the 3-month recovery period, despite treatment with conventional anti-failure medication in 85% of patients. No significant correlates of BNP effect (other than TTS) were identified. Conclusions (1) While TTS is associated with marked and prolonged release of BNP, there is virtually total loss of the ability of BNP to suppress neutrophil O 2 À release and its impact on tissue inflammation. (2) BNP responses do not recover for at least 3 months post-attacks, suggesting that this might contribute to perpetuation of myocardial inflammation in TTS patients.

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“…There is evidence that many cancers may exhibit paracrine effects [27]. In general, such effects are potentially independent of the induction of TTS, or of the mechanisms, including Gi-protein biased post-receptor β 2 -adrenoceptor signalling and induction of nitrosative stress [7,28], thought to underlie the pathogenesis of TTS. Figure 5, a schematic view of potential reciprocity between TTS and cancer both at the level of initiation and progression, represents an integrated view of our current mechanistic speculation in this regard.…”

Section: Discussionmentioning

confidence: 99%

“…However, it is also known that both ovarian and breast cancers may rely crucially on induction of activity of poly (ADPribose)polymerase-1 (PARP-1) [29], which appears to play a crucial role in myocardial energy impairment in a rat model of TTS [7]. To date, there is no suggested mechanism to explain multi-organ induction of PARP-1 activity, so this possibility remains to be tested.…”

Section: Discussionmentioning

confidence: 99%

“…The precise range of stimuli for development of attacks of TTS remains uncertain, as does the basis for predominance of female gender and advanced patient age. There is increasing evidence that inflammation of the myocardium may be triggered by Gi-biased postreceptor responses to β 2 -adrenoceptor agonist stimulation in susceptible individuals [4,5], and that excessive β 2 -adrenoceptor [6,7] triggered nitric oxide release may initiate nitrosative stress and thus inflammation. However, precisely why this tends to occur in aging women remains uncertain.…”

Section: Introductionmentioning

confidence: 99%

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Antecedent cancer in Takotsubo syndrome predicts both cardiovascular and long-term mortality

et al. 2019

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Background: Takotsubo syndrome (TTS), primarily an acute myocardial inflammatory condition engendered by catecholamine exposure, is associated with similar long-term mortality rates to those of patients with acute myocardial infarction. However, there is increasing evidence of a nexus between TTS and underlying malignancies:many patients have antecedent cancer (A/Ca), while incremental risk of late cancer-related death has also been reported. Purpose: To evaluate potential interactions between A/Ca among TTS patients and both early and late clinical course.Methods: Three hundred forty-six consecutive TTS patients [aged 69 ± 13 (SD) years, males: 8.2%] were prospectively followed up for a median duration of 4.1 (IQR 2.2-6.4) years. Associations between A/Ca and severity of acute attacks, in-hospital complications and long-term death rates were sought utilising univariate analyses followed by multiple logistic regression analysis. Results: A/Ca (present in 16.8% of patients) was associated with (i) greater elevation of hs-CRP and NT-proBNP concentrations (p = 0.01 and 0.04, respectively), (ii) more complicated in-hospital clinical course, with major adverse cardiac events (MACE) in 30.9% of patients, compared to 18.2% in non-A/Ca patients (p = 0.04). Long-term all-cause mortality rate was also greater [hazard ratio (HR) = 2.4, p = 0.0001] in A/Ca patients, with an excess cardiovascular (CVS) fatality rate (HR = 3.1, p = 0.001). On multivariate analysis, male gender, peak plasma concentrations of normetanephrine and hs-CRP, early arrhythmias and development of shock, but not A/Ca per se, were all independently associated with increased long-term mortality rate. Furthermore, patients discharged on β-adrenoceptor antagonists (βBl) or angiotensin converting enzyme inhibitors/ angiotensin receptor blockers (ACEi/ARB) had lower long-term mortality rates (β = − 0.2, p = 0.01; β = − 0.14, p = 0.05, respectively). Conclusions: (1) A/Ca is associated with greater clinical severity of initial TTS attacks and substantially greater longterm CVS-related as well as all-cause mortality.(2) Post-discharge therapy with either βBl or ACEi/ARB is associated with reductions in long-term mortality rates. Overall, the current data suggest operation of substantial interactions between neoplasia and TTS, both at the level of pathogenesis and of outcomes.

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Nitrosative Stress as a Modulator of Inflammatory Change in a Model of Takotsubo Syndrome

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Cited by 48 publications

References 51 publications

Speckle tracking echocardiography in early detection of myocardial injury in a rat model with stress cardiomyopathy

Speckle tracking echocardiography in early detection of myocardial injury in a rat model with stress cardiomyopathy

Prolonged suppression of the anti‐oxidant/anti‐inflammatory effects of BNP post‐Takotsubo syndrome

Antecedent cancer in Takotsubo syndrome predicts both cardiovascular and long-term mortality

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