Department of Cardiology and Clinical Pharmacology, Basil Hetzel Institute, The Queen Elizabeth Hospital, The University of Adelaide, 28 Woodville Road, Woodville South, South Australia, 5011, Australia.
Department of Cardiology, The Queen Elizabeth Hospital, South Australia, Australia.
ESC Heart Fail. 2020 Oct;7(5):2250-2257. doi: 10.1002/ehf2.12729. Epub 2020 Jun 29.
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 ) release from neutrophils are transiently impaired in acute heart failure. We also evaluated the extent and duration of BNP-induced suppression of O release post-TTS.
TTS patients were studied acutely (n = 34) and 3 months thereafter (n = 13) and compared with control subjects (n = 25). O 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-methionyl-leucyl-phenylalanine-induced O 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.
(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 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.
心肌顿抑综合征（TTS）发作主要由儿茶酚胺“脉冲”释放引发，在易感个体（主要是老年女性）中诱导中性粒细胞浸润和心肌炎症。急性 TTS 发作后≥3 个月，心肌炎症和相关能量损伤的证据持续存在，提示存在额外的“持续”机制。B 型利钠肽（BNP）抑制中性粒细胞超氧化物（O ）释放的作用在急性心力衰竭中是短暂受损的。我们还评估了 TTS 后 BNP 诱导的 O 释放抑制的程度和持续时间。
研究了急性 TTS 患者（n=34）和 3 个月后的患者（n=13），并与对照组（n=25）进行了比较。通过体外测量中性粒细胞被 N-甲酰基-甲硫氨酸-亮氨酸-苯丙氨酸和佛波醇肉豆蔻酸乙酯触发的 O 生成及其被 BNP 抑制的情况。通过单变量和多变量分析寻找 BNP 效应变异性的决定因素。与对照组相比，TTS 患者的中性粒细胞中，BNP 对佛波醇肉豆蔻酸乙酯和 N-甲酰基-甲硫氨酸-亮氨酸-苯丙氨酸诱导的 O 释放的抑制作用在急性期受损（两者均 P<0.05）；尽管 85%的患者接受了常规抗心力衰竭药物治疗，但在 3 个月的恢复期内并未改善。除 TTS 外，BNP 效应无明显相关因素（其他）。
（1）虽然 TTS 与明显和持续释放 BNP 相关，但 BNP 几乎完全丧失了抑制中性粒细胞 O 释放的能力及其对组织炎症的影响。（2）BNP 反应至少在发作后 3 个月内无法恢复，这表明这可能导致 TTS 患者心肌炎症的持续存在。
