Coronary microcirculation damage in anthracycline cardiotoxicity.
Coronary microcirculation damage in anthracycline cardiotoxicity.
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蒽环类药物心脏毒性对冠脉微循环的损害。
DOI：
10.1093/cvr/cvab053
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发表时间：
2022-01-29
影响因子：
10.8
通讯作者：
Ibanez B
中科院分区：
文献类型：
--
作者：
Galán-Arriola C;Vílchez-Tschischke JP;Lobo M;López GJ;de Molina-Iracheta A;Pérez-Martínez C;Villena-Gutiérrez R;Macías Á;Díaz-Rengifo IA;Oliver E;Fuster V;Sánchez-González J;Ibanez B
这项研究的目的是研究在几个周期的蒽环类药物治疗期间和之后冠脉微循环状态的变化。将40头大白公猪纳入不同实验方案(Expr.)根据蒽环类药物累积暴露[冠状动脉内(IC)阿霉素每次注射0.45 mg/kg]和随访：对照组(不注射阿霉素)；单次注射和48h处死(Exr.1)或2 Week(Exr.2)；3次注射间隔2周(低累积剂量)，牺牲2 周(Expr.3)或12 Week(Exr.4)第3次注射后，间隔2周5次注射(高累积剂量)，第5次注射后8周处死 (Expr.5)。所有患者均接受连续心脏磁共振(CMR)检查，以量化冠脉血流储备(CFR)的血流灌注和有创测量。在每个方案结束时，动物被处死以进行体外分析。对移植的猪冠状动脉行Expr后，通过肌图进一步评价其血管功能。3和控制。单次注射阿霉素对微循环状态没有影响，不包括直接的化学毒性。连续两周注射五次阿霉素(高累积剂量)导致微循环状态进行性下降，表现为基于CMR的心肌灌注减少和CFR测量的功能微循环受损。在高累积剂量区域(Exr.5)微循环改变早在任何收缩缺陷出现之前就已出现。低累积阿霉素剂量(每两周注射三次)与长期随访中的任何收缩缺陷无关，但会引起持续性微循环损害，在第三次注射后不久明显。组织学和肌图学评估证实，即使在经历低累积剂量方案的动物中，所有口径的动脉也会受到结构性损伤。相反，小动脉损伤和毛细血管床改变只有在高累积剂量后才会发生。使用最先进的CMR和侵入性CFR对微循环状态进行的一系列体内评估表明，蒽环类药物治疗与对微循环的进行性和不可逆转的损害有关。即使在与心脏收缩功能缺陷无关的低累积剂量范围内，这种长期的损害也存在。微循环损害可能解释了接受了蒽环类药物但没有表现出心脏收缩缺陷的癌症幸存者心血管事件发生率增加的部分原因。
The aim of this study was to study changes in coronary microcirculation status during and after several cycles of anthracycline treatment. Large-white male pigs (n=40) were included in different experimental protocols (ExPr.) according to anthracycline cumulative exposure [0.45 mg/kg intracoronary (IC) doxorubicin per injection] and follow-up: control (no doxorubicin); single injection and sacrifice either at 48 h (ExPr. 1) or 2 weeks (ExPr. 2); 3 injections 2 weeks apart (low cumulative dose) and sacrifice either 2 weeks (ExPr. 3) or 12 weeks (ExPr. 4) after third injection; five injections 2 weeks apart (high cumulative dose) and sacrifice 8 weeks after fifth injection (ExPr. 5). All groups were assessed by serial cardiac magnetic resonance (CMR) to quantify perfusion and invasive measurement of coronary flow reserve (CFR). At the end of each protocol, animals were sacrificed for ex vivo analyses. Vascular function was further evaluated by myography in explanted coronary arteries of pigs undergoing ExPr. 3 and controls. A single doxorubicin injection had no impact on microcirculation status, excluding a direct chemical toxicity. A series of five fortnightly doxorubicin injections (high cumulative dose) triggered a progressive decline in microcirculation status, evidenced by reduced CMR-based myocardial perfusion and CFR-measured impaired functional microcirculation. In the high cumulative dose regime (ExPr. 5), microcirculation changes appeared long before any contractile defect became apparent. Low cumulative doxorubicin dose (three bi-weekly injections) was not associated with any contractile defect across long-term follow-up, but provoked persistent microcirculation damage, evident soon after third dose injection. Histological and myograph evaluations confirmed structural damage to arteries of all calibres even in animals undergoing low cumulative dose regimes. Conversely, arteriole damage and capillary bed alteration occurred only after high cumulative dose regime. Serial in vivo evaluations of microcirculation status using state-of-the-art CMR and invasive CFR show that anthracyclines treatment is associated with progressive and irreversible damage to the microcirculation. This long-persisting damage is present even in low cumulative dose regimes, which are not associated with cardiac contractile deficits. Microcirculation damage might explain some of the increased incidence of cardiovascular events in cancer survivors who received anthracyclines without showing cardiac contractile defects.
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影响因子：
2.4
作者：
Laursen, Adam Hogsbro;Elming, Marie Bayer;Hutchings, Martin
通讯作者：
Hutchings, Martin
影响因子：
37.8
作者：
Huang C;Zhang X;Ramil JM;Rikka S;Kim L;Lee Y;Gude NA;Thistlethwaite PA;Sussman MA;Gottlieb RA;Gustafsson AB
通讯作者：
Gustafsson AB
DOI：
10.1186/s12968-015-0116-2
发表时间：
2015-02-19
期刊：
Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance
影响因子：
--
作者：
Sánchez-González J;Fernandez-Jiménez R;Nothnagel ND;López-Martín G;Fuster V;Ibañez B
通讯作者：
Ibañez B
影响因子：
3.7
作者：
Eckman DM;Stacey RB;Rowe R;D'Agostino R Jr;Kock ND;Sane DC;Torti FM;Yeboah J;Workman S;Lane KS;Hundley WG
通讯作者：
Hundley WG
影响因子：
3.7
作者：
Bar-Joseph H;Ben-Aharon I;Tzabari M;Tsarfaty G;Stemmer SM;Shalgi R
通讯作者：
Shalgi R