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Abnormal skeletal muscle and myocardial vasoreactivity manifests prior to heart failure in a diabetic cardiomyopathy rat model. 在糖尿病性心肌病大鼠模型中,骨骼肌和心肌血管反应性异常在心力衰竭前表现出来。
Pub Date : 2025-01-01 Epub Date: 2025-01-06 DOI: 10.1007/s44337-025-00192-1
Sadi Loai, Hai-Ling Margaret Cheng

Background: Microvascular dysfunction (MVD) is a recognized sign of disease in heart failure progression. Intact blood vessels exhibit abnormal vasoreactivity in early stage, subsequently deteriorating to rarefaction and reduced perfusion. In managing heart failure with preserved ejection fraction (HFpEF), earlier diagnosis is key to improving management. In this study, we applied a steady-state blood-pool magnetic resonance imaging (MRI) method to investigate if it can sensitively detect abnormal leg muscle vasoreactivity, a sign of MVD, posited to manifest before structural and functional cardiac changes emerge in a diabetes model of HFpEF.

Methods: Male and female Sprague-Dawley rats were maintained on either a high-fat, high-sugar diet or a control diet for 6 months after the induction of diabetes (n = 5 per group). Beginning at month 1 or 2 post-diabetes and every 2 months thereafter, rats underwent steady-state blood-pool MRI to assess vasoreactivity in the heart or skeletal muscle, respectively. A T1-reducing blood-pool agent was administered and the T1 relaxation time dynamically measured as animals breathed in elevated CO2 levels to modulate vessels.

Results: In male rats, the normally unresponsive heart to 10% CO2 revealed a pro-vasoconstriction response beginning at 5 months post-diabetes. Abnormal leg skeletal muscle vasoreactivity appeared even earlier, at 2 months: the usual vasodilatory response to 5% CO2 was interrupted with periods of vasoconstriction in diseased rats. In female rats, differences were observed between healthy and diseased animals only in the first 2 months post-diabetes and not later. In the heart, vasodilation to 10% CO2 seen in healthy females was abolished in diabetic females. In skeletal muscle, 5% CO2 was suboptimal in inducing reproducible vasoreactivity, but young diabetic females responded by vasodilation only.

Conclusions: Abnormal vasoreactivity presented earlier than overt functional changes in both heart and skeletal muscle in diabetic cardiomyopathy, and steady-state blood-pool MRI offered early diagnosis of microvascular dysfunction.

背景:微血管功能障碍(MVD)是心衰进展中公认的疾病体征。完整的血管在早期表现出异常的血管反应性,随后恶化为稀疏和灌注减少。在保留射血分数(HFpEF)的心力衰竭治疗中,早期诊断是改善治疗的关键。在这项研究中,我们应用稳态血池磁共振成像(MRI)方法来研究它是否能敏感地检测异常腿部肌肉血管反应性,这是MVD的一个迹象,在HFpEF糖尿病模型中出现结构和功能改变之前就已经表现出来。方法:在诱导糖尿病后,将雄性和雌性Sprague-Dawley大鼠分别饲喂高脂高糖饮食和对照组饮食6个月(每组5只)。从糖尿病后1个月或2个月开始,此后每2个月,对大鼠进行稳态血池MRI,分别评估心脏或骨骼肌的血管反应性。给予T1降低血池剂,并动态测量动物吸入升高的CO2水平以调节血管时T1松弛时间。结果:在雄性大鼠中,正常情况下对10% CO2无反应的心脏在糖尿病后5个月开始出现促血管收缩反应。腿部骨骼肌血管反应性异常出现的时间甚至更早,在2个月时:患病大鼠对5% CO2的正常血管舒张反应被血管收缩期打断。在雌性大鼠中,健康动物和患病动物之间的差异仅在糖尿病后的前2个月出现,之后则没有。在心脏中,在健康女性中看到的10% CO2的血管舒张在糖尿病女性中消失了。在骨骼肌中,5%的CO2在诱导可重复的血管反应性方面是次优的,但年轻的糖尿病女性只对血管舒张有反应。结论:糖尿病性心肌病患者心脏和骨骼肌血管反应性异常早于明显的功能改变,稳态血池MRI可早期诊断微血管功能障碍。
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引用次数: 0
A novel recommender framework with chatbot to stratify heart attack risk. 一种基于聊天机器人的心脏病发作风险分层推荐框架。
Pub Date : 2024-01-01 Epub Date: 2024-12-17 DOI: 10.1007/s44337-024-00174-9
Tursun Wali, Almat Bolatbekov, Ehesan Maimaitijiang, Dilbar Salman, Yasin Mamatjan

Cardiovascular diseases are a major cause of mortality and morbidity. Fast detection of life-threatening emergency events and an earlier start of the therapy would save many lives and reduce successive disabilities. Understanding the specific risk factors associated with heart attack and the degree of association is crucial in the clinical diagnosis. Considering the potential benefits of intelligent models in healthcare, many researchers have developed a variety of machine learning (ML)-based models to identify patients at risk of a heart attack. However, the common problem of previous works that used ML concepts was the lack of transparency in black-box models, which makes it difficult to understand how the model made the prediction. In this study, an automated smart recommender system (Explainable Artificial Intelligence) for heart attack prediction and risk stratification was developed. For the purpose, the CatBoost classifier was applied as the initial step. Then, the SHAP (SHapley Additive exPlanation) explainable algorithm was employed to determine reasons behind high or low risk classification. The recommender system can provide insights into the reasoning behind the predictions, including group-based and patient-specific explanations. In the final step, we integrated a Large Language Model (LLM) called BioMistral for chatting functionally to talk to users based on the model output as a digital doctor for consultation. Our smart recommender system achieved high accuracy in predicting a patient risk level with an average AUC of 0.88 and can explain the results transparently. Moreover, a Django-based online application that uses patient data to update medical information about an individual's heart attack risk was created. The LLM chatbot component would answer user questions about heart attacks and serve as a virtual companion on the route to heart health, our system also can locate nearby hospitals by applying Google Maps API and alert the users. The recommender system could improve patient management and lower heart attack risk while timely therapy aids in avoiding subsequent disabilities.

心血管疾病是造成死亡和发病的主要原因。快速发现危及生命的紧急事件并尽早开始治疗将挽救许多生命并减少连续的残疾。了解与心脏病发作相关的具体危险因素及其关联程度对临床诊断至关重要。考虑到智能模型在医疗保健中的潜在好处,许多研究人员开发了各种基于机器学习(ML)的模型来识别有心脏病发作风险的患者。然而,以前使用ML概念的作品的共同问题是黑盒模型缺乏透明度,这使得很难理解模型如何进行预测。在本研究中,开发了一个用于心脏病发作预测和风险分层的自动智能推荐系统(可解释人工智能)。为此,使用CatBoost分类器作为初始步骤。然后,采用SHapley加性解释(SHapley Additive exPlanation)可解释算法来确定高低风险分类背后的原因。推荐系统可以深入了解预测背后的原因,包括基于群体和针对患者的解释。在最后一步,我们集成了一个名为BioMistral的大型语言模型(LLM),用于聊天功能,根据模型输出与用户交谈,作为数字医生进行咨询。我们的智能推荐系统在预测患者风险水平方面取得了很高的准确性,平均AUC为0.88,并且可以透明地解释结果。此外,还创建了一个基于django的在线应用程序,该应用程序使用患者数据来更新有关个人心脏病发作风险的医疗信息。LLM聊天机器人组件将回答用户关于心脏病发作的问题,并作为心脏健康路线上的虚拟伴侣,我们的系统还可以通过应用谷歌Maps API定位附近的医院并提醒用户。推荐系统可以改善患者管理,降低心脏病发作风险,及时治疗有助于避免后续残疾。
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