| 1. |
- Soliman, Ahmed Elmahdy, 1994, et al.
(author)
-
Ischemic preconditioning affects phosphosites and accentuates myocardial stunning while reducing infarction size in rats.
- 2024
-
In: Frontiers in cardiovascular medicine. - 2297-055X. ; 11
-
Journal article (peer-reviewed)abstract
- Ischemic preconditioning (IPC), i.e., brief periods of ischemia, protect the heart from subsequent prolonged ischemic injury, and reduces infarction size. Myocardial stunning refers to transient loss of contractility in the heart after myocardial ischemia that recovers without permanent damage. The relationship between IPC and myocardial stunning remains incompletely understood. This study aimed primarily to examine the effects of IPC on the relationship between ischemia duration, stunning, and infarct size in an ischemia-reperfusion injury model. Secondarily, this study aimed to examine to which extent the phosphoproteomic changes induced by IPC relate to myocardial contractile function.Rats were subjected to different durations of left anterior descending artery (LAD) occlusion, with or without preceding IPC. Echocardiograms were acquired to assess cardiac contraction in the affected myocardial segment. Infarction size was evaluated using triphenyl tetrazolium chloride staining. Phosphoproteomic analysis was performed in heart tissue from preconditioned and non-preconditioned animals. In contrast to rats without IPC, reversible akinesia was observed in a majority of the rats that were subjected to IPC and subsequently exposed to ischemia of 13.5 or 15min of ischemia. Phosphoproteomic analysis revealed significant differential regulation of 786 phosphopeptides between IPC and non-IPC groups, with significant associations with the sarcomere, Z-disc, and actin binding.IPC induces changes in phosphosites of proteins involved in myocardial contraction; and both accentuates post-ischemic myocardial stunning and reduces infarct size.
|
|
| 2. |
- Zulfaj, Ermir, 1993, et al.
(author)
-
Animal models of Takotsubo syndrome: bridging the gap to the human condition.
- 2024
-
In: Frontiers in Cardiovascular Medicine. - 2297-055X. ; 11
-
Journal article (peer-reviewed)abstract
- Modelling human diseases serves as a crucial tool to unveil underlying mechanisms and pathophysiology. Takotsubo syndrome (TS), an acute form of heart failure resembling myocardial infarction, manifests with reversible regional wall motion abnormalities (RWMA) of the ventricles. Despite its mortality and clinical similarity to myocardial infarction, TS aetiology remains elusive, with stress and catecholamines playing central roles. This review delves into current animal models of TS, aiming to assess their ability to replicate key clinical traits and identifying limitations. An in-depth evaluation of published animal models reveals a variation in the definition of TS among studies. We notice a substantial prevalence of catecholamine-induced models, particularly in rodents. While these models shed light on TS, there remains potential for refinement. Translational success in TS research hinges on models that align with human TS features and exhibit the key features, including transient RWMA. Animal models should be comprehensively evaluated regarding the various systemic changes of the applied trigger(s) for a proper interpretation. This review acts as a guide for researchers, advocating for stringent TS model standards and enhancing translational validity.
|
|
| 3. |
- Zulfaj, Ermir, 1993, et al.
(author)
-
Development of a small animal model replicating core characteristics of takotsubo syndrome in humans.
- 2024
-
In: European heart journal open. - 2752-4191. ; 4:4
-
Journal article (peer-reviewed)abstract
- Adequate animal models are necessary to understand human conditions, such as takotsubo syndrome (TS) characterized by the heart's transient regional wall motion abnormalities. This study aims to develop a reproducible, low-mortality TS model that closely mimics the human condition and addresses the limitations of existing models.We conducted six experiments using 309 Sprague Dawley rats, each approximately 300 g and aged 7-8 weeks. Initially, we replicated an established model using intraperitoneal isoprenaline injections. Subsequent experiments varied the doses and infusion durations of intravenous isoprenaline and assessed the effects of sex, strain, and breeder on the development of reversible akinetic segments. High-resolution echocardiography monitored the regional wall motion over 30 days to correlate with histological changes. Increasing the isoprenaline dose and the infusion time significantly enhanced akinesia (P < 0.01), resulting in pronounced apical ballooning observed in three-dimensional imaging. Akinesia peaked at 6 h post-infusion, with recovery observed at 24 h; most rats recovered from akinetic segments within 48-72 h. Optimizing the mode of administration, dose, and duration achieved a TS-like phenotype in 90% of cases, with a 16.7% mortality rate. Histological examinations confirmed that myocardial injury occurred, independent of apical ballooning.This study presents a refined TS model that reliably replicates the syndrome's key features, including morphological and electrocardiographic changes, demonstrating its transient nature with high fidelity and reduced mortality. The model's reproducibility, evidenced by consistent results across trials, suggests its potential for broader application pending further validation.
|
|
