The effects of cerebral ischemia on cardiac function and adaptation with ischemic stroke model
医学essay代做 Current studies have shown that in animal (rat and mouse) studies, occlusion of cerebral arteries affects the closure of calcium ion
The organic damage and dysfunction left by ischemic cardiovascular and cerebrovascular diseases has always been a difficult problem for clinicians. Research to date has shown that the direct relationship between cardiac and neurological ischemia is inextricably linked. However, no empirical studies have demonstrated the impact of ischemic stroke on myocardial function. The purpose of the study by Alexandre Meloux, MSc et al. is to explore the effects of cerebrovascular embolism on myocardial function and signaling pathways in vivo and in vitro, also to provide guidance for clinical treatment through experimental results.
Worldwide, 15 million individuals decease from cardiovascular and cerebrovascular diseases every year. Generally, it refers to the ischemia or hemorrhage of the heart and brain caused by the increase of human blood pressure, and other symptoms. It is a disease that seriously threatens people's health . Among them, ischemic stroke and atherosclerosis is the basic cause. 医学essay代做
Ischemic cerebral apoplexy is mainly due to cerebral vascular blockage leading to ischemic necrosis of brain tissue caused by the dysfunction of the body . Although certain cardiac diseases are responsible for ischemic stroke, there is evidence that acute cerebral ischemia may contribute to the development of cardiovascular disease. Some stroke patients have elevated levels of cardiac muscle protein, a marker of myocardial injury . Therefore, ischemic stroke may cause myocardial dysfunction and damage.
Current studies have shown that in animal (rat and mouse) studies, occlusion of cerebral arteries affects the closure of calcium ion and other particle channels in cardiomyocytes, leading to arrhythmias and cardiac contractility disorders . In addition, after an ischemic stroke, brain tissue sends a death signal to the heart. And certain circulating components, such as MiR-12620 or catecholamines, may be associated with cardiac function .
However, no studies to date have directly demonstrated a direct correlation of ischemic stroke on cardiac function. 医学essay代做
Therefore, it is a promising and meaningful study to evaluate and verify the effect of cerebral ischemia after ischemic stroke on myocardial function and myocardial stress adaptation through actual experiments, and to explore the affected changes in signaling pathways. In this study, an animal model of ischemic stroke was constructed to study the changes in cardiomyocyte function in vitro and in vivo.
The study by Alexandre Meloux, MSc et al. observed that ischemic stroke resulted in neurological deficits, cardiac dysfunction in vitro and in vivo, and an increased risk of cardiac ischemia-reperfusion injury. 医学essay代做
It has been shown that ischemic stroke affects cardiac contractility and renders the myocardium vulnerable to ischemia. In addition, experiments have shown that cardiac dysfunction after ischemic stroke is associated with increased levels of circulating catecholamines and GDF15. Furthermore, cerebral embolism altered nitroxidative signaling in the heart and impaired ADRB1 myocardial expression and cardiac activator-enhanced signaling pathways.
Ischemic stroke model establishment
In the study by Alexandre Meloux, MSc et al., polystyrene microspheres were used to construct an ischemic stroke model. This method adopts the endovascular intervention method to prepare the focal cerebral ischemia model, which is consistent with the pathogenesis of human stroke, and is the best animal model for simulating the pathogenesis and treatment of ischemic stroke 。
Polystyrene microspheres are commonly used to construct permanent ischemia models. Injecting emboli into the MCA of NHPs through a microcatheter, focal cerebral ischemia occurs in the vascular region occluded by the emboli, and recanalization cannot be achieved by administering thrombolytic drugs.. This method has the advantages of complete occlusion of the target vessel and clear infarction.
Assessment of neurological deficits after the establishment of the ischemic model 医学essay代做
The neurological assessment method used in this study was developed by Longa et al.  Assessment scores range with higher scores indicating more severe dyskinesia. The experiment evaluated the performance of rats at three time points after the establishment of the ischemic stroke model.
This study observed and recorded the evaluation of severe neurological impairment at three time points after the establishment of the ischemic stroke model. Among them, the results at 2 hours showed that there were 397±33 microspheres in the ipsilateral hemisphere. 2,3,5-Triphenyl-tetrazolium chloride staining was performed on 24-hour brain sections. 医学essay代做
The results indicated that microsphere cerebral embolism caused neurological deficit. This is similar to some clinical record data. That is, in most patients with progressive stroke, neurological deficits in unilateral limbs progressively progress (usually from upper extremity involvement and then to the entire hemilateral body). Moreover, the progression of its symptoms is stepped, that is, after a period of stability, it increases again .
Assessment of Modeled Cardiac Function with Echocardiography
The study by Alexandre Meloux, MSc et al. performed echocardiography in rats undergoing ischemic stroke using the Vevo770 imaging system. Aiming to avoid the influence of extra irrelevant interference items on the experiment, the authors isolated the hearts of perfused rats and measured the parameters of left ventricular function.
Among the results, 2 hours after cerebral embolism, the left ventricle (LV) development pressure in the two groups of stroke rats was significantly lower. And for in vivo study, in the 24-hour group, the stroke volume of the LV was 31±4% and that of the right ventricle was 29±4%. There were no significant differences in arterial systolic group throughout 7-day observation period. However, compared with the control group, the fractional shortening of LV in each experimental group increased with time.
Measurement of myocardial ischemia-reperfusion injury in vitro 医学essay代做
Following the above measurements, perfusion was turned off to induce systemic normothermic ischemia, followed by reperfusion for 1 hour. Since the heart is in ischemic state for 30 minutes after the ischemic stroke model is established, the functional damage of the heart is irreversible .
The experimental results showed that myocardial recovery after ischemia of coronary blood flow was significantly lower in the right stroke. Elevated LV diastolic blood pressure after ischemic contracture existed in both the experimental and control groups, even when the heart stopped. A sudden and dramatic increase in LV diastolic pressure was observed in the one-hour reperfusion experiment.
This judgment is related to post-ischemic contracture. From the 20th minute of reperfusion, the right-sided stroke group was even higher than the sham group. Reperfusion was performed after 30 minutes of global ischemia, and only a partial recovery of myocardial contractility was observed. After 60 min of reperfusion, the LV-generated pressure were significantly lower in the left and right stroke. Therefore, studies have shown that ischemic stroke has damage to myocardial ischemia-reperfusion. Even the experimental design of reperfusion for one hour resulted in only limited recovery of cardiac function.
Determination of several growth factors 医学essay代做
Norepinephrine is an adrenergic receptor agonist, and its main effect on the cardiovascular system is to stimulate both alpha receptors and beta receptors. Norepinephrine actives α receptors, which can produce a strong vasoconstriction effect, increase blood pressure, and increase coronary blood flow .
Catecholamines have a strong excitatory effect on the cardiovascular system, which can increase the heart rate, conduction velocity, contractility, and cardiac output . GDF-15 can be released by cardiomyocyte cells, and plays a variety of roles in the state of histopathological damage such as cardiovascular disease,. Serum GDF-15 levels correlate with disease severity, and GDF-15 is a highly reliable predictor and factor of cardiomyocytes as a disease biomarker . 医学essay代做
The results showed that plasma epinephrine, norepinephrine, catecholamines, and GDF15 significantly increased in the ischemic stroke disease compared to the control group at 2 and 24 hours after embolization. Hence, the by Alexandre Meloux, MSc et al. suggests that embolism leads to impaired cardiac function.
RT-PCR and Western Blot for signal factors
For the detection of endothelial nitric oxide synthase, glutathione peroxidase 1, catalase, adrenergic receptor beta 1, janus kinase 2 and Signal transducers and activators of transcription 3, a semi-quantitative analysis and the detection of protein expression were performed. The results showed that ischemic stroke decreased ADRB1 expression on cardiomyocytes and enhanced cardioprotective activator signaling.
The study by Alexandre Meloux, MSc et al. demonstrated that in a rat model of ischemic stroke, vascular embolization impairs myocardial contractility and worsens susceptibility to ischemia. The study also explored changes in certain signaling pathways in ischemic stroke, confirming their involvement in neural mechanisms. From the perspective of clinical treatment, these targets may become the focus of treatment.
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