evaluation-coronary-flow-reserve-after-myocardial-ischemia

Evaluation of Coronary Flow Reserve After Myocardial Ischemia Reperfusion in Rats

Coronary artery disease is the leading cause of death worldwide. After an acute myocardial infarction, early and successful myocardial intervention via ...

University of Louisville

Successful matching of cardiac metabolism to perfusion is accomplished primarily through vasodilation of the coronary resistance arterioles, but the mechanism that achieves this effect changes significantly as aging progresses and involves the contribution of reactive oxygen species (ROS). Recent Advances: A matricellular protein, thrombospondin-1 (Thbs-1), has been shown to be a prolific contributor to the production and modulation of ROS in large conductance vessels and in the peripheral circulation. Recently, the presence of physiologically relevant circulating Thbs-1 levels was proven to also disrupt vasodilation to nitric oxide (NO) in coronary arterioles from aged animals, negatively impacting coronary blood flow reserve.

Thrombospondin-1, Free Radicals, and the Coronary Microcirculation: The Aging Conundrum.

Advancing age will affect every individual and its impact on cardiac health deserves significant attention. The age-related physiological changes occurring in the coronary vasculature, myocardium, and valves set the stage upon which cardiovascular disease can escalate in the elderly population. The overall focus of this review is to highlight new and noteworthy studies and to incorporate reviews related to cardiac senescence in the context of the current state of the field. Lastly, future directions in the field of cardiac aging and the development of novel therapeutics to treat pathophysiological conditions typically associated with advancing age will be discussed.

Current themes in myocardial and coronary vascular aging.

An early manifestation of coronary artery disease in advanced age is the development of microvascular dysfunction leading to deficits in diastolic function. Our lab has previously shown that epicardial treatment with adipose-derived stromal vascular fraction (SVF) preserves microvascular function following coronary ischemia in a young rodent model. Follow-up studies showed intravenous (i.v.) delivery of SVF allows the cells to migrate to the walls of small vessels and reset vasomotor tone. Therefore we tested the hypothesis that the i.v. cell injection of SVF would reverse the coronary microvascular dysfunction associated with aging in a rodent model. Fischer 344 rats were divided into 4 groups: young control (YC), old control (OC), old + rat aortic endothelial cells (O+EC) and old + GFP+ SVF cells (O+SVF). After four weeks, cardiac function and coronary flow reserve (CFR) were measured via echocardiography, and hearts were explanted either for histology or isolation of coronary arterioles for vessel reactivity studies. In a subgroup of animals, microspheres were injected during resting and dobutamine-stimulated conditions to measure coronary blood flow. GFP+ SVF cells engrafted and persisted in the myocardium and coronary vasculature four weeks following i.v. injection. Echocardiography showed age-related diastolic dysfunction without accompanying systolic dysfunction; diastolic function was improved in old rats after SVF treatment. Ultrasound and microsphere data both showed increased stimulated coronary blood flow in O+SVF rats compared to OC and O+EC, while isolated vessel reactivity was mostly unchanged. I.v.-injected SVF cells were capable of incorporating into the vasculature of the aging heart and are shown in this study to improve CFR and diastolic function in a model of advanced age. Importantly, SVF injection did not lead to arrhythmias or increased mortality in aged rats. SVF cells provide an autologous cell therapy option for treatment of microvascular and cardiac dysfunction in aged populations.

Article	Year
Thrombospondin-1, Free Radicals, and the Coronary Microcirculation: The Aging Conundrum. Antioxidants & redox signaling\| PubMed ID: 28762749	2017
Current themes in myocardial and coronary vascular aging. Current opinion in physiology\| PubMed ID: 29520392	2018
Adipose-derived cells improve left ventricular diastolic function and increase microvascular perfusion in advanced age. PloS one\| PubMed ID: 30142193	2018

Natia Q. Kelm

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