Cerebral blood flow alteration following acute myocardial infarction in mice

Abstract

Heart failure is associated with low cardiac output (CO) and low brain perfusion that imposes a significant risk for accelerated brain ageing and Alzheimer’s disease (AD) development. Although clinical heart failure can emerge several years following acute myocardial infarction (AMI), the impact of AMI on cerebral blood flow (CBF) at early stages and up to 30 days following MI is unknown. Sixteen months old male mice underwent left anterior descending (LAD) coronary artery ligation. Hemodynamics analyses were performed at baseline and at days 1, 7, and 30 post-MI. Left ventricular (LV) ejection fraction (EF), LV volumes, CO, and right common carotid artery (RCCA) diameter were recorded by echocardiography. RCCA flow (RCCA FL) was measured by Doppler echocardiography. LV volumes consistently increased (P<0.0012) and LV systolic function progressively deteriorated (P<0.0001) post-MI. CO and RCCA FL showed a moderate but significant decrease over the course of MI with similar fluctuation pattern such that both variables were decreased at day 1, increased at day 7, and decreased at 30 days post-MI. Correlation and regression analyses between CO and RCCA FL showed a strong correlation with significance at baseline and day 30 post-MI (R = 0.71, P=0.03, and R = 0.72, P=0.03, respectively). Days 1 and 7 analyses between CO and RCCA FL showed moderate correlation with non-significance post-MI (R = 0.51, P=0.2, and R = 0.56, P=0.12, respectively). In summary, CBF significantly decreased following AMI and remained significantly decreased for up to 30 days, suggesting a potential risk for brain damage that could contribute to cognitive dysfunction later in life.

Impact of the Renin–Angiotensin System on the Endothelium in Vascular Dementia: Unresolved Issues and Future Perspectives

“…Interestingly, Alzheimer’s disease mice also showed increased amyloid levels in cerebral vessels and brain tissue [ 10 ]. Similar vascular-related mechanisms contribute to the increased risk of dementia associated with traumatic brain injury and several age-related conditions like myocardial infarction and ischemic stroke [ 11 , 12 , 13 ].…”

Cognitive impairment in myocardial infarction and heart failure

“…Regarding a decreased CBF in HF, a reduction of CBP showed a strong positive correlation with a lower cardiac output, and these parameters were inversely associated with the infarct size in mice with MI. 45 In a clinical study, CBF was reduced in HF patients for approximately 30%, 46 and it principally found in temporal, parietal and occipital regions, particularly in the bilateral prefrontal, frontal, temporal and occipital cortex, thalamus, cerebellum, corona radiate, corpus callosum, hippocampus and amygdala. 10 Previous studies reported that 50% reduction of CBF are expected to cause cognitive change, whereas a sustain reduction in CBF around 20%-30% impaired cognitive function in particular to spatial memory and attention.…”

“…HF usually develops following MI and leads to both the impairment of cardiac contractility and the reduction of systemic blood flow to other vital organs including the brain. 10,11 Cerebral hypoperfusion has been observed in animal models of HF, 12,13 along with cognitive impairment and reduction in dendritic spine density. [7][8][9]14 During cerebral hypoperfusion, nutrients, oxygen and chemical energy are suppressed, leading to reactive oxygen species (ROS) overproduction, brain mitochondrial dysfunction and brain cell death, which contributes to reduce brain function, particularly synaptic dysfunction.…”

Intramyocardial injection of human adipose-derived stem cells ameliorates cognitive deficit by regulating oxidative stress–mediated hippocampal damage after myocardial infarction

“…Myocardial infarction (MI) has been associated with cognitive impairment [1,2]. Previous studies have shown that cerebral blood flow decreases at the onset of MI and remains lower than baseline for 30 days [3]. Increased reactive oxygen species (ROS) were interconnected between cardiac and brain [4].…”