Influence of cardiac nerve status on cardiovascular regulation and cardioprotection

Neural elements of the intrinsic cardiac nervous system transduce sensory inputs from the heart, blood vessels and other organs to ensure adequate cardiac function on a beat-to-beat basis. This inter-organ crosstalk is critical for normal function of the heart and other organs; derangements within the nervous system hierarchy contribute to pathogenesis of organ dysfunction. The role of intact cardiac nerves in development of, as well as protection against, ischemic injury is of current interest since it may involve recruitment of intrinsic cardiac ganglia. For instance, ischemic conditioning, a novel protection strategy against organ injury, and in particular remote conditioning, is likely mediated by activation of neural pathways or by endogenous cytoprotective bloodborne substances that stimulate different signalling pathways. This discovery reinforces the concept that inter-organ communication, and maintenance thereof, is key. As such, greater understanding of mechanisms and elucidation of treatment strategies is imperative to improve clinical outcomes particularly in patients with comorbidities. For instance, autonomic imbalance between sympathetic and parasympathetic nervous system regulation can initiate cardiovascular autonomic neuropathy that compromises cardiac stability and function. Neuromodulation therapies that directly target the intrinsic cardiac nervous system or other elements of the nervous system hierarchy are currently being investigated for treatment of different maladies in animal and human studies.

On the Blood Pressure in the Cardiovascular System

Background: Hemodynamics is a practical and complicated theoretical problem. The aim of this paper is to analyze the characteristics of blood pressure in the cardiovascular system changing with the mechanical parameters of blood vessels and the storage of some visceral organs. Method: The fluid network model was used for the study. The cardiovascular system was modeled as a system consisting of 20 segments of vessels. The main controlling parameters were determined first by using dimensional analysis. Then the responses of blood pressure of each segment of vessels were analyzed by changing the controlling parameters. Results: The parameters of the blood vessel of brain have the least influence on the pressures of other parts. The pressures of the system of blood vessels will decrease if some blood is stored in the liver or the abdominal vein system. Vice versa. The effects of regulation of blood on the variation of blood pressure are larger than the other controlling parameters. Conclusions: The controlling parameters of the abdominal aorta and ascending aorta affect greatly the blood pressure of each vessel.

AB042.Pericytes on microvessels lead to vascular dysfunction during retinal ischemia

Background:Pericytes are contractile cells that wrap along the walls of capillaries.In the brain,pericytes play a crucial role in the regulation of capillary diameter and vascular blood flow in response to metabolic demand.During ischemia,it has been suggested that pericytes may constrict capillaries,and that pericytes remain constricted after reperfusion thus resulting in impaired blood flow.Methods:Here,we used a mouse model of retinal ischemia based on ligation of the central retinal artery to characterize the role of pericytes on capillary constriction.Ischemia was induced in transgenic mice carrying the NG2 promoter driving red fluorescent protein expression to selectively visualize pericytes(line NG2:DsRed).Changes in retinal capillary diameter at 1 hr after ischemia were measured ex vivo in whole-mounted retinas from ischemic and control eyes(n=4-6/group)using a stereological approach.Vessels and pericytes were three-dimensionally reconstructed using IMARIS(Bitplane).Furthermore,we used a novel and minimally invasive two-photon microscopy approach that allowed live imaging of microvasculature changes in the retina.Results:Our data show a generalized reduction in capillary diameter in ischemic retinas relative to sham-operated controls in all vascular plexus(ischemia:4.7±0.2μm,control:5.2±0.2µm,student’s t-test,P<0.001).Analysis of the number of capillary constrictions at pericyte locations,visualized in NG2:DsRed mice,demonstrated a substantial increase in ischemic retinas relative to the physiological capillary diameter reductions observed in controls(ischemia:1,038±277 constrictions at pericyte locations,control:60±36 constrictions at pericyte locations,student’s t-test,P<0.01).Live imaging using two-photon microscopy confirmed robust capillary constriction at the level of pericytes on retinal capillaries during ischemia(n=6-8/group).Conclusions:Collectively,our data demonstrate that ischemia promotes rapid pericyte constriction on retinal capillaries causing major microvascular dysfunction in this tissue.To identify the molecular mechanisms underlying the pathological response of pericytes during ischemia,we are currently carrying out experiments in mice and zebrafish to modulate signaling pathways involved in calcium dynamics leading to contractility in these cells.