An empirical model for world record running speeds with distance, age, and sex: anaerobic and aerobic contributions to performance.

The objective of this study is to derive mathematical equations that closely describe published data on world record running speed as a function of distance, age, and sex. Running speed declines with increasing distance and age. Over long distances, where aerobic metabolism is dominant, speed declines in proportion to the logarithm of distance.

Analysis of potassium ion diffusion from neurons to capillaries: Effects of astrocyte endfeet geometry.

Neurovascular coupling (NVC) refers to a local increase in cerebral blood flow in response to increased neuronal activity. Mechanisms of communication between neurons and blood vessels remain unclear. Astrocyte endfeet almost completely cover cerebral capillaries, suggesting that astrocytes play a role in NVC by releasing vasoactive substances near capillaries.

Estimation of shear stress heterogeneity along capillary segments in angiogenic rat mesenteric microvascular networks.

Objective: Fluid shear stress is thought to be a regulator of endothelial cell behavior during angiogenesis. The link, however, requires an understanding of stress values at the capillary level in angiogenic microvascular networks. Critical questions remain.

The dependence of maximum oxygen uptake and utilization (V̇O max) on hemoglobin-oxygen affinity and altitude.

Oxygen transport from the lungs to peripheral tissue is dependent on the affinity of hemoglobin for oxygen. Recent experimental data have suggested that the maximum human capacity for oxygen uptake and utilization (V̇O max) at sea level and altitude (~3000 m) is sensitive to alterations in hemoglobin-oxygen affinity. However, the effect of such alterations on V̇O max at extreme altitudes remains largely unknown due to the rarity of mutations affecting hemoglobin-oxygen affinity.

Cortical microvascular blood flow velocity mapping by combining dynamic light scattering optical coherence tomography and two-photon microscopy.

Significance: The accurate large-scale mapping of cerebral microvascular blood flow velocity is crucial for a better understanding of cerebral blood flow (CBF) regulation. Although optical imaging techniques enable both high-resolution microvascular angiography and fast absolute CBF velocity measurements in the mouse cortex, they usually require different imaging techniques with independent system configurations to maximize their performances. Consequently, it is still a challenge to accurately combine functional and morphological measurements to co-register CBF speed distribution from hundreds of microvessels with high-resolution microvascular angiograms.

An autonomous mathematical model for the mammalian cell cycle.

A mathematical model for the mammalian cell cycle is developed as a system of 13 coupled nonlinear ordinary differential equations. The variables and interactions included in the model are based on detailed consideration of available experimental data. A novel feature of the model is inclusion of cycle tasks such as origin licensing and initiation, nuclear envelope breakdown and kinetochore attachment, and their interactions with controllers (molecular complexes involved in cycle control).

Simulation of Angiogenesis in Three Dimensions: Development of the Retinal Circulation.

A theoretical model is used to describe the three-dimensional development of the retinal circulation in the human eye, which occurs after the initial spread of vasculature across the inner surface of the retina. In the model, random sprouting angiogenesis is driven by a growth factor that is produced in tissue at a rate dependent on oxygen level and diffuses to existing vessels. Vessel sprouts connect to form pathways for blood flow and undergo remodeling and pruning.

A fast computational model for circulatory dynamics: effects of left ventricle-aorta coupling.

The course of diseases such as hypertension, systolic heart failure and heart failure with a preserved ejection fraction is affected by interactions between the left ventricle (LV) and the vasculature. To study these interactions, a computationally efficient, biophysically based mathematical model for the circulatory system is presented. In a four-chamber model of the heart, the LV is represented by a previously described low-order, wall volume-preserving model that includes torsion and base-to-apex and circumferential wall shortening and lengthening, and the other chambers are represented using spherical geometries.

Conditions for Kir-induced bistability of membrane potential in capillary endothelial cells.

A simplified model for electrophysiology of endothelial cells is used to examine the conditions that can lead to bistability of membrane resting potential. The model includes the effects of inward-rectifying potassium (Kir) ion channels, whose current-voltage relationship shows an interval of negative slope and whose maximum conductance is dependent on the extracellular potassium concentration. The background current resulting from other types of channels is assumed to be linearly related to membrane potential.

Novel method for kinetic analysis applied to transport by the uniporter OCT2.

The kinetics of solute transport shed light on the roles these processes play in cellular physiology, and the absolute values of the kinetic parameters that quantitatively describe transport are increasingly used to model its impact on drug clearance. However, accurate assessment of transport kinetics is challenging. Although most carrier-mediated transport is adequately described by the Michaelis-Menten equation, its use presupposes that the rates of uptake used in the analysis of maximal rates of transport () and half-saturation constants () reflect true unidirectional rates of influx from known concentrations of substrate.

Spreading mechanics and differentiation of astrocytes during retinal development.

The retinal vasculature supplies oxygen to the inner layers of the retina, the light-sensitive tissue in the eye. During development, formation of the retinal vasculature depends on prior establishment of a mesh of astrocytes, a type of glial cell, which guide the growth of the vascular network. Astrocytes emerge from the optic nerve head and proliferate and spread, forming a mesh-like layer over the retinal surface.

Functional implications of microvascular heterogeneity for oxygen uptake and utilization.

In the vascular system, an extensive network structure provides convective and diffusive transport of oxygen to tissue. In the microcirculation, parameters describing network structure, blood flow, and oxygen transport are highly heterogeneous. This heterogeneity can strongly affect oxygen supply and organ function, including reduced oxygen uptake in the lung and decreased oxygen delivery to tissue.

Accurate Three-Dimensional Thermal Dosimetry and Assessment of Physiologic Response Are Essential for Optimizing Thermoradiotherapy.

Numerous randomized trials have revealed that hyperthermia (HT) + radiotherapy or chemotherapy improves local tumor control, progression free and overall survival vs. radiotherapy or chemotherapy alone. Despite these successes, however, some individuals fail combination therapy; not every patient will obtain maximal benefit from HT.

Coalescent angiogenesis-evidence for a novel concept of vascular network maturation.

Angiogenesis describes the formation of new blood vessels from pre-existing vascular structures. While the most studied mode of angiogenesis is vascular sprouting, specific conditions or organs favor intussusception, i.e.

Analysis of flow resistance in the pulmonary arterial circulation: implications for hypoxic pulmonary vasoconstriction.

Hypoxic pulmonary vasoconstriction (HPV) plays an essential role in distributing blood in the lung to enhance ventilation-perfusion matching and blood oxygenation. In this study, a theoretical model of the pulmonary vasculature is used to predict the effects of vasoconstriction over specified ranges of vessel diameters on pulmonary vascular resistance (PVR). The model is used to evaluate the ability of hypothesized mechanisms of HPV to account for observed levels of PVR elevation during hypoxia.

Simulation of angiogenesis in three dimensions: Application to cerebral cortex.

The vasculature is a dynamic structure, growing and regressing in response to embryonic development, growth, changing physiological demands, wound healing, tumor growth and other stimuli. At the microvascular level, network geometry is not predetermined, but emerges as a result of biological responses of each vessel to the stimuli that it receives. These responses may be summarized as angiogenesis, remodeling and pruning.

The Oxygen Cascade During Exercise in Health and Disease.

The oxygen transport cascade describes the physiological steps that bring atmospheric oxygen into the body where it is delivered and consumed by metabolically active tissue. As such, the oxygen cascade is fundamental to our understanding of exercise in health and disease. Our narrative review will highlight each step of the oxygen transport cascade from inspiration of atmospheric oxygen down to mitochondrial consumption in both healthy active males and females along with clinical conditions.

Distinct roles of red-blood-cell-derived and wall-derived mechanisms in metabolic regulation of blood flow.

Objective: A theoretical model is used to analyze combinations of RBC-derived and wall-derived (RBC-independent) mechanisms for metabolic blood flow regulation, with regard to their oxygen transport properties.

Methods: Heterogeneous microvascular network structures are derived from observations in rat mesentery and hamster cremaster. The effectiveness of metabolic blood flow regulation using combinations of RBC-dependent and RBC-independent mechanisms is simulated in these networks under conditions of reduced oxygen delivery and increased oxygen demand.

Effects of impaired microvascular flow regulation on metabolism-perfusion matching and organ function.

Impaired tissue oxygen delivery is a major cause of organ damage and failure in critically ill patients, which can occur even when systemic parameters, including cardiac output and arterial hemoglobin saturation, are close to normal. This review addresses oxygen transport mechanisms at the microcirculatory scale, and how hypoxia may occur in spite of adequate convective oxygen supply. The structure of the microcirculation is intrinsically heterogeneous, with wide variations in vessel diameters and flow pathway lengths, and consequently also in blood flow rates and oxygen levels.

Optical measurement of microvascular oxygenation and blood flow responses in awake mouse cortex during functional activation.

The cerebral cortex has a number of conserved morphological and functional characteristics across brain regions and species. Among them, the laminar differences in microvascular density and mitochondrial cytochrome c oxidase staining suggest potential laminar variability in the baseline O metabolism and/or laminar variability in both O demand and hemodynamic response. Here, we investigate the laminar profile of stimulus-induced intravascular partial pressure of O (pO2) transients to stimulus-induced neuronal activation in fully awake mice using two-photon phosphorescence lifetime microscopy.

Simulation of oxygen transport and estimation of tissue perfusion in extensive microvascular networks: Application to cerebral cortex.

Advanced imaging techniques have made available extensive three-dimensional microvascular network structures. Simulation of oxygen transport by such networks requires information on blood flow rates and oxygen levels in vessels crossing boundaries of the imaged region, which is difficult to obtain experimentally. Here, a computational method is presented for estimating blood flow rates, oxygen levels, tissue perfusion and oxygen extraction, based on incomplete boundary conditions.

Patients Taking Antithrombotic Medications Present Less Frequently with Ruptured Aneurysms.

Background: Conflicting findings exist on the protective role of aspirin against aneurysmal subarachnoid hemorrhage (SAH). In this retrospective analysis, we compare the risk of SAH at presentation between patients treated microsurgically who were regularly taking an antithrombotic medication versus those who were not.

Methods: Consecutive patients with solitary aneurysms treated by the senior author using a microsurgical approach were included from a database of patients treated between January 2010 and April 2013 at a tertiary academic medical center.

A Systems Pharmacology Model for Drug Delivery to Solid Tumors by Antibody-Drug Conjugates: Implications for Bystander Effects.

Antibody-drug conjugates (ADCs) are cancer drugs composed of a humanized antibody linked to a cytotoxic payload, allowing preferential release of payload in cancer cells expressing the antibody-targeted antigen. Here, a systems pharmacology model is used to simulate ADC transport from blood to tumor tissue and ADC uptake by tumor cells. The model includes effects of spatial gradients in drug concentration in a three-dimensional network of tumor blood vessels with realistic geometry and accounts for diffusion of ADC in the tumor extracellular space, binding to antigen, internalization, intracellular processing, and payload efflux from cells.

Gap junctions regulate vessel diameter in chick chorioallantoic membrane vasculature by both tone-dependent and structural mechanisms.

Objective: In this study, we examined the impact of gap junction blockade on chick chorioallantoic membrane microvessels.

Methods: Expression of Cx37, Cx40/42, and Cx43 in chick chorioallantoic membrane tissue was studied by PCR, Western blot, and confocal immunofluorescence microscopy. Vessel diameter changes occurring under gap junction blockade with carbenoxolone (175 µmol/L), palmitoleic acid (100 µmol/L), GAP27 (1 mmol/L) were analyzed by intravital microscopy.

The mass transfer coefficient for oxygen transport from blood to tissue in cerebral cortex.

The functioning of cerebral cortex depends on adequate tissue oxygenation. MRI-based techniques allow estimation of blood oxygen levels, tissue perfusion, and oxygen consumption rate (CMRO), but do not directly measure partial pressure of oxygen (PO) in tissue. To address the estimation of tissue PO, the oxygen mass transfer coefficient (KTO) is here defined as the CMRO divided by the difference in spatially averaged PO between blood and tissue, and is estimated by analyzing Krogh-cylinder type models.