Regulation of cerebrovascular compliance compared with forearm vascular compliance in humans: a pharmacological study.

Increasing evidence indicates that cerebrovascular compliance contributes to the dynamic regulation of cerebral blood flow but the mechanisms regulating cerebrovascular compliance in humans are unknown. This retrospective study investigated the impact of neural, endothelial, and myogenic mechanisms on the regulation of vascular compliance in the cerebral vascular bed compared with the forearm vascular bed. An index of vascular compliance (Ci) was assessed using a Windkessel model applied to blood pressure waveforms (finger photoplethysmography) and corresponding middle cerebral artery blood velocity or brachial artery blood velocity waveforms (Doppler ultrasound). Data were analyzed during a 5-min baseline period (10 waveforms) under control conditions and during distinct sympathetic blockade (experiment 1, phentolamine; 10 adults), cholinergic blockade (experiment 2, glycopyrrolate; 9 adults), and myogenic blockade (experiment 3, nicardipine; 14 adults). In experiment 1, phentolamine increased Ci similarly in the cerebral vascular bed (131 ± 135%) and forearm vascular bed (93 ± 75%; P = 0.45). In experiment 2, glycopyrrolate increased cerebrovascular Ci (72 ± 61%) and forearm vascular Ci (74 ± 64%) to a similar extent (P = 0.88). In experiment 3, nicardipine increased Ci but to a greater extent in the cerebral vascular bed (88 ± 88%) than forearm vascular bed (20 ± 45%; P = 0.01). Therefore, adrenergic, cholinergic, and myogenic mechanisms contribute to the regulation of cerebrovascular and forearm vascular compliance. However, myogenic mechanisms appear to exert more specific control over vascular compliance in the brain relative to the forearm.NEW & NOTEWORTHY Vascular compliance represents an important determinant in the dynamics and regulation of blood flow through a vascular bed. However, the mechanisms that regulate vascular compliance remain poorly understood. This study examined the impact of neural, endothelial, and myogenic mechanisms on cerebrovascular compliance compared with forearm vascular compliance. Distinct pharmacological blockade of α-adrenergic, endothelial muscarinic, and myogenic inputs altered cerebrovascular and forearm vascular compliance. These results further our understanding of vascular control and blood flow regulation in the brain.

Vasodilatation by carbon dioxide and sodium nitroglycerin reduces compliance of the cerebral arteries in humans.

NEW FINDINGS: What is the central question of this study? Vascular compliance importantly contributes to the regulation of cerebral perfusion and complex mechanisms are known to influence compliance of a vascular bed: while vasodilatation mediates changes in vascular resistance, does it also affect compliance, particularly in the cerebral vasculature? What is the main finding and its importance? Cerebral vasodilatation, elicited by hypercapnia and sodium nitroglycerin administration, reduced cerebrovascular compliance by approximately 26% from baseline. This study provides new insight into mechanisms mediating cerebrovascular compliance. ABSTRACT: Changes in vascular resistance and vascular compliance contribute to the regulation of cerebral perfusion. While changes in vascular resistance are known to be mediated by vasodilatation, the mechanisms contributing to changes in vascular compliance are complex. In particular, whether vasodilatation affects compliance of the vasculature within the cranium remains unknown. Therefore, the present study examined the impact of two vasodilatation pathways on cerebrovascular compliance in humans. Fifteen young, healthy adults (26 ± 5 years, seven females) completed two protocols: (i) sublingual sodium nitroglycerin (SNG; 0.4 mg) and (ii) hypercapnia (5-6% carbon dioxide gas mixture for 4 min). Blood pressure waveforms (finger photoplethysmography) and middle cerebral artery blood velocity waveforms (transcranial Doppler ultrasound) were input into a modified Windkessel model and an index of cerebrovascular compliance (Ci) was calculated. During the SNG protocol, Ci decreased 24 ± 17% from baseline ((5.0 ± 2.3) × 10-4  cm s-1  mmHg-1 ) to minute 10 ((3.6 ± 1.2) × 10-4  cm s-1  mmHg-1 ; P = 0.009). During the hypercapnia protocol, Ci decreased 28 ± 9% from baseline ((4.4 ± 1.9) × 10-4  cm s-1  mmHg-1 ) to minute 4 ((3.1 ± 1.4) × 10-4  cm s-1  mmHg-1 ; P < 0.001). Cerebral vasodilatory stimuli induced by nitric oxide and carbon dioxide mechanisms reduced compliance of the cerebral vascular bed by approximately 26% from supine baseline values.

Hemodynamic consequences of incomplete uterine spiral artery transformation in human pregnancy, with implications for placental dysfunction and preeclampsia.

Normal human pregnancy requires a dramatic increase in uteroplacental blood flow, which is achieved by a transformation in the geometry of uterine spiral arteries, a key element in this blood supply system. The transformation is mediated by trophoblast invasion directed at converting a portion of the spiral artery into an open funnel, thereby greatly reducing resistance to flow. The converted portion lies within the depth of the decidua and part of the myometrium. Insufficient depth of trophoblast invasion in early pregnancy predisposes to inadequate perfusion of the developing placenta and fetus and may lead to preeclampsia, fetal growth restriction, and preterm delivery, sometimes referred to as the "Great Obstetrical Syndromes." We examine the hemodynamic consequences of spiral artery transformation in human pregnancy and the relationship between the degree of transformation and the corresponding change in flow rate and resistance to flow. We identify two key variables in determining the hemodynamic change: the longitudinal converted fraction of the spiral artery and the relative downstream diameter of the open funnel. Our results indicate that there is a critical threshold in the value of the converted fraction required to achieve the marked increase in uteroplacental blood flow in normal pregnancy. This finding validates common clinical observations that the depth of trophoblast invasion reflects the "adequacy" of the increase in uteroplacental blood supply required in normal human pregnancy. Our results provide a quantitative measure of that adequacy and may serve as a future diagnostic marker for high-risk pregnancy.NEW & NOTEWORTHY Human pregnancy requires dramatic increase in uteroplacental blood supply achieved by geometric transformation of uterine spiral arteries and facilitated by trophoblast invasion of these arteries to greatly reduce resistance to flow. Incomplete transformation has been associated with failed pregnancies, preeclampsia, and other pathologies, but a quantitative measure of "incompleteness" has been unavailable so far. We use a mathematical model to obtain a numerical threshold for this measure which may serve as a future diagnostic marker.

Rapid changes in vascular compliance contribute to cerebrovascular adjustments during transient reductions in blood pressure in young, healthy adults.

Characterization of dynamic cerebral autoregulation has focused primarily on adjustments in cerebrovascular resistance in response to blood pressure (BP) alterations. However, the role of vascular compliance in dynamic autoregulatory processes remains elusive. The present study examined changes in cerebrovascular compliance and resistance during standing-induced transient BP reductions in nine young, healthy adults (3 women). Brachial artery BP (Finometer) and middle cerebral artery blood velocity (BV; Multigon) waveforms were collected. Beginning 20 beats before standing and continuing 40 beats after standing, individual BP and BV waveforms of every second heartbeat were extracted and input into a four-element modified Windkessel model to calculate indexes of cerebrovascular resistance (Ri) and compliance (Ci). Standing elicited a transient reduction in mean BP of 20 ± 9 mmHg. In all participants, a large increase in Ci (165 ± 84%; P < 0.001 vs. seated baseline) occurred 2 ± 2 beats following standing. Reductions in Ri occurred 11 ± 3 beats after standing (Ci vs. Ri delay: P < 0.001). The increase in Ci contributed to maintained systolic BV before the decrease in Ri. The present results demonstrate rapid, large but transient increases in Ci that precede reductions in Ri, in response to standing-induced reductions in BP. Therefore, Ci represents a discreet component of cerebrovascular responses during acute decreases in BP and, consequently, dynamic autoregulation.NEW & NOTEWORTHY Historically, dynamic cerebral autoregulation has been characterized by adjustments in cerebrovascular resistance following systematic changes in blood pressure. However, with the use of Windkessel modeling approaches, this study revealed rapid and large increases in cerebrovascular compliance that preceded reductions in cerebrovascular resistance following standing-induced blood pressure reductions. Importantly, the rapid cerebrovascular compliance response contributed to preservation of systolic blood velocity during the transient hypotensive phase. These results broaden our understanding of dynamic cerebral autoregulation.

Cerebrovascular Compliance Within the Rigid Confines of the Skull.

Pulsatile blood flow is generally mediated by the compliance of blood vessels whereby they distend locally and momentarily to accommodate the passage of the pressure wave. This freedom of the blood vessels to exercise their compliance may be suppressed within the confines of the rigid skull. The effect of this on the mechanics of pulsatile blood flow within the cerebral circulation is not known, and the situation is compounded by experimental access difficulties. We present an approach which we have developed to overcome these difficulties in a study of the mechanics of pulsatile cerebral blood flow. The main finding is that while the innate compliance of cerebral vessels is indeed suppressed within the confines of the skull, this is compensated somewhat by compliance provided by other "extravascular" elements within the skull. The net result is what we have termed "intracranial compliance," which we argue is more pertinent to the mechanics of pulsatile cerebral blood flow than is intracranial pressure.

Geometric and hemodynamic characterization of uterine spiral arteries: The concept of resistance reserve.

BACKGROUND: The coiled geometry of spiral arteries in the human uteroplacental circulation is a hemodynamic enigma because of added length of a spiral artery compared with that of a straight artery, as well as added complexity of the flow within the vessel because of the coiling curvature. METHODS: We examined the geometric and hemodynamic characteristics of mathematically defined helical and spiral arteries and compared these with the corresponding characteristics of a straight artery traversing the same depth of tissue, with the aim of gaining some insight into the possible role of spiral geometry in uteroplacental perfusion. RESULTS: The results indicate that the added length of a spiral artery provides the uteroplacental circulation with a reserve of high resistance to flow. The effect of coiling geometry on the flow within the artery is the development of churning vortices in planes normal (perpendicular) to the main flow direction. CONCLUSIONS: In the early stages of pregnancy the reserve of high resistance is intact, thus keeping blood supply low. As pregnancy progresses, the reserve is gradually purged by trophoblast invasion and transformation of the distal portion of the spiral artery into an open funnel, thus providing the required high blood supply. The development of churning vortices within the spiral artery support earlier suggestions in the literature that the "spurts" of maternal blood emerging from these arteries may play a role in shaping the anatomy of the villous trees among placental lobules.

Cardiac Baroreflex Variability and Resetting during Sustained Mild Effort.

This exploratory study assessed the pattern of closed-loop baroreflex resetting using multi-logistic-curve analysis. Operating point gain and ranges of RR-interval (RRI) and systolic blood pressure (SBP) are derived to examine how these relate to sympathetic activation. Sustained low-intensity isometric handgrip exercise, with a period of post-exercise circulatory occlusion (PECO), provided a model to study baroreflex resetting because the progression toward fatigue at constant tension induces a continuous increase in volitional contribution to neuro-cardiovascular control. Continuous measurements of muscle sympathetic nerve activity (MSNA), blood pressure, and RRI were made simultaneously throughout the experimental session. Spontaneous sequence analysis was used to detect episodes of baroreflex "engagements", but the results are examined with a view to the fundamental difference between experimental conditions that isolate the carotid sinus (open-loop) and intact physiological conditions (closed-loop). While baroreflex function under open-loop conditions can be described in terms of a single logistic curve, intact physiologic conditions require a family of logistic curves. The results suggest that the baroreflex is in a "floating" state whereby it is continuously resetting during the timeline of the experiment but with minute-by-minute average values that mimic the less complex step-wise resetting pattern reported under open-loop conditions. Furthermore, the results indicate that baroreflex function and resetting of the operating point gain is reflected not in terms of change in the values of blood pressure or RR-interval but in terms of change in the range of values of these variables prevailing under different experimental conditions.

Bee++: An Object-Oriented, Agent-Based Simulator for Honey Bee Colonies.

We present a model and associated simulation package (www.beeplusplus.ca) to capture the natural dynamics of a honey bee colony in a spatially-explicit landscape, with temporally-variable, weather-dependent parameters. The simulation tracks bees of different ages and castes, food stores within the colony, pollen and nectar sources and the spatial position of individual foragers outside the hive. We track explicitly the intake of pesticides in individual bees and their ability to metabolize these toxins, such that the impact of sub-lethal doses of pesticides can be explored. Moreover, pathogen populations (in particular, Nosema apis, Nosema cerenae and Varroa mites) have been included in the model and may be introduced at any time or location. The ability to study interactions among pesticides, climate, biodiversity and pathogens in this predictive framework should prove useful to a wide range of researchers studying honey bee populations. To this end, the simulation package is written in open source, object-oriented code (C++) and can be easily modified by the user. Here, we demonstrate the use of the model by exploring the effects of sub-lethal pesticide exposure on the flight behaviour of foragers.

Effects of acute and chronic interval sprint exercise performed on a manually propelled treadmill on upper limb vascular mechanics in healthy young men.

Interval sprint exercise performed on a manually propelled treadmill, where the hands grip the handle bars, engages lower and upper limb skeletal muscle, but little is known regarding the effects of this exercise modality on the upper limb vasculature. We tested the hypotheses that an acute bout of sprint exercise and 6 weeks of training induces brachial artery (BA) and forearm vascular remodeling, favoring a more compliant system. Before and following a single bout of exercise as well as 6 weeks of training three types of vascular properties/methodologies were examined in healthy men: (1) stiffness of the entire upper limb vascular system (pulse wave velocity (PWV); (2) local stiffness of the BA; and (3) properties of the entire forearm vascular bed (determined by a modified lumped parameter Windkessel model). Following sprint exercise, PWV declined (P < 0.01), indices of BA stiffness did not change (P ≥ 0.10), and forearm vascular bed compliance increased and inertance and viscoelasticity decreased (P ≤ 0.03). Following manually propelled treadmill training, PWV remained unchanged (P = 0.31), indices of BA stiffness increased (P ≤ 0.05) and forearm vascular bed viscoelasticity declined (P = 0.02), but resistance, compliance, and inertance remained unchanged (P ≥ 0.10) compared with pretraining values. Sprint exercise induced a more compliant forearm vascular bed, without altering indices of BA stiffness. These effects were transient, as following training the forearm vascular bed was not more compliant and indices of BA stiffness increased. On the basis of these data, we conclude that adaptations to acute and chronic sprint exercise on a manually propelled treadmill are not uniform along the arterial tree in upper limb.

Myocardial Perfusion: Characteristics of Distal Intramyocardial Arteriolar Trees.

A combination of experimental, theoretical, and imaging methodologies is used to examine the hierarchical structure and function of intramyocardial arteriolar trees in porcine hearts to provide a window onto a region of myocardial microvasculature which has been difficult to fully explore so far. A total of 66 microvascular trees from 6 isolated myocardial specimens were analyzed, with a cumulative number of 2438 arteriolar branches greater than or equal to 40 µm lumen diameter. The distribution of flow rates within each tree was derived from an assumed power law relationship for that tree between the diameter of vessel segments and flow rates that are consistent with that power law and subject to conservation of mass along hierarchical structure of the tree. The results indicate that the power law index increases at levels of arteriolar vasculature closer to the capillary level, consistent with a concomitant decrease in shear stress acting on endothelial tissue. These results resolve a long standing predicament which could not be resolved previously because of lack of data about the 3D, interconnected, arterioles. In the context of myocardial perfusion, the results indicate that the coefficient of variation of flow rate in pre-capillary distal arterioles is high, suggesting that heterogeneity of flow rate in these arterioles is not entirely random but may be due at least in part to active control.

Vagal nerve stimulation therapy: what is being stimulated?

Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity.

Effects of infection on honey bee population dynamics: a model.

We propose a model that combines the dynamics of the spread of disease within a bee colony with the underlying demographic dynamics of the colony to determine the ultimate fate of the colony under different scenarios. The model suggests that key factors in the survival or collapse of a honey bee colony in the face of an infection are the rate of transmission of the infection and the disease-induced death rate. An increase in the disease-induced death rate, which can be thought of as an increase in the severity of the disease, may actually help the colony overcome the disease and survive through winter. By contrast, an increase in the transmission rate, which means that bees are being infected at an earlier age, has a drastic deleterious effect. Another important finding relates to the timing of infection in relation to the onset of winter, indicating that in a time interval of approximately 20 days before the onset of winter the colony is most affected by the onset of infection. The results suggest further that the age of recruitment of hive bees to foraging duties is a good early marker for the survival or collapse of a honey bee colony in the face of infection, which is consistent with experimental evidence but the model provides insight into the underlying mechanisms. The most important result of the study is a clear distinction between an exposure of the honey bee colony to an environmental hazard such as pesticides or insecticides, or an exposure to an infectious disease. The results indicate unequivocally that in the scenarios that we have examined, and perhaps more generally, an infectious disease is far more hazardous to the survival of a bee colony than an environmental hazard that causes an equal death rate in foraging bees.

Impact of a smoking cessation lifestyle intervention on vascular mechanics in young women.

We tested the hypotheses that smoking-induced changes in vascular mechanics would be detected earlier in the lumped properties of peripheral vascular beds, which include the properties of microvasculature, than in the local properties of central conduits, and that such changes are reversible with lifestyle changes that include smoking cessation and exercise. Vascular measures were made in 53 young (18-40 years) female smokers and 25 age-matched non-smokers. Twenty-two of the smokers were tested before and after a 14-week smoking cessation program and, of these, 13 were tested again after 52 weeks of smoking cessation. Compared with non-smokers, lumped forearm vascular bed compliance (C: mL/mm Hg) was lower, while lumped viscoelasticity (K: mm Hg/(mL·min)) and resistance (R: mm Hg/(mL·min)) were higher in the smoker group. Neither the carotid-to-toe pulse wave velocity nor local carotid artery elasticity indices were different between groups. Compared with non-smokers, brachial artery distensibility was less, and other markers of stiffness higher, in the smoker group. At 14 and 52 weeks of smoking cessation, forearm vascular R was reduced and C was increased while K was unchanged. The changes in C and R occurred while maintaining a constant R×C value, which represents a dynamic time constant. Thus, early changes in K were observed in the forearm vascular bed of smokers, which were not reflected in the local properties of central conduit vessels. Forearm C, but not K, was reversed following smoking cessation, a finding that may represent a persistent effect of smoking on the intercellular matrix of the vessel wall.

Vascularity of myocardium and gastrocnemius muscle in rats selectively bred for endurance running capacity.

We tested the hypothesis that changes in the arteriolar branching architecture contributed to increased running capacity of rats subjected to two-way artificial selection for intrinsic aerobic endurance treadmill running capacity resulting in strains of low-capacity and high-capacity endurance rats. Hearts and gastrocnemius muscles were harvested from each strain, and the microvasculature's branching geometry measured from micro-CT images. The vascular branching geometry of the hearts and skeletal muscle from the high capacity was indistinguishable from low-capacity rats. Our hypothesis was not supported. Neither remodeling nor an increase in arteriolar microvasculature branching appears to play a role in the enhanced performance of the high capacity rats. We are led to speculate that endothelial tolerance for shear stress and/or increased coupling of myocardial muscle fiber metabolic-to-contractile function is increased in the high-capacity runner strain to the effect of allowing either higher flow rate per unit volume of muscle or more efficient use of oxygen and nutrients in the high-capacity endurance rats.

Intrinsic microvasculature of the sciatic nerve in the rat.

Microvasculature associated with the sciatic nerve was examined using high-resolution micro-CT scanning in one group of rats and surgical exploration in another. The results indicate that blood supply to the sciatic nerve is an "open-ended" system in which the vessels run longitudinally within the epineurium and connect with external vasculature primarily at junction points. Although the range of vasculature found extended down to 4-5 µ, only a few isolated vessels of this size were found, with no capillary "mesh" as such, possibly because of the close proximity of the intrinsic vessel to nerve fibers within the epineurium. While the study did not include direct measurements of flow or nerve function, the "open-ended" pattern of vasculature found has important implications regarding the relationship between the two. Specifically, the nerve is less vulnerable to a severe or complete disruption in blood supply than it would be under a close-ended system such as that of the heart or brain, where a severe disruption can occur with the obstruction of only a single vessel. Indeed, the pattern of vasculature found, subject to further study of vasculature at the capillary level, suggests that flow within the intrinsic vessels may be in either direction, depending on circumstances, somewhat like flow within the circle of Willis in the cerebral circulation.

Relating function to branching geometry: a micro-CT study of the hepatic artery, portal vein, and biliary tree.

Utilizing micro-computed tomography images, the hierarchical structure, interbranch segment lengths and diameters of a hepatic artery, a portal vein, and two biliary trees from intact rat liver lobes were characterized. The data were investigated by analyzing the geometric properties of the vascular structures, such as how interbranch segment diameters change at bifurcation points. In the case of the hepatic artery and portal vein trees (in which the flow rate is high by comparison with that in the biliary tree), the vascular geometry is consistent with a fluid transport system which aims to simultaneously minimize both the power loss of laminar flow, and a cost function proportional to the total volume of material needed to maintain the system (lumenal contents). In comparison, the biliary tree (which has a low flow rate and an opposite flow direction to that of the hepatic artery and portal vein) was found to have a geometry in which the lumen cross-sectional area is maintained at bifurcations. These findings imply that the histological makeup and therefore the pathophysiology of biliary tree vasculature are likely very different from that of the vasculature within the systemic arterial tree. The extent to which the characteristic variability/scatter in the data may have resulted from imaging and/or measurement errors was examined by simulating such errors in a theoretical tree model and comparing the results with the measured data.

Accuracy of microvascular measurements obtained from micro-CT images.

Early changes in branching geometry of microvasculature and its associated impact on the perfusion distribution in diseases, especially those in which different branching generations are affected differently, require the ability to analyze intact vascular trees over a wide range of scales. Micro-CT offers an excellent framework to analyze the microvascular branching geometry. Such an analysis requires methods to be developed that can accurately characterize branching properties, such as branch diameter, length, branching angle, and branch interconnectivity of the microvasculature. The purpose of this article is to report the results of a study of two human intramyocardial coronary vascular tree casts in which the accuracy of micro-CT vascular imaging and its analysis are tested against measurements made through an optical microscope (used as the "gold-standard"). Methods related to image segmentation of the vascular lumen, vessel tree centerline extraction, individual branch segment measurement, and compensating for the non-ideal modulation transfer function of micro-CT scanners are presented. The extracted centerline accurately characterized the hierarchical structure of the vascular tree casts in terms of "parent-branch" relationships which allowed each interbranch segments' dimensions to be compared to the optical measurement method. The comparison results show a close to ideal 1:1 relationship for both length and diameter measurements made by the two methods. Combining the results from both specimens, the standard deviation of the difference between measurement methods was 19 microm for the measurement of interbranch segment diameters (ranging from 12 to 769 microm), and 172 microm for the measurement of interbranch segment lengths (ranging from 14 to 3252 microm). These results suggest that our micro-CT image analysis method can be used to characterize a vascular tree's hierarchical structure, and accurately measure interbranch segment lengths and diameters.

Biofluid mechanics of special organs and the issue of system control. Sixth International Bio-Fluid Mechanics Symposium and Workshop, March 28-30, 2008 Pasadena, California.

In the field of fluid flow within the human body, focus has been placed on the transportation of blood in the systemic circulation since the discovery of that system; but, other fluids and fluid flow phenomena pervade the body. Some of the most fascinating fluid flow phenomena within the human body involve fluids other than blood and a service other than transport--the lymphatic and pulmonary systems are two striking examples. While transport is still involved in both cases, this is not the only service which they provide and blood is not the only fluid involved. In both systems, filtration, extraction, enrichment, and in general some "treatment" of the fluid itself is the primary function. The study of the systemic circulation has also been conventionally limited to treating the system as if it were an open-loop system governed by the laws of fluid mechanics alone, independent of physiological controls and regulations. This implies that system failures can be explained fully in terms of the laws of fluid mechanics, which of course is not the case. In this paper we examine the clinical implications of these issues and of the special biofluid mechanics issues involved in the lymphatic and pulmonary systems.

Dynamic responsiveness of the vascular bed as a regulatory mechanism in vasomotor control.

The dynamics of blood supply to a vascular bed depend on lumped mechanical properties of that bed, namely the compliance (C), resistance (R), viscoelasticity (K), and inertance (L). While the study of regulatory mechanisms has so far placed the emphasis largely on R, it is not known how the remaining properties contribute collectively to the play of dynamics in vasomotor control. To examine this question and to establish some benchmark values of these properties, simultaneous measurements of pressure and flow waveforms in the vascular bed of the forearm were obtained from three groups: young healthy individuals, older hypertensives with controlled blood pressure, and older hypertensives with uncontrolled blood pressure. The values of R and C were found to vary within a wide range in each of the three groups to the extent that neither R nor C could be used independently as an indicator of health or age of the subjects tested. However, higher level dynamic properties of the bed, such as the time constants and damping index, which depend on combinations of C,K, and L, and which may reflect measures of the dynamic responsiveness or "sluggishness" of the system, were found to be maintained over a wide range of pulse pressures. These findings support a hypothesis that the pulsatile dynamics of blood supply to a vascular bed are adapted to the individual baseline values of R and C in different subjects with the effect of optimizing the level of dynamic responsiveness to changes in pressure or flow, and that this dynamic property of the vascular bed may be a protected and/or regulated property.

Microvascular development in porcine right and left ventricular walls.

Patients with congenital heart disease who have a morphological right ventricle (RV) serving as a systemic ventricle have an increased incidence of RV dysfunction. A different structural response of microvessels to increased pressure load in the RV is a possible mechanism for this dysfunction. To examine the merit of this hypothesis, we explored the possibility that in the normal heart, the branching architecture of microvasculature in walls of the left ventricle (LV) and RV mature differently. The branching structure of intramyocardial arterioles and their downstream branches were investigated using three-dimensional (3D) micro-computed tomography (CT) images in different regions of the RV and LV walls of normal fetal, 1-mo, and 5-mo old pigs. The results point to a significant difference in the volume of myocardium perfused per vessel cross-sectional area (CSA) between the LV and RV walls at 5 mo. We speculate that this difference may be related to the reserve functional capacity of the LV, which requires a corresponding reserve in the expansion capacity of vasculature in the LV wall.