Flow In Vascular Beds Research Articles

Release of vascular agonists from liposome-microbubble conjugate by ultrasound-mediated microbubble destruction: effect on vascular function.

The endothelium is a single cell layer of the vessel wall and a key regulator of blood flow in vascular beds. Local and systemic pathologies have been associated with alterations in endothelial function. However, targeting the endothelium with vasoconstrictor or vasodilator drugs is often accompanied by systemic effects. Here, we evaluated a liposome-microbubble delivery system as a vascular hydrophilic agonist carrier. Phenylephrine (Phe) or acetylcholine (Ach)-loaded liposomes were conjugated to microbubbles. The drug release was triggered by ultrasound (US), and the vascular response was assessed in rat aortic rings using an isolated organ chamber. Aortic rings incubated with Phe-liposome-microbubble conjugate, exposed to US showed a marked contractile response (0.79±0.04g) compared to empty liposomes conjugated to microbubbles, aortic rings exposed only to US, and Phe-liposome-microbubble conjugate without US exposure that elicited a minimal or no response. Expressed as %, contractile responses were 85.24±4.31% and 12.62±3.23% for Phe-Chol-liposome-microbubble conjugate and empty Chol-liposome-microbubble conjugate exposed to US, respectively. Addition of 1×10-5M Ach to pre-contracted aortic rings decreased the contraction response from 1 to 0.21g. The addition of Ach-liposome conjugate and exposure to US decreased the contraction response to 0.32g. Additionally, the ED50 values for Phe and Ach released by US from liposome-microbubble conjugates were 3.6×10-8M±2.8×10-9M for Phe and 2.0×10-8M±1.8×10-9M. In conclusion, we evaluated a hybrid delivery system that consisted of loaded liposomes conjugated to microbubbles to deliver and release vascular agonists using UMMD.

Botulinum Neurotoxin as a Therapeutic Modality in Orthopaedic Surgery: More Than Twenty Years of Experience

Seyler, Thorsten M. MD1; Smith, Beth P. PhD1; Marker, David R. BS2; Ma, Jianjun MD, PhD1; Shen, Jian MD, PhD1; Smith, Tom L. PhD1; Mont, Michael A. MD2; Kolaski, Kat MD1; Koman, L. Andrew MD1 Author Information

Regional Blood Flow Dynamics in Response to Insulin and IGF-1 in Diabetic Animals

Vascular changes in diabetes characterized by increased contractile or decreased dilator responses have been demonstrated in isolated blood vessels as well as in vivosystems. Previous studies in our laboratory have demonstrated that insulin and insulin like growth factor-1 (IGF-1) can decrease mean arterial pressure (MAP) and increase blood flow in vascular beds. In this study we evaluated the regional hemodynamic responses to insulin and IGF-1 in normal and diabetic rats. Normal male rats were made diabetic with streptozotocin (55 mg/kg) i.v. and maintained 60 to 70 days. On the day of the study the rats were anesthetized with urethane/chloralose, the femoral artery and vein cannulated for blood pressure monitoring and blood sampling or infusion, respectively. Pulsed-Doppler flow probes were placed around the iliac artery, renal artery and superior mesenteric artery to monitor blood flow. Insulin (16 nmol/kg) was infused as a bolus via the femoral vein and it decreased the MAP approximately 17% in both normal and diabetic rats. Insulin enhanced vascular flow (expressed as conductance) in the iliac and renal vascular bed but not the superior mesenteric vascular bed in normals. In diabetic rats the flow response to insulin compared to normals was attenuated in the iliac and renal vascular beds and increased in the superior mesenteric vascular bed. A bolus infusion of IGF-1 (16 nmol/kg) also decreased the MAP in normals and diabetics. IGF-1 increased vascular flow in all three vascular beds in normals but in the diabetics the response to IGF-1 was artenuated in the iiiac, increased in h e renal vascular bed and suppressed in the superior mesenteric vascularure. From these studies we conciude that diabetes is associated with an anenllared vascular response to insulin and IGF-1 in the iliac and renal vessels while insulin augments and IGF-1 decreases blood flow in the superior mesenteric vasculature

Early Life Stage Toxicity of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Zebrafish (Danio rerio)

Toxicity and histopathology of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in zebrafish (Danio rerio) early life stages was characterized from 12 to 240 hr postfertilization (hpf) following waterborne exposure of newly fertilized eggs. TCDD did not increase egg mortality (0–48 hpf), nor did it affect time to hatching (48–96 hpf). Egg doses of 1.5 ng [3H]TCDD/g or greater elicited toxic responses in zebrafish larvae. Pericardial edema and craniofacial malformations were first observed at 72 hpf, followed by the onset of yolk sac edema (96 hpf) and mortality (132 hpf). At 240 hpf the ED50s for pericardial edema, yolk sac edema, and craniofacial malformations were 2.2, 2.1, and 1.9 ng [3H]TCDD/g egg, respectively. The LD50, determined at 240 hpf, was 2.5 ng [3H]TCDD/g egg. Severe hemodynamic changes, observed as slowed blood flow in vascular beds of the trunk, head, and gills and slowed heart rate, occurred in TCDD-treated zebrafish prior to or coincident with the onset of gross signs of toxicity. Histological examination of TCDD-treated zebrafish revealed a variety of epithelial tissue lesions including arrested gill development and ballooning degeneration and/or necrosis of the renal tubules, hepatocytes, pancreas, and all major brain regions. Mesenchymal tissue lesions included subcutaneous edema in the head, trunk, and yolk sac, edema of the pericardium and skeletal muscle, and underdevelopment of the swim bladder. This demonstration of zebrafish responsiveness to TCDD early life stage toxicity coupled with the considerable information on developmental biology and genetics of zebrafish provides a foundation for future investigations into the mechanism of TCDD developmental toxicity.

Neuropeptide Y mimics a non-adrenergic component of sympathetic vasoconstriction in the bullfrog

The effects of preganglionic sympathetic nerve stimulation and exogenous agents upon vascular tone were observed in hindlimb preparations of pithed adult bullfrogs. Repetitive electrical stimulation of the sympathetic C, but not the B, system elicited arterial vasoconstriction and reduced blood flow in vascular beds supplying the sartorius muscle and the skin. Close-arterial injections of epinephrine and neuropeptide Y each mimicked neurogenic vasoconstriction. After close-arterial injection of phentolamine, an α-adrenergic antagonist, the maximal effects of nerve stimulation were delayed in onset and reduced in magnitude, but not eliminated. Pretreatment with phentolamine blocked the vasoconstriction caused by injection of epinephrine, and produced a mild reduction in responses to neuropeptide Y. These observations demonstrate the vasomotor function of the sympathetic C system and they support the hypothesis that neuropeptide Y and epinephrine function as cotransmitters in postganglionic C neurons.

Distribution of blood flow in vascular beds: model study of geometrical, rheological and hydrodynamical effects.

The problem of regional blood flow distribution in small vessels is considered by means of a passive model of a portion of the vascular bed. The following complexities are considered: (1) non-Newtonian behavior of blood including effects of red cell aggregation, (2) the complexity of the vascular g eometry including taper, curvature and effects at bifurcations, and (3) flow unsteadiness. Three rheological models are considered, namely Newtonian, power-law and Casson fluids. It is shown that changes in flow distribution and even reversal of flow direction can occur if the fluid is non-Newtonian but not a power-law fluid. It is shown that this condition is satisfied for blood in the low flow-rate regime where erythrocyte aggregation is important. Computations indicate that local pressure changes due to inertial effects as a result of vessel non-uniformity are not important. It is suggested that alterations in blood flow distribution due to rheological changes will show up experimentally in measurements of ventilation-perfusion relationships in the lung or in analysis of in vivo dye-dilution curves.

Resistance to Flow in Vascular Beds

CARLILL'S attempt1 to dispel confusion in the use of the Ohm's law analogy in blood circulation theory requires further clarification, since it is only the incorrect application of this analogy that needs to be abandoned not the analogy itself, but it raises an important point. This is confirmed by Burton2 when he insists that, for vascular circuits: Resistance to flow (R) = For a definition consistent with the electrical analogy we must have R = (P—p)/F where p is the critical closing pressure as referred to by Carlill. This gives F = P/R — p/R, which is of the form y = mx — c since p/R is constant for any single one of the lines in Carlill's Fig. 1 and gives the same result for dF/dP as in Burton's equation (4) derived from his incomplete expression of form y = mx.

Resistance to Flow in Vascular Beds

DR. S. D. CARLILL1 has attacked the standard concept of resistance to flow (R) as the ratio of the driving force (the pressure drop P across the bed) to the flow F, and advocates that the ‘dynamic resistance’, that is, the differential dP/dF be substituted. His argument seems to assume what he is trying to prove.

Resistance to flow in vascular beds.

THE concept of resistance to flow is widely used by physiologists and clinicians when inferring vessel behaviour from pressure and flow data. For a great number of years ‘resistance to flow’ has been defined by physiologists as the ratio of the pressure drop across a vessel system to the flow that results. As so defined, Burton1 has pointed out that “… resistance to flow is strictly analogous to ‘resistance’ in electrical measurements, which is defined by Ohm's Law”, and he believes that “resistance to flow remains a useful clarifying concept”. The resistance unit most widely used is the peripheral resistance unit (p.r.u.), which is, according to Green2, “equivalent to the ohm”, and is defined as 1 p.r.u. = 1 mm. mercury/1 ml. per min.