Vessel Pairs Research Articles

Disclosure of the significant thermal effects of large blood vessels during cryosurgery through infrared temperature mapping

During cryosurgery the large blood vessels entering the frozen volume can be an important source of temperature non-uniformity and possible under-dosage for the target tissues. In this study, the thermal effects of large vessels during cryosurgery were experimentally investigated by introducing infrared thermography system on monitoring both simulated and animal experiments. For all experiments, the freezing was supplied by a 5 mm diameter cryoprobe with liquid nitrogen running through. Tissue temperature responses during freezing and thawing were recorded by an infrared thermography system. It was demonstrated that for different geometrical configurations between the simulated vessels and the positioning of the cryoprobe, a very different temperature profile will be induced even under the same freezing. The results for the cases with single vessel and with count-current vessel pairs indicated that different vascular models produce significantly different temperature responses for a given freezing pattern. Both the simulated and animal experiments suggested that the heating nature of the flowing blood in the large vessels can produce steep temperature gradients and inadequate cooling to the frozen tissues, and therefore may seriously contribute to failed-killing of tumor during cryosurgery. The physical pictures disclosed in this paper may help planning more successful cryosurgery in the near future.

A New Fundamental Bioheat Equation for Muscle Tissue—Part II: Temperature of SAV Vessels

In this study, a new theoretical framework was developed to investigate temperature variations along countercurrent SAV blood vessels from 300 to 1000 microm diameter in skeletal muscle. Vessels of this size lie outside the range of validity of the Weinbaum-Jiji bioheat equation and, heretofore, have been treated using discrete numerical methods. A new tissue cylinder surrounding these vessel pairs is defined based on vascular anatomy, Murray's law, and the assumption of uniform perfusion. The thermal interaction between the blood vessel pair and surrounding tissue is investigated for two vascular branching patterns, pure branching and pure perfusion. It is shown that temperature variations along these large vessel pairs strongly depend on the branching pattern and the local blood perfusion rate. The arterial supply temperature in different vessel generations was evaluated to estimate the arterial inlet temperature in the modified perfusion source term for the s vessels in Part I of this study. In addition, results from the current research enable one to explore the relative contribution of the SAV vessels and the s vessels to the overall thermal equilibration between blood and tissue.

Structural and spatial organisation of brain parenchymal vessels in the lizard, Podarcis sicula: a light, transmission and scanning electron microscopy study.

The structure and 3-dimensional pattern of the intraparenchymal microvessels in the brain of the lizard, Podarcis sicula, were studied by a combination of light and transmission electron microscopy as well as scanning electron microscopy of vascular corrosion casts. The angioarchitecture pattern consists of narrow hairpin-shaped microvascular loops of different length originating from the meningeal surface. In each loop, descending and ascending vessels are closely apposed to one another throughout their length and are connected by a narrow U-shaped terminal loop at their tips. The 2 limbs of the vessel pairs show a slightly different diameter but lack other structural differences. While some paired vessels give rise to a secondary hairpin-shaped loop with 2 possible branching patterns, there are no anastomotic intraparenchymal connections with analogous neighbouring structures. The cerebral vascular pattern of Podarcis sicula resembles that found in a few representatives of other vertebrate classes. All cerebral vessels structurally appear to be capillaries. Also the observations carried out on semithin and thin sections strongly support the capillary loop model in the Podarcis brain vasculature and, in accordance with studies carried out on various vertebrates, the general submicroscopic features of the brain capillary wall suggest the presence of an endothelial type blood-brain barrier.

Bipolar coagulation with small diameter forceps in animal models for in-utero cord obliteration.

The objective of this study was to evaluate the feasibility, efficacy and safety of bipolar coagulation using endoscopic forceps of diameters of 2.7 mm and less in animal models mimicking in-utero conditions. Forceps of 2.2, 2.3, 2.5 and 2.7 mm were tested in rabbits (n = 36). Vessel pairs were dissected and coagulated in a fluid environment under endoscopic vision at 15 and 25 W. The main outcome measure was the perforation rate. In fetal lambs (n = 25), umbilical cords were coagulated under sono-endoscopic control with power settings from 10 to 35 W. Main outcome measures were the duration of coagulation, perforation rate, change in the temperature of the amniotic fluid and efficacy of vessel occlusion rate. At 20-25 W, all cords were coagulated successfully without any perforation using 2.3, 2.5 or 2.7 mm forceps. Coagulation with the 2. 2 mm forceps was associated with a high perforation rate, although the design rather than the diameter of the forceps may have influenced this outcome. Bipolar coagulation with forceps between 2. 3 and 2.7 mm and appropriate power settings achieves efficacious and safe coagulation in animal models for umbilical cord occlusion.

Mechanism of increased vessel wall nitric oxide concentrations during intestinal absorption.

Vasoactive compounds, including nitric oxide (NO) and hypertonic sodium, may diffuse from venous endothelial cells and blood to the arterial wall during intestinal absorption. This hypothesis was tested by measuring the perivascular NO concentration ([NO]) for paired small arteries and veins with NO-sensitive microelectrodes. Resting arterial and venous wall concentrations for nine vessel pairs (5 rats) were 353 +/- 28 and 401 +/- 48 (SE) nM. During mucosal absorption of 100 and 300 mg/dl glucose, the artery dilated 12 +/- 1.5 and 17 +/- 2%, [NO] increased to 540 +/- 68 and 550 +/- 49 nM, and venous wall [NO] increased to 557 +/- 60 and 633 +/- 70 nM. During venous occlusion to block diffusion of materials from venous blood to the artery wall, the arterial and venous [NO] decreased by 70-80%, and one-half of the arterial dilation subsided. Superfusion with 320 and 360 mosmol/l hypertonic sodium medium to simulate the sodium hyperosmolarity during mucosal absorption of glucose increased the arterial [NO] by 20-30 and 40-50%; 360 mosmol/l saline made hypertonic with mannitol did not significantly increase the [NO]. Although venous to arterial diffusion of NO occurred, the increased arterial [NO] during mucosal glucose absorption was primarily generated by the arterial wall in response to materials that diffused from venous blood, such as hypertonic sodium.

Enhancement in the effective thermal conductivity in rat spinotrapezius due to vasoregulation.

This study was undertaken to gain a better understanding of the countercurrent heat exchange of thermally significant blood vessels in skeletal muscle by measuring the vascular structure and flow in an exteriorized rat spinotrapezius muscle and estimating the enhancement in the effective thermal conductivity of the muscle. Detailed anatomic measurements of the number density and length of countercurrent vessel pairs between 45 and 165 microns diameter were obtained. Moreover, diameter and blood flow in the 1A to 3A vessels were measured for muscles in which pharmacological vasoactive agents were introduced, allowing one to vary the local blood flow Peclet number from 1 to 18 in the major feeding arteries. These combined measurements have been used to estimate the range of possible enhancement in the effective thermal conductivity of the tissue. The newly derived conduction shape factor in Zhu et al. for countercurrent vessels in two-dimensional tissue preparations was used in this analysis. Our experimental data indicated that the value of this conduction shape factor was about one-third to two-thirds the value for two countercurrent vessels of the same size and spacing in an infinite medium. The experiment also revealed that the Weinbaum-Jiji expression for keff was valid for the spinotrapezius muscle when the largest vessels were less than 195 microns diameter. A fivefold increase in keff was predicted for 195 microns diameter vessels. Vasoregulation was also shown to have a dramatic effect on keff. A tissue that exhibits only small increases in keff due to countercurrent convection in its vasoconstricted state can exhibit a more than fivefold increase in keff in its vasodilated state.

Tests of the geometrical description of blood vessels in a thermal model using counter-current geometries

We have developed a thermal model, for use in hyperthermia treatment planning, in which blood vessels are described as geometrical objects; 3D curves with associated diameters. For the calculation of the heat exchange with the tissue an analytic result is used. To arrive at this result some assumptions were made. One of these assumptions is a cylindrically symmetric temperature distribution. In this paper the behaviour of the model is examined for counter-current vessel geometries for which this assumption is not valid. Counter-current vessel pairs intersecting a circular tissue slice are tested. For these 2D geometries vessel spacing, tissue radius and resolution are varied, as well as the position of the vessel pair with respect to the discretized tissue grid. The simulation results are evaluated by comparison of the different heat flow rates with analytical predictions. The tests show that for a fixed vessel configuration the accuracy is not a simple decreasing function of the voxel dimensions, but is also sensitive to the position of the configuration with respect to the discretized tissue grid.

Local delivery of c-myb antisense oligonucleotides during balloon angioplasty.

Intraluminal delivery of antisense oligonucleotides to c-myb was assessed following balloon angioplasty in swine peripheral arteries. Successful delivery and intramural persistence of oligonucleotide for over 24 h were demonstrated following angioplasty with hydrogel balloons coated with 32P-labeled antisense. Delivery of fluorescein-labeled antisense demonstrated further localization within the arterial media and intracellularly. Preliminary in vitro studies demonstrated the feasibility of inhibition of porcine lymphocyte proliferation using the murine antisense to c-myb. Twelve iliac or carotid arteries underwent angioplasty with antisense-coated balloons, while the contralateral vessels underwent angioplasty with the same-sized balloons coated with the complementary sense strand. Six to seven days later, dilated arterial segments were surgically isolated. In 10 of 12 vessel pairs, antisense-treated vessels demonstrated less cellular proliferation than did contralateral sense-treated vessels, as assessed by quantitative immunohistochemical staining of proliferating cell nuclear antigen, and smooth muscle cell proliferation was reduced 18% in antisense-treated vessels compared to the contralateral sense-treated vessels (PCNA-positive nuclear area: 7.7 +/- 4.9% vs. 9.3 +/- 5.2%, P < 0.04)-intraluminal delivery of antisense oligonucleotides to c-myb is feasible with a catheter-based system and may reduce smooth muscle cell proliferation following arterial injury.

Diameter control in the arteriolar tree by changes in post-capillary resistance. A theoretical study.

Presently, the mechanisms underlying local adjustment of organ perfusion to the metabolic needs of the tissue are not well understood. Even though a large number of vasoactive substances is known to be released upon variations in tissue metabolism,24,28 the exact mechanisms of their action are unclear: Because diffusion is a slow and inefficient transport process for covering long distances, arterioles can only sense those changes in concentration and hence in release rate of these mediators with acceptable spatial and temporal resolution that originate from their immediate vicinity. On the other hand, perfusion needs to be regulated such that also the worst supplied tissue regions located remote from the arterioles (“lethal corners”) receive sufficient supply of oxygen and nutrients. Thus, the question arises: how can the information about the metabolic status of these tissue regions be transmitted to the arteriolar tree in order to adjust blood flow to their needs? A number of suggestions has been advanced on how this gap in the signal chain might be bridged9,13,26,29 all of which, however, fail to furnish satisfactory explanations: Tissue diffusion of vasoactive substances has been ruled out before. Upstream conduction of dilator signals along the capillary wall appears to be effective in controlling the feeding arteriole only if signals are generated within the proximal one third of the capillary29 which excludes the “lethal corners”. Diffusion of vasodilator substances from venules to their accompanying arterioles, despite being the best supported one of all presently proposed explanations,9,13,26 is not adequate because venular-arteriolar distances are highly variable,7 the smallest branches of the vascular tree are not arranged as such pairs at all, and in the larger vessel pairs, an arteriole often supplies a tissue microregion different from the one drained by its accompanying venule.22

772-4 Intravascular Heating Facilitates Local Heparin Delivery and Attenuates Washout During Balloon Angioplasty with Hydrogel-Coated Balloons

Although previous studies have demonstrated that heparin can be delivered to the arterial wall during balloon angioplasty with hydrogel-coated balloons, drug washout over the first hour is rapid. The purpose of this study was to determine whether vascular heating during local heparin delivery with hydrogel-coated, radiofrequency-powered thermal angioplasty balloons would affect immediate drug deposition and the subsequent persistence of heparin within the arterial wall. To evaluate the effect ofheat on heparin deposition, fluorescein-labeled heparin was delivered in vitro to 13 bovine coronary arteries either at 50°C (n = 3), at 60°C (n = 3) or without heat (n = 7). Heparin deposition was graded on a 1–3 scale as extending into the inner 1/3, the middle 1/3 or outer 1/3 of the arterial wall. To assess the effect of heat on the intramural persistence of heparin , 3 H-heparin was delivered in vivo to 13 porcine peripheral artery pairs. The balloon:artery ratio was 1.2: 1 as guided by intravascular ultrasound. One artery in each pair was heated during heparin delivery to either 50°C (n = 11) or 80°C (n = 2). The contralateral control vessel was not heated. Arteries were harvested at one hour for scintillation counting. In both the in vivo and in vitro studies, balloon inflations were at 6 atm for 2.5 minutes. In all heated vessels thermal energy was applied for 90 secs. Supplemental heating during local drug delivery significantly increased both the immediate deposition and the persistence of intramurally delivered heparin. In vitro, the heparin deposition score was 2.3 ± 0.5 for heated arteries and 1.3 ± 0.8 for controls (p = &lt; 0.03). In vivo, more heparin was present at one hour in the heated arteries than in the control arteries in 11 of 13 vessel pairs (heated vessels, 58 ± 46 units; non-heated controls, 43 ± 42 units, p = 0.02). Vascular heating at the time of local heparin delivery with hydrogei-coated balloons increases both the immediate delivery and the persistence of heparin in the arterial wall.

A new approach for predicting the enhancement in the effective conductivity of perfused muscle tissue due to hyperthermia.

This study attempts to measure the hyperthermic response of individual microvessels in skeletal muscle tissue subject to local heating and then to predict the enhancement in thermal conductivity that results from the observed changes in vascular diameter and flow. In contrast to existing studies, which have tried to relate changes in tissue thermal conductivity to local blood perfusion using thermal clearance and self-heated thermistor techniques, we have developed a two-dimensional muscle tissue preparation in which the hyperemic response has been quantified by measuring the in vivo changes in diameter and blood flow of 1A to 4A generation vessels of rat cremaster muscle when the temperature was raised in 2 degrees increments from 34 to 42 degrees C. Only 3A and 4A vessels showed vasodilation when subject to hyperthermia, indicating that the measured increase in flow in the 1A and 2A vessels was the result of a decrease in downstream resistance. Our cremaster muscle preparations have also been used to obtain the first detailed anatomic measurements of the number density and length of countercurrent vessel pairs between 50-200 microns diameter. These combined measurements have been used to establish the limits of validity of the Weinbaum-Jiji theory. Our experimental data indicate that the Weinbaum-Jiji expression for keff is valid in cremaster muscle and cat mesentery tissue for both normal and hyperthermic conditions provided the largest vessels are < 200 microns in diameter. The theory predicts that significant enhancements in keff start to occur for vessels that are 70 microns in diameter or larger, that a 2.5-fold increase in keff can be achieved for a maximally dilated 200 microns diameter 1A vessel pair in cremaster muscle of larger rats, and a 6-fold increase is predicted for maximally dilated 200 microns diameter vessels in the cat mesentery. The experiments also show that maximally dilated 1A to 4A vessels in the microcirculation closely satisfy the condition Q(flow)/(2a)3 = constant, which is consistent with the hypothesis that there is an adaptive regulation of vessel diameter which keeps the wall shear stress nearly constant during temporal changes in flow.

The Simulation of Discrete Vessel Effects in Experimental Hyperthermia

The ability of two simple thermal models to predict experimentally measured in vivo temperature profiles was compared. These comparisons were done both with and without the inclusion of separate, discrete blood vessels. The two tissue models were: 1) Pennes' Bio-Heat Transfer equation (BHTE), and 2) an effective thermal conductivity equation (ETCE). The experimental temperature data were measured (Moros, 1990; Moros et al., 1993) in the thighs of anesthetized greyhound dogs under hyperthermic conditions generated by scanned focused ultrasound. Blood vessels were added to the thermal models in counter-current pairs transiting the model domain. The blood vessels in both models were assumed to have a constant heat transfer coefficient, and an axially varying mixed mean temperature. The vessel locations were determined a posteriori, via inspection of the experimental temperature data. Least square error fits of the predicted model temperatures to the experimental temperature data were obtained by adjusting both (a) the mass flow rate within and (b) the position of each blood vessel, and (c) the value of either the perfusion parameter (W) in the BHTE or the effective thermal conductivity parameter (Keff) in the ETCE. When small numbers (3-4) of blood vessel pairs were included, both of the models showed significant improvement in their ability to predict the experimental temperatures. Although both models performed well in terms of predicting temperatures near large vessels, the BHTE had a statistically significant better ability to predict the complete set of measured temperatures at all locations.

O2 Gradients and Countercurrent Exchange in the Cat Vitreous Humor near Retinal Arterioles and Venules

Recessed cathode O2 microelectrodes were used to measure spatially detailed oxygen tension (PO2) gradients in the vitreous humor near the cat retina. Measurement sites (n = 41 in 8 cats) included single arterioles and venules and parallel vessel pairs. Mean vitreous PO2 was 37.9 ± 1.5 (SE) Torr. Close to the retinal surface (approximately 200 μm), PO2 was found to be both higher and lower than the vitreous PO2, depending on the proximity of the microelectrode tip to retinal vessels. Both positive (inward) and negative (outward) O2 fluxes (JO2) were measured, consistent with the anatomy and expected boundary conditions in the eye. The PO2 at the closest approach above arterioles was 55.2 ± 2.3 Torr, significantly higher than in the vitreous (P < 0.0001). All arterioles had outward JO2 with an overall mean of -2.58 · 10-6 ml O2/sec/cm2. Some of the venules were also losing O2, but at much lower rates than arterioles. Several venules were gaining O2. Countercurrent transport (A-V shunting) was also seen between vessel pairs. Our experimental results allow theoretical predictions to be made for the axial drop in blood PO2 along an arteriole as a function of blood flow.

Microvascular Geometry in the Brain of the Lizard Trachydosaurus-Rugosus

The vasculature and microvasculature in the central nervous system of the lizard Trnchydosaurus rugosus was examined by means of scanning electron microscopy of vascular corrosion casts. The arterial supply to the brain is from paired internal carotids. Secondary branches from these feeder arteries form a network over the surface of the lizard brain, giving rise to artery-vein vessel pairs. The vessel pairs bend at right angles to the brain surface, giving rise to terminal arteriole-venular pairs which penetrate the brain substance. Capillaries arise at fairly regular intervals along the vessel pairs, each originating from the arteriole and terminating in the venule at a site contiguous with its origin from the arteriole. In this way all of the capillaries in the central nervous system of the lizard form countercurrent loops. Anastomotic connections between arteriole-venular pairs do not occur, each arterial vessel being an end artery.

Anatomic relationship between the common femoral artery and vein: CT evaluation and clinical significance.

Knowledge of the anatomy of the common femoral artery (CFA) and common femoral vein (CFV) is important to minimize complications associated with transfemoral angiographic procedures. The authors assessed variations in the relationship between the CFA and the adjacent CFV by reviewing the inguinal region of 100 computed tomographic scans of the pelvis (200 vessel pairs). In 65% of the vessel pairs studied, a portion of the CFA overlapped the CFV in an anteroposterior plane. In addition, more than 25% of the artery overlapped the vein in 8% of the vessel pairs. This variation in anatomic relationship between the CFA and CFV is clinically significant, since a femoral vein puncture can be associated with simultaneous passage of the entry needle through the artery and thus formation of an arteriovenous fistula.

Heat transfer normal to paired arterioles and venules embedded in perfused tissue during hyperthermia.

A numerical model of the heat transer normal to an arteriole-venule pair embedded in muscle tissue has been constructed. Anatomical data describing the blood vessel size, spacing, and density have been incorporated into the model. This model computes temperatures along the vessel walls as well as the temperature throughout the tissue which comprises an infinitely long Krogh cylinder around the vessel pair. Tissue temperatures were computed in the steady-state under resting conditions, while transient calculations were made under hyperthermic conditions. Results show that for both large- (1st generation) and medium-sized (5th generation) vessel pairs, the mean tissue temperature within the tissue cylinder is not equal to the mean of the arteriole and venule blood temperatures under both steady-state and transient conditions. The numerical data were reduced so that a comparison could be made with the predictions of a simple two-dimensional superposition of line sources and sinks presented by Baish et al. This comparison reveals that the superposition model accurately describes the heat transfer effects during hyperthermia, permitting subsequent incorporation of this theory into a realistic three-dimensional model of heat transfer in a whole limb during hyperthermia.

Computer programs for the numerical and graphic evaluation of two-vessel manometry experiments and for the calculation of substrate determinations

This paper describes and makes available two computer programs written in ALGOL 60 language. The first program processes data obtained from complete Warbung two-vessel experiments with up to 6 vessel pairs. The time courses of X O 2 and X M are plotted. The second program processes the corresponding data obtained from an EPPENDORF photometer, measuring productions of pyruvate and lactate, concentrations and consumptions of glucose. The program is flexible enough to handle other substrate determinations.