Effects of Externally Applied Pressure on the Haemodynamics of the Lower Limb

The effects of externally applied pressure of 5-150 mm Hg on the haemodynamics of the leg of dog and man were investigated. The criteria used for the assessments included femoral arterial and venous blood flow as well as vascular hydraulic conductance. The results indicated that external pressure of 5 mm Hg results in a very small non-significant increase in the femoral arterial and venous flow. Higher external pressure of 15 mm Hg or more significantly reduces the femoral arterial and venous flows as well as the vascular conductance. It therefore seems that compression produced by bandaging in horizontal supine subjects has little or no haemodynamic value and may prove to be harmful unless carefully controlled.     

Procedure for Human Saphenous Veins Ex Vivo Perfusion and External Reinforcement

The mainstay of contemporary therapies for extensive occlusive arterial disease is venous bypass graft. However, its durability is threatened by intimal hyperplasia (IH) that eventually leads to vessel occlusion and graft failure. Mechanical forces, particularly low shear stress and high wall tension, are thought to initiate and to sustain these cellular and molecular changes, but their exact contribution remains to be unraveled. To selectively evaluate the role of pressure and shear stress on the biology of IH, an ex vivo perfusion system (EVPS) was created to perfuse segments of human saphenous veins under arterial regimen (high shear stress and high pressure). Further technical innovations allowed the simultaneous perfusion of two segments from the same vein, one reinforced with an external mesh. Veins were harvested using a no-touch technique and immediately transferred to the laboratory for assembly in the EVPS. One segment of the freshly isolated vein was not perfused (control, day 0). The two others segments were perfused for up to 7 days, one being completely sheltered with a 4 mm (diameter) external mesh. The pressure, flow velocity, and pulse rate were continuously monitored and adjusted to mimic the hemodynamic conditions prevailing in the femoral artery. Upon completion of the perfusion, veins were dismounted and used for histological and molecular analysis. Under ex vivo conditions, high pressure perfusion (arterial, mean = 100 mm Hg) is sufficient to generate IH and remodeling of human veins. These alterations are reduced in the presence of an external polyester mesh.     

The recovery of terminal lymph flow following occlusion

The effects of external pressure on the relative terminal lymphatic flow rate following occlusion of the lymph system were studied. Sulfur colloid tagged with 99mTc was injected into the hind thigh of dogs prior to compressive loading. Initially, the lymphatic clearance of the tracer was measured for approximately forty minutes with no applied external pressure. The terminal lymph vessels were then occluded for thirty minutes with the application of an applied external pressure of 75 mm Hg. Finally, the lymphatic clearance following occlusion was measured with the application of a nonocclusive pressure. External pressures of 0, 30, and 45 mm Hg were tested to determine the effects of post-occlusive pressure application on terminal lymphatic clearance. Results indicated that terminal lymphatic clearance did not resume for an applied pressure of 45 mm Hg following occlusion. The relative lymphatic clearance rate at an external pressure of 30 mm Hg following occlusion was 54% of the clearance rate for a 0 mm Hg applied pressure prior to lymph occlusion. The results for a 0 mm Hg external pressure following occlusion indicated a 23 percent clearance rate compared to the pre-occlusive state. A two compartment model was utilized to determine the lymphatic clearance rate per unit tissue volume of subcutaneous tissue from the experimental data for each pressure phase.     

Comparison of direct and indirect blood pressure measurement in anesthetized dogs.

This study was conducted to determine whether blood pressures and pulse rate could be determined accurately by indirect measurements from the front and hind legs of 15- to 40-kg dogs anesthetized with isoflurane. Indirect measurements from each animal were compared to direct measurements obtained from a catheter placed into the abdominal aorta via the femoral artery at four ranges of systolic pressure. When systolic pressure was above 80 mm Hg, indirect measurements were either the same as direct measurements or slightly lower. However, when systolic pressures were below 80 mm Hg, indirect systolic pressure measurements were 6 to 15% higher than direct measurements. Larger differences in diastolic pressures were found, which resulted in differences in mean pressure. The most accurate measurements were found when the cuff width-to-limb circumference ratio was between 0.4 and 0.6 and when systolic pressure was between 80 and 100 mm Hg.     

Insufficient flow reduction during LBNP in both splanchnic and lower limb areas is associated with orthostatic intolerance after bedrest

We quantified the impact of a 60-day head-down tilt bed rest (HDBR) with countermeasures on the arterial response to supine lower body negative pressure (LBNP). Twenty-four women [8 control (Con), 8 exercise + LBNP (Ex-LBNP), and 8 nutrition (Nut) subjects] were studied during LBNP (0 to -45 mmHg) before (pre) and on HDBR day 55 (HDBR-55). Left ventricle diastolic volume (LVDV) and mass, flow velocities in the middle cerebral artery (MCA flow) and femoral artery (femoral flow), portal vein cross-sectional area (portal flow), and lower limb resistance (femoral resistance index) were measured. Muscle sympathetic nerve activity (MSNA) was measured in the fibular nerve. Subjects were identified as finishers or nonfinishers of the 10-min post-HDBR tilt test. At HDBR-55, LVDV, mass, and portal flow were decreased from pre-HDBR (P < 0.05) in the Con and Nut groups only. During LBNP at HDBR-55, femoral and portal flow decreased less, whereas leg MSNA increased similarly, compared with pre-HDBR in the Con, Nut, and NF groups; 11 of 13 nonfinishers showed smaller LBNP-induced reductions in both femoral and portal flow (less vasoconstriction), whereas 10 of 11 finishers maintained vasoconstriction in either one or both regions. The relative distribution of blood flow in the cerebral versus portal and femoral beds during LBNP [MCA flow/(femoral + portal flow)] increased or reduced < 15% from pre-HDBR in 10 of 11 finishers but decreased > 15% from pre-HDBR in 11 of 13 nonfinishers. Abnormal vasoconstriction in both the portal and femoral vascular areas was associated with orthostatic intolerance. The vascular deconditioning was partially prevented by Ex-LBNP.     

The mechanics of terminal lymph flow

The effects of external pressure on the terminal lymphatic clearance rate are studied. Sulfur colloid tagged with 99mTc is injected into the subcutaneous tissue in the hind thigh of canines. The activity of the tracer is measured over the injection site for 90 min to determine the lymphatic clearance rate of the sulfur colloid. Several experiments are performed at different external pressures applied to the surface of the canine thigh. A two-compartment model is defined to determine both the terminal lymphatic flow rate per unit volume of tissue and the diffusion constant (sulfur colloid/interstitial fluid) from the raw data. Experimental results indicate that increases in the external pressure applied to the skin cause terminal lymphatic clearance rates to increase until the pressure reaches 60 mm Hg. At this level, some test results showed reduced levels of clearance. At 75 mm Hg, the lymphatic clearance of sulfur colloid from the subcutaneous tissue was stopped suggesting occlusion of the vessels resulting from vessel collapse.     

Mechanical effects of compression of peripheral nerves

Effects of graded compression on nerve function were analyzed in order to evaluate the relative importance of pressure level and duration of compression for functional deterioration. The pressure was applied by means of a small inflatable cuff. The effects of two pressure levels, i.e., 80 mm Hg applied for 2 hr or 400 mm Hg applied for 15 min, were studied in rabbit tibial nerves. The lower pressure tested, which is known to induce ischemia of the compressed nerve segment, also causes some degree of mechanical deformation of the nerve trunk, which leads to incomplete recovery following pressure release. The duration of compression is of importance for the degree of nerve injury even at the higher pressure level tested.     

Ink Perfusion for Displaying Capillaries in the Chicken

A chicken was anesthetized with Na-phenobarbital, 130 mg/kg, and the external ischiatic artery was exposed. Heparin, 90 units/kg, was injected into the brachial vein, after which a cannula was inserted into the exposed ischiatic artery. Heat was applied to the head to produce vasodilation. Perfusion through the cannula was made at about 150 mm Hg pressure and consisted of 30 ml of a biological type of Pelikan ink to which was added NaNO₂ to make a 0.02% solution. After the bird was killed by an overdose of anesthetic, the skin around the perimeter of the femoral feather tract was cauterized, the tract removed, attached to a stainless steel wire net, fixed for 1 hr in 10% formic acid, then dehydrated in 4 changes of acetone, 1 hr each, followed by a 5th change for 12 hr. The dehydrated specimens were placed in methyl benzoate, the 1st change for 1 hr and the 2nd until clear (3-15 hr). This procedure exhibits small vessels and capillary networks within the integument, but if only the vessels larger than capillaries are to be studied, they can be shown by slowly injecting 15-30 ml of the perfusion mixture into a peripheral vein. The still beating heart will distribute the ink to other regions of the body, thus allowing the vessels to be traced in excised tissue.     

Biomechanical response of femoral vein to chronic elevation of blood pressure in rabbits

Venous diseases like iliofemoral deep vein thrombosis and valvular dysfunction induce venous hypertension. To know the effects of the hypertension on venous mechanics, blood pressure in the left femoral vein in the rabbit was chronically elevated by the constriction of the left external iliac vein. Wall dimensions and biomechanical properties of the femoral vein were studied in vitro at 1, 2, or 4 wk after surgery. Blood pressure measured immediately before the animal was killed was significantly higher in the left femoral vein than in the sham-operated, contralateral vein. Wall thickness was increased by blood pressure elevation even at 1 wk, which restored circumferential wall stress to a control level. The stress was kept at normal up to 4 wk. Vascular tone and vascular contractility were increased by the elevation of blood pressure; however, wall elasticity and compliance were kept at a normal level. These results are very similar to those observed in hypertensive arteries, indicating that not only arteries but veins optimally operate against blood pressure elevation.     

Systemic and regional blood flows during graded treadmill exercise in dogs

The purpose of the study was to describe hemodynamic response and regional blood flows through various organs and tissues (microsphere technique) in dogs (n = 8), at rest and during mild (4 km/h, 13% slope; heart rate = 154 bpm), moderate (4 km/h, 26% slope; heart rate = 201 bpm), and severe (4 km/h, 39% slope; heart rate = 266 bpm) exercise on treadmill. Cardiac output (rest: 3.2 +/- 0.3; 39% slope: 10.2 +/- 1.3 l/min; mean +/- SE), systolic aortic pressure (rest: 122 +/- 4; 39% slope: 158 +/- 9 mm Hg), and left atrial pressure (rest: 5 +/- 0.7; 39% slope: 11.0 +/- 0.6 mm Hg) increased linearly with workload. On the contrary stroke volume increased from rest (35 +/- 2 ml) to mild (38 +/- 2 ml) and moderate (42 +/- 3 ml) exercise but decreased in response to the severe workload (38 +/- 5 ml). Regional blood flows across the brain, femoral bone, adrenal glands and temporalis muscle were not modified during exercise. On the contrary, a marked increase in regional blood flow was observed through the flexor and extensor muscles of the limb (X 5 to X 15), the muscles of the back (X 4) and the diaphragm (X 2.5). The small inconsistent increase in nutritional tongue blood flow probably underestimated the increased perfusion through arteriovenous shunts in the mucosa for heat-loss purposes. Myocardial blood flow increased in a linear fashion with work load in both ventricles.(ABSTRACT TRUNCATED AT 250 WORDS)     

The erect posture as an aid to the circulation in the feet in the presence of arterial obstruction

When the main artery in the lower limb is occluded and narrow collateral vessels by-passing the obstruction offer the limiting resistance to blood flow, the increase in arterial pressure at the ankle on assuming the erect posture is greater than would be predicted by consideration of the hydrostatic factors. In seven patients with femoral artery occlusion the pressure at the ankle was greater than expected in all and on the average by 8.0 mm. Hg±1.5 S.E. when sitting, (P<0.01) and in the four patients tested, by 12.4 mm. Hg±0.5 S.E. when standing (P<0.01). Rate of blood flow in subdermal tissue of the forefoot estimated by xenon-133 clearance was an average of 21% less when sitting than when supine in five limbs of four normal subjects while in five limbs with occlusion or severe stenosis of the superficial femoral artery the rate of flow was an average of 44% greater.     

Intramuscular gene transfer of FGF-2 attenuates endothelial dysfunction and inhibits intimal hyperplasia of vein grafts in poor-runoff limbs of rabbit

We previously demonstrated that sustained disturbance of endothelium-dependent vasorelaxation and poor distal runoff in ischemic limbs were critical factors affecting the neointimal development of autologous vein grafts (VGs). Also, we recently showed the superior therapeutic potential of basic fibroblast growth factor (bFGF/FGF-2) boosted by the recombinant Sendai virus (SeV) for severe limb ischemia compared with that of vascular endothelial growth factor. Here, the effect of FGF-2 on neointimal hyperplasia of VGs was examined in a rabbit model of poor-runoff limbs. Two weeks after initial surgery for the induction of poor-runoff, SeV-expressing human FGF-2 (SeV-hFGF2) or that encoding firefly luciferase (109 plaque-forming units/head) was injected into the thigh and calf muscle. At that time, the femoral vein was implanted in the femoral artery in an end-to-end manner in some groups. FGF-2 gene-transferred limbs demonstrated significantly increased blood flow assessed not only by laser Doppler flow image but also by ultrasonic transit-time flowmeter (USTF). USTF also showed a significant increase in the blood flow ratio of the deep femoral artery to external iliac artery, indicating that collateral flow was significantly restored in the thigh muscles (P < 0.01). Reduction of neointimal hyperplasia was also observed in the VGs treated by SeV-hFGF2; these grafts demonstrated significant restoration of endothelium-dependent vasorelaxation. These findings thus extend the indications of therapeutic angiogenesis using SeV-hFGF2 to include not only limb salvage but also prevention of late graft failure.     

Comparison of Invasive Blood Pressure Measurements from the Caudal Ventral Artery and the Femoral Artery in Male Adult SD and Wistar Rats

Background and Purpose

Studies have suggested that the caudal ventral artery is a potential site for continuous arterial blood pressure monitoring in rats. However, the agreement of mean arterial pressure values between the femoral artery and the caudal ventral artery has not been investigated. This study was performed to identify whether the caudal ventral artery could be safely used for continuous blood pressure monitoring as an alternative site to the femoral artery.

Methods

Rats were randomized into four groups: Sprague Dawley rats under normothermia; Wistar rats under normothermia; Sprague Dawley rats under hypothermia; Wistar rats under hypothermia. Each rat underwent simultaneous monitoring of blood pressure using femoral artery and caudal ventral artery catheterization during a stable hemodynamic state and three periods of acute severe hemodynamic changes. The effects of rat strain, rectal temperature, experimental time course and hemodynamic factors on pressure gradients, the concordance of mean arterial pressure values between the femoral artery and the caudal ventral artery, and the rates of distal ischemia after surgery were determined.

Results

There was a significant difference in the rate of distal ischemia between femoral and caudal ventral arteries after catheterization (25% vs 5%, P<0.05). The overall mean gradient and the mean gradient under a steady hemodynamic state were 4.9±3.7 mm Hg and 5.5±2.5 mm Hg, respectively. The limits of agreement (bias±1.96 SD) were (−2.5 mm Hg, 12.3 mm Hg) and (-0.5 mm Hg, 10.5 mm Hg), respectively. Although the concordance decreased during the first 30 sec of each period of severe hemodynamic changes, the degree of agreement was acceptable regardless of the effects of rat strain and rectal temperature.

Conclusions

Based on the degree of agreement and the safety of catheterization, the caudal ventral artery may be a preferred site for continuous arterial blood pressure monitoring without acute severe hemodynamic changes.     

Effects of forskolin on placental vascular resistance in rabbits

Forskolin is a direct stimulant of adenylate cyclase and increases cAMP production. It also acts as a vasodilator. To study the effect of forskolin infusion on rabbit maternal vascular resistance, we instrumented 11 pregnant rabbits with catheters in the left ventricle, jugular vein, and left and right femoral arteries. After a 2-day recovery period, one of two protocols was performed. In the control period of the first protocol (N = 6), 50% ethanol in saline was infused at 0.103 ml.min-1 for 5-min. Forskolin (10(-3) M) in 50% ethanol was then infused for 5 min at 0.103 ml.min-1. After each infusion period, regional blood flows were measured by microsphere injection. Data are expressed as means +/- SEM. Blood pressure decreased from 81 +/- 3 to 79 +/- 3 mm Hg, (P less than 0.05, N = 10) during forskolin infusion. Total placental resistance fell from 180.3 +/- 10.7 to 133.8 +/- 12.0 mm Hg.min.ml-1 per gram, P less than 0.05. Cerebral, coronary, and renal vascular resistance fell significantly. During the second protocol (N = 5), angiotensin II (0.05 microgram.min-1) was infused for 5 min followed by the addition of forskolin (10(-3) M at 0.103 ml.min-1) to the infusate. Regional blood flows, vascular resistances and blood pressures were determined. Blood pressure fell from 99 +/- 6 to 92 +/- 7 mm Hg (P less than 0.05) when forskolin was added to the infusate. Placental resistance fell from 202.5 +/- 21.6 to 158.0 +/- 29.0 mm Hg.min.ml-1 per gram (P less than 0.05). While cerebral vascular resistance did not change, renal and coronary resistances fell in response to forskolin. This study demonstrates that forskolin is able to dilate rabbit placental vessels alone and in the presence of the vasoconstrictive agent angiotensin II.     

Identification and quantification of prosthetic mitral regurgitation by flow convergence method using transthoracic approach

Ultrasound is the preferred imaging modality in diagnosis of vascular complications following cardiac catheterization and intervention. In some cases, however, bleeding surrounding the femoral vessels, may severely distort the color Doppler images, making detection of venous complications especially difficult. This report refers to such a case where post-catheterization haematoma was suspected to cause an obstruction of the femoral vein. Spectral Doppler recordings of blood flow in the common femoral vein, up-stream, distal to the hemorrhagic area, confirmed the diagnosis of obstruction by demonstrating changes in the venous flow pattern in the common femoral vein, consistent with venous hypertension. Due to the poor quality of the ultrasound images, the exact cause of the obstruction had to be established by another imaging modality, not affected by haemorrhages. CT showed that the common femoral vein was compressed at the puncture site by surrounding haemorrhages. Thus, when bleeding due to cardiac catheterization is associated with possible venous obstruction and findings by color Doppler are equivocal due to degradation of the color-Doppler image, detection of venous hypertension by spectral Doppler, performed distal to the bleeding area, strongly supports the presence of venous obstruction where the exact cause may be established by CT.     

Hemodynamic response to LBNP during the 14 month MIR spaceflight (94-95)

Lower body negative pressure (LBNP) was used during the Mir spaceflight in a study of orthostatic tolerance. Hemodynamic responses were measured including heart rate, blood pressure, cerebral artery blood flow, and lower limb vascular resistance. Results showed that femoral flow volume decreased, which may be due to hypovolemia and reduced cardiac output. Additional changes in femoral vascular response and cerebral to femoral blood flow are discussed.     

Impaired leg vasodilation during dynamic exercise in healthy older women.

The purpose of the present study was to test the hypothesis that leg blood flow responses during leg cycle ergometry are reduced with age in healthy non-estrogen-replaced women. Thirteen younger (20-27 yr) and thirteen older (61-71 yr) normotensive, non-endurance-trained women performed both graded and constant-load bouts of leg cycling at the same absolute exercise intensities. Leg blood flow (femoral vein thermodilution), mean arterial pressure (MAP; radial artery), mean femoral venous pressure, cardiac output (acetylene rebreathing), and blood O2 contents were measured. Leg blood flow responses at light workloads (20-40 W) were similar in younger and older women. However, at moderate workloads (50-60 W), leg blood flow responses were significantly attenuated in older women. MAP was 20-25 mmHg higher (P < 0.01) in the older women across all work intensities, and calculated leg vascular conductance (leg blood flow/estimated leg perfusion pressure) was lower (P < 0.05). Exercise-induced increases in leg arteriovenous O2 difference and O2 extraction were identical between groups (P > 0.6). Leg O2 uptake was tightly correlated with leg blood flow across all workloads in both subject groups (r2 = 0.80). These results suggest the ability of healthy older women to undergo limb vasodilation in response to submaximal exercise is impaired and that the legs are a potentially important contributor to the augmented systemic vascular resistance seen during dynamic exercise in older women.     

Restoration of microcirculation in the brain during ischemia

The work shows that, after slinging two carotids in rats, the blood pressure in the circle of Willis decreases to approximately 40 mm Hg. The developing ischemia is accompanied by a mass adhesion of leukocytes to the walls of the brain venules and smallest veins. In two hours after slinging, the blood pressure in the vessels of the circle of Willis decreases to 16-20 mm Hg. The rate of adhesion increases abruptly. In these vessels the leukocyte conglomerates are formed which results in complete occlusion of the vessels and the death of animals. These processes are shown to be reversible. The insertion of 4.0-4.5 ml of plasmosubstituent polyglucin into the vessels of the circle of Willis "washes away" the leukocyte conglomerates as well as a part of adhered leukocytes and restores the blood flow in the venules and smallest veins for 10-15 min.     

Improvement of the microcirculation in the acute ischemic rat limb during intravenous infusion of drag-reducing polymers

Drag-reducing polymers (DRPs) are blood-soluble macromolecules that can increase blood flow and reduce vascular resistance. The purpose of the present study is to examine the effects of DRPs on microcirculation in rat hind limb during acute femoral artery occlusion. Two groups of 20 male Wistar rats were subjected to either hemodynamic measurement or contrast enhanced ultrasound (CEU) imaging during peripheral ischemia. Both groups were further subdivided into a DRP-treated group or a saline-treated group. Polyethylene oxide (PEO) was chosen as the test DRP, and rats were injected with either 10 ppm PEO solution or saline through the caudal vein at a constant rate of 5 ml/h for 20 min. Abdominal aortic flow, iliac artery pressure, iliac vein pressure, heart rate, carotid artery pressure and central venous pressure (CVP) were monitored, and vascular resistance was calculated by (iliac artery pressure-iliac vein pressure)/abdominal aortic blood flow. Flow perfusion and capillary volume of skeletal muscle were measured by CEU. During PEO infusion, abdominal aortic blood flow increased (p<0.001) and vascular resistance decreased (p<0.001) compared to rats that received saline during peripheral ischemia. There was no significant change in ischemic skeletal capillary volume (A) with DRP treatment (p>0.05), but red blood cell velocity (β) and capillary blood flow (A×β) increased significantly (p<0.05) during PEO infusion. In addition, A, β and A×β all increased (p<0.05) in the contralateral hind limb muscle. In contrast, PEO had no significant influence on heart rate, mean carotid artery blood pressure or CVP. Intravenous infusion of drag reducing polymers may offer a novel hydrodynamic approach for improving microcirculation during acute peripheral ischemia.     

Sex differences in leg vasodilation during graded knee extensor exercise in young adults.

Limb vascular conductance responses to pharmacological and nonexercise vasodilator stimuli are generally augmented in women compared with men. In the present investigation, we tested the hypothesis that exercise-induced vasodilator responses are also greater in women than men. Sixteen women and 15 men (20-30 yr) with similar fitness and activity levels performed graded quadriceps exercise (supine, single-leg knee extensions, 40 contractions/min) to maximal exertion. Active limb hemodynamics (left common femoral artery diameter and volumetric blood flow), heart rate (ECG), and beat-to-beat mean arterial blood pressure (MAP; radial artery tonometry) were measured during each 3-min workload (4.8 and 8 W/stage for women and men, respectively). The hyperemic response to exercise (slope of femoral blood flow vs. workload) was greater (P < 0.01) in women as was femoral blood flow at workloads >15 W. The leg vasodilatory response to exercise (slope of calculated femoral vascular conductance vs. absolute workload) was also greater in women than in men (P < 0.01) because of the sex difference in hyperemia and the women's lower MAP ( approximately 10-15 mmHg) at all workloads (P < 0.05). The femoral artery dilated to a significantly greater extent in the women ( approximately 0.5 mm) than in the men ( approximately 0.1 mm) across all submaximal workloads. At maximal exertion, femoral vascular conductance was lower in the men (men, 18.0 +/- 0.6 ml.min(-1)xmmHg(-1); women, 22.6 +/- 1.4 mlxmin(-1)xmmHg(-1); P < 0.01). Collectively, these findings suggest that the vasodilatory response to dynamic leg exercise is greater in young women vs. men.