Forefoot capillary filtration rate measured during lowering in normal subjects and in patients with occlusive arterial disease before and after arterial reconstruction

Capillary filtration rate (CFR) was measured by a mercury-in-silastic strain-gauge around the forefoot when the forefoot was lowered 40 cm below heart level. In seven normal limbs, CFR was 0.061 (0.049-0.086) ml (100 g min)-1 against 0.049 (0.016-0.071) ml (100 g min)-1 in 24 limbs with occlusive arterial disease (P = 0.01). About 8 days after arterial reconstruction CFR decreased to 0.039 (0.018-0.071) ml (100 g min)-1, but before 3 months after reconstruction CFR increased to normal values 0.061 (0.037-0.071) ml (100 g min)-1. The explanation offered for the reduced CFR before and immediately after arterial reconstruction is temporary thrombosis in the smallest distributing arteries and in the arterioles resulting in heterogeneous flow distribution and decreased fluid filtration in poorly perfused segments of the capillary bed. The results speak against increased capillary filtration as the aetiology of the post-reconstructive oedema.     

Effect of chronic sympathetic denervation upon the transcapillary filtration rate induced by venous stasis

The effect of venous pressure elevation upon capillary filtration rate in the limb was studied in 6 chronically sympathectomized patients. Five healthy subjects served as controls. Volume changes of the forearm or calf were recorded by a strain-gauge plethysmograph. Relative blod flow in subcutaneous and muscle tissue during venous stasis was measured by the local ¹³³Xe washout technique. In the denervated limbs there was a linear relationship between net capillary filtration rate and venous pressure elevation. In the controls a non-linear relationship was seen as venous pressure elevation of 40 mmHg only caused an increase in net filtration rate of about 66% of that expected from a linear relationship. In the denervated limbs blood flow in muscle and subcutaneous tissue remained constant during venous pressure elevation of more than 30 mmHg whereas in the non-denervated limbs blood flow decreased by about 50% in both tissues. The results suggest that a local sympathetic veno-arteriolar (axon) reflex plays a dominant role for the reduced increase in net capillary filtration rate during large increases in venous pressure. The local axon reflex may therefore act as an edema protecting factor.     

Intrinsic Regulation of Blood Flow in Adipose Tissue

Previous studies on intact human subcutaneous tissue have shown, that blood flow remains constant during minor changes in perfusion pressure. This so-called auto regulatory response has not been demonstrable in isolated preparations of adipose tissue. In the present study on isolated, denervated subcutaneous tissue in female rabbits only 2 of 12 expts. revealed an auto regulatory response during reduction in arterial perfusion pressure. Effluent blood flow from the tissue in the control state was 15.5 ml/100 g·min (S.D. 6.4, n = 12) corresponding to slight vasodilatation of the exposed tissue. Following total ischemia all experiments showed a period with reactive hyperemia, and both duration of hyperemia and excess flow was related to the duration of the ischemia. This response therefore seems more resistant to the experimental procedure, while auto regulation of blood flow to lowered pressure is more susceptible to surgical exposure of the tissue. During elevation of arterial perfusion pressure blood flow in the isolated tissue showed a transient increase and then almost returned to the level during normotension, indicating an elevated vascular resistance. Raising of venous pressure elicited vasoconstriction with pronounced flow reduction. These two reactions may be important for local regulation of blood flow in subcutaneous tissue during orthostatic changes in arterial and venous pressure. It is concluded that the response in adipose tissue to changes in arterial pressure (auto regulation), venous pressure and total ischemia appear to be elicited by different mechanisms.     

Pressure and volume measurements from the eye for detecting possible arterial obstruction

Detection and evaluation of functionally significant carotid occlusive disease are effectively achieved by noninvasive pressure and/or volume measurements from the eye. Ocular arterial blood pressure is measured by applying either direct compression or suction to evaluate intraocular pressure to the point of arterial collapse. Carotid blood flow is evaluated as it affects ocular volume waveforms, which result from the difference between pulsatile arterial flow and relatively constant venous flow. The relationship between noninvasive measurements from the eyes and carotid blood flow can be predicted using simple models of the cervical-cerebral circulatory system. Proper models verify clinically observed correlations between pressure and volume measurements from the eye and the underlying carotid occlusive disease. Electrical analog circuits provide a method for varying model parameters to simulate abnormalities, producing waveforms with good similarity to waveforms recorded from patients with known vascular or ophthalmic pathology. Further model refinements can be contributed by interested investigators. By using the improved models the strengths and weaknesses of current tests and techniques can then be better defined. Techniques that have been widely used for screening and evaluating potential stroke patients can thereby be modified to give improved functional analysis of these patients.     

Erythrocyte deformability in peripheral occlusive arterial disease.

A rheological study of 32 patients with peripheral occlusive arterial disease (POAD), compared with 32 matched healthy controls, has shown no loss of erythrocyte deformability as measured by filtration methods (using initial flow rate and positive pressure instruments, polycarbonate and silver membranes, and 3 microns and 5 microns diameter pores) or by viscometry (using laser visco-diffractometric and high shear rate viscosity methods). Erythrocyte ATP concentration in POAD was also normal. Patients with POAD showed a small (4 fl) increase in mean erythrocyte volume, associated with a raised serum gamma-glutamyl transpeptidase concentration, which correlated with erythrocyte filtration and viscometric measurements. Previous reports of impaired blood filterability in POAD probably reflect the effects of accompanying leucocytosis, plasma hyperfibrinogenaemia, or an increase in erythrocyte size, but not an intrinsic loss of erythrocyte deformability.     

Redistribution of skin blood flow during leg dependency in peripheral arterial occlusive disease.

A disturbed autoregulation of cutaneous blood flow in legs with peripheral arterial occlusive disease (PAOD) has previously been demonstrated for circumscribed skin areas. In the present study, posturally-induced changes of skin perfusion distribution along ischaemic limbs were investigated topographically in 35 PAOD patients by means of fluorescein perfusography. Among the 68 legs studied, 7 had patent arteries and 61 could be assigned to FONTAINE stages I to IV. Limbs with peripheral skin lesions (stage IV) were further differentiated according to either healing (stage IV+) or non-healing (stage IV-) on conservative treatment. Sitting-up always led to prolonged calf as well as foot fluorescein appearance times (AT) except for legs in stage III or IV- disease. In the latter two groups, decreased sitting as compared to supine AT foot-to-calf ratios indicated a relative shift of dye delivery from proximal towards distal skin regions during posture. In contrast, this measure of blood flow redistribution did not change in the other groups. The redirection of fluorescein influx was significantly correlated with the systolic arterial pressure ankle-to-arm ratios. In conclusion, besides small perfusion pressure increases or passive microvessel distension, a shift of the peripheral resistance ratios may contribute to the improved blood supply of ischaemic skin regions during leg dependency. An arteriolar vasoparalysis does not regularly exist in limbs with skin lesions not primarily originating from ischaemia (stage IV+).     

Cerebral venous outflow and arterial microsphere flow with elevated venous pressure

The cerebral blood flow response to cerebral venous pressure elevation was studied in pentobarbital-anesthetized dogs using the cerebral venous outflow and radiolabeled microsphere techniques. Cerebral venous pressure elevation resulted in a significant reduction in cerebral venous outflow at a pressure of approximately 2.0 mmHg (referenced at the level of the external auditory meatus). At higher pressures, cerebral venous outflow decreased at a rate of 0.5 ml x min-1 x mmHg-1. Mean arterial pressure was 102.0 mmHg, and thus cerebral perfusion pressure (mean arterial pressure minus cerebral venous pressure) was well within the range for cerebral autoregulation. These results were obtained regardless of whether cerebrospinal fluid pressure was allowed to rise concomitantly with cerebral venous pressure (11 dogs) or was maintained at atmospheric pressure (7 dogs). However, simultaneous measurement of cerebral venous outflow and total and regional cerebral blood flow with the radiolabeled microsphere technique with venous pressure elevation (6 dogs) produced discrepant results. As cerebral venous pressure was elevated to approximately 16.0 mmHg, cerebral venous outflow decreased to 40% of control while total and regional cerebral blood flow values remained unchanged, so that regional and cerebral vascular resistances decreased. These results suggest that cerebral venous pressure elevation opens intracranial venous anastomotic channels and diverts blood flow from the measured venous drainage through other drainage sites. In addition, our results suggest that the dominant mechanism of cerebral autoregulation is metabolic, not myogenic.     

The regulation of subcutaneous adipose tissue blood flow in the ischaemic forefoot during 24 hours. Studies using the 133-xenon wash-out technique continuously over 24 hours

A method for continuous measurement of subcutaneous adipose tissue blood flow in the forefoot during 24 hours (SBF) is described. The method is based on the radioisotope wash-out principle using 133-Xenon. A portable semiconductor detector is placed just above a local depot of 1-2 microCi 133-Xenon in 0.1 ml isotonic saline injected into the subcutaneous adipose tissue in the forefoot. The detector is connected to a memory unit allowing for storage of data. Due to the short distance, the recorded elimination rate constant must be corrected for combined convection and diffusion of the radioactive indicator. Characteristic 24-hour blood flow patterns were unveiled in patients with normal peripheral circulation and in patients having ischaemic nocturnal rest pain. In normals SBF doubled from day to night. This is ascribed to the local veno-arteriolar sympathetic axon reflex, which induces arteriolar vasoconstriction when the transmural pressure of the veins exceeds approximately 25 mmHg. In patients having ischaemic rest pains SBF was reduced by 37% on the average from day to night. This was caused by nocturnal hypotension, which is reflected proportionally in the foot. As the resistance vessels most probably are fully dilatated in feet with rest pain, the blood pressure drop during sleep causes the perfusion pressure and thus blood flow to come below a certain critical limit. There was a pronounced correlation between the reduction of systemic mean arterial blood pressure and SBF. The patients complaining of intermittent claudication, but no rest pains showed a variety of changes in SBF compatible with the continuous spectrum of the peripheral arteriosclerotic disease. After reconstructive vascular surgery, the 24-hour blood flow pattern normalized although the ankle/arm systolic blood pressure index did not come within normal range. SBF during day-time activities decreased by up to 50% postoperatively. This is caused by the reappearance of the local, sympathetic, veno-arteriolar vasoconstrictor response. During sleep SBF increased by 71%. The term postreconstructive hyperaemia seems improper, at least in a long-term context, normalization of preoperative ischaemia is a more correct notation. The coefficient of variation of nocturnal SBF was calculated to 10%. The method thus seems apt as a monitor in medical therapy for occlusive arterial disease. Changes of lambda has, however, to be considered in each study.     

Skin perfusion patterns (fluorescein perfusography) during reactive hyperaemia in peripheral arterial occlusive disease.

From the pathophysiological point of view the regional distribution of blood flow is of special importance in ischaemic tissues. Within this study foot sole skin perfusion was investigated by means of fluorescein perfusography at rest and during reactive hyperaemia in patients with peripheral arterial occlusive disease confined to one limb (Fontaine stage II). Ambient temperatures were maintained around 21 degrees C. Mean fluorescein appearance times on the one side and their standard deviations (SD) and coefficients of variation (CV) on the other side were taken as measures of overall blood supply and homogeneity of flow, respectively. At rest no differences in these parameters could be detected between diseased legs and controls. After a 3-min supra-systolic circulatory arrest at the thigh, a significant reduction of fluorescein appearance times was observed for both groups but was statistically more pronounced in the controls. Furthermore, during reactive hyperaemia standard deviations as well as coefficients of variation decreased significantly only in normal limbs whereas they either remained constant (SD) or even increased (CV) in those with arterial obstructions. All effects associated with reactive hyperaemia showed statistically significant correlations with systolic ankle pressure indices. From these results it is concluded that haemodynamically effective arterial obstructions are followed by not only a restriction of overall hyperaemic blood supply but also a failure to homogenize microcirculatory perfusion in the case of increased flow requirements.     

Changes in the total hepatic blood flow soon after resuscitation

The total hepatic blood flow during the first 2 hours after resuscitation was studied by local thermodilution and obturating catheter methods in experiments on cats anesthetized with pentobarbital. Changes in the blood flow occurred in stages. The brief increase in volume velocity of perfusion immediately after resumption of cardiac contractions was replaced by a rapid fall below the control level, after which the blood flow continued to decrease gradually. Changes in the total hepatic blood flow correspond largely to changes in the minute volume of the heart. Drip infusion of dextran in doses maintaining the central venous pressure at its initial level restored the normal hepatic blood flow and arterial pressure during the period after resuscitation.     

Cerebrovascular transmural pressure and autoregulation

The cerebral blood flow (CBF) response to changes in perfusion pressure mediated through decreases in arterial pressure, increases in cerebrospinal fluid (CSF) pressure and increases in jugular venous pressure was studied in anesthetized dogs. A preparation was developed in which each of the three relevant pressures could be controlled and manipulated independently of each other. In this preparation, the superior vena cava and femoral vein were cannulated and drained into a reservoir. Blood was pumped from the reservoir into the right atrium. With this system, mean arterial pressure and jugular venous pressure could be independently controlled. CSF pressure (measured in the lateral ventricle) could be manipulated via a cisternal puncture. Total and regional CBF responses to alterations in perfusion pressure were studied with the radiolabelled microsphere technique. Each hemisphere was sectioned into 13 regions: spinal cord, cerebellum, medulla, pons, midbrain, diencephalon, caudate, hippocampus, parahippocampal gyrus, and occipital, temporal, parietal and frontal lobes. Despite 30 mm Hg reductions in arterial pressure or increases in jugular venous pressure or CSF pressure, little change in CBF was observed provided the perfusion pressure (arterial pressure minus jugular venous pressure or CSF pressure depending on which pressure was of greater magnitude) was greater than the lower limit for cerebral autoregulation (approximately 60 mm Hg). However, when the perfusion pressure was reduced by any of the three different methods to levels less than 60 mm Hg (average of 48 mm Hg), a comparable reduction (25–35%) in both total and regional CBF was obtained. Thus comparable changes in the perfusion pressure gradient established by decreasing arterial pressure, increasing jugular venous pressure and increasing CSF pressure resulted in similar total and regional blood flow responses. Independent alterations of arterial and CSF pressures, and jugular venous pressure produce opposite changes in vascular transmural pressure yet result in similar CBF responses. These results show that cerebral autoregulation is a function of the perfusion pressure gradient and cannot be accounted for predominantly by myogenic mechanisms.     

Hepatic arterial perfusion decreases intrahepatic shunting and maintains glucose uptake in the rat liver

Intrahepatic shunts have an important function in the regulation of portal venous pressure in the normal rat liver. The present study determined their location, the region of confluence between the hepatic arterial and portal venous vasculatures, regions within the liver that are bypassed and the effects of hepatic arterial perfusion upon the intrahepatic redistribution of portal venous flow. Livers of male Sprague-Dawley rats were excised and perfused in vitro. Hepatic bromosulphthalein (BSP) and glucose uptake were measured in hepatic venous samples. Diversion of the hepatic arterial supply into the portal venous vasculature opened the portal venous intrahepatic shunts and resulted in a 50% reduction in portal venous glucose uptake from 29.6+/-1.6% to 14.9+/-0.9% ( P<0.0001 Student's paired t-test). Portal venous injection of 15-microm-diameter microspheres also opened the intrahepatic shunts and reduced portal venous glucose uptake to 10% from 29.0+/-1.6% to 7.8+/-0.9% ( P<0.0001 Student's paired t-test). No significant reductions in portal venous BSP uptake (43.0+/-6.9 to 48.0+/-4.8%) or hepatic arterial glucose uptake, from an average value of 94.0%, occurred. Therefore, cessation of hepatic arterial perfusion or portal venous injection of microspheres reduced portal venous glucose uptake without affecting BSP uptake. It is concluded that intrahepatic shunts divert perfusate away from the perivenous, sinusoidal (zone III) regions and into the hepatic venous vasculature, distal to zone III. The microsphere data indicate that confluence between the hepatic arterial and portal venous vasculatures occurs mainly in sinusoidal zone II.     

Local regulation of subcutaneous blood flow in normal subjects and in migraine patients before and after single-dose ergotamine tartrate

Local blood flow regulation of the foot was studied in 15 normal subjects and in nine migraine patients. Changes in arterial and venous pressures were induced by lowering and elevation of the limb. Changes in blood flow were estimated from the changes in the wash-out rate of a subcutaneous 133-Xenon depot. The local vasoconstrictor response to increased venous pressure elicited during lowering was identical in the normal subjects and in the migraine patients. During elevation, however, an abnormality in the autoregulation of blood flow could be demonstrated, as a decrease in blood flow during elevation to +40 cm was more pronounced in the patients than in the normal subjects (P = 0.04). About 3 h after 0.5 mg ergotamine tartrate/70 kg body weight i.v. the local regulation of blood flow had markedly changed in normal subjects as well as in migraine patients. During elevation to +20 and to +40 cm, blood flow increased significantly (P = 0.01 and P = 0.02). In two subjects the isotope depot was infiltrated with lidocaine and the ergotamine-induced increase in blood flow during elevation was blocked. The results may indicate that the veno-receptor of the veno-arteriolar reflex underlying the local vasoconstrictor response is a tension receptor, which due to the veno-constrictor effect of ergotamine is triggered even at heart level.     

Modeling the hepatic arterial buffer response in the liver

In this paper we present an electrical analog model for the hepatic arterial buffer response (HABR), an intrinsic regulation mechanism in the liver whereby the arterial flow counteracts the changes in portal venous flow. The model itself is a substantial simplification of a previously published model, with nonlinear arterial and portal resistors introduced to account for the dynamic HABR effects. We calibrate the baseline model using published hemodynamic data, and then perform a virtual portal occlusion simulation where the portal vein is half or fully occluded. The simulation results, which suggest that the increased arterial flow cannot fully compensate lost portal perfusion, are consistent with clinical reports and animal model findings. Since HABR functions in both the whole liver and liver graft after transplantation, we also simulate blood flow in a virtual right-lobe graft by adjusting the electronic component parameters in the electric circuit, and our model is able to reproduce the portal venous hyperperfusion and hepatic arterial hypoperfusion conditions due to the HABR effects.     

Contribution of local blood flow regulation mechanisms to the maintenance of arterial pressure in upright position during epidural blockade

The contribution of local blood flow regulation mechanisms to the maintenance of arterial pressure in upright position was studied in 5 normal subjects. Central sympathetic blockade was induced by epidural anesthesia. Blood flow in anterior tibial muscle in both legs and in brachioradial muscle in one arm was measured by the local 133Xe washout technique. Arterial blood pressure was recorded directly from the radial artery. Slow head-up tilt (about 30 degrees) caused a decrease in blood flow of about 36% in the dependent legs and in arm remaining at heart level. Arterial pressure decreased by about 10%. Blockade of the local sympathetic veno-arteriolar "axon reflex" in one leg by injection of phentolamine into the common femoral artery caused a vasodilatation in the ipsilateral muscle, while muscle blood flow did not change in the other leg or arm. Within 20 s after the injection of phentolamine arterial pressure decreased by about 7%. This cannot be explained by a "systemic" effect because injection of phentolamine into the femoral vein did not effect arterial pressure within the first 40 s. Vasoconstriction due to blood-borne factors is ruled out since preventing the increase in vascular transmural pressure in the leg by inducing counterpressure locally, abolished the vasoconstriction. Thus, the results suggest that the local veno-arteriolar "axon reflex" together with myogenic mechanisms contribute to the maintenance of arterial pressure in the upright position.     

Heterogeneous blood flow response in the foot on dependency,assessed by laser Doppler perfusion imaging

The exact nature of the decrease in foot skin blood flow seen after a change in posture remains unsettled. This mechanism has previously been examined by non-invasive techniques such as the laser Doppler perfusion monitor (laser Doppler flowmetry). Taking into account the shortcomings of laser Doppler perfusion monitoring when applied to the determination of skin blood flow, which normally shows substantial heterogeneity, we have applied an emerging technology, the laser Doppler perfusion imager (LDPI). This technique provides a more comprehensive picture of the blood flow distribution in the skin, as it maps skin blood flow over a surface area (120×120 mm, 4096 measurement sites). It was used to examine if the reduction in tissue perfusion or the alterations in flow distributions seen after a change in posture (supine to dependency) could be fully explained by an increase in venous pressure (venous stasis of 50 mmHg) or if the data suggest a complementary mechanism. Skin blood flow of the forefoot decreased from 0.60 V (volt) (median) during rest to 0.40 and 0.38 V during venous stasis and dependency, respectively. Although almost identical median values were obtained during stasis and dependency, the flow distributions were different, with a loss of high flow values during venous stasis. Biological zero was 0.24 V. As the LDPI technique readily records skin perfusion during variations in venous stasis and posture, as well as information on flow distribution changes, it appears promising for future application in stimuli-response studies of skin blood flow. The difference in flow distribution seen between increased venous pressure and dependency suggests an additive regulatory mechanism to the veni-vasomotor reflex during a change in posture.     

Resetting of the pressure range for blood flow autoregulation in the rat kidney

Both a myogenic response and the tubuloglomerular feedback control mechanism seem to be involved in autoregulation of glomerular filtration rate (GFR) and renal blood flow (RBF). Earlier experiments have shown that clamping of renal arterial perfusion pressure, below the autoregulatory range, reduces single-nephron GFR, and that this low value is maintained during the first 10-15 min after release of the clamp. It was also found that the tubuloglomerular feedback mechanism in the early declamp phase was strongly activated to reduce GFR. These findings can not be easily understood with the current knowledge of autoregulation, but would suggest a resetting of RBF and GFR autoregulation to a new level. To test this, left renal arterial perfusion pressure was reduced from 100 to 60 mmHg during 20 min with and without angiotensin converting enzyme inhibition (0.5 mg i.v. enalapril). Renal blood flow was measured with laser-Doppler flowmetry. When arterial perfusion pressure was reduced from 100 to 60 mmHg for 20 min, RBF was reduced to 77% of control and remained at this low level during the first minutes of declamp. In this situation there was an autoregulation to a new level. Renal blood flow was then slowly normalized (16.1 min). In the enalapril-treated animals RBF was only reduced to 85% during the 20 min of clamping and returned immediately to the control level at declamp. Thus, these experiments demonstrate that if renal blood flow is decreased by reducing the perfusion pressure below the normal autoregulatory range the pressure range for blood flow autoregulation resets to a lower level and that this change is mediated via the renin-angiotensin system.     

基于电磁驱动的体外膜肺氧合搏动式泵血系统

根据电磁学原理建立梯度线圈-永磁体模型,本研究设计了一款新型电磁驱动搏动式血泵,主要包括驱动装置、泵头装置、冷却系统以及体外循环管路等.搏动式血泵运动速率接近正常人体心率,模仿心脏的节律跳动,产生搏动式血流,实现了搏动式泵血.通过搭建实验平台,采集基于电磁驱动的体外膜肺氧合(extracorporeal membran...     

Two models of glomerular filtration rate and renal blood flow in the rat

Two mathematical models of glomerular filtration and blood flow are derived. The first is based on principles of fluid and mass conservation in individual capillaries. The model explains why the filtration rate (GFR) is strongly dependent on local hydrostatic and protein oncotic pressures, and on plasma flow rate (GCPF), but only weakly dependent on exact numbers, lengths, radii, or filtration coefficient of glomerular capillaries. The model shows that much of the increased GFR in both isooncotic plasma loading and isotonic Ringer's loading is due to increased GCPF caused by diluting erythrocytes. The second model uses several approximations and reduces to a quadratic in afferent arteriolar blood flow. When arterial pressure, hematocrit, plasma protein concentration, and afferent and efferent arteriolar resistances are specified, the model predicts GFR, afferent arteriolar blood flow, and filtration fraction. Alternatively, if any two of these three variables are known, the model predicts segmental arteriolar resistances. The model indicates that GFR and blood flow regulation must be located in the afferent arteriole, despite the strong dependence of GFR on GCPF.