Regional Tissue Blood Flow Research Articles

Body temperature influences regional tissue blood flow during retrograde cerebral perfusion

Objective: This study compared the cerebral microcirculation during retrograde cerebral perfusion with that during antegrade cardiopulmonary bypass under normothermic and hypothermic conditions. Methods: Brain tissue blood flow was measured with the hydrogen-clearance and colored microsphere (15 and 50 μm) methods during antegrade cardiopulmonary bypass and retrograde cerebral perfusion. Measurements were performed during normothermia (37° C), moderate hypothermia (28° C) and deep hypothermia (20° C) in groups of mongrel dogs ( n = 8). Results: During antegrade cardiopulmonary bypass, the microsphere method showed a significant decrease in cerebral blood flow as body temperature decreased (40.1 ± 20.8 ml/min/100 gm at 37° C, 16.2 ± 18.0 ml/min/100 gm at 20° C with 50 μm microspheres) At 20° C, the cerebral blood flow measured with the 15 μm microspheres was significantly lower than that assessed with the hydrogen-clearance method (11.3 ± 7.0 vs 24.8 ± 7.0 ml/min/100 gm). During retrograde cerebral perfusion, the microsphere method also showed a significant decrease in cerebral blood flow with cooling. At 37° C, the cerebral blood flow measured with the 15 μm microspheres (0.8 ± 0.7 mI/min/100 gm) was significantly lower than that assessed with the hydrogen-clearance method (10.1 ± 3.5 ml/min/100 gm). At both 28° and 20° C, the hydrogen-clearance method showed significantly higher cerebral blood flow (10.1 ± 5.8 and 8.2 ± 3.7 ml/min/100 gm) than did the 50 μm microspheres (1.8 ± 0.6 and 1.0 ± 0.8 ml/min/100 gm) and 15 μm microspheres (0.23 ± 0.14 and 0.18 ± 0.15 ml/min/100 gm). Conclusion: (1) Cerebral blood flow that shunts to capillaries is increased during antegrade cardiopulmonary bypass under deep hypothermia. (2) During retrograde perfusion, the majority of the blood flow shunts away from brain capillaries, even under normothermic conditions, and blood flow through large venoarterial shunts increases as body temperature decreases, Although the cerebral microcirculation during retrograde perfusion is decreased, retrograde perfusion provides some degree of oxygenation to the body. (J Thorac Cardiovasc Surg 1997;114:440-7)

Cardiovascular response to blood loss during high intracranial pressure.

The authors hypothesized that the combination of hemorrhage and increased intracranial pressure (ICP) has deleterious effects on cardiovascular function. The effect of blood loss during normal and increased ICP was studied in eight pigs. The mean arterial pressure (MAP), pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac output, and cerebrospinal fluid (CSF) pressure were measured. The regional tissue blood flow was determined with radioactive microspheres labeled with four different nuclides. High ICP (80% of MAP) was induced by infusion of artificial CSF into the cisterna magna. The response to rapid arterial bleeding of 25% of blood volume was measured. The decrease in blood flow to the intestine, skeletal muscle, and the kidneys after blood loss was significantly greater during high ICP. The decrease in blood flow to the spleen and pancreas tended to be greater during high ICP, whereas the changes in blood flow to the liver, adrenal glands, and heart muscle showed no such tendency. The fall in cardiac output and heart stroke volume after blood loss were more pronounced when the ICP was high, and the increase in systemic vascular resistance was considerably greater. These observations suggest that during high ICP the physiological protective mechanisms against blood loss are impaired in the systemic circulation, and a loss of 25% of the blood volume, normally well compensated for, may induce a state of shock.

Retrograde abdominal visceral perfusion: Is it beneficial?

It is proposed that retrograde abdominal perfusion be used in combination with retrograde cerebral perfusion to provide total body visceral protection during aortic reconstruction; however, its physiologic effects remain unknown. We compared the effect of superior vena caval perfusion alone with that of combined superior and inferior vena caval perfusion on the liver and kidney in 6 mongrel dogs. Organ blood flow was measured using ultrasonic flow probes on the hepatic artery, the portal vein, and the renal artery. Regional tissue blood flow to the liver and the kidney was assessed using colored microspheres and pH probes. Anesthetized dogs were placed on total cardiopulmonary bypass. After cooling to 20 degrees C, retrograde perfusion was begun with 30 minutes of superior vena caval perfusion followed by another 30 minutes of bicaval perfusion, or vice versa. Very little renal blood flow was measured with either method of retrograde perfusion. Although the liver received more blood flow in comparison to the kidney, there was no significant difference between superior vena caval perfusion alone and bicaval perfusion. The addition of inferior vena caval perfusion results in portal hypertension, hepatic congestion, ascites, and bowel edema. In the canine model, bicaval perfusion does not provide superior protection to the liver and kidneys when compared with superior vena caval perfusion alone.

Role of EDRF in the regulation of regional blood flow and vascular resistance at rest and during exercise in conscious dogs.

The contribution of endothelium-derived relaxing factor (EDRF) to the regulation of regional vascular resistance and tissue blood flow at rest and during acute moderate exercise was studied in chronically instrumented conscious dogs. Radioactive microspheres were injected before and during exercise to measure regional blood flow. An infusion of nitro-L-arginine (L-NA), an analogue of L-arginine, was used to inhibit the synthesis of EDRF and resulted in a significant increase in mean arterial pressure, associated with significantly elevated vascular resistance in heart, skeletal muscle, renal and splanchnic circulations and with decreases in tissue blood flow in those regions at rest. Acute exercise caused a typical redistribution of blood flow, in which there was vasodilation in heart and working skeletal muscles, accompanied by vasoconstriction in kidney and splanchnic circulations. L-NA resulted in significantly elevated vascular resistance during vasodilation in heart and working skeletal muscles and also significantly increased vasoconstriction in renal cortex, stomach, pancreas, liver, and colon during exercise. Blood flows during exercise were largely unaffected by L-NA treatment. Our results suggest that whereas EDRF functions to regulate basal vascular tone and vascular resistance during exercise, EDRF has a minor role in determining the pattern of the redistribution of tissue blood flow during exercise.

Effect of propofol and thiopentone on regional blood flow in brain and peripheral tissues during normoxia and hypoxia in the dog.

The effect of propofol and thiopentone on cerebral (CBF), myocardial (MBF), muscular, and arterial hepatic blood flow was assessed with radiolabelled microspheres in 12 chronically instrumented dogs, six given propofol and six thiopentone. Tissue blood flows were measured in the awake animal, after 30 min of normoxic anaesthesia (room air), and after 30 min of hypoxic anaesthesia using a mixture of 10% O2 and 3% CO2 in nitrogen. The decrease in CBF from awake to normoxic anaesthesia was similar with propofol and thiopentone (propofol: 77 +/- 8 to 38 +/- 3 ml min-1 100 g-1, P < 0.01; thiopentone: 66 +/- 3 to 33 +/- 2 ml min-1 100 g-1, P < 0.01). During hypoxia, CBF rose moderately in the two groups (respectively +19% and +28%, P < 0.05). The MBF increased in propofol and thiopentone groups after 30 min of anaesthesia with air (propofol: 97 +/- 23 to 137 +/- 15 ml min-1 100 g-1; thiopentone: 82 +/- 7 to 141 +/- 10 ml min-1 100 g-1) and increased still more during hypoxia. The increase in MBF was related to an increase in heart rate and blood pressure. The quadriceps blood flow decreased during anaesthesia in normoxia and in hypoxia. The diaphragmatic blood flow increased with thiopentone under hypoxia. The hepatic arterial blood flow was unchanged. It is concluded that the effects of propofol on regional blood flows are very similar to those of thiopentone.

Non-radioactive coloured microsphere measurement of regional tissue blood flow for axial pattern flaps in rabbits

We administered non-radioactive coloured microspheres (NRACM) to measure the regional tissue blood flow (RTBF) of eight axial pattern flaps and four kidneys in four rabbits using four repeated injections into each animal. As a control, we used radioactive microspheres (RAM) for six kidneys in three rabbits. There were no significant differences for RTBF values between NRACM and RAM, between the numbers of microspheres used (2 × 10 6 and 4 × 10 6), or between the number of injections. These results showed that NRACM is a useful and safe laboratory method.

Myocardial transit time of the echocardiographic contrast media

The mean transit time of a tracer through a sample of tissue is a quantitative marker most closely related to regional tissue blood flow. Therefore, an accurate estimation of the mean time of transit of an ultrasonic tracer through a sample of myocardial tissue, obtained by contrast echocardiography, may provide a quantitative noninvasive estimate of myocardial perfusion. We hereby present an algorithm for the determination of the mean transit time by computerized analysis of a series of contrast-enhanced echocardiographic images. The algorithm comprises the evaluation of the echocardiographic impulse response function of a selected region of interest, using a deconvolution technique based on a fast Fourier transform and a frequency domain division of the videointensities measured in the sample, by that measured in a predetermined reference region. An extensive computer simulation study was designed to facilitate the optimization of the steps of analysis. We present the results of the evaluation study performed in order to assess the accuracy of the procedure in computer-simulated echocardiographic images. Within a wide range of parameters chosen to define these functions, the analysis is shown to be essentially independent of the rise and decay times of the impulse response function of the tissue sample as well as of the simulated intensities. The effects of random noise introduced into the simulated intensity curves and of their variable width were investigated. The mean transit time was found to be accurately evaluated within about 10% of error for the variety of widths and noise levels permitted. The reconvolution error did not correlate with the accuracy of the evaluation of the mean transit time, indicating that the reconvolution error cannot be used as an estimate of the accuracy of the procedure. The numerical methods and the results of the computer study are discussed in detail. The approach is proposed to be used as part of a more general technique for the quantitative measurement of regional myocardial tissue blood flow.

Inhibitory effect of methysergide on calcitonin gene-related peptide-induced vasodilatation and ocular irritative changes in the rabbit.

1. Calcitonin gene-related peptide (CGRP) is involved in ocular neurogenic inflammation in the rabbit, causing vasodilatation in the anterior uvea, breakdown of the blood-aqueous barrier, increase in the intraocular pressure (IOP) and rise in the adenosine 3':5'-cyclic monophosphate (cyclic AMP) content in the aqueous humour. So far there is no means of preventing these CGRP-induced ocular effects. 2. In the present study, the effect of intravenous methysergide (1-10 mg kg-1, b.w.) on CGRP-induced changes in the IOP, blood-aqueous barrier and cyclic AMP content in the aqueous humour was studied in vivo. The effect of methysergide on CGRP-induced vasodilatation both in vivo and in vitro was also investigated. 3. Methysergide decreased intraocular pressure but had only a transient effect on blood pressure. Methysergide decreased the regional blood flow in ocular tissues by 53-65%, but did not have such a vasoconstrictor effect in most extra-ocular tissues studied. 4. Methysergide inhibited CGRP-induced vasodilatation, increase in the IOP, breakdown of the blood-aqueous barrier and increase in the cyclic AMP content in the aqueous humour in vivo. 5. In vitro, methysergide alone did not have effects on the vascular tone in isolated ophthalmic artery of rabbit. However, it potentiated noradrenaline (NA)-induced contraction. There were no differences in the IC50 values for CGRP on the NA-induced contraction in the presence and absence of methysergide, indicating that methysergide has no direct effect on the vasorelaxant effect of CGRP in vitro. 6. The present study demonstrates that in the rabbit eye methysergide inhibits CGRP-induced changes.One inhibitory mechanism of methysergide may be to enhance the effect of a vasoconstrictor (NA) to antagonize the vasodilator effect of CGRP. The present findings suggest that a methysergide-sensitive mechanism may be used to limit some pathophysiological conditions in the eye that involve neurogenic inflammation and the release of CGRP.

Experimental study in a rabbit model of ischemia-reperfusion lung injury during cardiopulmonary bypass

Adult white rabbits were subjected to 2 hours of partial cardiopulmonary bypass (flow rate 90 ml/min/kg) at 32 degrees C, and unilateral pulmonary artery occlusion was used to simulate total cardiopulmonary bypass in the lung subjected to arterial occlusion, with the other side used as the control lung. The lung subjected to arterial occlusion was reperfused by one of the following methods: (1) by whole blood (WB group), (2) by leukocyte-depleted blood (LD group), and (3) by whole blood with protease inhibitor (nafamostat mesilate, FUT group), expecting its anticomplement action. In the fourth group, the lung was inflated with oxygen during pulmonary artery occlusion followed by whole blood reperfusion (OXY group). As a result, lungs subjected to pulmonary artery occlusion showed significant decreases in tissue concentrations of adenosine triphosphate and regional tissue blood flow during cardiopulmonary bypass. Furthermore, recovery of adenosine triphosphate was depressed in the WB group and recovery of regional tissue blood flow in the WB and OXY groups. Ultrastructural findings in alveolar epithelial cells and capillary endothelial cells showed worsening at reperfusion in only the WB group. Transpulmonary gradients of C5a and leukocyte showed significant increases at reperfusion in the WB and OXY groups. Alveolar-arterial oxygen difference was significantly higher in the WB group than in the others. Results indicate that complete cessation of pulmonary artery flow in normothermic cardiopulmonary bypass may cause ischemia of the lung followed by reperfusion injuries with the no-reflow phenomenon, with possible involvement of activation of leukocytes and complement.

The effect of preoperative needle abrasion of the recipient site on survival of autologous free fat grafts in rats.

Pads of fat ranging from 670-1758 mg in weight were taken from the right groins of 20 rats and implanted subcutaneously over their right pectoral muscles. One week previously the recipient site on the thorax had been abraded with a needle in 10 of the rats. After three months the transplanted fat was taken out, weighed, and examined histologically by light microscopy. Regional tissue blood flow in the transplanted fat and in the fat from the left groin was measured by the microsphere technique. The amount of surviving fat and blood flow in the fat transplanted to an abraded recipient site was significantly higher than in the control group after three months. We conclude that preoperative needle abrasion of the recipient site may increase the chance of revascularisation and survival of the transplanted fat in rats.

Effects of small changes of plasma vasopressin on subcutaneous and skeletal muscle blood flow in man.

The effect of vasopressin (AVP) on subcutaneous blood flow was studied by the 133Xenon wash-out method in 13 healthy subjects during three consecutive infusions of synthetic AVP, using increasing infusion rates. In seven of them, both subcutaneous and skeletal muscle blood flows were measured during the first infusion. The preinfusion, and infusion pAVP levels were 1.6 +/- 0.4, 3.4 +/- 0.4, 4.9 +/- 0.5 and 8.8 +/- 0.7 pg ml-1, respectively (mean +/- SE). The values are within the range normally found during dehydration. During the AVP infusions, the blood flow in subcutaneous tissues decreased 30-40% and the vascular resistance increased 60-80%. Neither heart rate nor blood pressure change significantly during the infusions. Plasma renin activity (PRA) decreased significantly. After cessation of the infusions, blood flow and vascular resistance rapidly returned to preinfusion values, while PRA increased very slowly. Skeletal muscle and subcutaneous tissues blood flows were found to be equally sensitive to small changes in the pAVP level. The present study has demonstrated that even minor increments of pAVP levels, as seen during dehydration, can significantly alter the regional blood flow in subcutaneous and skeletal muscle tissues in man.

Canine normal and tumor tissue estimated blood flow during fractionated hyperthermia

Time-temperature relationships are of critical importance in hyperthermia effects on tumors. Knowledge of temperature distributions within tumors is necessary to achieve maximal tumor response, and because blood flow is the major determinant of heat dissipation within tissue, knowledge of blood flow parameters is equally important. A mathematical model has been developed which estimates a parameter that may be related to regional tissue blood flow and is readily adaptable to clinical observations. Eight canine mast cell tumors were heated with interstitial radiofrequency (100 mHz) hyperthermia to a temperature range of 44°C, ±0.5°C, for 40 minutes. Estimated blood flow increased over the 40-minute treatment interval from 81 ml/min/100 gm of tissue at 10 minutes post-initiation of treatment to a maximum of 101.2 ml/min/100 gm of tissue at 30 minutes post-initiation of treatment. Over a 9-day period, during which both tumor and normal tissues were treated four times, values increased within the volume of interest. Maximum estimated blood flow within normal tissue increased from 115.7 ml/min/100 gm of tissue after 10 minutes of heating to a maximum of 121.7 ml/min/100 gm of tissue at 40 minutes. In contrast to normal tissue, eight canine mast cell sarcomas showed little change in estimated blood flow during 40 minutes of treatment. However, tumor tissue appears to undergo compensatory changes over the 9-day treatment interval with increases occurring in blood flow over that time period. These data underscore the importance of knowing blood flow characteristics within tumor and normal tissue.

Positron emission tomography in the study of human tumors

To increase our understanding of cancer and improve cancer treatment on a rational basis we need to identify both qualitative and quantitative differences between normal and neoplastic tissue. The multimodality approach to cancer treatment includes radiotherapy, chemotherapy, hyperthermia, and immunotherapy. Most of the data on which we base our therapeutic strategies have been derived from in vitro studies or animal tumor models. More information is required on the physiology of in vivo human tumors and their response to therapy. Positron emission tomography allows the regional tissue concentration of a positron emitting radionuclide to be measured in absolute units. If valid tracer models can be formulated that accurately describe the fate of an administered "biological" tracer then the physiological process under investigation can be measured quantitatively. The sequential inhalation of C15O2, 15O2, and 11CO allows regional tissue blood flow, oxygen utilization and blood volume to be measured in absolute units. Tissue perfusion, a measure of nutrient (eg, oxygen) supply, drug delivery, or a means of heat dissipation, is of immense importance to oncologists. The oxygen-15 technique has been used not only to study regional blood flow and oxygen utilization in both tumor and normal tissue but also their response to therapeutic intervention. In those studies were tracer models are thought to be less than complete (eg, due to insufficient biological data) then only a semiquantitative or qualitative assessment of the pathophysiological state may be possible. In this respect, tumor function has been characterized by the rate of uptake of 18F-2-deoxyglucose. This technique has provided a means of tumor grading and differentiating between radiation-induced tissue necrosis and tumor recurrence. Metabolic imaging with labeled amino acids appears particularly useful in the delineation of tumor extent. Blood brain barrier integrity and the pharmacokinetics of cytotoxic drugs have also been studied quantitatively. In the future, receptor studies are likely to play an increasing role. In this review dealing with the positron emission tomography oncologic work to date, emphasis has been placed on the physiological information obtainable and how it may further our understanding of cancer and its treatment.

Positron emission tomography in venous ulceration and liposclerosis: study of regional tissue function.

Oxygen-15 administered by continuous inhalation and emission computed tomography were used to study regional tissue oxygen utilisation and blood flow in the limbs of 11 patients with venous ulceration and five patients with liposclerosis due to venous insufficiency. The results showed increased blood flow and appreciably reduced fractional oxygen extraction in the diseased tissues. These findings indicated a local, functional shunting of blood through the abnormal microcirculation of the skin and subcutaneous tissues. This may be an important factor in the aetiology of the skin changes seen in patients with calf muscle pump failure.

Noninvasive assessment of microcirculation of living organs and tissues using laser.

For studying microcirculation of intact tissues or organs, a new noninvasive, heat-transient method using laser photoexcitation is described. As a heating source an argon ion laser or R6G dye laser was used via a quartz fiber optic guide. Infrared radiation from heated tissue was detected by a thermography apparatus. After switching the laser irradiation on and off, a thermal transient curve of a model tissue, the skin, was biphasic: a component with a fast time constant and the other with a slow time constant. The temperature increases of both phases following laser irradiation were linear to the applied power from the laser onto the tissue. The temperature rises as a function of the wavelength of irradiated light have shown that the absorption of the light by tissue hemoglobin is a main heat-generation source. Furthermore, the temperature rises as a function of tissue blood volume and flow have shown that the component with a slow time constant is more related to the tissue hemoglobin concentration and tissue blood flow and heat conductivity. Thus, the analysis of heat-transient curves following laser irradiation gives information as to regional tissue blood volume, blood flow, and tissue heat conductivity.

Studies on regional blood flow of the mouse using whole-body autoradiography of 14C-iodoantipyrine.

In order to visualize regional blood flow in various tissues of the mouse at the same time, the distribution of radioactive carbon from 14C-iodoantipyrine was studied by whole-body autoradiography. The mice were frozen with Dry-Ice-hexane at 1, 10, 30 min, and 1 h and 3 h after intravenous injection of 14C-iodoantipyrine. Whole-sagittal sections of the frozen mouse, obtained by using a cryostat microtome, were dried in a cryostat and subjected to autoradiograhy. The resulting dry autoradiographs are called untreated autoradiographs in the present work. The sections were then fixed in cold 6% (w/v) HClO4, dried at room temperature and again subjected to autoradiography. Autoradiographs thus obtained are referred to as treated autoradiographs. It was found that the method could be suitable for the estimation of regional blood flow of the renal cortex, spleen, lung, skeletal muscle, bone marrow, thymus, testes, and brain.

A simple cutter for fresh tissue to facilitate the investigation of intramyocardial blood flow with tracer microspheres in cats and rabbits

Tracer microspheres (TM) allow the measurement of regional tissue blood flow. For this purpose the tissue must be cut into the regions selected for measurements. We describe a simple tissue cutter, that greatly facilitates accurate and reproducible cutting of fresh tissue. We have demonstrated its usefulness for obtaining measurements of myocardial blood flow in different layers of the left ventricular free wall of hearts of anesthetized cats and conscious rabbits. Since complete trapping of the TM is essential for blood flow measurements by this method, we investigated the minimal TM size needed by comparing results obtained with different size microspheres. 25 and 15 μm TM were trapped equally well by all layers of the left ventricle, but TM smaller than 15 μm were not trapped completely. From the size distribution of the 7–10 μm TM, we estimated that the functional diameter of the largest capillaries was somewhat smaller (about 7.6 μm) in the subepicardial (epi) than in the subendocardial (endo) layer (7.9 μm) in both species. When measured with 15 μm TM, intramyocardial distribution of blood flow was comparable to that reported for dogs and sheep. In open chest cats, the endo/epi ratio was 1.25 and 1.28, and in conscious rabbits it was 1.35. We conclude that TM with diameters between 10 and 15 μm are suitable for measuring intramyocardial blood flow in cats' and rabbits' hearts, and that unlike in dogs and sheep, 7–10 μm TM cannot be used.

Transient intestinal ischaemia induced by degradable starch microspheres. Experiments in the cat.

Temporary ischaemia was induced in cat small intestine by degradable starch microspheres. Regional arterial and tissue blood flow immediately fell by 85 per cent with subsequent normalization within 26 min after microsphere injection. Degraded 99Tcm-labelled microspheres were exponentially removed from intestinal vessels and accumulated in the liver. Provided near-total arteriolar obstruction is induced, external isotope detection may permit assessment of the duration of the induced ischaemia, which implies a selection of the appropriate time for radiation therapy.

A new instrument for continuous measurement of tissue blood flow by light beating spectroscopy.

A new instrument for measurement of regional tissue blood flow based on the laser Doppler principle is reported. The theoretical background of light beating spectroscopy is discussed and a detection technique which makes possible the suppression of the adverse effects of laser-mode interference and wide-band beam amplitude noise is described. Instead of using a single square-law photodetector a differential detector technique is introduced that reduces common-mode noise to a negligible level, without influencing the blood flow related signal. The new instrument has proved to be highly stable and sensitive. Continuous recordings of tissue blood flow can be performed in the laboratory as well as at the bedside.

The distribution of cardiac output in the anaesthetized spontaneously hypertensive rat.

1. Radioactive 15 micrometer and 50 micrometer diameter microspheres were used to determine cardiac output, its regional distribution and tissue blood flow in adult normotensive Wistar and Okamoto spontaneously hypertensive rats. 2. Cardiac output in the spontaneously hypertensive rats was the same as in Wistar normotensive rats, but its distribution in the hypertensive rats appeared to differ: there was a significant increase in the proportion of microspheres trapped in the liver whereas fewer were found in the gastrointestinal tract. This indicates that a greater fraction of the cardiac output passes along the hepatic artery and less through the splanchnic bed. 3. Blood flow in skin and skeletal muscle in spontaneously hypertensive rats was approximately 50% of that in Wistar normotensive rats.