85Kr Clearance Research Articles

Measurement of hepatic perfusion in rats by laser Doppler flowmetry.

Little is known about the performance of the laser Doppler flowmeter (LDF) with changes in flow characteristics in the hepatic microcirculation. Red blood cell (RBC) flux, as measured by LDF, is sensitive to alterations in RBC velocity and RBC concentration, and both parameters must be considered when evaluating the technique. In vitro, linearity of LDF signal with RBC velocity up to 4 mm/s (r greater than 0.99) and RBC volume fractions up to 1.5% were demonstrated (r greater than 0.98). At higher velocities and volume fractions, RBC flux was underestimated. In portally perfused rat liver, LDF output was linearly related to total liver blood flow (TLBF; r greater than 0.9) for perfusate hematocrits between 2.5 and 40%, although the slope varied between preparations. At constant TLBF (2 ml.min-1.g-1), the LDF output changed linearly with perfusate hematocrit up to 20% (r greater than 0.99) but underestimated the increase at 40%. These results suggest that the LDF responds linearly to velocity-mediated flow changes but that it may underestimate a change if mediated through alteration in tissue RBC concentration. With hepatic nerve stimulation, TLBF fell to 51 +/- 14% of prestimulation (P less than 0.001), whereas the LDF output and superficial flow measured by 85Kr clearance fell to 12 +/- 10 and 14 +/- 10% (both P less than 0.01 vs. TLBF), respectively, suggesting that the LDF may be used to follow rapid flow changes in the periphery of the liver.

Effect of Injectable or Inhalational Anesthetics and of Neuroleptic, Neuroleptanalgesic, and Sedative Agents on Tumor Blood Flow

Among other parameters, varying blood flow values may be responsible for tumor-to-tumor variabilities in the radiobiologically hypoxic cell fraction of experimental rodent tumors. To test whether changes in tumor blood flow may be caused by anesthetic agents often used in radiobiology, the effect of injectable and inhalational anesthetics and of neuroleptic, neuroleptanalgesic, and sedative agents on blood flow in subcutaneous DS-carcinosarcomas implanted in Sprague-Dawley rats has been investigated using the 85Kr clearance technique. In conscious rats, 20-100 min after animal instrumentation mean blood flow is 0.62 +/- 0.17 ml/g/min (mean +/- SD) in 0.75 +/- 0.15 g tumors at a mean arterial blood pressure of 125 +/- 12 mm Hg. In animals receiving thiobutabarbital, chloral hydrate, or methoxyflurane tumor blood flow is somewhat higher than that measured in conscious rats. Tumor blood flow in animals receiving etomidate, ketamine-xylazine, fentanyl-fluanisone, or urethane is significantly lower than that in the thiobutabarbital group and somewhat lower than in the conscious animals. Blood flow values observed with midazolam, ketamine-midazolam, fentanyl-droperidol, droperidol, diazepam, and pentobarbital are similar to those measured in conscious rats. Virtually no flow alterations with time are detectable in conscious rats and with most of the drugs used. In animals anesthetized with urethane or methoxyflurane, tumor blood flow increases and tumor vascular resistance diminishes slightly with time.

Blood flow measurement in the canine pancreas

Blood flow in the anesthetized animal has been measured indirectly by plethysmography and directly with the stromuhr, venous outflow, and electromagnetic flow techniques. Tissue perfusion in the gland has been assessed qualitatively with thermocouples and quantitatively by isotope fractionation, the distribution of microspheres, hydrogen desaturation, and clearance of either 133Xe or 85Kr. The results of these investigations have been conflicting as there is a large variation in both flow and perfusion measurements, not only overall but also in the values reported by each technique (Table 1). Taking all methods into account flow measurements have been recorded from 9 to 63 (mean 29.8) ml/min, and 10 to 200 (mean 66.1) ml/min/100 g. The mean percentage of the cardiac output distributed to the pancreas is 1.28. Some of these differences are due to various drawbacks associated with each of the techniques; some are almost certainly due to variations in the surgical preparations, and others are undoubtedly caused by the complexity of the pancreatic circulation. Measurements of perfusion in different regions of the pancreas of individual dogs show no difference if all vessels are intact, but accessory vessel ligation affects perfusion in certain areas. In ambulant dogs the studies suggest that pancreatic blood flow is higher than in the anesthetized animal. This is probably true despite inaccuracies associated with each of the techniques. In addition to this drawback there is also the problem of obtaining measurements with the dogs in a relaxed state. It is probably for this reason that the majority of investigators have preferred to examine blood flow and perfusion in the canine pancreas in the anesthetized animal. It is not possible to make a definitive statement regarding the best model and measurement technique available to measure blood flow or tissue perfusion in the canine pancreas. The choice should undoubtedly be governed by the aims of the proposed study. In studies of tissue perfusion in the intact gland, it is obviously preferable that all vessels should be intact, as division of any vessels supplying the gland has been shown to affect perfusion in certain areas. Measurements in such a preparation could be taken using the 85Kr clearance technique, with a flow probe placed around the gastroduodenal artery to ensure stable flow during measurements. It is difficult to assess total arterial blood flow to the whole gland due to the number of vessels supplying the organ.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of Intravenous Dopamine Infusion on Intramural Blood Flow Distribution and Fluid Absorption in the Feline Small Intestine

The aim of the study was to investigate the effects of dopamine on the intestinal mucosal blood flow and transport function. Dopamine was infused intravenously at 20 micrograms X kg-1 X min-1 in anesthetized cats. Total and intramural blood flow in an isolated jejunal segment was measured by a combined drop-flow and 85Kr clearance technique. Net fluid transport was recorded by two independent perfusion methods. Unidirectional sodium transport was estimated from luminal 22Na disappearance. Dopamine induced a pronounced mucosal vasodilatation up to 400% of control values. Concomitantly, net fluid and sodium absorption increased by 50%. The effect on sodium transport was due to a pronounced decrease in tissue-to-lumen sodium flux, a pattern similar to the one seen on alpha-adrenergic stimulation. The effect of dopamine on blood flow was unaffected by phentolamine, 1 mg X kg-1, whereas the absorptive response was abolished. The findings indicate that dopamine induces a mucosal vasodilation via one mechanism (possibly dopaminergic) and enhances fluid transport via another mechanism, probably alpha-adrenergic.

Effect of four primary prostaglandins and relaxin on blood flow in the ovine endometrium and myometrium.

The effect of the prostaglandins (PG) D2, E2, F2 alpha and I2 (infusions of 250 ng/min for 10 min into the uterine artery) and relaxin (1 microgram/min) on uterine contractions and on the myometrial and endometrial blood flow to the uterus of ovariectomized, estrogen-primed ewes was investigated. The 85Kr clearance method was used to measure blood flow. PGD2 and PGI2 increased both myometrial and endometrial capillary blood flow, whereas PGE2 and relaxin did not. PGF2 alpha reduced the myometrial blood flow only at a significance level of P less than 0.1 but induced no significant changes in the endometrial flow. PGE2, PGF2 alpha and, notably, PGD2 caused a uterine hypertonus. PGI2 and relaxin did not affect the uterine motility. There is a parallel effect of the investigated substances on the blood flow of myometrium and endometrium but PGD2 induces contractions of the smooth muscle cells in the myometrium while relaxing comparative cells in blood vessels.

Effects of hypercapnia on enhancement of decreased perfusion flow in non-infarcted brain tissues.

The effects of hypercapnia on enhancement of reduced cerebral perfusion were re-evaluated in areas of ischemia produced by occlusion of the canine middle cerebral artery. Perfusion was measured by 85Kr (beta-ray) and 133Xe (gamma-ray) clearances, fluorescein angiography and diameter measurement of arteries. Between 45 and 55 mm Hg of PaCO2 rCBF measured with both isotopes increased significantly. When PaCO2 was elevated above 55 mm Hg, there was a remarkable dissociation in the rCBF measured by both isotopes. Cortical blood flow measured by 85Kr clearance decreased and, conversely, rCBF measured by 133Xe continued to increase. Arteries of less than 50 mu in diameter in areas of ischemia dilated significantly during hypercapnia. At PaCO2 above 65 mm Hg, progressive sub-pial hemorrhage and extravasation of dye were observed as side effects of hypercapnia. The use of mannitol combined with hypercapnia appeared to be harmful. A PaCO2 level between 45 and 55 mm Hg increases perfusion in areas of mildly reduced rCBF.

Endometrial blood flow in anaesthetized sheep as measured with krypton-85 clearance and microsphere techniques.

Uterine blood flow rates were obtained with a Krypton (85Kr) clearance technique and with radio-active microspheres in six anaesthetized, non-pregnant ewes (a total of ten comparisons). 85Kr was administered, via a catheter, into the abdominal aorta and beta-emissions were detected with a catheter-type semi-conductor detector probe situated in the lumen of a uterine horn. In seven instances, the 85Kr clearance curve had only one component while in the remaining three instances the curves could be resolved into two components. The flow rates derived from the single component curves and the mean flow rates calculated from the curves with two components were of the same order as, and highly correlated with, estimates of capillary blood flow obtained with microspheres for either the caruncles, the inter-caruncular endometrium or the total endometrium (r = 0.832, r = 0.822 and r = 0.841, respectively, P less than 0.005). There was no correlation between the flow rates obtained with the 85Kr technique and estimates of myometrial capillary blood flow obtained with microspheres.

The role of blood flow in the control of liver size

Recent reports by Starzl [T. E. Starzl], A. Francavilla, C. G. Halgrimson, F. R. Francavilla, K. A. Porter, T. H. Brown, and C. W. Putman, Surg. Gynecol. Obstet. 137: 179, 1973; T. E. Starzl, K. A. Porter, N. Kashiwagi, I. Y. Lee, W. J. I. Russell, and C. W. Putnam, Surg. Gynecol. Obstet. 140: 549, 1975] have described a splanchnic flow division experiment in the dog, in which portal blood from the upper gastrointestinal tract (including pancreas) was directed to the right lobes of the liver, while the left lobes received blood exclusively from the intestines via a vein graft. It was shown that the right lobes increased in weight, whereas the left lobes atrophied, and it was concluded that portal blood contains hepatotrophic factors of pancreatic origin. In the present experiments, the possible existence of differences in blood flow in the two hepatic segments was examined as an alternative explanation for the changes observed. Tissue perfusion was measured by 85Kr clearance in the right and left hepatic lobes of five dogs 60 days after splanchnic division, and it was found that there was no difference between the flows through the two segments, while changes in liver weight similar to those of the previous workers were seen. The results therefore confirm the observations of Starzl that the size of the liver depends on its portal circulation, and is mainly related to the quality of the blood that it supplies to the liver rather than on quantity of flow.

Measurement of liver blood flow in the dog using krypton-85 clearance: A comparison with electromagnetic flowmeter measurements

Blood flow in the superficial liver tissue was measured by recording the clearance rate of the β emissions of 85Kr following its injection into the portal vein. The flow values calculated from monoexponential clearance curves were compared to portal venous blood flow simultaneously recorded with a calibrated electromagnetic flow probe in six dogs whose hepatic artery had been ligated. The liver: blood partition coefficient of 85Kr was measured in these dogs and was found to be 0.91. There was a close correlation ( r = 0.95) between the blood flow values obtained from the two techniques over a wide range of flow values. This shows that measurement of liver blood flow in the surface layers of the liver using the 85Kr clearance method provides a true reflection of the blood flow in the liver tissue as a whole.

A study of method for enhancement of perfusion flow in experimental cerebral ischemia--Part 2. Hypercapnia with mannitol (author's transl)

In terms of increase of perfusion flow into an area of ischemia, carbon dioxide must be one of the most promising candidates, even though complete agreement has still not been obtained. A controversial, but attractive point in this field is that there is a discrepancy between experimental results obtained by beta-emitting 85Kr and gamma-emitting 133Xe clearance techniques. To resolve this discrepancy in the results from the two isotopes, the experiment of this series were undertaken and our first report clarified that between 45 and 55 mmHg of arterial carbon dioxide pressure (PaCO2), microregional cerebral blood flow (rCBF), measured with both the 85Kr and 133Xe clearance techniques, increased significantly. However, in the same study, as PaCO2 was elevated above this level, there was a remarkable dissociation in rCBF change as measured by each isotope. The cortical blood flow measured with 85Kr clearance method decreased and conversely, global miniregional cerebral blood flow measured by 133Xe continued to increase steadily. In our first report, occurrence of subpial hemorrhage, extravasation of dye and increase of brain volume were considered as possible factors contributing to decrease in cortical blood flow by 85Kr clearance following a stage of its definite increase. In that report, the former two factors were analyzed in detail. Since cerebrovascular occlusive disease in humans tends to produce intracranial hypertension of varying degrees, depending upon secondary brain edema, the elevation of intracranial pressure by inhalation of carbon dioxide must be carefully investigated. If two methods of management, increase of perfusion flow by inhalation of carbon dioxide and reduction of increased brain volume by infusion of hypertonic solution are compatible on treatment and are capable of extending the range of PaCO2 which permits an increase of cortical blood flow measured with 85Kr clearance, an application of carbon dioxide to humans will be much safer and its therapeutic indication will be much wider. Therefore, Part 2 of our experiments was done with administration of 20% mannitol solution, using the same materials and methods as in the previous experiment and a comparison of the results with and without mannitol was made. In results, between 45 and 55 mmHg of PaCO2, cortical blood flow measured with the 85Kr clearance method, increased significantly with a gradual decline at PaCO2 higher than this level, which was very similar to the previous work done without mannitol. With the combined use of these two agents, subpial hemorrhage of more marked degree was observed at a PaCO2 above 65 mmHg with extravasation of dye appearing at lower PaCO2 level than with hypercapnia alone. The use of mannitol combined with hypercapnia appeared to be harmful.

A study of method for enhancement of perfusion flow in experimental cerebral ischemia--Part 1. Effects of hypercapnia (author's transl))

In terms of increase of perfusion flow into an area of ischemia, carbon dioxide must be one of the most promising candidates, even though complete agreement has still not been obtained. A controversial, but attractive point in this field is that there is a discrepancy between experimental results obtained by beta-emitting 85Kr and gamma-emitting 133Xe clearance techniques. To resolve this discrepancy in the results from the two isotopes, the experiment of this series were undertaken and our first report clarified that between 45 and 55 mmHg of arterial carbon dioxide pressure (PaCO2), microregional cerebral blood flow (rCBF), measured with both the 85Kr and 133Xe clearance techniques, increased significantly. However, in the same study, as PaCO2 was elevated above this level, there was a remarkable dissociation in rCBF change as measured by each isotope. The cortical blood flow measured with 85Kr clearance method decreased and conversely, global miniregional cerebral blood flow measured by 133Xe continued to increase steadily. In our first report, occurrence of subpial hemorrhage, extravasation of dye and increase of brain volume were considered as possible factors contributing to decrease in cortical blood flow by 85Kr clearance following a stage of its definite increase. In that report, the former two factors were analyzed in detail. Since cerebrovascular occlusive disease in humans tends to produce intracranial hypertension of varying degrees, depending upon secondary brain edema, the elevation of intracranial pressure by inhalation of carbon dioxide must be carefully investigated. If two methods of management, increase of perfusion flow by inhalation of carbon dioxide and reduction of increased brain volume by infusion of hypertonic solution are compatible on treatment and are capable of extending the range of PaCO2 which permits an increase of cortical blood flow measured with 85Kr clearance, an application of carbon dioxide to humans will be much safer and its therapeutic indication will be much wider. Therefore, Part 2 of our experiments was done with administration of 20% mannitol solution, using the same materials and methods as in the previous experiment and a comparison of the results with and without mannitol was made. In results, between 45 and 55 mmHg of PaCO2, cortical blood flow measured with the 85Kr clearance method, increased significantly with a gradual decline at PaCO2 higher than this level, which was very similar to the previous work done without mannitol. With the combined use of these two agents, subpial hemorrhage of more marked degree was observed at a PaCO2 above 65 mmHg with extravasation of dye appearing at lower PaCO2 level than with hypercapnia alone. The use of mannitol combined with hypercapnia appeared to be harmful.

Myocardial function and coronary blood flow response to acute ischemia in chronic canine diabetes.

To examine the influence of preexistent diabetes mellitus on left ventricular performance and coronary blood flow responses to acute ischemia, mild normoglycemic diabetes was induced in nine mongrel dogs after three doses of alloxan, (20 mg/kg, iv), at monthly intervals. Hemodynamic measurements and coronary blood flow (85Kr clearance) were obtained before and after the onset of ischemia. This was produced by occlusion of the proximal left anterior descending coronary artery via a balloon-type catheter in nine intact anesthetized diabetic dogs and 10 nondiabetic dogs. During the 1st hour of ischemia in the diabetic group, the end-diastolic pressure rose from 7 +/- 1.1 (mean +/- SE) mm Hg to 23.8 +/- 2.3 without a significant increase of end-diastolic volume. In controls end-diastolic pressure rose from 8.6 +/- 1.1 mm Hg to 15.3 +/- 1.4, and end-diastolic volume was significantly increased, so that the ratio of end-diastolic pressure and volume was significantly higher in the diabetic group (P less than 0.005). Although indices of contractility did not differ, stroke volume and work reductions were significantly greater in diabetics, despite the fact that coronary blood flow was reduced to a similar extent. Size of the ischemic areas appeared comparable as judged by distribution of dye injected distal to the occlusion. Since potassium loss and sodium gain in the inner and outer layers of ischemic tissue did not differ between the two groups, the intensity of ischemia seemed similar. Glycogenolysis was unimpaired in the diabetic ischemic muscle but triglyceride levels remained elevated. Morphologically the diabetic myocardium was characterized by a diffuse accumulation of periodic acid-Schiff-positive glycoprotein in the interstitium, which was thought to limit diastolic filling of the ischemic ventricle and to contribute to the substantial reduction of ventricular performance.

Coronary blood flow of unanaesthetized dogs with experimental coronary artery disease.

Experimental coronary artery disease (CAD) was produced in dogs which had chronically implanted catheters for the measurement of mean arterial pressure (MAP) and coronary blood flow (CBF) using the 85Kr clearance technique. Resting CBF was determined in the conscious animal during intracoronary infusion of saline and the 'maximum' CBF was determined by infusion of ATP (0s·6 and 0·8 mg/min). Repeated observations revealed only small and variable changes in MAP and CBF of control dogs over a two-month period and of dogs fed an atherogenic diet containing thiouracil and cholesterol for 47 and 54 days. CAD was produced by intracoronary infusion of allylamine and intravenous infusion of egg yolk emulsion. This treatment results in arteritis, lipid deposition, and fibrosis. The disease was associated with a 37% decrease in maximum CBF within two to five days. Resting CBF decreased 16% and MAP was not altered significantly. After the initial decrease in maximum CBF, there is a stable period with decreased maximum CBF for at least six weeks.