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Relation of global and regional left ventricular function to tomographic thallium-201 myocardial perfusion in patients with prior myocardial infarction.

To determine the relation between regional myocardial perfusion and regional wall motion in humans, tomographic thallium-201 imaging and two-dimensional echocardiography at rest were performed on the same day in 83 patients 4 to 12 weeks after myocardial infarction. Myocardial perfusion and wall motion were assessed independently in five left ventricular regions (total 415 regions). Regional myocardial perfusion was quantitated as a percent of the region infarcted (range 0 to 100%) using a previously validated method. Wall motion was graded on a four point scale as 1 = normal (n = 266 regions), 2 = hypokinesia (n = 64), 3 = akinesia (n = 70), 4 = dyskinesia (n = 13) or not evaluable (n = 2). Regional wall motion correlated directly with the severity of the perfusion deficit (r = 0.68, p less than 0.0001). Among normally contracting regions, the mean perfusion defect score was only 2 +/- 4. Increasingly severe wall motion abnormalities were associated with larger perfusion defect scores (hypokinesia = 6 +/- 5, akinesia = 11 +/- 7 and dyskinesia = 18 +/- 5, all p less than 0.01 versus normal. Among regions with normal wall motion, only 3% had a perfusion defect score greater than or equal to 10. Conversely, among 68 regions with a large (greater than or equal to 10) perfusion defect, only 13% had normal motion whereas 87% had abnormal wall motion. The relation between perfusion and wall motion noted for the entire cohort was also present in subgroups of patients with anterior or inferior infarction. In patients with prior myocardial infarction, the severity of the tomographic thallium perfusion defect correlates directly with echocardiographically defined wall motion abnormalities, both globally and regionally.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Antegrade versus retrograde isolated lung perfusion: doxorubicin uptake and distribution in a sarcoma model.

BACKGROUND: Antegrade and retrograde doxorubicin-based isolated lung perfusions were compared in rodents bearing a sarcomatous tumor in the perfused lung. Inasmuch as these tumors derive their vascularization from the bronchial artery system, we hypothesized that retrograde isolated lung perfusion through the pulmonary vein might result in an improved tumor drug uptake. METHODS: Single-pass antegrade (n = 9) and retrograde (n = 9) isolated left lung perfusions were performed with 100 microg of doxorubicin in Fischer rats 10 days after subpleural tumor cell injection. The perfusion, washout, and recirculation times were 20, 10, and 60 minutes, respectively, followed by harvesting of the lung. The doxorubicin concentration and compartmental distribution in the tumor and in normal parenchyma of each perfused lung were measured by high-pressure liquid chromatography (6 animals of each group) and fluorescence microscopy (3 animals of each group). RESULTS: Doxorubicin concentration and pattern of doxorubicin-based fluorescence signaling were comparable for both perfusion techniques in normal lung tissue. Antegrade and retrograde isolated lung perfusion resulted in similar tumor drug uptake, which was lower than in normal lung parenchyma, and in weak and sporadic fluorescence signaling emerging from the tumor periphery and from blood vessels situated within the tumor tissue. CONCLUSIONS: Retrograde isolated lung perfusion did not confer a better doxorubicin uptake in the tumor as compared with antegrade lung perfusion despite the fact that the tumor vascularization in this model is based on the bronchial artery circulation.

Animals↗

Naproxen-induced oxidative stress in the isolated perfused rat liver.

We previously showed that naproxen induced the oxidative stress in the liver microsomes and the isolated hepatocytes of rats. In this study, the in situ effect of naproxen on the rat liver tissue was investigated, using the isolated perfused liver from the view-point of the naproxen-induced hepatotoxicity. The leakage of glutamic-oxaloacetic transaminase (GOT) from the perfused liver and appearance of thiobarbituric acid reactive substances (TBARS) in the perfusate increased with the progress of perfusion after a lag time of about 1h. The naproxen-perfusion of the liver decreased the biliary excretion of glutathione (GSH) and oxidized glutathione, glutathione disulfide (GSSG) prior to TBARS production and GOT leakage. GSSG content in the naproxen-perfused liver was significantly higher than in the control. TBARS appeared in the perfusate of the naproxen-perfused liver for 30 min, but not in the control. The biliary excretion clearance (CL(bile)) of indocyanine green (ICG), a reagent for testing the liver function, in the liver perfused with naproxen decreased to a half of that in the liver perfused without naproxen. Thus, the naproxen-induced oxidative stress in the liver was shown to affect the physiological function of liver through the impairment of biliary excretion, which is recognized as a detoxification system.

Animals↗

Cold visceral perfusion improves early survival in patients with acute renal failure after thoracoabdominal aortic aneurysm repair.

INTRODUCTION: Despite advances in organ protection during thoracoabdominal aortic aneurysm (TAAA) repair, acute renal failure (ARF) remains a significant clinical problem, associated with increased morbidity and mortality. We studied outcome of ARF after TAAA repair in patients who underwent either warm or cold visceral perfusion. METHOD: Between 1991 and 2001 657 TAAA repairs were performed, of which 359 (55%) had either warm or cold visceral perfusion. Twelve patients with renal failure who had undergone preoperative dialysis were excluded from the study. Of the remaining 347 patients, ARF developed in 81 (23%) after TAAA repair. Forty-four (54%) of the 81 patients with ARF received cold visceral perfusion, and 37 (46%) patients received warm visceral perfusion. ARF was defined as either an increase of 1 mg/dL in serum creatinine (SCr) concentration per day for 2 consecutive days or dialysis requirement. Patient records were reviewed through hospital discharge. RESULTS: Twenty six (32%) of the 81 patients in whom ARF developed died, 17 of 37 (46%) patients in the warm perfusion group versus 9 of 44 (21%) patients in the cold perfusion group (P <.02). Median onset of ARF was on postoperative day 1 in both groups. Twenty-six of 81 (32%) patients recovered renal function, 10 of 37 (27%) patients in the warm perfusion group versus 16 of 44 (36%) patients in the cold perfusion group. Preoperative SCr concentration was predictive of recovery of renal function (odds ratio, 4.5 per mg/dL increase; P <.03) in patients who received either warm or cold visceral perfusion. CONCLUSIONS: ARF after TAAA repair remains a significant clinical problem. Recovery of renal function occurred in approximately one third of patients. Preoperative SCr concentration was the only significant determinant of recovered renal function. While cold visceral perfusion did not alter renal recovery, it significantly reduced hospital mortality.

Acute Kidney Injury↗

Artificial perfusion of the fetal circulation of the in situ mouse placenta: methodology and validation.

Here we present methodology and validation (including measurement of unidirectional maternofetal clearance (Kmf) of (45)Ca and (14)C-mannitol) for in situ perfusion of the mouse placenta. On day 18 of gestation (term=19 days) mice were anaesthetised and the uterus delivered into a saline bath (40 degrees C). A fetus was selected, the umbilical artery and vein catheterised and perfused with Krebs Ringer (pH 7.4) at 60 microl/min. (45)Ca/(14)C-mannitol (2 microCi/5 microCi in 50 microl saline) was injected via maternal tail vein. Perfusate samples were collected every 5 min for 45 min. Maternal carotid artery pressure was monitored throughout perfusion. A terminal maternal cardiac blood sample was taken and analysed. Placentas were immersion fixed and processed for electron microscopy. Kmf for (45)Ca and (14)C-mannitol was calculated as perfusate [(45)Ca or (14)C-mannitol] x perfusion rate/maternal plasma [(45)Ca or (14)C-mannitol]xplacental weight. Maternal cardiac blood chemistry at termination (n=8-15, mean+/-SEM) was as follows: pH 7.153+/-0.016, PCO(2) 45.48+/-2.06 mmHg, PO(2) 66.47+/-7.10 mmHg, Na(+) 151.4+/-1.2 mmol/l, K(+) 5.54+/-0.17 mmol/l, Ca(2+) 1.15+/-0.03 mmol/l, glucose 7.2+/-0.5 mmol/l, and lactate 1.76+/-0.77 mmol/l. A successful 45 min perfusion in which perfusate recovery was >95% occurred in >50% of animals. Perfusion did not alter placental morphology or carotid pressure. Kmf (microl/min/g placenta) for (45)Ca (66.0+/-8.4 (n=7)) was significantly higher than Kmf for (14)C-mannitol (20.0+/-2.4 (n=5)) (p<0.01). These data demonstrate physiological perfusion of the mouse placenta in situ and its usefulness for measurement of solute transfer.

Animals↗

The urethrodetrusor facilitative reflex in women: results of urethral perfusion studies.

OBJECTIVE: This study was undertaken to describe the effects of urethral perfusion on bladder activity, urethral pressure, and sensation in patients with either incontinence or prolapse or both of these. STUDY DESIGN: Among 76 consecutive patients who were seen for urodynamic evaluations, 63 had vesical, abdominal, and urethral pressures measured while the urethra was perfused with fluid. A perfusion study result was considered positive if the perfusion provoked a detrusor contraction. RESULTS: Of the 63 women 9 (14%) had a positive urethral perfusion study result, and all of them had detrusor instability independent of perfusion. Among the women with detrusor instability 53% (n = 9/17) had positive study results, versus none of the 46 women without detrusor instability (P =. 000001). Women with mixed incontinence were more likely to have a positive perfusion test result (n = 4/7; 57%) than were those without mixed incontinence (n = 5/56; 10%; P =.006), although urethral hypermobility was not significantly associated with a positive test result. Among the subjects 60% experienced urgency during perfusion, and in half of these urethral pressure was concurrently increased. Among those who had no urgency 84% demonstrated decreased urethral pressure (P =.01). CONCLUSIONS: Positive perfusion study results were more common among women with detrusor instability but did not discriminate any patient with detrusor instability whose condition was not diagnosed by standard urodynamic studies. The association of positive perfusion study results with mixed incontinence seems primarily related to poor central inhibition of detrusor activity rather than to urethral stimulation.

Adult↗

Constant-pressure coronary artery perfusion during aortic valve operations.

We considered the theoretical differences between the normal relationships of coronary blood flow and perfusion pressure in the working heart and those obtained with continuous, steady-flow perfusion by a roller pump during aortic valve replacement. Steady pump perfusion should deliver less blood flow to the endocardium because: 1. For the same mean artery perfusion pressure, the average coronary blood flow is less with constant-flow pump perfusion. 2. With constant pump perfusion, pressure would be excessively high during systole, and during diastole it would be significantly lower than the mean perfusion pressure. Instantaneous pressure and flow were measured in the left coronary artery in 8 patients undergoing aortic valve replacement, employing either roller pump perfusion or a gravity flow system to provide a steady pressure source. Although we did not attempt to demonstrate improved endocardial flow, the mean left coronary flow was always greater with gravity perfusion (297 versus 153 ml/min), lending support to the theoretically proposed differences between the two perfusion methods.

Aortic Valve↗

Effect of flush-perfusion on vascular endothelial and smooth muscle function.

BACKGROUND: The aim of this study was to investigate how much perfusion pressure an artery can tolerate without significant loss of endothelium-dependent relaxation (EDR) and vascular contractility. METHODS: The abdominal aortas of 396 Sprague-Dawley rats were used. One hundred twenty aortas were flush-perfused for 1 or 5 minutes with cold St. Thomas' Hospital cardioplegic (STHC) solution or with the same solution but modified by the addition of 3.5% dextran 40. Three perfusion pressures were tested: 50, 100, and 150 mm Hg. Two hundred eighty vessels were subjected to pressures of 50, 150, or 300 mm Hg using saline or STHC solution at 22 degrees C or STHC solution at 4 degrees C, for 10 or 60 seconds. The vessels were investigated in organ baths. Contractility was tested with the thromboxane analogue U-46619, acetylcholine was used to investigate EDR, and papaverine to elicit endothelium-independent relaxation. RESULTS: Flush-perfusion with cold STHC solution for 5 minutes at a perfusion pressure of 50 or 100 mm Hg affected neither contractility nor EDR. Vessels exposed to a flush-perfusion pressure of 150 mm Hg for 1 or 5 minutes lost 39% (p < 0.001) and 53% (p < 0.001) of their contractility, respectively. Flush-perfusion at 150 mm Hg for 1 minute did not affect EDR, whereas 5 minutes' perfusion caused a reduction of 7% (p < 0.05). A repetition of these experiments using STHC solution with 3.5% dextran 40 added gave no significantly different results. The impairment in contractility and EDR seen after perfusion at 150 mm Hg for 5 minutes disappeared after transplantation and reperfusion for 7 days. The vessels could be distended with saline or STHC solution at a pressure of 150 mm Hg without affecting contractility at 22 degrees C. At 4 degrees C, however, this pressure was harmful to contractility. Distention at a pressure of 300 mm Hg almost abolished contractility and 7 days after transplantation there had not yet been any recovery of contractility, but 30 days after transplantation the grafts had regained their normal contractility. CONCLUSIONS: Cold STHC solution, with or without dextran 40, can be used with a perfusion pressure of 100 but not 150 mm Hg without impairing EDR or vascular smooth muscle function.

Animals↗

Impact of retrograde cerebral perfusion on aortic arch aneurysm repair.

OBJECTIVE: Protection of the brain is a primary concern in aortic arch surgery. Retrograde cerebral perfusion is a relatively new technique used for cerebral protection during profound hypothermic circulatory arrest. This study was designed to compare, retrospectively, the outcome of 109 patients undergoing aortic arch operation with and without the use of retrograde cerebral perfusion. METHODS: Fifty-five patients had profound hypothermic circulatory arrest alone, and 54 patients had supplemental cerebral protection with retrograde cerebral perfusion. Mean age was 61 +/- 13 years and 58 +/- 14 years, respectively (mean +/- standard deviation). Twenty-two preoperative and intraoperative characteristics, including age, sex, acuity, presence of aortic dissection, and aneurysm rupture, were similar in the 2 groups (P >.05). RESULTS: Mean circulatory arrest times (in minutes) were 30 +/- 19 in the group without retrograde cerebral perfusion and 33 +/- 19 in the group with retrograde cerebral perfusion, respectively. chi(2) Analysis revealed that patients operated on with the use of retrograde cerebral perfusion had significantly lower hospital mortality (15% vs 31%; P =.04) and in-hospital permanent neurologic complications (9% vs 27%; P =.01). Retrograde cerebral perfusion failed to reduce the prevalence of temporary neurologic dysfunction (17% vs 18%; P =.9). Stepwise multiple logistic regression revealed that extracorporeal circulation time, age, and lack of retrograde cerebral perfusion were statistically significant independent risk factors for hospital mortality. The same analysis revealed that lack of retrograde cerebral perfusion was the only significant independent risk factor for permanent neurologic dysfunction. CONCLUSION: Retrograde cerebral perfusion decreased the prevalence of permanent neurologic complications and the hospital mortality in patients undergoing aortic arch operations.

Adult↗

Simultaneous comparison of cerebral dialysis and push-pull perfusion in the brain of rats: a critical review.

Over the last 30 years, studies of the in vivo activity of neurotransmitters and other endogenous factors in the brain have comprised a major effort in the neurosciences. Historically, the technology of push-pull perfusion was utilized as a major approach to investigations in this field. In the last 10 years, cerebral dialysis has been used as an alternative method essentially for the same scientific purpose, since the perfusion technique was viewed as difficult and excessively damaging to tissue. This review considers the representative literature in which both systems have been used to study local neurochemical responses to a drug or other chemical factor, a physiological condition or other situation. In addition, new experiments have been undertaken to compare, in the same animal and at the same time, the utility and properties inherent in the techniques of push-pull perfusion and cerebral dialysis in terms of the profile of a neurotransmitter activity and their local histopathological effects. A miniaturized 33/26 ga push-pull needle and a 24 ga dialysis probe were implanted simultaneously in the left and right caudate nuclei, respectively, in the anesthetized rat. An artificial cerebrospinal fluid (CSF) was perfused simultaneously through both devices at a rate of 10 microliters/min in the push-pull cannula and at 1.0 or 2.0 microliters/min in the dialysis probe. Within a series of 8-10 successive perfusions, excess K+ ions in a concentration of either 30 or 60 mM were incorporated in the CSF and delivered simultaneously to both the push-pull cannula and dialysis probe. Samples of perfusate and dialysate were assayed chromatographically by coulometric HPLC detector and quantitated in terms of the pg/min efflux of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA). The results showed that the resting level of DA was almost undetectable in dialysate samples from either structure; in push-pull perfusates the recovery of DA ranged between 7.0 to 10.0 pg/min, which was increased threefold by excess K+ ions. The recovery of DA and the three metabolites in samples of push-pull perfusate was two to four times that in samples of dialysate during the condition of excess K+ ions. Post-mortem histological analysis of the sites of perfusion and dialysis revealed little or no differences in the cytological damage induced by either the perfusion needle or dialysis probe. Finally, the advantages and limitations of each of these two experimental approaches to in vivo analysis of neurotransmitter efflux are reviewed in relation to the selection of an open or closed system for the on-line study of in vivo neurochemical events.

Animals↗

Prevention of lactate production and myocyte injury in isolated rat hearts perfused with perfluorochemical emulsion.

The ability of an oxygenated perfluorocarbon (PFC) emulsion to prevent early signs of myocardial cell stress associated with Krebs-Henseleit (KH) perfusion was evaluated in isolated rat hearts supported in a Langendorff apparatus. Throughout the two-hour perfusion, hearts in both perfusion groups had similar left ventricular pressure and rates of left ventricular pressure development (dP/dt). After 2 h, coronary perfusate flow was 6.6 +/- 1.0 ml/min in the KH group and 2.2 +/- 0.1 ml/min in the PFC group. Oxygen content was 1.5 +/- 0.1 ml/100 ml and 3.4 +/- 0.1 ml/100 ml, in KH and PFC groups, respectively. Perfusate lactate levels rose from zero to 24.0 +/- 8.0 microgram/ml in the KH group and to 10.0 +/- 3.0 micrograms/ml in the PFC group. Reduction in myocardial cell injury and in total calcium content was also observed in hearts perfused with PFC emulsion. At the electron microscopic level, mitochondrial structure was preserved in both normal and injured myocytes of hearts perfused with PFC. We conclude that early signs of anaerobic metabolism are retarded by perfusion with PFC emulsions and that ventricular contractile performance is maintained at approximately one-half coronary perfusate flow in the PFC hearts. The mechanism whereby coronary flow is regulated downward in the PFC perfused hearts remains unanswered.

Animals↗

Hepatic clearance and retention of aluminium: studies in the isolated perfused rat liver.

Aluminium (Al) exposure can result in Al accumulation in the liver and this metal can be toxic to the hepatic tissue at high concentrations. In the present study the model of the isolated perfused rat liver was used to investigate the hepatic handling of Al. Livers from male Wistar rats were perfused in a recirculating system for 240 min. The liver function remained unchanged at perfusate concentrations of Al ranging from 4.9 to 1530.0 micrograms/l. At higher Al levels of 6535.3-16694.9 micrograms/l signs of toxicity towards isolated perfused livers were observed as indicated by an increased release of the enzymes AST and ALT into the perfusate, a pronounced reduction of bile flow rate and a 50% suppression of oxygen consumption. The hepatic Al clearance was low and decreased with increasing concentrations of Al in the perfusate from 4.3 +/- 0.6 microliters/min per g liver at a nominal Al concentration of 9.1 micrograms/l in control perfusate to 0.04 +/- 0.02 microliter/min per g liver at the highest concentration group. There was almost a linear dose dependent retention of Al in the liver with 4.9-635.7 micrograms Al/l perfusate while at higher concentrations Al levels in this organ increased disproportionally. It is concluded that by using the isolated perfused rat changes of liver functions occur only at very high Al concentrations in the perfusate and that only negligible amounts of Al are eliminated by the liver.

Alanine Transaminase↗

Use of gated perfusion to study early effects of anoxia on cardiac energy metabolism: a new 31P NMR method.

A novel 31P NMR method is described that is capable of determining rapid changes in the intracellular levels of various phosphorus-containing compounds in an isolated, perfused working rat heart. This technique involves the gating of 31P NMR measurements to a heart that is alternately perfused with a modified Krebs-Henseleit medium containing 10 mM pyruvate and equilibrated with either 95% O2/5% CO2 or 95% N2/5% CO2. The experimental design allows up to three NMR measurements to be made during a single O2/N2 perfusion cycle. When these measurements are repeated at different intervals during the cycle, rapid changes in metabolite levels can be determined. Preliminary studies have shown that hearts remain hemodynamically stable to the aerobic/anoxic perfusion cycle as judged by heart rate, peak systolic pressure, aortic output, and coronary flow for at least 80 min in the magnet when subjected to cycle times of 4.5-s O2 and 1.5-s N2 perfusions. NMR measurements made under these conditions showed that a transition from full aerobic perfusion to this cycle revealed a new steady state, with an increased inorganic phosphate level from 6% total observable phosphorus to 10% and a possibly significant decreased measurement of creatine phosphate level (from 35 to 31%). Comparison of individual NMR measurements made during this perfusion cycle shows apparent rapid cyclical variations in intracellular pH and the levels of Pi, ATP, and NAD(H). These changes, expressed as variations above and below mean values measured during the cycle, showed that (a) intracellular pH, as measured by the chemical shift of Pi, reversibly decreases by more than 0.1 pH unit within 0.5-1 s following maximal anoxic perfusion and (b) coincident with a decrease in intracellular pH, Pi levels increased by a maximum of 30-40% whereas ATP levels decreased by a maximum of 15-20%. The amount of total observable phosphorous detected during the cycle is essentially constant. Unexpectedly, creatine phosphate levels are most stable, indicating that their levels are being maintained at the expense of ATP. Also unexpected is the finding that NAD(H) levels varied from maximal to undetectable levels during the perfusion cycle. The current method of aerobic/anoxic perfusion is capable of resolving metabolic events much faster than previous NMR methods and yielding information that is unobtainable by any other technique.

Adenosine Triphosphate↗

Ex vivo and extracorporeal perfusion with hDAF pig kidneys.

The present study was undertaken to determine whether human decay accelerating factor (hDAF) transgene would prevent hyperacute rejection (HAR) while perfused with human blood or extracorporeally in baboons. Four hDAF pig kidneys and three non-hDAF pig kidneys were perfused ex vivo with fresh human blood for 6 h. Additionally four hDAF pig kidneys and four non-hDAF pig kidneys were extracorporeally perfused in baboons and pigs, respectively, for 3 h. In ex vivo perfusion, the color of hDAF pig kidneys remained pink at the end of 6-h perfusion and they had normal histology, while non-hDAF kidneys developed HAR. HDAF pig kidneys had superior function over non-transgenic pig kidneys. Urine output was 17.31 +/- 3.70 ml/h for hDAF pig kidneys, and only 5.81 +/- 0.26 ml/h for non-hDAF kidneys (P < 0.05). Creatinine clearance was 1.16 +/- 1.24 ml/min for hDAF kidneys and 0.22 +/- 0.15 ml/min for non-hDAF kidneys (P < 0.05). Other functional data including potassium, urine specific density, and osmolality were normal in the hDAF kidneys, while in non-hDAF kidneys, serum potassium was elevated to over 9 mmol/l by the end of perfusion (P < 0.01). Non-hDAF kidneys also lost more sodium through urine than hDAF kidneys (173.67 +/- 14.05 mmol/l vs. 109 +/- 31 mmol/l, P < 0.05). In the extracorporeal perfusion, all the baboons tolerated the procedure well with normal hemodynamic and hemotologic profiles. These baboons were well until killed 42 to 56 days after perfusion, although their antiporcine antibodies were greatly elevated. We conclude that hDAF transgene protects against HAR, allowing the pig kidney to function normally while perfused with human blood, and that extracorporeal perfusion using hDAF pig kidneys is a safe procedure in baboons.

Animals↗

Error analysis of the double-integral method for calculating brain blood perfusion from inert gas clearance data.

A single-photon dynamic computer-assisted tomograph (DSPECT) has been built and is currently being used to evaluate regional cerebral blood perfusion in patients and volunteers. A computer simulation of the system was created to analyze the effects of data collection, Poisson noise, attenuation compensation, and the reconstruction technique now employed in the DSPECT. Several methods of attenuation compensation were used to generate perfusion images from both ideal and noisy data. The results indicate that the mean perfusion is calculated to within 10.4% accuracy for all perfusion rates in a region of interest if attenuation correction is used. Without attenuation correction, perfusions are underestimated by as much as 27%. The three correctors tested have different effects on the calculated perfusion value, depending on the location of the region of interest in the picture. The algorithm introduces random noise that is proportional to both the random error in the input data and the perfusion rate. Air-curve delay errors result in inaccuracies in the final perfusion picture that are proportional to perfusion rate. Physiological values (0.8-1.5) of the partition coefficient cause overestimation of both gray (0-34%) and white (7-67%) matter perfusion values. Compton scatter and collimator effects were not addressed in this study.

Brain↗

Effect of perfusion rate on the fluxes of water, sodium, chloride and urea across the proximal convoluted tubule.

Studies were undertaken to examine the mechanism whereby changes in intraluminal flow rates after reabsorption in the isolated perfused proximal tubule of the rabbit. All protocols employed the technique of in vitro perfusion of isolated segments of the proximal convoluted tubule. Stepwise elimination of d-glucose and l-alanine from an artifical perfusate stimulating ultrafiltrate decreased the unidirectional flux of sodium, transtubular potential difference, and net water absorption. Using isosmolal ultrafiltrate as the perfusate, net fluid reabsorption and the unidirectional lumen-to-bath flux of sodium and chloride decreased with a decrease in flow rate below 11 nl/min, but neither net fluid reabsorption nor the unidirectional fluxes of sodium and chloride increased further as the perfusion rate was increased above 11 nl/min. The unidirectional flux of 14C-urea was not affected by changes of perfusion rate from 1.6 to 44 nl/min. The dependence of net fluid reabsorption and unidirectional fluxes of sodium and chloride on flow rate per se, and not on intraluminal hydrostatic pressure or geometry, was established by demonstrating their decrease despite a rise in intraluminal pressure and inside diameter produced by counterpressure at the collecting end of the tubule, while flow was decreased. Ouabain decreased net fluid reabsorption to near zero at all flow rates, but ouabain had no effect on the flow-dependency of unidirectional sodium anf sodium was eliminated with a decrease in bicarbonate concentration and removal of d-glucose and l-alanine from the perfusate. Thus, the present studies demonstrate that net water and unidirectional sodium and chloride fluxes are flow-dependent. At flow rates somewhere below 11 nl/min, unidirectional fluxes decreased with decreasing perfusion rates; however, at perfusion rates greater than 11 nl/min, there was no further effect of perfusion rate on either net water absorption or the unidirectional fluxes of sodium or chloride. These effects may be partly mediated through the flow-dependent changes in the intraluminal concentration of bicarbonate, d-glucose, and 1-alanine.

Adsorption↗

Action of phosphorus on calcium release in isolated perfused rat tails.

A bone perfusion system using isolated rat tails was developed to study the action of inorganic phosphorus (Pi) on calcium (Ca) release in bone. Rats were either pre-labelled with 45Ca to study calcium removal from bone or 45Ca was added to the perfusate to study Ca deposition into bone. When perfusate Pi was increased from 3.5 to 5.25 mg/dl, a marked inhibition of 45Ca release was demonstrated. 85Sr microspheres, used to demonstrate differences in the flow of perfusate between bone and soft tissue, showed that the Pi effect was not due to alterations in perfusate flow to bone. Increasing the perfusate Pi concentration from 3.5 to 7 mg/dl did not increase 45Ca deposition into bone, nor did it affect baseline or PTH-stimulated cyclic AMP production. The Pi effect was inhibited by reducing the perfusate temperature to 4 degrees C, by using an anerobic perfusate, adding iodoacetate to the perfusate, and finally, by pre-treating the rats with actinomycin D prior to the experiment. Thus, in this model an increase in the Pi concentration of the perfusate inhibits Ca release from bone but does not increase Ca uptake by bone. The inhibitory effect appears to be dependent on normal cell metabolism.

Animals↗

Resin column perfusion with whole blood or plasma separated by the continuous flow celltrifuge.

1. The aim of this study was to define the factors influencing plasma separation from the continuous flow celltrifuge and to evaluate plasma as an alternative to whole blood for perfusion of exchange resins as part of a system of artificial liver support. 2. Studies in vitro showed the importance of packed cell volume, centrifugal force and duration of centrifugation on the degree of plasma separation. From these data it was possible to calculate plasma flow rates likely to be obtained from the celltrifuge when used in vivo. These predicted values correlated closely with plasma flow rate obtained in twenty-six studies in dogs. 3. Comparison of whole blood perfusion with plasma perfusion of exchange resins in another series of dog experiments showed that with whole blood perfusion there was often a considerable rise in pressure across the resin column but that this did not occur with plasma perfusion. 4. Measurements of platelet losses in the same series of experiments showed a 50% reduction of arterial platelet counts over a 31/2 h period of perfusion when whole blood was perfused. Although the fall was lower with plasma perfusion, the difference was not statistically significant. 5. Use of the celltrifuge provides a means of resin perfusion free of the mechanical difficulties of whole blood perfusion, but platelet losses still remain a problem.

Animals↗