Effect Of Perfusion Rate Research Articles

In vitro Perfusion of Whole Bovine Ovaries by Freezing Medium: Effect of Perfusion Rate and Elapsed Time after Extraction

Cryopreservation and transplantation of the whole ovary with vascular pedicle would be helpful to prevent posttransplantation ischemia. In fact, perfusion of the intact mammalian ovary through arteries and veins is the most technically difficult part of the whole cryopreservation process because of its complexity. It is important to develop the technology of long-time perfusion of intact ovaries by cryoprotectants at low temperatures because it was established earlier that 24-hour cooling to 5 degrees C before cryopreservation is beneficial for the freezing of human ovarian tissue. The aim of this research was to study the effectiveness of perfusion of intact bovine ovaries with different rates of perfusion and elapsed time between extraction of these ovaries and beginning of perfusion. Arteria ovarica was cannulated and ovaries were perfused with Leibovitz L-15 medium + 100 IU/mL heparin + 5% bovine calf serum + 6% dimethyl sulfoxide + 6% ethylene glycol + 0.15 M sucrose + Indian ink at room temperature (22 degrees C). In the first cycle of experiments, ovaries (n = 145) were perfused for 60 minutes during 1 to 1.5 hours after extraction of ovaries in the slaughter house at perfusion rates of 150 mL/hour (2.5 mL/minute), 100 mL/hour (1.67 mL/minute), 75 mL/hour (1.25 mL/minute), 50 mL/hour (0.83 mL/minute), 25 mL/hour (0.42 mL/minute), and 12.5 mL/hour (0.21 mL/minute) for groups 1, 2, 3, 4, 5, and 6, respectively. In the second cycle of experiments, ovaries (n = 29) were perfused with a rate of 25 mL/hour (0.42 mL/minute) for 60 minutes during the following time-periods elapsed after extraction of ovaries in the slaughter house: 3 hours (n = 18), 4 hours (n = 5), 5 hours (n = 3), and 6 hours (n = 3) for groups 1, 2, 3, and 4, respectively. Ovaries in luteal and follicular phase of development were distributed randomly into groups. Successful perfusion of blood vessels was detected visibly by a blue coloration of the vascular pedicle and ovarian tissues. The percentage of Indian ink-perfused tissues was detected. The intensity of the vascular leakage and tissue damage was scored microscopically and noted as follows: lack of disruption (-), weak disruption (+), moderate disruption (++), and strong disruption The first cycle of experiments shows that an optimal perfusion rate was established for groups 4 and 5 (50 and 25 mL/hour, respectively). In the second cycle of experiments, good perfusion of ovaries with the perfusion rate of 25 mL/hour was established only for ovaries of group 1 (3 hours after extraction). The effectiveness of perfusion in group 2 (4 hours after extraction) was sharply decreased. Effective perfusion of bovine intact ovaries with vascular pedicle with freezing medium (6% ethylene glycol + 6% dimethyl sulfoxide + 0.15 M sucrose) at room temperature includes a rate of perfusion 25 or 50 mL/ hour. Ovaries must be perfused no later than 3 hours after the death of animals.

Step-up/step-down perfusion approach for increased mAb 520C9 production by a hybridoma cell line

The hybridoma cell line, HB-8696, produces a monoclonal antibody, 520C9 (mouse IgG(1)) that recognizes the breast cancer oncoprotein, c-erbB2. The effect of perfusion rate (volume of fresh feed/working volume of reactor/day) on cell growth and mAb production was investigated but perfusion at a constant rate and at an arbitrarily increased rate could not maintain exponential cell growth or a higher specific mAb production rate. An optimum step-up/step-down perfusion strategy is therefore proposed for maintaining a steady state production phase at high cell density for ten days. The optimum step-up perfusion could achieve fast cell growth by avoiding any nutrient limited condition and the following optimum step-down perfusion could potentially maintain high live cell density and reduced product dilution as well. The maximum viable cell achieved under optimum perfusion strategy was 2.3×10(7)cells/ml which was 19-fold higher than in optimum batch culture. The mAb yield and volumetric productivity were significantly improved to 52 and 50mg/lday compared to 25 and 3.8mg/lday in optimum batch, respectively, and could be maintained for up to ten days.

On the Possibility of Real‐Time Monitoring of Glucose in Cell Culture by Microdialysis Using a Fluorescent Glucose Binding Protein Sensor

Although glucose sensors with millimolar sensitivity are still the norm, there is now a developing interest in glucose sensors with micromolar sensitivity for applications in minimally invasive sampling techniques such as fast microdialysis and extraction of interstitial fluid by iontophoresis and laser poration. In this regard, the glucose binding protein (GBP) with a binding constant for glucose in the micromolar range is of particular relevance. GBP is one of the soluble binding proteins found in the periplasmic space of Gram-negative bacteria. Because of its hinge-like tertiary structure, glucose binding induces a large conformational change, which can be used for glucose sensing by attaching a polarity sensitive fluorescent probe to a site on the protein that is allosterically responsive to glucose binding. Correspondingly, the resulting optical biosensor has micromolar sensitivity to glucose. Because binding is reversible, the biosensor is reusable and can be stored at 4 degrees C for 6 months without losing its sensitivity. In this paper, we show the feasibility of using the GBP biosensor to monitor glucose in microdialysis. The effect of perfusion rate, bulk glucose concentration and temperature on microdialysis efficiency was determined. Additionally, the glucose concentrations in mammalian cell culture were monitored to demonstrate the applicability of this sensor in complex and dynamic processes over a period of time. As the sensor is sensitive to micromolar glucose, high dialysis efficiency is not required when the bulk glucose concentration is within the millimolar physiological range. Thus, a perfusion rate of 10 microL/min or faster can be used, resulting in delay times of 1 min or less.

Insights into adenoviral vector production kinetics in acoustic filter-based perfusion cultures.

One of the major limitations in the production of adenoviral vectors is the reduction in cell-specific productivity observed for increasing cell density at infection in batch cultures. This observation strongly suggests some nutrient depletion and/or metabolite inhibition in the media. These limitations have been partially overcome through other feeding strategies, such as fed-batch and sequential batch operations. To improve these results, we evaluated perfusion as a strategy to increase the volumetric productivity of HEK-293 cell cultures, by allowing productive infection at higher cell densities. An acoustic cell separator was employed in consideration of the increased shear sensitivity of the cells during the infection phase. The effects of perfusion rate and cell density at infection on the production of a recombinant adenovirus expressing the GFP were investigated. The perfusion mode allowed successful infection at cell densities in the range of 2.4-3 x 10(6) cell/mL, while maintaining a similar cell specific productivity (17,900 +/- 2400 VP/cell) to that of a batch infected at a low cell density (5 x 10(5) cell/mL). The highest virus concentrations (4.1 +/- 0.6 x 10(10) VP/mL) were attained for a feed rate of 2 vol/d and constituted a fivefold increase compared to a batch with medium replacement. Rapid assessment of the infection status was achieved through the use of on-line monitoring of respiration, fluorescence, and biovolume. Analysis of the kinetics of nutrient consumption and metabolite production revealed that a reduction in specific productivity is correlated with reduced metabolic activity.

Effects of perfusion rate on permeability of frog and rat mesenteric microvessels to sodium fluorescein.

The permeability, P(S), to sodium fluorescein (Stokes-Einstein radius = 0.45 nm) has been measured in single mesenteric capillaries of pithed frogs and anaesthetised rats as perfusion velocity, U, was varied over a range from 400 up to 2000-10,000 microm s(-1). P(S) increased linearly with U. In 20 frog capillaries, mean (+/- S.E.M.) P(S) (in microm s(-1)) = 9.35 (+/- 1.55)U x 10(-5) + 0.244 (+/- 0.0291). Similarly, in nine rat venules, mean P(S) = 1.62 (+/- 0.385)U x 10(-4) + 0.375 (+/- 0.025). The flow-dependent component of permeability could be reversibly abolished in frog capillaries by superfusing with 100 microM noradrenaline and by superfusing rat venules with the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine (20 microM). It was shown that changes in microvascular pressure accompanying changes in U during free perfusion could account for only 15 % of the changes in P(S), i.e. 85 % of the changes in P(S) were changes in the permeability coefficient itself. A comparison between the changes in P(S) with U and the previously described changes in microvascular permeability to K(+) with U, suggest that if the flow-dependent component of permeability is modelled as a population of pores of constant size, these have radii of 0.8 nm. Such a pathway would limit flow-dependent permeability to small hydrophilic molecules and have minimal effect on net fluid exchange.

Effect of perfusion rate on the time course of insulin-mediated skeletal muscle glucose uptake.

To better define the time course of skeletal muscle glucose uptake and its modulation by changes in perfusion, we performed systemic euglycemic-hyperinsulinemic clamps (40 mU.m-2.min-1) for a 90-min period in a group of lean, insulin-sensitive subjects (n = 9) on two occasions (approximately 4 wk apart) with insulin-mediated vasodilation intact or inhibited. Insulin-mediated vasodilation was inhibited by an intrafemoral artery infusion of NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthase. During the study, leg blood flow (LBF) and arteriovenous glucose difference (AVG delta) were measured every 10 min; leg glucose uptake (LGU) was calculated as LGU = LBF x AVG delta. The systemic insulin infusion caused a time-dependent increase in LBF from 0.194 +/- 0.024 to 0.349 +/- 0.046 l/min (P < 0.01). The intrafemoral artery infusion of L-NMMA completely inhibited this increase in LBF. AVG delta, LGU, and whole body glucose disposal rates increased in a time-dependent manner in both studies. The maximum AVG delta was lower with insulin-mediated vasodilation intact than when inhibited (25.9 +/- 2.5 vs. 35.0 +/- 1.6 mg/dl, P < 0.001). The time to achieve half-maximal (T1/2) AVG delta was somewhat longer with insulin-mediated vasodilation intact compared with inhibited (35.6 +/- 4.1 vs. 29.7 +/- 1.6 min, P < 0.01). Maximal LGU was 93.9 +/- 26.8 and 57.2 +/- 11.6 mg/min (P < 0.005), and the T1/2 LGU was 50.2 +/- 16.0 and 36.3 +/- 8.8 min (P = 0.1) during intact and inhibited insulin-mediated vasodilation, respectively. Thus insulin-mediated vasodilation has a modest effect in slowing the time course at which insulin stimulates glucose uptake but has a marked effect in augmenting the maximal rate of insulin-stimulated glucose uptake in skeletal muscle. Impaired insulin-mediated vasodilation, as observed in patients with essential hypertension, may explain, at least in part, the insulin resistance observed in these patients.

On the significance of perfusion rate in the study of glutamate release from superfused synaptosomes.

The effect of perfusion rate on the apparent release of [(3)H]glutamate from prelabelled and superfused rat cortical synaptosomes was examined. The proportion of tissue [(3)H]glutamate released in response to a 4 ml depolarizing pulse of 15 mM K+ increased almost linearly with perfusion rates from 1 ml min(-1) to 10 ml min(-1). Release did not increase markedly between 10 ml min(-1) and 20 ml min(-1). The basal efflux of [(3)H]glutamate also increased with perfusion rate. The increase in both basal efflux and (K+)-induced release is interpreted as being due to a greater amount of released transmitter avoiding recapture by uptake processes as perfusion rate increases. This is supported by the observation that increasing the potential number of uptake sites in the tissue decreases both the basal and (K+)-evoked release of the transmitter. The significance of this with respect to optimal perfusion rates for studies on the regulation of glutamate release is discussed.

Lithium reabsorption in perfused loops of Henle: effects of perfusion rate and bumetanide

The contribution of the loop segments to lithium reabsorption in sodium-replete, anesthetized Sprague-Dawley rats was examined by perfusing superficial loops of Henle between late proximal convolutions and early distal tubules. Preliminary experiments in which lithium was initially present only inside or outside the perfused loop confirmed substantial permeability of one or more of the loop segments to lithium. In subsequent experiments, in which lithium was infused intravenously and included in the perfusate so that the perfusate-to-plasma lithium concentration ratio was close to that found in late proximal tubules during lithium clearance studies, lithium reabsorption was inversely related to the perfusion rate: values for fractional lithium reabsorption (FRLi) at perfusion rates of 10, 20, and 30 nl/min were 58 +/- 3, 17 +/- 2, and 2 +/- 2%, respectively. Bumetanide (10(-6) M) markedly inhibited FRLi but also reduced water reabsorption, suggesting an effect on the pars recta at this dose; 10(-7) M bumetanide, which was without effect on water reabsorption, had only a small effect on FRLi at a perfusion rate of 10 nl/min but reduced FRLi by approximately 70% at 20 nl/min. We argue that the remarkable flow dependency of lithium reabsorption, together with its bumetanide sensitivity, provides evidence for significant voltage-driven lithium reabsorption in the thick ascending limb of Henle.

Effects of perfusion rate and glucose concentration on glucose absorption in intestinal thiry-vella loop in sheep.

The effects of the perfusion rate and glucose concentration in perfusate on glucose absorption in the intestinal Thiry-Vella loop of conscious sheep were studied. When 10 mM glucose was perfused at the rates of 0.5, 1, 2 and 4 ml/min, the absorption rates were 77.1 +/- 2.2, 54.9 +/- 2.3, 31.6 +/- 2.1 and 12.9 +/- 0.3%, respectively. When 5, 10, 20 and 40 mM glucose solutions were perfused at 1 ml/min, the absorption rates were 75.5 +/- 1.7, 52.2 +/- 2.2, 29.4 +/- 1.9 and 19.5 +/- 0.1%, respectively. We conclude that the perfusion of 10 mM glucose solution at 1 ml/min, in which about a 50% absorption rate was obtained, are the optimal conditions for the study of glucose absorption in the intestinal loop of sheep.

薬物動態と高速ラプラス逆変換(FILT)

A curve fitting program, MULTI (FILT), in which an algorithm of fast inverse Laplace transform is incorporated, was introduced into the area of drug disposition. The reliance of MULTI (FILT) was verified by the Monte Carlo simulation based on compartment models. MULTI (FILT) was applied to the analysis of the local dispositions of drugs through the liver, including the construction of new dispersion model, the effect of albumin in perfusate, and the effect of perfusion rate. The elimination in the lung and the enterohepatic circulation were also evaluated using MULTI (FILT) in a simple manner.

The effect of perfusion rate on the apparent release of tritiated L-glutamate from superfused synaptosomes

The effect of perfusion rate on the apparent release of tritiated L-glutamate from superfused synaptosomes

Effect of luminal perfusion rate on duodenal alkalinization in the rat in vivo and in vitro.

This study investigates the effects of luminal perfusion rate on the observed rate of alkalinization of an unbuffered saline by anesthetized rat distal duodenum. Increases in perfusion rate (range 0.3-22 ml/min) increased both alkalinization (3-15 mumol/cm hr) and intraluminal pressure (6-22 mm Hg). Increases in pressure (6-30 mm Hg) at constant perfusion rate (3 ml/min) did not change alkalinization. The effect of perfusion rate on alkalinization was rapid, reversible, and could be repeated several times. It was unaffected by indomethacin (10 mg/kg subcutaneously) or tetrodotoxin (1 mg/ml in perfusate). A limited in vitro study at two flow rates (0.3 and 22 ml/min) showed a similar enhancement of alkalinization. It is concluded that the rate of alkalinization is increased by raising the perfusion rate of the lumen both in vivo and in vitro. The mechanism remains to be established but may involve the reduction of a diffusion barrier between the mucosa and luminal bulk fluid. These results may have implications for the movement of other substances across intestinal segments.

A model of osmotic and hydrostatic pressure effects on volume absorption in the proximal tubule.

A computer model of the proximal tubule of the rabbit is described in which the tubule is treated as a single cylindrical barrier to the flow of solute and water between lumen and bath, and volume absorption is assumed to be driven exclusively by hydrostatic and osmotic pressure differences across this barrier. The model mimics the function of the tubule in two in vitro preparations: in simulations of the isolated tubule perfused under oil, the model correctly describes the solute concentration gradients that exist between the perfusate and absorbate and predicts differences in solute concentrations among absorbate droplets on the same tubule if luminal concentration becomes limiting. This prediction was tested experimentally with glucose and found to be correct. In simulations of the tubule perfused in an aqueous bath, the role of transmural hydrostatic pressure was explored; it is predicted that, at normal rates of in vitro perfusion (approximately 10 nl/min), increases in pressure have very little effect on volume absorption but can greatly alter the osmotic differences present across the wall of the tubule, especially with high values of osmotic water permeability. At high rates of perfusion, the ability of the tubule to produce a lumen hypotonic to the bath is reduced, but the direct effects of pressure on volume absorption become more apparent, resulting in relatively little effect of perfusion rate on volume absorption if the osmotic water permeability is sufficiently high. A similar relationship was seen experimentally. In all, this simple model provides a good prediction of function in isolated perfused tubules without any assumptions of hypertonic compartments within the epithelium.

Effect of perfusion rate of cholinergic agonist on sinus node automaticity

Recent evidence supports a complex relationship between pressure in the sinus node artery and heart rate. In addition, it has been suggested that acetylcholine effects vary depending upon the pressure at which the drug is injected. We examined the cardiac chronotropic responses to acetylcholine, delivered via the sinus node artery using a constant flow perfusion technique. Dogs were anesthetized with chloralose and prepared to record ECG, arterial pressure and bipolar electrograms from the sinus node, sulcus terminalis, right atrium, right ventricle and His bundle. The sinus node artery was catheterized, distribution verified and autologously perfused via the femoral artery. Both vagi and both stellate ganglia were transected. Analog data were processed by computer for each cycle length during perfusion with normal Tyrode solution or Tyrode solution containing acetylcholine. Perfusion of normal Tyrode solution (1-4ml/min) resulted in prolongation in cycle length which was greater at higher flow rates but rapidly dissipated at all flow rates. Beyond mechanically-induced bradycardia, acetylcholine initially prolonged cycle length but cycle length prolongation faded with time. Delivery of acetylcholine at higher flow rates resulted in significantly greater prolongation of cycle length. Cycle length always returned back toward control although perfusion of acetylcholine continued. Thus, responses to acetylcholine are influenced not only by drug concentration but also by the flow rate at which the drug is delivered. This suggests a coupling of mechanical and pharmacologic components of chronotropic influences at the sinus node.

Effect of coronary perfusion rate on the hydrolysis of exogenous and endogenous acetylcholine in the isolated heart.

1. The effect of perfusion rate on the hydrolysis of acetylcholine in isolated chicken hearts was studied by measuring both the spontaneous and the evoked output of endogenous acetylcholine into the perfusate in response to vagal stimulation and the arterio-venous difference of exogenous acetylcholine. 2. A decrease in the perfusion rate from 30 to 20 and 10 ml/min caused a graded and significant decline of both the spontaneous overflow of acetylcholine and the overflow evoked by stimulation of both vagus nerves (20 Hz, 1 ms, 40V) for 20 min. The spontaneous and evoked overflow at 30 ml/min were 2 and 3 times, respectively, the overflow at 10 ml/min. 3. Physostigmine (10−6M) raised both the spontaneous and the evoked acetylcholine outputs into the perfusate. The rise of the evoked output was much more pronounced at 10 ml/min (7.5-fold) than at 30 ml/min (2.5-fold) so that the differences in the output at these perfusion rates were abolished after inhibition of cholinesterase. 4. Although vagal stimulation in the presence of physostigmine caused an output of acetylcholine into the perfusate equivalent to the content of the heart determined before stimulation, no change of the cardiac acetylcholine content was observed. Thus the total acetylcholine content must have been resynthesized during the 20-min period of vagal stimulation. Physostigmine raised the acetylcholine content by the same extent, both before and after stimulation. 5. The arterio-venous difference of acetylcholine during infusion of this compound (10−7 M) for 10 min was increased from 37±8 to 56±7% (n=10) of the arterial concentration, when the perfusion rate was decreased from 30 to 10 ml/min. Physostigmine abolished the effect of the perfusion rate upon the appearance of acetylcholine in the effluent. Moreover, the arterio-venous differences were less than 5% after inhibition of cholinesterase. 6. It is concluded that extracellular inactivation of the parasympathetic transmitter of the heart is dependent on both the cholinesterase activity and the rate of the coronary flow.

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.

Effect of Perfusion Rate on Absorption, Surface Area, Unstirred Water Layer Thickness, Permeability, and Intraluminal Pressure in the Rat Ileum in Vivo

Intestinal absorption and intraluminal pressures were measured at perfusion rates between 0.3 and 200 ml per min in the rat ileum in vivo. Glucose absorption from a 72 mM glucose solution and tritiated water ([3-H]water) diffusion rate were used to reflect changes in mucosal surface area. Glucose absorption from a 4 mM solution was used to indicate changes in unstirred water layer thickness, and mannitol and urea absorption were used as markers of passive mucosal permeability. In a partially obstructed intestinal segment, designed to keep the gut partially filled even at low perfusion rates and to minimize surface area change as perfusion rate was increased, glucose absorption from a 4 mM solution increased by 150% as perfusion rate was increased from 1 to 100 ml per min. Forty per cent of this increase was due to increased surface area (estimated from the change in [3-H]water absorption), and 110% of the increase is attributed to thinning of the unstirred water layer. Because mannitol absorption was zero at all perfusion rates, none of the enhanced glucose absorption rate need be attributed to enhanced mucosal permeability, even though intraluminal pressure was increased at higher perfusion rates. Urea absorption was apparently influenced by surface area and by permeability changes, but not by the thickness of the unstirred water layer. This model was also used to explore the effect of unstirred water layer thickness on the inhibitory effect of sodium replacement by magnesium on glucose absorption from a 4 mM glucose solution. Inhibition by sodium removal was equal at 1, 10, 100, and 200 ml per min perfusion rates, suggesting that unstirred water layer thickness does not play an important role in the interaction of glucose and sodium absorption when intraluminal sodium concentration is reduced. Additional experiments in an unobstructed ileal segment revealed that the major effect of enhanced perfusion rate is to increase mucosal surface area; relatively high rates of perfusion were required to thin significantly the unstirred water layer when intestinal outflow was not partially obstructed.

Influence of perfusion rate and compliance on esophageal manometry.

The accuracy of esophageal manometry using the conventional perfused three-lumen catheter depends on the proper choice of the perfusion rate. Previous investigators have used a wide range of perfusion rates without considering the compliance of the transducer-catheter assembly as a variable in the selection of the perfusion rate for the hydraulic systems. We present a relationship relating the perfusion rate and the compliance which specifies the minimum adequate perfusion rate for a given transducer-catheter assembly. This approach explains apparent discrepancies in the literature regarding the proper rate of perfusion for accurate measurement of esophageal contractions. Esophageal motility tests with 10 subjects confirmed the accuracy of manometric tests at the prescribed perfusion rate (1.25 ml/min) since they compared well with intraluminal pressures measured directly with a Honeywell intraesophageal transducer. The effect of perfusion rate on the apmlitude of esophageal contraction was also investigated and it is shown that high perfusion rates result in increased amplitudes of contraction. Furthermore, at large perfusion rates a large volume of liquid builds up in the esophagus. This fluid accumulation could possibly be responsible for the increased amplitudes of contraction.

Oxygen consumption and convective transport during cardiopulmonary bypass.

Described here are the progressive changes in blood-flow distribution that accompany four-hour heart-lung bypass in dogs and the effects of perfusion rate on flow distribution and oxygen consumption. The corresponding changes produced by anesthesia alone and by the thoracotomy needed for a bypass procedure are also shown for comparison purposes. These data indicate that the bypass procedure itself puts a very significant stress on the test animals and that perfusion rates in excess of resting cardiac output are required to prevent hypoxia induced irreversible tissue damage.KeywordsCardiac OutputPerfusion RateBypass ProcedureLeft Subclavian ArteryColloidal Osmotic PressureThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Effect of Perfusion Rate and Distribution Factors on Drug Elimination Kinetics in a Perfused Organ System

The effects of flow rate and volume of perfusate on the elimination of a drug from a perfusion fluid by an organ or tissue such as the liver, kidney, or intestine are examined. It is shown that the volume of perfusate (or the apparent volume of distribution of a drug) has a pronounced effect on the rate constant for the decline of drug concentration in the perfusate, but that perfusion rate has an effect only if the concentration of drug in the perfusate leaving the organ is appreciably lower than the concentration in the fluid entering the organ.