FC-43 Emulsion Research Articles

The use of a perfluorochemical emulsion as a vascular perfusate in drug absorption.

In-vitro simultaneous luminal and vascular perfusion using the perfluorochemical emulsion, FC-43 emulsion, as a vascular perfusate, was examined for drug absorption in rat jejunum. The intestinal membrane in this system was found to retain its normal barrier functions for drug transport, as evident from the following: (i) stable absorption clearance of tritiated water and salicylic acid at steady-state, (ii) agreement of this clearance with that by in-situ single-pass luminal perfusion, (iii) active transport of D-glucose and its inhibition by phloridzin and (iv) normal glutamate pyruvate transaminase activity in the intestinal mucosa. FC-43 emulsion gave a more normal absorption site blood flow than the usual vascular perfusate containing erythrocytes and albumin in Krebs-Henseleit bicarbonate buffer solution. Consequently, this emulsion was useful for examining the contribution of blood flow resistance toward drug absorption. The rate-limiting steps of absorption of tritiated water, antipyrine and salicylic acid were examined by perfusion using FC-43 emulsion. The absorption of tritiated water was almost completely blood flow-limited and its absorption clearance may possibly be an approximated absorption site blood flow. The contribution of blood flow resistance to total resistance for antipyrine absorption exceeded that for salicylic acid absorption.

Impaired recoloration of a discordant liver xenograft in the guinea pig-to-rat combination: physiological insults or immunological responses.

The aim of this study was to clarify, using guinea pig (GP) syngeneic and xenogeneic liver graft models, the mechanisms of impaired recoloration caused by immunological responses or physiological insults; and to examine the effect of an anti-complement agent, FC43 emulsion, on xenograft rejection. GP syngeneic and xenogeneic liver grafts flushed with 4 degrees C lactated Ringer's solution were poorly perfused around the porta hepatis, whereas those flushed with 15 degrees C solution were immediately recolored, and the portal venography confirmed homogeneous perfusion throughout the GP livers. Impaired recoloration of GP xenografts was also ameliorated by reduction of ischemic time. Pretreatments with FC43 emulsion significantly extended xenograft survivals. Rejected GP liver xenografts showed C3 deposits on sinusoids and central veins and IgM deposits faintly stained only on some small vessels, but there were no detectable deposits of IgG. The impaired recoloration in this model may be caused by physiological insults during the initial stage of revascularization, and the immunological responses that probably followed.

Postischemic synthesis of high energy phosphates in isolated porcine hearts during reperfusion with 11 or 25 degrees C hypothermic perfluorocarbon emulsion FC 43. A 31P magnetic resonance spectroscopy study.

One aim of coronary reperfusion after myocardial ischemia is to restore the myocardial content of high energy phosphates. The superiority of the artificial oxygen carrier perfluorocarbon emulsion FC43 over blood solution is known, therefore, in this paper we examined the temperature-dependence of this substance. The changes of the high energy phosphates phosphocreatine (PCr) and inorganic phosphate (Pi) were documented in 29 isolated pig hearts, employing a 4.7 Tesla magnetic-resonance-spectroscope (MRS). After 15 min warm ischemia, reperfusion with warm blood and a cardioplegic ischemia period of 45 min, these hearts were reperfused with either 11 or 25 degrees C hypothermic oxygenated perfluorocarbon emulsion FC43, both under continuous spectroscopy. MRS is able to directly measure PCr as well as Pi. Their relation expresses the state of myocardial energy stores. Reperfusion with 11 degrees C hypothermic FC43 (n = 14) caused an increase of the relation PCr to Pi by a factor of 9, compared to an increase by a factor of 4 with 25 degrees C emulsion (n = 15) (P < 0.05). During 80 min of reperfusion with 11 degrees C cold FC43 emulsion the average flow rate was 90 +/- 12 and 96 +/- 11 ml/min during reperfusion with 25 degrees C hypothermic FC43 emulsion. Both rates fell only slightly in the course of time. We conclude that reperfusion with 11 degrees C hypothermic oxygenated FC43 in isolated ischemic porcine hearts leads to a clear increase of the index PCr/Pi compared with reperfusion at 25 degrees C. The correlation between the synthesis of myocardial high energy phosphates with postcardioplegic ventricular function is questionable. If further studies will show an improvement of myocardial function after perfusion with hypothermic oxygenated perfluorocarbon emulsion FC43, this solution may find clinical application in the storage of explanted human hearts for transplantation, during transportation to the recipient.

Suppressive effect of FC-43 perfluorocarbon emulsion on enhanced oxidative haemolysis in the early postburn phase

The effect of FC-43 perfluorocarbon emulsion on resistance of red blood cells to oxidative haemolysis and lipid peroxidation was evaluated in rats (full skin thickness burns over 15–20 per cent of total body surface area). The content of erythrocyte malonyl dialdehyde (MDA), α-tocopherol, glutathione (reduced and oxidized forms) and oxidative haemolysis were measured at 24 h after burn injury. Four groups were employed: (1) non-burned non-treated, (2) non-burned but treated with FC-43 perfluorocarbon emulsion (5 ml/kg bodymass i.v.), (3) burned non-treated, (4) burned but treated with FC-43 emulsion (5 ml/kg bodymass i.v.). The non-burned groups showed no significant differences in oxidative haemolysis, MDA levels or α-tocopherol and glutathione content. In the burned non-treated group the oxidative haemolysis elevated by 190 per cent (P < 0.001), MDA content increased by 43 per cent (P < 0.05), whereas the concentration of α-tocopherol and reduced glutathione (GSH) decreased significantly by 36 per cent and 18 per cent, respectively. The results showed reduction in the postburn MDA content by 30 per cent (P < 0.02) and oxidative haemolysis by 44 per cent (P < 0.001) after treatment with FC-43 emulsion. FC-43 emulsion did not change significantly the levels of α-tocopherol and GSH in erythrocytes after thermal injury. It is concluded that FC-43 perfluorocarbon emulsion administration suppresses early postburn lipid peroxidation and increases the resistance of red blood cells to oxidative haemolysis.

Solubility of volatile anesthetics in plasma substitutes, albumin, intravenous fat emulsions, perfluorochemical emulsion, and aqueous solutions.

Using the gas chromatographic headspace sampling technique, we determined the solubility of volatile anesthetics (halothane, enflurane, isoflurane, and sevoflurane) in plasma substitutes, albumin solution, intravenous fat emulsions, perfluorochemical FC-43 emulsion, and aqueous solutions at 37°C. The order of magnitude of λ value (liquid/gas partition coefficients) was halothane >enflurane>isoflurane> sevoflurane in all the parenteral infusion fluids except the perfluorochemical emulsion (FC-43). The FC-43/gas partition coefficients of the volatile anesthetics were almost the same at 5.5. The partition coefficients were affected by the osmolarity of solutions, hydrophobicity, and the structure of solutes. Also, the blood/gas partition coefficients in intravenous fat emulsions and FC-43 were calculated. It is suggested that fluid therapy, especially with intravenous fat emulsions or FC-43, may influence the blood/gas partition coefficients of anesthetics, and affect the induction of anesthesia.

Kinetic analysis of cell proliferation using bromodeoxyuridine labeling and in situ detection of dying cells in the tympanic membrane and middle ear cholesteatoma.

Using specimens from the posterior-superior quadrant of the human tympanic membrane, meatal skin, retroauricular skin and middle ear cholesteatoma, epidermal cell proliferation was studied by cultures in FC43 emulsion containing bromodeoxyuridine (BrdU), and cell death was detected by in situ labeling of nuclear DNA fragmentation (TUNEL staining). The culture of specimens with BrdU revealed labeling in the basal cell layer and/or the layer immediately above it. The counts of BrdU-labeled cells both at and beside the malleus handle and at the annulus were significantly higher than those in the tympanic membrane, meatal skin, retroauricular skin and cholesteatoma, indicating the existence of epidermal proliferation centers in the annulus and malleus handle. TUNEL-positive cells were observed in the uppermost layer of the epidermis, and counts of dying cells did not show any significant differences among specimens from the different areas. From these observations, we conclude that addition of newly proliferated cells at the proliferation center and uniform cell death cause epidermal cell migration over the tympanic membrane and ear canal. In addition, no proliferation center was seen in the epidermis of cholesteatoma, suggesting a disturbance of epidermal cell migration. Furthermore, BrdU-labeling at the margin of persistently perforated tympanic membranes from patients with chronic otitis media revealed that, at the perforation margin, the counts of BrdU-labeled cells were not higher than those of the normal tympanic membrane. In addition, a few BrdU-labeled cells were observed in the lamina propria and mucosal cell layer, indicating that persistent perforation of the tympanic membrane results from the failure of proliferating cells to increase at the margin of the perforation.

Effects of perfluorocarbon exchange transfusion on reducing myocardial infarct size in a primate model of ischemia-reperfusion injury: A prospective, randomized study

This study was undertaken to test the hypothesis that perfluorocarbons were able to reduce myocardial infarct size in a baboon model of ischemia-reperfusion injury. Exchange transfusion of perfluorocarbons has been shown to reduce myocardial infarct size in the dog, who, unlike the baboon, has an extensive collateral circulation. After 15 minutes of occlusion of the left anterior descending coronary artery, 14 baboons were bled to attain a hematocrit of 24% to 26% and were simultaneously transfused, six with Fluosol-DA 20% emulsion and eight with FC-43 emulsion. After 2 hours of ligation, the coronary arteries were reperfused. Baboons were killed 24 hours after ligation, and the hearts were excised. Microvascular dye was infused into the coronary artery to delineate its perfusion bed. Ratios of the mean volume of infarct to the mean volume of perfusion bed were calculated and compared by use of planimetry. A similar protocol was followed in two other groups of baboons except that lactated Ringer's solution was infused into six of them, whereas eight had no exchange transfusions. The ratios of the mean volume of infarct to the mean volume of perfusion bed of the four groups were as follows: Fluosol-DA, 38.1% +/- 7.5%; FC-43, 37.7% +/- 8.3%; lactated Ringer's, 46.9% +/- 10.5%; controls, 65.6% +/- 6.9%. Statistical significance was reached when comparing both perfluorocarbon-treated groups with the controls (p < 0.05 for both groups) but not significant when comparing them with the Ringer's lactate-treated group. Results suggest that the beneficial effects of exchange transfusion with the perfluorocarbons may be primarily due to hemodilution.

Effects of artificial blood (FC-43 emulsion) on myocardial energy metabolism in the rat heart-lung preparation

We have assessed the effects of artificial blood (FC-43 emulsion) on myocardial energy metabolism in the rat heart-lung preparation. Animals were allocated to four groups (n = 8 each group) according to the ratio of perfusion blood and FC-43 as follows: group 1 = control, perfusion blood only; group 2 = 50% FC-43; group 3 = 75% FC-43; and group 4 = 100% FC-43. Hearts were perfused initially to a cardiac output of 30 ml min-1 and mean arterial pressure of 50 mm Hg. Thirty minutes after perfusion, the hearts were freeze-dried for 6 days. Myocardial high energy phosphates (ATP, ADP and AMP) were measured by high pressure liquid chromatography. Myocardial lactate and glycogen concentrations were measured by enzymatic methods. There were almost no significant differences in cardiac output, systolic pressure, right atrial pressure and heart rate among the groups. Oxygen contents of the perfusate in all FC-43 groups were significantly lower than those in the control group. Myocardial ATP concentrations in rats receiving 50%, 75% and 100% FC-43 were significantly lower than those in the control group. In addition, myocardial ADP and AMP concentrations in rats receiving 75% and 100% FC-43 were significantly higher than those in the control group. Although there is adequate oxygen-carrying capacity in FC-43 to maintain cardiac function during perfusion, the energy levels in the hearts perfused with FC-43 were lower than those in normal hearts.

Endotoxin Clearance Through Whole Body Rinse Out in Relation to Histologic Integrity in the Rat

The effects of normothermic whole body rinse out (NWBRO) with FC-43 perfluorocarbon emulsion on the course of endotoxic shock were examined in male Wistar rats. These animals, conscious and unrestrained, were infused over 10 min with 60 mg/kg of E. coli endotoxin (LD100) and observed for 6 hr. The rats developed hypotension, plasma extravasation, metabolic acidosis, increase in serum GPT and GOT, and extensive hemorrhages in the small intestine. Another group of rats was subjected to blood substitution with FC-43 emulsion (artificial blood) 30 min after endotoxin infusion, until the hematocrit dropped to less than 3%, after which 6-9 ml of donor blood was exchange transfused with the emulsion. NWBRO caused a transitory rise in the GOT level, but more importantly it resulted in 98% endotoxin clearance, improved blood alkaline reserves, trimmed elevated GPT and GOT levels, and attenuated hemorrhage and epithelial necrosis in the small intestine.

Intracellular distribution of the hydrophobic triterpene, bryonolic acid, in cultured cells of Luffa cylindrica L.

Intracellular localization of bryonolic acid, an antiallergic pentacyclic triterpene, in cultured cells of Luffa cylindrica was investigated with reference to the sites of its biosynthesis and accumulation. The results of cell fractionation showed that bryonolic acid was mostly located in the cell wall fraction. The addition of FC-43 emulsion to the culture medium was found to cause the release of bryonolic acid from the cell wall into the medium without affecting cell growth and bryonolic acid production. Under this culture condition, (14)C-labeled sodium acetate administered to the cells was rapidly incorporated into bryonolic acid which was then excreted into the medium within 10 min after administration. Electron microscopic observations suggested that spherical vesicles (ca 0.1 μm in diameter) derived from the rough endoplasmic reticulum may be associated with the biosynthesis and excretion of this compound into the cell wall. Furthermore, the activity of 2,3-oxidosqualene cyclase, a key enzyme involved in the biosynthesis of bryonolic acid, was detected in the microsomal fraction containing the endoplasmic reticulum.

Effect of Endotoxin Clearance Using Whole Body Rinse-Out on Some Blood-Gas and Metabolic Parameters in Rats

Conscious and unrestrained male Wistar rats were infused over a 10 min period with 60 mg/kg Escherichia coli endotoxin (LD100) and observed for 6 hr. Hypotension, metabolic acidosis, hyperlactemia, hypoglycemia, and elevated oxygen extraction from blood developed in the rats. Another group of rats was subjected to blood substitution with FC-43 emulsion (artificial blood) 30 min after endotoxin application until hematocrit dropped to 3%, after which 6-9 ml of donor blood was exchange transfused with the emulsion. This method resulted in 98% endotoxin clearance, improved blood alkaline reserves, preserved blood glucose, and normalized arterial mixed venous oxygen gradient and O2 extraction from the blood (which implies preserved blood circulation status). Side effects included hypotension, a transitory rise in blood lactate level, and a fall in arterial oxygen content due to the lower hemoglobin (erythrocyte) level.

A comparison of lipoprotein secretion, bile production and hepatic morphology in isolated rat livers perfused with a perfluorocarbon emulsion or rat erythrocytes

Isolated rat livers were perfused with an oxygenated perfluorocarbon emulsion, FC-43 emulsion for 1 to 4 hr. FC-43 emulsion contained 20% FC-43 (wt/vol) perfluorotributylamine (the fluorocarbon component for the transport of oxygen and carbon dioxide) emulsified with 2.56% Pluronic F-68 (a nonionic surfactant) in Krebs-Ringer bicarbonate buffer. FC-43 emulsion also contained 3% hydroxyethyl starch as an oncotic agent and 1.8 mg/ml glucose. The viability (oxygen consumption), bile secretion, structural integrity and secretion of nascent lipoproteins by FC-43-perfused rat livers was compared with livers perfused with Krebs-Henseleit bicarbonate buffer that contained rat erythrocytes (25% hematocrit) and 1.5 mg/ml glucose (red blood cell medium). Oxygen consumption was somewhat higher in livers perfused with FC-43 emulsion. Bile secretion of livers perfused with FC-43 emulsion for 4 hr was reduced significantly to 40% of that by red blood cell medium. The structural integrity of livers perfused with FC-43 emulsion varied from normal to marked cellular damage. Light-microscopical examination of rat livers perfused with FC-43 emulsion showed ballooning of sinusoids, presence of vacuoles in sinusoidal lining cells in some hepatocytes and detachment of endothelium in sinusoids. The number of vacuoles progressively increased in longer perfusions. Electron-microscopical studies showed the presence of small (60 to 100 nm) vesicles of varying electron density, presumably fluorocarbon particles inside the vacuoles in sinusoidal lining cells (Kupffer and endothelial) and hepatocytes. After 4 hr of perfusion with FC-43 emulsion, most of the sinusoidal endothelia were denuded, and the microvilli of the hepatocytes all but disappeared. In contrast, the ultrastructure of rat livers perfused with red blood cell medium for 4 hr was unaltered. The accumulation of nascent lipoproteins in perfusates of FC-43-perfused livers was markedly reduced, and no normal very-low-density lipoprotein, low-density lipoprotein or high-density lipoprotein were isolated. Chemical analysis showed the presence of Pluronic F-68 in all lipoprotein fractions. Our data strongly suggest that, during recirculating liver perfusions with FC-43 emulsion (between 1 and 4 hr), the nonionic surfactant detergent Pluronic F-68 dissociated from the emulsion and markedly affected hepatic structure, lipoprotein secretion and the composition of lipoproteins isolated from perfusate. Therefore FC-43 emulsion is not a suitable liver-perfusion medium for studies of lipoprotein metabolism.

Experimental Hyperthermia: Protective Effect of Oxygen Carrying Fluorocarbon and Crystalloids Intraperitoneally

The treatment of hyperthermia produced by passive warming was studied in anesthetized rats weighing 250-300 grams. In the first set of seven experiments, the authors found that venous blood oxygen fell as core temperature rose. Intraperitoneal injection of 20 ml of the oxygen carrying fluorocarbon (perfluorotributylamine, FC-43) emulsion in three of the animals shifted the curve to the right improving venous oxygen content (p less than 0.1). In the second series of experiments, a catheter was placed in the carotid artery. This catheter was attached to a pressure transducer for continuous recording of blood pressure and heart rate. Periodic blood samples were removed for measurement of blood gases, pH, and lactate. Four of the animals received 20 ml of isotonic saline, three received 20 ml of FC-43 emulsion both given intraperitoneally, and four served as controls. In the control group, there was an increase in systolic blood pressure and heart rate which peaked at a colon temperature of 42 degrees C, followed by cardiovascular collapse and death around 43 degrees C. Arterial PO2 (corrected for temperature) remained relatively constant up to 42 degrees C, and then fell. The arterial PCO2 rose sharply when the core temperature exceeded 43 degrees C. Arterial lactate content began to increase at 42 degrees C and above 43 degrees C was 2.5 fold elevated. Isotonic saline provided circulatory support but did not change the hypoxia or mixed acidosis from CO2 and lactate above 43 degrees C. FC-43 emulsion decreased hypoxia and improved circulatory performance but was associated with a mild respiratory alkalosis as arterial PCO2 fell.(ABSTRACT TRUNCATED AT 250 WORDS)

Colorimetric assay for Pluronic F-68 as measured in isolated rat liver perfusion systems

A colorimetric assay has been developed for the quantitation of Pluronic F-68, a nonionic detergent (surfactant) which is a polyoxypropylene-polyoxyethylene (POP-POE) block copolymer. We measured this substance in organic extracts of rat liver perfusates from livers which had been perfused with an oxygenated perfluorocarbon, FC-43 Emulsion (Oxypherol).

Deconvolution of chemical shift spectra in two- or three-dimensional [19F] MR imaging.

The chemical shift spectra of 19F in perfluorinated compounds (PFCs) present a nontrivial impulse response function for magnetic resonance (MR) imaging. The 19F images of organs containing PFCs can be degraded by blurring and ghost image artifacts. Two methods (noise masked deconvolution and maximum entropy deconvolution) are presented that allow the chemical shift spectra of 19F in PFCs to be used to extract high quality MR images free of chemical shift artifact. Both techniques rely on postprocessing of either the raw data or the original image to produce images that are not degraded by the chemical shift spectra of the compound being imaged and that exhibit a signal-to-noise ratio equal to or better than that observed in the original image. The techniques are general in that they can be used with many PFC spectra. Using MR imaging data obtained from phantoms filled with cis/transperfluorodecalin and perfluorotributylamine (FC-43), the methods are compared in terms of their (a) ability to eliminate the chemical shift artifact associated with the PFC spectrum; (b) signal-to-noise performance; and (c) ability to preserve information related to the density and the longitudinal relaxation rate of the resonant nuclei. The utility of these techniques is demonstrated by a series of three-dimensional Fourier transform in vivo images of FC-43 emulsion in a mouse liver.

Inhibition of vasoactive agents by perfluorochemical emulsion

Perfluorochemicals are widely used in clinical and experimental studies as volume expanders with high oxygen carrying capacity. We noticed that contractions of rabbit aortic strips, induced by norepinephrine, were inhibited in FC-43 emulsion as compared to Krebs-Henseleit solution (KH). To study this inhibition, a comparative evaluation was made of the contractile responses of norepinephrine, serotonin and histamine in FC-43 emulsion and KH. The effect of these agents was significantly diminished in FC-43 emulsion; concentration-response curves were shifted to the right and the maximum response was diminished. A search was made for the individual constituents of FC-43 responsible for diminution of contraction of vascular smooth muscle. After centrifugation of FC-43 emulsion, the supernatant caused a reduction of contractility and reduced EC50-values of norepinephrine to the same degree as the fully constituted emulsion. This excluded perfluorotributylamine, the oxygen carrying particles, as being responsible for this inhibition. When the detergent Pluronic F-68 was added to KH in concentrations equal to that in FC-43 emulsion, inhibition of contraction occured and EC50-values increased. Contractions induced by norepinephrine were equally inhibited by the addition to KH of a volume expander, hydroxyethylstarch, in a concentration equal to that in FC-43 emulsion. It is concluded that FC-43 emulsion inhibits vasoactive agents and attenuates its pharmacologic effects on vascular smooth muscle. The fractions of FC-43 emulsion responsible for inhibiting the effect of vasoactive agents are Pluronic F-68 and hydroxyethylstarch.

Advantages of perfluorochemical perfusion in the isolated working rabbit heart preparation using 31P-NMR

Quantitative 31P-NMR and enzymatic analysis of high-energy phosphates were used to characterize an isolated perfused working rabbit heart preparation. In this model, the left side of the heart works against a physiological after-load. Two perfusates, Krebs-Henseleit saline and the perfluorocarbon emulsion FC-43 (perfluorotributylamine), were evaluated in their ability to maintain cardiac function and high-energy phosphate metabolites over a period of 2–3 h. Adenine nucleotides ATP, ADP, phosphocreatine and inorganic phosphate (P i) were measured by 31P-NMR while monitoring cardiac output and coronary flow. Intracellular pH was determined using the chemical shift of P i. At the end of each experiment, hearts were freeze clamped and enzymatically assayed for adenine nucleotides, phosphocreatine and P i. In every experiment, hearts perfused with FC-43 emulsion maintained the same rate of cardiac output as hearts perfused with Krebs-Henseleit saline, but with half the coronary flow rate: FC-43, 22 ± 2.5 ( n = 5), Krebs-Henseleit saline 42 ± 2.7 ( n = 6) ml/min, P < 0.001. Hearts perfused with FC-43 emulsion showed higher [phosphocreatine] and [ATP] measured by 31P-NMR. For [phosphocreatine]: FC-43 3.2 ± 0.7 ( n = 5), Krebs-Henseleit saline 1.7 ± 0.2 ( n = 6) μmol/g wet wt., P < 0.01. For [ATP]: FC-43 1.8 ± 0.7 ( n = 5), Krebs-Henseleit saline 0.9 ± 0.2 ( n = 6) μmol/g wet wt., P < 0.02. [phosphocreatine] and [ATP] determined by 31P-NMR values were identical within experimental error to those values obtained by enzymatic analysis. Comparing [P i] determined by both methods, 36% of P i in FC-43-perfused hearts, and only 24% of P i in Krebs-Henseleit saline-perfused hearts were visible by NMR, indicating that a large proportion of P i is bound in the intact functioning heart. Similar results were obtained for [ADP]. Using the combined techniques of 31P-NMR and enzymatic assay, we have shown in this model of the isolated working rabbit heart preparation, that FC-43 emulsion maintains significantly better function and high-energy phosphate levels than Krebs-Henseleit saline.

Effect of carotid artery ligation and infusion of fluosol FC-43 emulsion on brain surface oxygen tensions.

In eight rabbits, the common carotid artery was ligated and multiple estimations of brain surface oxygen tension performed using a seven barrelled mini-electrode. In five rabbits ligation of the carotid artery resulted in impairment of cortical oxygenation. The remaining three rabbits showed no impairment in the supply of oxygen to the cerebral cortex after carotid occlusion. In the five rabbits who displayed a reduction in oxygen supply after carotid ligation, ventilation with 33% oxygen after the infusion of 15 ml/kg of Fluosol FC-43 produced an improvement in cortical oxygenation in only three of the five rabbits. When these animals were ventilated with 100% oxygen after carotid ligation and Fluosol infusion, oxygen supply in all five was commensurate with or greater than that during control conditions.

Simultaneous vascular and luminal perfusion of rat small intestine.

A method is described which allows simultaneous vascular and luminal perfusion of the jejunal segment of rat intestine. Perfluorochemical artificial blood (FC-43 Emulsion) was utilized as a vascular perfusion medium. The viability of this preparation can be maintained for 1h as indicated by morphological findings, competitive inhibition between L-phenylalanine and L-methionine, and the transport of L-phenylalanine against a concentration gradient. This preparation was used for investigation of the transport behavior of several amino β-lactam antibiotics.

Crystalloid and perfluorochemical perfusates in an isolated working rabbit heart preparation

Krebs-Henseleit buffer (KH) and a perfluorochemical (FC-43) were compared as perfusates in an isolated working rabbit heart preparation. Both perfusates were oxygenated in an identical manner using an infant bubble oxygenator. After 60 min of perfusion, no difference could be detected in the ratio of wet to dry heart weight between KH- and FC-43-perfused hearts (KH, 6.25 +/- 0.3; FC-43, 5.99 +/- 0.20). Left ventricular systolic pressure, maximal rate of left ventricular pressure rise, mean aortic systolic pressure, cardiac output, aortic flow, left ventricular power, and myocardial O2 consumption (MVO2) were significantly higher in FC-43-perfused hearts throughout the time of perfusion. However, there were no differences in resistance to cardiac output and heart rate. In KH- and FC-43-perfused hearts, MVO2 and left ventricular power were closely correlated (KH, r = 0.793; FC-43, r = 0.831). Significantly higher coronary flow of KH-perfused hearts could be attributed to the lower viscosity of KH (1.05 Pa . s) compared with FC-43 (1.91 Pa . s). Increased O2 extraction during KH perfusion could not compensate for low O2-carrying capacity of KH buffer (345 compared with 705 nmol O2 X ml-1 in FC-43 emulsion). A postischemic increase of coronary flow was observed only in FC-43-perfused hearts (28%). These results demonstrate a different response of perfused heart preparations to FC-43 and KH buffer.