Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PERFUSION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,009 records · Page 56Linked to original sources
PubMed1984

Evaluation of kidney viability during hypothermic perfusion or cold storage.

The effect of up to 6 days of hypothermic perfusion and up to 72 h of cold storage on tissue viability were studied from measurements of sodium potassium pump activity and adenosine nucleotide content. For the hypothermic perfusion two different albumin-based perfusates were used, one with, the other without addition of caprylic acid and amino acids. No difference could be found in the parameters studied between perfusion with these two perfusates. For both perfusates total adenine nucleotide content (TAN) decreased by approximately 60% during perfusion while energy charge potential (ECP) and the ATP/ADP ratio remained constant. During cold storage a decrease of both TAN and ECP and the ratio ATP/ADP was seen, the main decrease occurring within the 1st h. The transmembrane potassium influx as deduced from potassium content in incubated cortical slices during steady state conditions decreased during 6 days of hypothermic storage to 24.5 +/- 2.4 mumol/kg which was a significantly higher level than after 24 h of cold storage. Thus, addition of extra substrate to the perfusate does not seem to improve kidney cortex viability during hypothermic perfusion. Parenchymal viability is better preserved with continuous hypothermic perfusion, compared to simple cold storage in a solution of the same ionic composition as that used for perfusion.

Adenine Nucleotides↗
PubMedDate not supplied

Influence of ketamine and pentobarbital on microvascular perfusion in normal skin and skin flaps.

The influence of two anesthetics, ketamine and sodium pentobarbital, on the microvascular perfusion of normal skin and skin flaps was evaluated by the use of a laser Doppler perfusion imager which allows the rapid scanning of tissue perfusion. Arterial skin flaps with a distal random random portion were created on the ears of hairless mice (n = 20), and perfusion was measured in the proximal, central, and distal parts of the flap. No differences in microvascular perfusion throughout the whole experiment were found between the ketamine and the pentobarbital group. In normal skin microvascular perfusion decreased to 83-73% of baseline values after induction of anesthesia. After flap creation, the perfusion was further reduced in the distal and central parts of the flap to 48-43% of baseline values, whereas no significant change was found in the proximal part. Six hours after flap creation, with the animal awake, perfusion had increased again in all parts of the flap, remaining at a constant level during the rest of the experiment. Anesthesia had less effects on microvascular perfusion in skin flaps as observed 1 day after flap creation. Perfusion of the central and distal parts of the flap decreased by 10-16%, whereas, in contrast to normal skin, the proximal part remained unaffected. Our study shows that baseline measurements are required in skin flap models when the microvascular perfusion in skin flaps is analyzed under general anesthesia.

Animals↗
PubMed1976

The regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the isolated perfused rat liver.

The effect of perfusion of an isolated rat liver on hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase was studied. In liver removed during the basal period of the diurnal cycle of enzyme activity, a 227 +/- 41% increase in enzyme activity occurred after 3 h of a plasma-free perfusion. This could be prevented by the addition of cycloheximide or pure cholesterol (dispersed with lecithin) to the perfusate. In contrast, the continuous addition of taurocholate or taurochenodeoxycholate, alone or in combination, at a variety of rates did not prevent the increase in enzyme activity. The added bile salts were efficiently extracted from the perfusate and excreted in the bile. The addition of these bile salts to a cholesterol-enriched perfusate did not alter the effect obtained with cholesterol alone. If the perfusate contained whole serum, the increase induced by perfusion in the basal period was smaller (88 +/- 27%) than with plasma-free perfusate. Again, the major bile salts of the rat failed to prevent the increase in enzyme activity induced by liver perfusion. If livers were removed and perfused at the height of the diurnal cycle of enzyme activity, the enzyme activity remained high (2 +/- 10% increase) rather than decreasing, as occurs in vivo. If cholesterol was added to these perfusions, a 52 +/- 4% decrease was induced. Bile salt addition induced no decrease. From the results it is concluded that the major bile salts are not direct regulators of hepatic cholesterol synthesis, but pure cholesterol, in the absence of bile salt or lipoprotein, is able to initiate the mechanism that represses hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase.

Alcohol Oxidoreductases↗
PubMed1978

Experimental glomerulonephritis in the isolated perfused rat kidney.

The development of immune deposits on the subepithelial surface of the glomerular capillary wall was studied in isolated rat kidneys perfused at controlled perfusion pressure, pH, temperature, and flow rates with recirculating oxygenated perfusate containing bovine serum albumin (BSA) in buffer and sheep antibody to rat proximal tubular epithelial cell brush border antigen (Fx1A). Control kidney were perfused with equal concentrations of non-antibody immunoglobulin (Ig)G. Renal function was monitored by measuring inulin clearance, sodium reabsorption, and urine flow as well as BSA excretion and fractional clearance. Perfused kidneys were studied by light, immunofluorescence, and electron microscopy. All kidneys perfused with anti-Fx1A developed diffuse, finely granular deposits of IgG along the glomerular capillary wall by immunofluorescence. Electron microscopy revealed these deposits to be localized exclusively in the subepithelial space and slit pores. Similar deposits were produced in a nonrecirculating perfusion system, thereby excluding the formation of immune complexes in the perfusate caused by renal release of tubular antigen. Control kidneys perfused with nonantibody IgG did not develop glomerular immune deposits. Renal function and BSA excretion were the same in experimental and control kidneys. Glomerular deposits in antibody perfused kidneys were indistinguishable from deposits in rats injected with anti-Fx1A or immunized with Fx1A to produce autologous immune complex nephropathy. These studies demonstrate that subepithelial immune deposits can be produced in the isolated rat kidney by perfusion with specific antibody to Fx1A in the absence of circulating immune complexes. In this model deposits result from in situ complex formation rather than circulating immune complex deposition.

Animals↗
PubMed1993

Locally produced angiotensin II induces ovulation by stimulating prostaglandin production in in vitro perfused rabbit ovaries.

The present study was undertaken to investigate the role of exogenous and endogenous angiotensin II (Ang II) in ovarian steroidogenesis and production of prostaglandin (PG) in in vitro perfused rabbit ovaries. The addition of 100 or 10 micrograms Ang II at 2-h intervals to the perfusate did not stimulate progesterone production, but significantly stimulated estradiol (E2) production by perfused rabbit ovaries. When the specific antagonist of Ang II, saralasin at 2 x 10(-6) M, was added to the perfusate 30 min before the onset of Ang II administration, Ang II-stimulated production of E2 was significantly blocked. Ang II also significantly stimulated both PGE2 and PGF2 alpha production, while the addition of saralasin to the perfusate significantly inhibited the Ang II-stimulated production of PG. The levels of PGs in ovaries perfused with saralasin plus 100 micrograms Ang II did not differ significantly from those in control ovaries perfused with medium alone. Exposure to human CG (hCG) significantly stimulated production of progesterone and E2 by perfused rabbit ovaries, while the concomitant administration of 2 x 10(-6) M saralasin significantly reduced only E2 production. Addition of saralasin to the perfusate inhibited hCG-stimulated PG production in a dose-dependent manner. The ovulatory efficiency in ovaries treated with hCG alone or hCG plus saralasin was significantly correlated with PG production by perfused rabbit ovaries at 12 h after exposure to hCG. The production of PG stimulated by Ang II was completely reduced by indomethacin treatment during the entire perfusion period. Indomethacin completely blocked Ang II-induced ovulation, but not Ang II-stimulated oocyte maturation. Concurrent administration of staurosporine, a protein kinase C inhibitor, at 10(-6) M significantly inhibited Ang II-stimulated meiotic maturation of ovulated ova and follicular oocytes. In conclusion, these results indicate that Ang II has a direct role in ovarian production of E2 and PG. An intrinsic renin-angiotensin system in the rabbit ovary may act as an intermediary of gonadotropin-stimulated PG production. Locally produced Ang II may induce ovulation in the rabbit ovary, at least in part, by stimulating PG production.

Angiotensin II↗
PubMedDate not supplied

Heat response of HT29 cells depends strongly on perfusion--a 31P NMR spectroscopy, HPLC and cell survival analysis.

A model system of perfused human colon adenocarcinoma cells (HT29) encapsulated in alginate was used to examine metabolic response to heat therapy with 31P NMR spectroscopy, HPLC and cell survival analysis. The presented data show, that perfused (medium flow during hyperthermia) and non-perfused (no medium flow during hyperthermia) cells are very difficult in their sensitivity to hyperthermia. Under equivalent experimental conditions with respect to medium pH, oxygen and nutrient concentration, encapsulated perfused HT 29 cells display a significantly lower thermal sensitivity than non-perfused cells. This reduced sensitivity of perfused cells is characterized by an increased cell survival and relative ATP concentration, and reduced drop of the NTP/Pi ratio in the long-term follow up towards zero. The relative ATP concentration determined by HPLC after hyperthermia is correlated with the clonogenic survival fraction. There is a direct relationship, depending on the specific experimental conditions (perfused, non-perfused). For perfused cells only a slight dependency of survival and relative ATP concentration on heat dose is observed. In consequence, the correlation between survival and relative ATP concentration is weak, described by log(SFperf) = 0.7*[ATP-12.4, R2 = 0.79, p < 0.04. For non-perfused cells the correlation is stronger resulting in a relationship of log(SFno perf) = 0.6*[ATP]-9.0, R2 = 0.98, p < 0.0002. Altogether, the presented data suggest that the relative ATP concentration measured by HPLC after hyperthermia might be predictive for cell survival. On the other hand, a dependence between cell survival and long-term changes of NTP/Pi has been found. The results confirm the importance of tumour perfusion for hyperthermia-induced metabolic changes and cytotoxicity and therefore, for the therapeutic outcome.

Adenosine Triphosphate↗
PubMed1989

Effects of using the oxygen-carrying fluorocarbon, FC43, on the ERG of the arterially perfused cat eye.

Arterial perfusion of the isolated cat eye with a perfusate augmented with a 20% (wt/vol) emulsion of the oxygen carrying-fluorocarbon, FC43, produces a much larger b-wave in the electroretinogram than use of the same perfusate lacking FC43. The c-wave is either unchanged or slightly reduced by use of this solution. Halving the oxygen content of the FC43-augmented perfusate also reversibly reduces the b-wave. The use of perfusates with and without FC43 but containing similar amounts of oxygen produces b-waves of similar amplitude. The large b-wave recorded during use of a well-oxygenated, FC43-augmented perfusate suggests that the use of perfusates containing less oxygen produces retinal hypoxia. The b-wave recorded in vivo is considerably smaller than that recorded from the isolated eye during perfusion with a well-oxygenated, FC43-augmented perfusate, but the waveforms are very similar. In particular, the ratios of the b-wave to a-wave are almost identical. The larger ERG recorded in vitro is a result of increasing the shunt resistance to ground upon enucleation. Histological examination of retinas perfused for two hours with the FC43-augmented and standard perfusate reveal no clear signs of tissue hypoxia in either retina. However, even two hours of complete ischemia produces limited inner retinal deterioration and virtually no outer retinal damage, suggesting that the histological state of the retina may not be a reliable indicator of its physiological state. Despite the improved electrophysiological state of the retina produced by increasing its oxygen supply, the survival time of the isolated eye was not increased.

Animals↗
PubMedDate not supplied

High-dose mitomycin C in isolated hyperthermic liver perfusion for unresectable liver metastases.

In order to reduce systemic side effects and increase intrahepatic mitomycin C (MMC) concentrations, isolated hyperthermic liver perfusion (IHLP) has been performed using MMC. This article describes the pharmacokinetics of MMC in IHLP and presents our clinical experience with its use in six patients suffering from unresectable liver metastases. Primary tumors consisted of colorectal carcinomas in three cases, breast cancer in two, and a choroidal melanoma in one. Dosages of MMC varied between 0.5 and 1.0 mg MMC/kg body weight. MMC was added as a bolus directly into the extracorporeal circuit. Intrahepatic temperature was elevated to 40.0-41.0 degrees C by hyperthermic perfusion. MMC concentrations were measured in peripheral blood (preperfusion, then at 5, 30, and 55 min during perfusion, and finally at 5 and 60 min and 6 and 24 h after perfusion) and in recirculating perfusate (5, 30, and 55 min). While markedly elevated MMC concentrations (maximum 6290 ng/mL) were found in the liver perfusate, systemic concentrations remained low (maximum 45 ng/mL), indicating no considerable leakage. MMC concentrations in the perfusate constantly decreased during perfusion. After rinsing with 1500 mL saline, a mean concentration of 52.5+/-33 ng MMC/mL was measured in the washout from 5 patients. In 1 patient with a colorectal carcinoma, MMC concentrations in the perfusion medium were 10-fold and in the plasma 2-fold higher than in the other patients. This high MMC concentration caused severe intrahepatic vascular damage and finally led to the patient's death. In conclusion, IHLP and intrahepatic perfusion with MMC resulted in a high response of hepatic tumors. Systemic exposure of MMC can be reduced effectively by isolated perfusion. However, hepatic toxicity of MMC must be considered.

Adult↗
PubMed2000

Development of an improved technique for the perfusion of the isolated caudal lobe of sheep liver.

The study was designed to develop an improved technique for perfusing the isolated caudal lobe of sheep liver. Twenty caudal lobes were perfused for 3-4 h, in a non-recirculating mode, with Krebs-Henseleit bicarbonate buffer. The perfusion system was designed to give a constant flow. The hepatic viability and functional normality of the perfused lobe were assessed by measuring the perfusion flow rate, pH, K+ efflux, O2 uptake, substrate uptake, gluconeogenesis from propionate and amino acids, and ureagenesis from ammonia and amino acids. Liver tissue was sampled for histological examination, as well as for the determination of liver glycogen and wet : dry weight ratio. The perfusion flow rate and pH were both stable throughout the perfusion. The potassium concentration in the effluent perfusate did not increase during the perfusion, suggesting that there was no loss of viability or hypoxia. The perfused lobe extracted more than 50% of the O2 supply. The rate of oxygen consumption was comparable to the rate reported in vivo. The initial glycogen content was reduced by about 40% after 4 h perfusion. The wet : dry weight ratio was 3.6, consistent with the absence of tissue oedema. Urea production was stimulated when NH4Cl (0.3 mM) was added to the medium but there was no significant increase in urea release when alanine (0.15 mM), glutamine (0.2 mM) or lysine (0.2 mM) was added. Urea production, however, increased by about 171% when a physiological mixture of amino acids was added. Propionate (0.5 mM), alanine and glutamine stimulated glucose production but not lysine or the complete amino acid mixture. Glutamine release was lower than that reported in the rat liver. Changing the direction of flow also revealed an apparent difference between livers from sheep and rats in their metabolism of ammonia. The improved technique offers a simple practical and inexpensive approach to many problems in ruminant physiology and nutritional biochemistry.

Amino Acids↗
PubMed2006

[SPECT lung perfusion scans in predicting radiation pneumonitis in lung cancer patients].

OBJECTIVE: To evaluate single photon emission computed tomography (SPECT) lung perfusion in predicting radiation pneumonitis in lung cancer patients. METHODS: From April 2003 to March 2004, 31 lung cancer patients treated with radical radiotherapy received SPECT lung perfusion scans, among whom, 23 had had perfusion scans both before and at the time of 40 Gy irradiation. The perfusion changes in the region of interest (ROI) after irradiation were obtained through comparing post-radiotherapy with pre-radiotherapy average proportion of SPECT counts within the ROI relative to average counts of the whole lung. Endpoint was defined as grade 2 and above radiation pneumonitis according to RTOG criteria. RESULTS: Lung perfusion defect was observed in all the patients at baseline. > or = grade 2 lung perfusion defect was found in 68.2% (15/22) of patients with central lesion and in 22.2% (2/9) of patients with peripheral lesions (P = 0.04). Seventy percent of the patients (16/23) experienced improved perfusion at 40 - 50 Gy. > or = grade 2 radiation pneumonitis was observed in 12 patients (38.7%) in the whole group, with 6 in those with grade 1 perfusion defects and another 6 in > or = grade 2 group, respectively; Of the 23 patients who had had both pre- and post-radiotherapy SPECT perfusion scan, 5 > or = grade 2 radiation pneumonitis occurred in the 16 perfusion-improved patients and 3 in the 7 unimproved patients. CONCLUSION: There is no significant correlation between radiation pneumonitis and the extent of perfusion defect either before or after 40 - 50 Gy irradiation based on our limited data analysis in this series.

Adult↗
PubMed1988

[Perfluorochemical emulsion as a perfusate in 24-hour liver preservation prior to transplantation in the rat].

Perfluorochemical (PFC) emulsion as a perfusate of liver preservation prior to transplantation was evaluated in continuous hypothermic perfusion for 24 hours followed by orthotopic transplantation in inbred male Lewis rat. Three different contents of PFC emulsion that is, 20% (original Fluosol DA), 10% and 0% PFC solution were prepared as a perfusate. Isolated liver was stored for up to 24 hours using a continuous non-pulsatile perfusion technique of closed circuit with each perfusate. Gas content, GOT, GPT, LDH, potassium and glucose of the perfusate were measured. Oxygen consumption of perfused liver was higher in PFC emulsion than non PFC perfusate. Biochemical analysis of perfusate suggested that liver was preserved best in 10% PFC emulsion. Histological findings, especially, acid phosphatase staining, showed better result in PFC groups. One week survival rates after liver graft were 4/6 (66.7%) in 10% PFC solution, 1/6 (16.7%) in 20% and 0/6 (0%) in 0% solution. In spite of the highest oxygen consumption of perfused liver in early phase, 20% PFC emulsion did not bring the good preservation of perfused liver because of impaired circulation due to higher viscosity in low temperature. Ten percent PFC solution is considered the best in hypothermic preservation of the liver.

Animals↗
PubMed1988

Identification of linoleic and arachidonic acids as the factors in hyperlipemic blood that increase [3H]thymidine incorporation in hepatoma 7288CTC perfused in situ.

Tumor growth and the incorporation of [3H]thymidine into tumor DNA in vivo are increased about 3 times in adult rats (greater than 250 g) after 1 to 2 days of starvation or the induction of diabetes with streptozotocin. These tumor growth responses require hyperlipemia and are reversed by refeeding or insulin treatment, respectively. They do not occur in young tumor-bearing rats (less than about 150 g) that lack appreciable fat stores. A direct relationship between the increased rates of both [3H]thymidine incorporation and tumor growth and host hyperlipemia suggests that tumor cell renewal in vivo in fed rats is limited by substances that are present in hyperlipemic blood. In this study we used a procedure for perfusion of solid tumors in situ to measure the sensitivity of tumor [3H]thymidine incorporation to hyperlipemic blood and to identify the rate-limiting substances. Tissue-isolated Morris hepatomas (7288CTC) growing in young or adult Buffalo rats were perfused with blood from donor rats. Hyperlipemic blood for perfusion was obtained from 2-day starved tumor-bearing (Buffalo) or non-tumor-bearing (Buffalo or Lewis) rats. At the end of the perfusions the tumors were labeled with a pulse of [3H]thymidine (2 microCi/g estimated tumor wet weight). [3H]Thymidine incorporation in tumors growing in fed adult rats was increased from 80 +/- 5 (SD) dpm/micrograms DNA at zero time (before perfusion) to 209 +/- 9 dpm/micrograms DNA (n = 3) after perfusion for 3 h. Tumors growing in fed or starved young rats showed similar responses, and hyperlipemic blood from non-tumor-bearing rats was as effective as hyperlipemic blood from tumor-bearing rats. Perfusion of tumors growing in starved rats with normolipemic blood from fed adult rats decreased [3H]thymidine incorporation from 211 +/- 13 dpm/micrograms DNA before perfusion to 68 +/- 9 dpm/micrograms DNA (n = 3) after perfusion for 3 h. Cells, plasma, and plasma subfractions from hyperlipemic blood were reconstituted to whole blood using plasma, cells, and whole blood, respectively, from fed rats and the mixtures were perfused into tumors growing in fed adult rats. Mixtures containing hyperlipemic plasma, lipid extracts (ethanol:acetone, 1:1) of hyperlipemic plasma, or albumin from hyperlipemic plasma increased tumor [3H]thymidine incorporation. Free fatty acid concentrations were increased about five times in hyperlipemic plasma and perfusion of tumors with normolipemic blood containing added linoleic and arachidonic acids increased [3H]thymidine incorporation. Blood mixtures containing palmitic, stearic, and oleic acids were inactive.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1981

Intramyocardial arteriovenous shunting of blood with nonpulsatile perfusion.

Coronary blood drains through three types of channels: the subepicardial veins, the thebesian veins, and the arteriosinusoidal vessels. In this study the changes in the blood draining through the subepicardial and thebesian veins were measured in relation to time, up to 180 minutes. Analysis of the data yielded useful information about the relatively inaccessible microcirculation in the working heart. The first group of eight dogs was subjected to pulsatile perfusion and the second to nonpulsatile perfusion. The arteriovenous oxygen difference decreased at an identical rate of 0.01 ml of oxygen per minute per 100 ml of blood in both groups. Spontaneous increase in drainage (milliliters of blood per 100 gm of myocardium per minute) occurred as follows: Subepicardial venous drainage increased at a rate of 0.34 +/- 0.03 (mean +/- SE) with pulsatile perfusion and at a rate of 0.23 +/- 0.03 with nonpulsatile perfusion; the values were significantly different (p < 0.025). Corresponding values for thebesian venous drainage were 0.08 +/- 0.01 with pulsatile perfusion and 0.06 +/- 0.01 with nonpulsatile perfusion (p < 0.05). As a result, there was a linear increase in total myocardial oxygen utilization (MVO2) with pulsatile perfusion and a decrease with nonpulsatile perfusion. The increase in drainage with nonpulsatile perfusion, therefore, may have been due predominantly to abnormal shunt activity. The difference in drainage increase may then represent nutritive flow, the absence of which led to a fall in MVO2 with nonpulsatile perfusion. There was also some evidence that the "thebesian system" may play a compensatory role during shunting. Abnormal shunting of blood may be partly responsible for the perfusion-related myocardial damage reported in the literature.

Animals↗
PubMed1994

Is there an indication for a double perfusion schedule with melphalan for patients with recurrent melanoma of the limbs?

It has been reported that a double perfusion schedule shows a better complete remission rate than does the single procedure for recurrent melanoma of the limb. As more perfusion strategies approach the ideal of a 100% complete remission rate, the main issue now is to prolong the period of disease control in the limb, ie to reduce the limb recurrence rate. The follow up of 42 patients treated with a double perfusion schedule and of 45 patients treated with a single perfusion procedure was updated to compare the duration of limb disease control. Both treatment groups were well balanced with respect to patient and tumour characteristics. For patients treated with a double schedule, the dose of melphalan given in the first perfusion was low (6 mg/l limb volume; 1 h; normothermic) in order to make it possible to carry out a second perfusion (9 mg/l; 1 h; normothermic) with a planned short interval of 3-4 weeks. In the single perfusion group a normothermic perfusion with 10 mg melphalan/l was carried out. The acute tissue reactions and long-term side effects did not differ between the two treatment modalities. The response rate was significantly higher in the double perfusion group owing to a higher complete remission rate (76% vs 48%; P = 0.006). However, no significant difference was seen in limb disease control rates 3 years after perfusion (double schedule, 36%; single schedule, 30%), nor in overall 3-year survival (double schedule, 52%; single schedule, 45%). When evaluating perfusion regimens with equally high complete remission rates, attention should be focused on the duration of limb disease control.

Adult↗
PubMed1994

Comparative experimental study between retrograde cerebral perfusion and circulatory arrest.

To evaluate the efficacy of retrograde cerebral perfusion in protecting the brain, we comparatively studied retrograde cerebral perfusion and total circulatory arrest in 18 hypothermic (20 degrees C) mongrel dogs (retrograde cerebral perfusion, n = 10; total circulatory arrest, n = 8). Retrograde cerebral perfusion was performed, maintaining an external jugular venous pressure of 25 mm Hg for 60 minutes. Retrograde cerebral perfusion provided half the cerebral blood flow and a third of the oxygen that was supplied during hypothermic cardiopulmonary bypass, which had a flow rate of 100 ml/min per kilogram. Oxygen consumption and carbon dioxide exudation did not increase on resuming cardiopulmonary bypass after retrograde cerebral perfusion, whereas they increased after total circulatory arrest (oxygen consumption 10.7 +/- 5.3 versus 19.1 +/- 8.6 ml/min, p < 0.05; carbon dioxide exudation, 0.92 +/- 0.54 versus 1.64 +/- 0.78 mmol/min, p < 0.05). Therefore, oxygen debt during retrograde cerebral perfusion was smaller than during total circulatory arrest. Retrograde cerebral perfusion also cooled the brain better than did total circulatory arrest (20.4 degrees +/- 1.5 degrees C versus 22.7 degrees +/- 0.7 degrees C, p < 0.01). Cerebral tissue oxygen tension decreased slightly (27.5 +/- 7.7 versus 12.3 +/- 3.0 mm Hg, p < 0.01), and cerebral tissue carbon dioxide tension increased slowly during retrograde cerebral perfusion (95 +/- 34 versus 147 +/- 44 mm Hg, p < 0.05). These changes were smaller than those seen in total circulatory arrest. Tissue concentrations of adenosine triphosphate in the brain remained relatively high during retrograde cerebral perfusion but decreased rapidly during total circulatory arrest (0.49 +/- 0.16 versus 0.21 +/- 0.05 mmol/gm, p < 0.01, just before resuming cardiopulmonary bypass). Retrograde cerebral perfusion cannot maintain aerobic metabolism but may reduce ischemic damage of the brain and may safely extend the cerebral circulation interruption time.

Adenosine Triphosphate↗
PubMed1998

Safety and efficacy of isolated perfusion of extremities for recurrent tumor in elderly patients.

BACKGROUND: The treatment of bulky recurrent melanotic lesions of extremities with isolated limb perfusion with high dose chemotherapy offers palliation in a number of patients. However, the question is raised whether these major surgical procedures are too risky to warrant performing them in elderly patients. METHODS: Sixty-seven limbs were perfused in 60 patients with various drugs from 1976 through 1996 (35, imidazole carboxamide; 7, cisplatin; 20, carboplatin; 5, thiotepa). Among the 67 perfusions, 20 were in patients aged 70 years and older. Perfusion was performed for 16 upper extremities and 51 lower extremities by using the pump oxygenator for 1 hour. RESULTS: A total of 19 complications were noted after a total of 14 of the 67 perfusions (21%) (postoperative edema, 5; seroma, 4; wound separation or infection, 9; nonfatal pulmonary embolus, 1). The complications in 4 of 20 perfusions in the older patients (20%) were less than in 15 of 47 perfusions in the younger patients (32%). Among the 17 patients older than 70 years of age who were treated with perfusions for recurrent disease, four patients (24%) are alive with no evidence of disease (NED) for a median of 29 months (range, 16 to 80 months); one patient is now more than 6 years with NED after her third perfusion for repeated in-transit disease. Another 2 of 17 patients (12%) are alive with disease for a median of 89 months (range, 54 to 123 mos). The remaining 11 patients (64%) are dead of their disease. These data are comparable to the control rates in the group of younger patients in the study. Overall, half of all the patients (14 of 28) who died of their disease in both groups had maintained local control of their involved extremities. CONCLUSIONS: Aggressive treatment in selected patients with regional isolated perfusion of limbs for melanoma can lead to significant palliation of symptoms and salvage of limbs with adequate disease-free control and occasional survival benefit. This series of patients was associated with meaningful disease control and with few serious complications. Perfusions are tolerated well by patients in their 70s and 80s; therefore advanced age is not a contraindication to this procedure in carefully selected patients.

Adult↗
PubMed1976

[Studies on the functional ability of swine liver perfused with human blood in machine recirculation attempt. 2. Behavior of serochemical parameters].

In the present paper is reported on the behavior of different serochemical parameters in heterologous perfusion of the liver of pigs. The perfusion of the animal livers was carried out with preserved human blood in 11 recirculation experiments (closed machine circulations). In addition to this an empty circulation with human blood without attachment to an animal liver was carried out, whereby otherwise the arrangement of the experiment was the same, in order to take into consideration the effects of the blood traumatisation in the interpretation of the results. The enzymes GOT and LAP proved as sensible indicators of the lesion of the liver cells occurring in the perfusion of the liver of the pigs. The behavior of the mitochondrial GDH as well as of the lysosomal enzymes SP and BETA-GC which scarcely increased during the recirculations in the perfusate blood, however, allows the conclusion that there did not appear a severe lesion of the liver cells (necrobiosis) during several hours of perfusion. A cholestasis did not develop during the perfusions, when one takes as basis the behavior of the enzymes AP, GGTP and AAP indicating cholestasis. Compared with GOT the enzyme GPT showed by far less elevations in the perfusate blood so that with increasing duration of the perfusion the De-Ritis-quotient significantly increased. Increased LDH-activities above all revealed the increasing during perfusion haemolysis and less reliably a lesion of the liver of the pig. The increase of ADA in the perfusate blood proved as nearly exclusively conditioned by haemolysis. Total protein, albumins, immunoglobulins, cholinesterase and thymol turbidity test remained unchanged in the course of the perfusions.

Acid Phosphatase↗
PubMed1998

Reduction of dimesna to mesna by the isolated perfused rat liver.

Mesna is administered with ifosfamide and cyclophosphamide to reduce the incidence of hemorrhagic cystitis. In the present model of mesna metabolism and disposition, mesna is rapidly and irreversibly oxidized to dimesna in the plasma, passes unchanged through the liver, and is then reduced by the kidney and excreted. Our detection of a high ratio of mesna to dimesna in the plasma of clinical samples led us to reinvestigate the hepatic metabolism of mesna and dimesna. We perfused isolated rat livers from female Sprague Dawley rats with protein-free buffered solution containing dimesna at concentrations observed during therapy. In single-pass perfusions, each liver was perfused with up to three dimesna concentrations during consecutive 20-min periods. Recirculating perfusions were used to study single supratherapeutic concentrations of dimesna or mesna. Mesna and dimesna concentrations were measured by specific chromatographic procedures. Dimesna reduction, adjusted by the effluent flow rate and liver weight (0.4-58.5 nmol/min/g liver), correlated closely by linear regression (r = 0.98; n = 36) to the perfused dimesna concentration (4.2-249 microM), indicating a clearance of 0.20 ml/min/g liver. The concentration of dimesna that entered the liver closely matched the summed concentration of mesna and dimesna emerging in the effluent perfusate (single-pass experiments: slope, 0.98; intercept, -0.30; r = 1.00; n = 31). Only trace amounts of unidentified thiols were detected in the bile during recirculation of perfusates with 1 mM mesna or 250 microM dimesna. The effluent mesna concentration correlated inversely with the flow rate, which was consistent with a low extraction ratio in the perfusion model. These data suggested that the dimesna reduction rate was limited by hepatic uptake. Dimesna reduction was decreased by agents that deplete glutathione. Pretreatment of rats with up to 100 mg/kg ifosfamide did not impair hepatic dimesna reduction. In control experiments, dimesna was not reduced during recirculation through the apparatus without a liver. Mesna was oxidized to dimesna during oxygenation of the perfusate in the reservoir, but mesna injected directly into the perfusate just before entry into the liver passed unchanged into the effluent. Extrapolation of the dimesna clearance data from the perfusion model to humans suggests that hepatic dimesna reduction may counterbalance the rapid oxidation of mesna in plasma. The proposed equilibrium is consistent with clinical observations and suggests a new model for mesna metabolism and disposition.

Animals↗