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PubMed1995

Increasing organ blood flow during cardiopulmonary bypass in pigs: comparison of dopamine and perfusion pressure.

OBJECTIVE: To determine whether low-dose dopamine infusion (5 micrograms/kg/min) during cardiopulmonary bypass selectively increases perfusion to the kidney, splanchnic organs, and brain at low (45 mm Hg) as well as high (90 mm Hg) perfusion pressures. DESIGN: Randomized crossover trial. SETTING: Animal research laboratory in a university medical center. SUBJECTS: Ten female Yorkshire pigs (weight 29.9 +/- 1.2 kg). INTERVENTION: Anesthetized pigs were placed on normothermic cardiopulmonary bypass at a 100-mL/kg/min flow rate. After baseline measurements, the animal was subjected, in random sequence, to 15-min periods of low perfusion pressure (45 mm Hg), low perfusion pressure with dopamine (5 micrograms/kg/min), high perfusion pressure (90 mm Hg), and high perfusion pressure with dopamine. Regional perfusion (radioactive microspheres) was measured in tissue samples (2 to 10 g) from the renal cortex (outer two-third and inner one-third segments), stomach, duodenum, jejunum, ileum, colon, pancreas, and cerebral hemispheres. MEASUREMENTS AND MAIN RESULTS: Systemic perfusion pressure was altered by adjusting pump flow rate (r2 = .61; p < .05). In the kidney, cortical perfusion pressure increased from 178 +/- 16 mL/min/100 g at the low perfusion pressure to 399 +/- 23 mL/min/100 g at the high perfusion pressure (p < .05). Perfusion pressure augmentation increased the ratio of outer/inner renal cortical blood flow from 0.9 +/- 0.1 to 1.2 +/- 0.1 (p < .05). At each perfusion pressure, low-dose dopamine had no beneficial effect on renal perfusion or flow distribution. Similar results were found in the splanchnic organs, where regional perfusion was altered by perfusion pressure but not by dopamine. In contrast, neither changing perfusion pressure nor adding low-dose dopamine altered blood flow to the cerebral cortex. CONCLUSIONS: These data indicate that the lower autoregulatory limits of perfusion to the kidneys and splanchnic organs differ from those limits to the brain during normothermic bypass. Selective vasodilation from low-dose dopamine was not found in renal, splanchnic, or cerebral vascular beds. Increasing the perfusion pressure by pump flow, rather than by the addition of low-dose dopamine, enhanced renal and splanchnic but not cerebral blood flows during cardiopulmonary bypass.

Animals↗

PubMed1998

The dependence of hepatic function upon sufficient oxygen supply during prolonged isolated rat liver perfusion.

It is unclear how the omission of a perfusate oxygen carrier may influence data derived from prolonged in vitro liver perfusions. The effects of reduced perfusate oxygen content upon liver function tests conducted in livers from male Sprague-Dawley rats perfused for 6 h, were studied using diluted rat blood (PCV = 10%) (group 1) and compared to lines perfused with Krebs' buffer (group 2). Perfusate and bile samples were withdrawn at the start and at hourly intervals following the commencement of perfusion for biochemical analysis of aspartate-serine transaminase, alkaline phosphatase, bilirubin, urea and potassium concentrations, and also for perfusate gas measurements for calculations of hepatic oxygen uptake. There were no significant differences between the initial perfusion pressures of 11.4+/-1.6 and 15.7+/-2.4 mm Hg at the start of perfusion (group 1 versus group 2, respectively). Maintenance of comparable perfusion pressures at the start of perfusion, however, resulted in a significant difference in the fixed flow rate between the two groups of 1.9+/-0.1 and 2.6+/-0.2* ml/min/g liver and resulted in significantly higher perfusion pressures in group 2 than in group 1 after 6 h of perfusion (18.2+/-2.0 versus 8.7+/-1.7 mmHg, respectively). Bile volume production was significantly greater in group 1 than in group 2, at 784+/-84 vs 458+/-75 microl/h** respectively. Hepatic oxygen uptake (HOU) was significantly greater in group 1 than in group 2, and maximal at 0.93+/-0.13 vs 0.32+/-0.08** micromol/min/g, respectively. Bile concentrations of bilirubin and potassium were significantly greater in group 1 than in group 2, 23.0+/-0.6 vs 4.9+/-0.4 micromol/l*** and 4.7+/-0.5 vs 1.1+/-0.2 mmol/l**, respectively. Perfusate concentrations of urea, bilirubin, and glucose were significantly higher in group 1 than group 2, 5.7+/-0.5 versus 1.4+/-0.2 micromol/l**; 2.4+/-0.5 versus 0.7+/-0.1 micromol/l** and 22.1+/-1.4 versus 17.8+/-0.9 micromol/l***. It is concluded that in vitro perfusion of the rat liver with Krebs'-Henseleit buffer (KHB) via the portal vein alone may be insufficient to maintain optimum liver function as assessed by the tests used. Inclusion of a perfusate oxygen carrier is optimal if livers are to be perfused at physiological pressures. *p < 0.05; **p < 0.01; ***p < 0.001; group 1 versus group 2, Student's unpaired t test.

Alkaline Phosphatase↗

PubMedDate not supplied

Plasma versus whole blood perfusion in a bioartificial liver assist device.

The ramifications of using whole blood or plasma for perfusion off an hepatocyte containing bioartificial liver bioreactor in which the hepatocytes are separated by a membrane or other physical barrier from the perfusate stream on the rate of change of patient blood concentrations are explored through dynamic modeling of whole blood perfusion as a two compartment system (patient tissue and blood compartments), and plasma perfusion as a three compartment system (patient tissue and blood compartments, and a plasma reservoir). The whole blood perfusion model is described by three dimensionless parameters: the Damkohler number, Da, which represents the ratio of the rate of conversion by the bioreactor to the rate of perfusion; kappa, which represents the ratio of the rate of internal reequilibration between the tissue and blood compartments and the rate of perfusion; and Vtb, the tissue/blood volume ratio. The plasma perfusion model has three additional dimensionless parameters: f, the fraction of plasma withdrawn from the blood in a plasma separator; alpha, the ratio of the plasma perfusion rate in the bioreactor to the blood draw rate; and Vbr, the blood/plasma reservoir volume ratio. Within the physiologic range of parameters, the rate of reduction in blood concentration in both the whole blood-perfused and plasma-perfused systems are sensitive to Damkohler number up to Da approximately 2. Neither system is sensitive to variations in kappa, and the plasma perfusion system has little sensitivity to alpha. Given bioreactors of equivalent activity, a greater rate of blood concentration reduction and lower endpoint blood concentration at equivalent perfusion times will be achieved with whole blood perfusion. There are two physical reasons for this. The first is that the plasma perfused system is only processing a fraction, f, of the blood compared with the whole blood perfusion system. The second reason is that, although the blood-perfused system is limited by overall bioreactor performance, the plasma-perfused system is mass transfer limited to the rate of blood concentration dilution into the plasma reservoir rather than limited by the overall bioreactor performance.

Bioreactors↗

PubMedDate not supplied

Hyperthermic regional perfusion using membrane- instead of bubble-oxygenators. An experimental and clinical study.

To achieve adequate tissue perfusion during hyperthermic regional perfusion, perfusion pressures should be maintained at near normal mean systemic arterial pressures. During experimental as well as during clinical perfusions however, unphysiologically high perfusion flows were needed to keep the perfusion pressure at the desired level. Since both high perfusion flows and high perfusion pressures have been associated with the post-operative complications such as severe edema and tissue damage, as well as with an increased leakage of perfusate to the systemic circulation, low perfusion flows have been used in regional perfusion. High perfusion flows in our previous experimental studies were attributable to a marked reduction in vascular resistance. This decrease is believed to be caused by the release of vasodilatory constituents of damaged blood cells, and it is the extra-corporeal circuit, and in particular the bubble-oxygenator that is thought to be responsible. The superior haemocompatibility of membrane-oxygenators over bubble-oxygenators has been established in cardio-pulmonary bypass. We compared the use of a membrane-oxygenator with that of a bubble-oxygenator in regional perfusion to see if more normal haemodynamics could be maintained and vasodilatation prevented. In the experimental as well as in the clinical perfusions the use of a bubble-oxygenator required unphysiologically high perfusion flows to maintain the perfusion pressure at the level required to obtain an adequate microcirculation. In contrast the use of a membrane-oxygenator permitted a nearly physiological perfusion flow to maintain an adequate perfusion pressure as well as an adequate micro-circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Optimal perfusion flow rate for the brain during deep hypothermic cardiopulmonary bypass at 20 degrees C. An experimental study.

The relationship between the perfusion flow rate and cerebral oxygen consumption during deep hypothermic cardiopulmonary bypass at 20 degrees C was investigated in dogs. In 10 dogs the perfusion flow rate was decreased in steps from 100 to 60, 30, and 15 ml/kg/min every 30 minutes. Although cerebral blood flow decreased as perfusion flow rate decreased, the ratio of cerebral blood flow to the perfusion flow rate increased significantly (p less than 0.05) at a perfusion flow rate of 15 ml/kg/min compared to that at a perfusion flow rate of 100 or 60 ml/kg/min. The arterial-sagittal sinus blood oxygen content difference increased as perfusion flow rate decreased. Consequently, cerebral oxygen consumption did not vary significantly at perfusion flow rates of 100 (0.48 +/- 0.10), 60 (0.43 +/- 0.14), and 30 ml/kg/min (0.44 +/- 0.12 ml/100 gm/min), and it decreased significantly to 0.31 +/- 0.22 ml/100 gm/min at a perfusion flow rate of 15 ml/kg/min. In five dogs the perfusion flow rate was decreased in one step from 100 to 15 ml/kg/min, and after 60 minutes' perfusion at a perfusion flow rate of 15 ml/kg/min, the perfusion flow rate was returned to 100 ml/kg/min. Cerebral oxygen consumption decreased significantly during 60 minutes' perfusion at a perfusion flow rate of 15 ml/kg/min and did not return to its initial value after the perfusion flow rate was returned to 100 ml/kg/min. These data indicate that the optimal perfusion flow rate for the brain during deep hypothermic cardiopulmonary bypass at 20 degrees C appears to be 30 ml/kg/min, with a possible oxygen debt in the brain resulting in anaerobic metabolism if the perfusion flow rate is kept at 15 ml/kg/min or less.

Animals↗

PubMed2001

Retrograde cerebral perfusion provides negligible flow through brain capillaries in the pig.

OBJECTIVES: Although retrograde cerebral perfusion is being used clinically during aortic arch surgery, whether retrograde flow perfuses the brain effectively is still uncertain. METHODS: Fourteen pigs were cooled to 20 degrees C with cardiopulmonary bypass and perfused retrogradely via the superior vena cava for 30 minutes: 7 underwent standard retrograde cerebral perfusion and 7 underwent retrograde perfusion with occlusion of the inferior vena cava. Antegrade and retrograde cerebral blood flow were calculated by quantitating fluorescent microspheres trapped in brain tissue after the animals were put to death; microspheres returning to the aortic arch, the inferior vena cava, and the descending aorta were also analyzed during retrograde cerebral perfusion. RESULTS: Antegrade cerebral blood flow was 16 +/- 7.7 mL. min(-1). 100 g(-1) before retrograde cerebral perfusion and 22 +/- 6.3 mL. min(-1). 100 g(-1) before perfusion with caval occlusion (P =.14). During retrograde perfusion, calculations based on the number of microspheres trapped in the brain showed negligible flows (0.02 +/- 0.02 mL. min(-1). 100 g(-1) with retrograde cerebral perfusion and 0.04 +/- 0.02 mL. min(-1). 100 g(-1) with perfusion with caval occlusion; P =.09): only 0.01% and 0.02% of superior vena caval inflow, respectively. Less than 13% of retrograde superior vena caval inflow blood returned to the aortic arch with either technique. During retrograde cerebral perfusion, more than 90% of superior vena caval input was shunted to the inferior vena cava and was then recirculated, as indicated by rapid development of an equilibrium in microspheres between the superior and inferior venae cavae. With retrograde perfusion and inferior vena caval occlusion, less than 12% of inflow returned to the descending aorta and only 0.01% of microspheres. CONCLUSIONS: The paucity of microspheres trapped within the brain indicates that retrograde cerebral perfusion, either alone or combined with inferior vena caval occlusion, does not provide sufficient cerebral capillary perfusion to confer any metabolic benefit. The slightly improved outcome previously reported with retrograde cerebral perfusion during prolonged circulatory arrest in this model may be a consequence of enhanced cooling resulting from perfusion of nonbrain capillaries and from venoarterial and venovenous shunting.

Analysis of Variance↗

PubMed1992

Effect of perfusion pressure on force of contraction in thin papillary muscles and trabeculae from rat heart.

1. Increased coronary perfusion leads to increased myocardial contraction and oxygen consumption (Gregg's phenomenon) even when oxygen supply is presumably sufficient. Previous studies concerned whole hearts, however, in which local hypoxia may play a role. We developed techniques for internal perfusion of thin papillary muscles from rat heart. The influence of perfusion pressure on muscle contraction was studied. We investigated whether Gregg's phenomenon is due to (a) hypoxia, (b) stretch of the muscle fibres, or (c) increased contractility. 2. The effectiveness of the perfusion technique was demonstrated in four ways: (a) the diameter of the capillaries increased with perfusion pressure; (b) 14 +/- 4% (mean +/- S.D., n = 11) increase in muscle diameter was observed on a change of perfusion pressure from 0 to 50 cmH2O; (c) addition of India ink to the perfusate caused rapid staining of the entire muscle; (d) during internal perfusion and external superfusion peak force was mainly determined by the [Ca2+] in the internal perfusate. 3. An increase of perfusion pressure from 0 to 70 cmH2O induced 74 +/- 20% (mean +/- S.D., n = 11) increase in peak force of contraction. In the absence of internal perfusion peak force was not affected by approximately 50% reduction of the PO2 in the bathing solution (from 700 to 350 mmHg). Hence, oxygen supply was not a limiting factor, i.e. the effect of internal perfusion on force was not related to hypoxia. 4. Segment length was measured with markers attached to the surface of the muscle. Perfusion-induced changes in segment length were negligible (-0.2 +/- 1.5%, n = 11). Force-length relationships at different perfusion pressures show that the perfusion-induced increase in force was generally larger than the maximum increase in force that could be induced by stretch. Furthermore, the time course of stretch and perfusion effects on force was different. We conclude that Gregg's phenomenon is not related to changes in fibre length, i.e. the hypothesis of pressure-induced stretch ('garden hose' effect) does not apply to papillary muscles. 5. The pressure-induced changes in the force-length relationship were similar to the changes obtained with interventions that increase contractility, such as increased [Ca2+]. 6. Since hypoxia and length effects were not involved, and the effect of perfusion pressure was similar to that of inotropic interventions, we conclude that Gregg's phenomenon is a change in contractility. Possible explanations include changes in the ionic composition or volume of the interstitium, and inotropic factors produced by the endothelium or intramyocardial neurons.

Animals↗

PubMed1992

Determination of optimal perfusion flow rate for deep hypothermic cardiopulmonary bypass in the adult based on distributions of blood flow and oxygen consumption.

To determine the optimal perfusion flow in deep hypothermic cardiopulmonary bypass at 20 degrees C in human beings, we studied the relationship of perfusion flow to the whole body and to regional oxygen consumption. In adult patients (n = 11, average age 54 years) with valvular or coronary heart disease, the distributions of perfusion flow rate and oxygen consumption were analyzed by dividing into the superior and inferior vena caval areas. Measurements (n = 39) were made at various perfusion flow rates (perfusion flow rate in the superior vena caval area plus that in the inferior vena caval area equals whole-body perfusion flow rate: 0.4 to 2.2 L/min/m2) in a setting of average hemoglobin levels of 8.1 gm/dl. Between whole-body perfusion flow rate and oxygen consumption (total oxygen consumption equals superior plus inferior vena caval oxygen consumption), there was a hyperbolic correlation (r = 0.73; p less than 0.001; asymptote = 29.0 ml/min/m2). A positive linear correlation was found between whole-body perfusion flow rate and inferior vena caval oxygen consumption (r = 0.75; p less than 0.001), whereas no significant relation was seen between whole-body perfusion flow rate and superior vena caval oxygen consumption. For distributional changes in inferior vena caval perfusion flow rate/whole body perfusion flow rate and inferior vena caval oxygen consumption/whole body oxygen consumption, the broken-line regression analysis showed respective critical points where both parameters started to drop when whole-body perfusion flow rate was gradually reduced: 1.2 L/min/m2 for inferior vena caval perfusion flow rate/whole-body perfusion flow rate and 0.8 L/min/m2 for inferior vena caval oxygen consumption/whole-body oxygen consumption. The results indicate that (1) the oxygen consumption to the superior vena caval area was maintained independent of the perfusion in a relatively wide range in contrast to that for the inferior vena caval area and (2) when the redistribution of oxygen consumption is considered as undesirable under low-flow perfusion, the optimal perfusion flow for 20 degrees C deep hypothermic cardiopulmonary bypass appeared to be 0.8 L/min/m2.

Adult↗

PubMed1997

Recovery of Schistosoma japonicum from experimentally infected pigs by perfusion of liver and mesenteric veins.

An optimized procedure for perfusion of pigs infected with Schistosoma japonicum was developed. The technique involves insertion of a perfusion influx tube into the thoracic descending aorta, clamping vessels to parts of the body which did not need to be perfused (the kidneys, hind legs, etc.) and placing a collection tube directly into the portal vein. In addition, the clamping technique allows for separate perfusion of the liver and intestinal veins. The perfusion medium was a sodium citrate buffer (40 degrees C) to which the vasodilator sodium nitroprusside was added. Furthermore, an experiment was conducted to investigate if the perfusion efficiency, measured by total worm recovery, could be increased if praziquantel was administered prior to perfusion. Twelve pigs were each infected with 1000 S. japonicum cercariae and their schistosomes were collected 11 weeks later by separate perfusion of the liver and intestinal veins. Six of these pigs were treated orally with praziquantel one hour before perfusion. In general, the vessels of the livers and intestines of all pigs were well perfused, judging by the resulting pale colour of the tissues. Worms from praziquantel treated pigs were collected within 5 min of perfusion as opposed to approximately 20 min in the non-treated pigs. More worms were collected from the livers of the praziquantel treated pigs, indicating a hepatic shift of schistosomes from the intestinal mesenteries. However, comparable numbers of worms were retained in the mesenteric veins following perfusion in the 2 groups, indicating that manual recovery of schistosomes from the intestinal mesenteries is necessary in addition to perfusion for obtaining the total worm counts. Another experiment was conducted to determine if the intensity and/or duration of infection had an effect on the number of worms collected by the perfusion technique. Seventy-two pigs were allocated into 3 groups of 24 pigs each, which were infected with either 100, 500 or 2000 cercariae per pig. The 3 groups were further divided into 4 subgroups of 6 pigs each which were perfused with our selective technique at 4, 11, 17 or 24 weeks post infection, respectively. All of the pigs received an oral praziquantel treatment prior to perfusion. The results indicated that increasing intensities and/or duration of infection resulted in trapping of schistosomes in intravascular inflammatory reactions which made it more difficult to collect the adult schistosomes by perfusion.

Animals↗

PubMed1996

Nipple-areolar perfusion and reduction mammaplasty: correlation of laser Doppler readings with surgical complications.

Clinical assessment of nipple-areolar perfusion by color, capillary refill, and temperature during and after reduction mammaplasty is generally satisfactory. However, the estimation of vascular perfusion in patients with very large breasts or dark-skinned women is difficult. If marginal perfusion of the nipple-areolar areas is undetected, necrosis is likely. To this point, no studies have tested the ability of the laser Doppler perfusion monitor to give absolute alarm values that would suggest marginal perfusion in the nipple-areola following reduction mammaplasty. We therefore completed a prospective study of areolar perfusion during surgery and for up to 24 hours following reduction mammaplasty. Fifty-four patients were studied and data collected from 104 breasts. Laser Doppler perfusion was measured with a LASERFLO BPM2 Blood Perfusion Monitor (Vasamedics, St. Paul, Minn.). Perfusion values were recorded for each breast following anesthesia but prior to the incisions, at the end of surgery, and every 2 hours for 24 hours. Patients were divided into three groups according to their follow-up results: no complications (92 breasts), minor complications (9 breasts), and patients with tissue necrosis (3 breasts). The no complications group had a perfusion of 4.8 ml/min/100 gm following the reduction procedure, while the minor complications and tissue necrosis groups had average perfusions of 1.4 and 0.8, respectively, immediately after incision closure. The average tissue removed from each group was 811, 1171, and 2118 gm for the no complications, minor complications, and tissue necrosis groups, respectively. The results from this study suggest that a laser Doppler perfusion monitor could prove useful for monitoring areolar perfusion following reduction mammaplasty, especially in patients with extremely large breasts and/or dark skin. Our studies have shown that laser Doppler perfusion values that consistently are in the range of 1.0 to 2.0 ml/min/100 gm indicate marginal perfusion, and the recovery of these patients should be followed closely. Furthermore, patients with consistent perfusion values equal to or less than 1.0 coupled with other clinical signs of low perfusion should be considered for suture removal and/or free nipple graft.

Adult↗

PubMed2005

Regional distribution and extent of perfusion abnormalities, and the lung to heart uptake ratios during exercise thallium-201 SPECT imaging in patients with cardiac syndrome X.

BACKGROUND: Cardiac syndrome X is defined as angina-like chest pain with transient ischemic ST-segment changes during exercise and angiographically normal epicardial coronary arteries. Studies with myocardial perfusion imaging in this syndrome have indicated that some patients, but not all, have an abnormality on perfusion scan. However, the impact of these perfusion abnormalities on pulmonary thallium uptake is not clear in this group of patients. OBJECTIVE: To evaluate the regional distribution and extent of perfusion abnormalities, and the lung to heart (L:H) uptake ratios using exercise thallium-201 single-photon emission computed tomography (TI-201 SPECT) in patients with cardiac syndrome X. METHODS: The study group consisted of 31 selected cardiac syndrome X patients with regional perfusion abnormalities during exercise TI-201 SPECT imaging. A control group included 26 healthy subjects with normal coronary angiograms, exercise testing and exercise TI-201 SPECT imaging. Exercise TI-201 SPECT results were analyzed with further estimation of the L:H ratios, number and localization of regional perfusion defects, and their mean extent scores expressed in pixels and in per cent of the left ventricular wall. Twenty-two patients with known coronary artery disease were also included in the analysis of the L:H ratios. RESULTS: Multiple perfusion defects were detected in 13 (42%) patients and perfusion defects of single localization were detected 18 (58%) patients. All patients had reversible perfusion abnormalities: 21 (67.7%) had anterior, 14 (45.2%) had inferior and 12 (38.7%) had lateral localization of perfusion defects. The analysis of the extent of the perfusion defects revealed that the mean scores of the extent of the single regional defects were 38.61+/-43.8 pixels and those of multiregional defects were 106.1+/-55.2 pixels, which corresponded to 6.05+/-1.8% and 16.6+/-5.4% of the left ventricular wall defects, respectively. Patients with cardiac syndrome X had a significantly higher L:H ratio during exercise than the healthy subjects (0.46+/-0.02 versus 0.34+/-0.03, P<0.01). In addition, L:H ratios were found to be higher in patients with multiple perfusion defects (0.50+/-0.02) than in patients who had only anterior (0.45+/-0.08) or inferior (0.43+/-0.02) perfusion defects (P<0.05 for both). There were no statistically significant differences in the rest L:H ratios between the study and control groups. Also, no significant differences were observed in exercise L:H ratios between the cardiac syndrome X patients and the patients with coronary artery disease (0.46+/-0.02 versus 0.49+/-0.03, P>0.05). CONCLUSIONS: The results suggest that multiple perfusion defects in multiple vascular regions are relatively common in cardiac syndrome X patients, with the majority of these patients having at least one abnormal perfusion bed. Patients with this syndrome who have perfusion abnormalities also had significantly higher L:H ratios during exercise than did the control patients. Increased exercise L:H ratios were more prominent in patients with multiple perfusion defects.

Adult↗

PubMed1999

Pharmacokinetic differences between rat tumour and lung tissues following isolated lung perfusion with cisplatin.

Isolated lung perfusion has been performed for the treatment of unresectable lung tumours; however, the pharmacokinetics of this procedure remain unclear. This study was conducted to investigate the changes in antitumour drug concentrations in tumour and lung tissues after isolated lung perfusion, using different perfusion times and perfusate drug concentrations. Isolated left lungs were perfused for 20, 40 or 60 min with 25, 50 or 100 micrograms/ml of cisplatin after solitary lung tumour nodules were established in rats, and the total platinum concentrations in the perfused lung and tumour tissues were determined by flameless atomic absorption spectroscopy. The oedema in the perfused lung tissues was evaluated by histological examination and by the wet to dry weight ratios of the lungs. The total platinum concentration increased significantly with perfusion time and increasing perfusate cisplatin concentrations in the lung tissue, but it did not change in the tumour tissue. The wet to dry weight ratios of the lung tissues did not differ significantly among the perfusion groups. Oedema of the perfused lung tissue did not change significantly with the perfusion time or perfusate cisplatin concentration. The results of this study indicate the possibility that different pharmacokinetics exist between tumour and lung tissues following isolated lung perfusion with cisplatin, which could be used as a clinical guide for the selection of appropriate perfusion times and perfusate drug concentrations.

Animals↗

PubMed1989

Metabolism of cysteinyl leukotrienes in non-recirculating rat liver perfusion. Hepatocyte heterogeneity in uptake and biliary excretion.

1. The uptake, metabolism and biliary excretion of the cysteinyl leukotrienes LTC4, LTD4 and LTE4, were studied in a non-recirculating rat liver perfusion system at constant flow in both antegrade (from the portal to the caval vein) and retrograde (from the caval to the portal vein) perfusion directions. During a 5-min infusion of [3H]LTC4, [3H]LTD4 and [3H]LTE4 (10 nmol/l each) in antegrade perfusions single-pass extractions of radioactivity from the perfusate were 66%, 81% and 83%, respectively. Corresponding values for LTC4 and LTD4 in retrograde perfusions were 83% and 93%, respectively, indicating a more efficient uptake of cysteinyl leukotrienes in retrograde than in antegrade perfusions. The concentrations of unmetabolized leukotrienes in the effluent perfusate were 8-12% in antegrade and 2-4% in retrograde perfusions. [14C]Taurocholate extraction from the perfusate was inhibited by LTC4 by only 3%, suggesting that an opening of portal-venous/hepatic-venous shunts does not explain the effects of perfusion direction on hepatic LTC4 uptake. 2. Following infusion of [3H]LTC4 and [3H]LTD4, in the antegrade perfusion direction, about 80% and 87%, respectively, of the radiolabel taken up by the liver was excreted into bile. In retrograde perfusions, however, only 40% and 57%, respectively, was excreted into bile and the remainder was slowly redistributed into the perfusate, indicating that leukotrienes were taken up into a hepatic compartment with less effective biliary elimination or converted to metabolites escaping biliary excretion. The metabolite pattern found in bile was not affected by the direction of perfusion. Biliary products of LTC4 were polar metabolites (31-38%), LTD4 (27-30%), LTE4 (about 1%) and N-acetyl-LTE4 (3-4%) in addition to unmodified LTC4 (17-18%). 3. LTC4 was identified as a major metabolite of [3H]LTD4 in bile, amounting to about 20% of the total radioactivity excreted into bile. This is probably due to a gamma-glutamyltransferase-catalyzed glutamyl transfer from glutathione in the biliary compartment, as demonstrated in in vitro experiments. The presence of sinusoidal gamma-glutamyltransferase activity in perfused rat liver was shown in experiments on the hydrolysis of infused gamma-glutamyl-p-nitroanilide. 90% inhibition of this enzyme activity by AT-125 did not affect the metabolism of LTC4. 4. When [3H]LTE4 was infused in the antegrade perfusion direction, biliary metabolites comprised N-acetyl-LTE4 (24%) and polar components (60%).(ABSTRACT TRUNCATED AT 400 WORDS)

Aniline Compounds↗

PubMed1985

Thyrotropin-releasing hormone metabolism and extraction by the perfused guinea pig placenta.

This report describes the extraction of synthetic TRH and its metabolic conversion in the perfused guinea pig placenta. These studies were performed to obtain an estimate of fractional fetal TRH losses through the placenta and to determine if some of these losses are due to TRH metabolism. The in situ guinea pig placenta was perfused through an umbilical artery for 90 min, and placental effluent fractions were collected at timed intervals from the umbilical vein. Experiments were performed in which the perfusion buffer contained 0.01, 1, and 10 micrograms/ml or no synthetic TRH. Synthetic TRH was always perfused in the presence of 3H2O. In experiments in which TRH was perfused, the perfusion reservoir contents and placental effluent fractions were counted for 3H, and TRH and deamido-TRH were determined by RIA. Similarly, cyclo(His-Pro) was measured when 10 micrograms/ml TRH were perfused. When no TRH was perfused, the perfusion reservoir and placental effluent contents were processed to determine their content of TRH immunoreactivity. When synthetic TRH was perfused, steady state TRH concentrations were achieved in placental effluent fractions by 20-30 min. The single pass extraction of TRH by the placenta was 11.4 +/- 2.6% (mean +/- SE) compared to 56.9 +/- 7.0% for 3H2O (P less than 0.001). No significant difference was detected regardless of whether 10, 1, or 0.01 micrograms/ml TRH were perfused. A portion of the TRH that perfused the placenta was converted to deamido-TRH at all concentrations of perfused TRH. No conversion of TRH to cyclo(His-Pro) was noted when the highest concentration (10 micrograms/ml) of TRH was perfused. The conversion of TRH to TRH-OH was 4.2 +/- 0.7% in a single pass. When the perfusion buffer was devoid of synthetic TRH, a small but significant increase in the content of TRH immunoreactivity was noted in the placental effluent compared to that in the perfusion reservoir. This was not large enough to affect calculations of the placental extraction of TRH. These studies, in addition to demonstrating that the placenta contains TRH deamidase activity, suggest that losses of fetal TRH through the placenta are not large. They do not support the current impression, based on the fetal TSH response to maternal TSH administration, that the placenta is freely permeable to TRH.

Animals↗

PubMed2002

Assessment of coronary artery disease with second harmonic myocardial perfusion contrast echocardiography.

OBJECTIVE: To assess the relationship between myocardial regional perfusion using second harmonic myocardial contrast echocardiography (MCE) by venous injection of Levovist and coronary artery stenosis detected by coronary angiography to determine whe ther MCE can be used to detect coronary artery disease (CAD) and its sensitivity and specificity for detecting CAD. METHODS: Thirty-six patients who underwent coronary artery angiography and MCE formed the study groups. Ten myocardial segments (5 each in the apical two- and four-chamber views) from the images were scored for detecting myocardial perfusion as follows: 1, normal perfusion; 2, decreased perfusion; and 3, perfusion defect. The arteries were classified as normal or diseased. The diseased arteries were classified into three groups according to the perfusion scores. RESULTS: There were significant differences in coronary diameter stenosis among the different perfusion score groups (P < 0.001). There were 10 total occluded arteries, and the myocardial perfusion scores were different because of different collateral circulation. In the normal perfusion group (Group A), the coronary diameter stenosis was 65% +/- 12%, and the myocardial perfusion score index was 1 +/- 0.00. In the decreased perfusion group (Group B), the average coronary diameter stenosis was 82% +/- 8%, and the myocardial perfusion score was 1.93 +/- 0.16. The diameter stenosis was less than 85% in 63% of the coronary arteries (including diameter stenosis < or = 75% in 12% of the vessels). The diameter stenosis was 85%-90% in 22% of the coronary arteries and > 90% in 15% of the arteries. In the perfusion defect group (Group C), the average diameter stenosis was 90% +/- 6%, and the myocardial perfusion score index was 2.89 +/- 0.24. The diameter stenosis was > or = 85% in 94% of the coronary arteries, and the diameter stenosis was < 85% and > 75% only in 6% of the coronary arteries. The overall sensitivity and specificity of MCE in identifying angiographic coronary diameter stenosis was 67% and 100%, respectively. The false negative rate was 32.6% for the 108 coronary arteries. Further subdivided analysis showed the sensitivities in Groups A, B and C were 0, 100%, and 100%, respectively. The sensitivity increased with increased lumen diameter stenosis of coronary arteries. CONCLUSIONS: There is a close relationship between coronary artery stenosis and MCE perfusion scores. MCE with venous injection of new generation contrast can define the presence of CAD and lesion graded classifications. Some disagreements between perfusion score and coronary diameter of stenosis may indicate other factors such as different collateral circulation, which should be further investigated. As artery stenosis increases, the sensitivity of MCE is increased.

Adult↗

PubMed2000

Usefulness of triphasic perfusion computed tomography for intravenous thrombolysis with tissue-type plasminogen activator in acute ischemic stroke.

BACKGROUND: Intravenous thrombolysis for acute ischemic stroke has been investigated in several clinical trials without enough information on collateral blood flow and perfusion deficit in the ischemic areas. The therapeutic time window varies from patient to patient depending on these factors. Triphasic perfusion computed tomography (TPCT) can provide this information as reliably as conventional angiography. OBJECTIVE: To assess the safety and efficacy of thrombolysis within 3 or 7 hours of stroke onset according to the extent of perfusion deficit on TPCT. METHODS: In 46 patients with acute middle cerebral artery (MCA) territory stroke, TPCT was performed with power injector-controlled, intravenous administration of contrast media after taking precontrast CT scans. Sequential scans of early, middle, and late phases were performed. The entire procedure took 5 minutes. Depending on collateral blood flow, the perfusion deficit on TPCT was graded as "severe perfusion deficit" or "moderate perfusion deficit." Twenty-nine patients were excluded based on clinical, laboratory, and TPCT findings. Seventeen patients were treated with an intravenous recombinant tissue-type plasminogen activator, 0.9 mg/kg. The 17 treated patients were divided into 2 groups: group 1 with small severe perfusion deficit (</=33% of the presumed MCA territory) and group 2 with medium-sized severe perfusion deficit (>33% but </=50% of the presumed MCA territory). The 13 patients in group 1 were treated within 7 hours of onset and the 4 patients in group 2 were treated within 3 hours. RESULTS: Initial mean National Institutes of Health Stroke Scale score was 12.1 (range, 6.0-20.0) in group 1 and 19.0 (range, 18.0-21. 0) in group 2. The initial score correlated better with the total extent of moderate perfusion deficit and severe perfusion deficit than that of severe perfusion deficit alone. Mean time lapse to thrombolysis was 4.2 hours (range, 1.5-7.0 hours) in group 1 and 2.2 hours (range, 1.9-2.5 hours) in group 2. Eight patients (47%), 7 from group 1 and 1 from group 2, improved by 4 points or more from baseline Stroke Scale score within 24 hours of thrombolysis. Patients with moderate perfusion deficit of 50% or more of MCA territory (n = 4) had a better chance of early improvement than did those (n = 13) with moderate perfusion deficit of less than 50% (4 of 4 vs 4 of 13). No fatal hemorrhage occurred. Only 1 patient (6%) had symptomatic small basal ganglia hemorrhage after thrombolysis. CONCLUSIONS: Thrombolysis can be safely performed within 3 or 7 hours of stroke onset according to the extent of severe perfusion deficit on TPCT. A larger extent of moderate perfusion deficit on TPCT may predict early improvement after thrombolysis.

Adult↗

PubMed1993

Magnetic resonance imaging of perfusion in the isolated rat heart using spin inversion of arterial water.

Measurement of regional myocardial perfusion is important for the diagnosis and treatment of coronary artery disease. Currently used methods for the measurement of myocardial tissue perfusion are either invasive or not quantitative. Here, we demonstrate a technique for the measurement of myocardial perfusion using magnetic resonance imaging (MRI) with spin tagging of arterial water. In addition, it is shown that changes in perfusion can be quantitated by measuring changes in tissue T1. Perfusion images are obtained in Langendorff-perfused, isolated rat hearts for perfusion rates ranging from 5 to 22 ml/g/min. The MRI-determined perfusion rates are in excellent agreement with perfusion rates determined from measurement of bulk perfusate flow (r = 0.98). The predicted linear dependence of the measured T1 (T1app) on perfusion is also demonstrated. The ability of perfusion imaging to measure regional variations in flow is demonstrated with hearts in which perfusion defects were created by ligation of a coronary artery. These results indicate that MRI of perfusion using spin inversion of arterial water gives quantitative maps of cardiac perfusion.

Animals↗

PubMed2005

Optimal temperature for selective cerebral perfusion.

OBJECTIVE: Although combinations of hypothermic circulatory arrest and antegrade selective cerebral perfusion are used for cerebral protection during arch surgery, there is no consensus regarding the optimal temperature during selective cerebral perfusion. This study explored the effect of different temperatures during selective cerebral perfusion on cerebral metabolism and neurologic outcome. METHODS: In this blinded study, 40 pigs (19-21 kg) were randomized into 4 groups after 30 minutes of hypothermic circulatory arrest at 20 degrees C. During a 60-minute interval of selective cerebral perfusion, with flow regulated to maintain a perfusion pressure of 50 mm Hg, pigs were perfused at 10 degrees C, 15 degrees C, 20 degrees C, and 25 degrees C. Fluorescent microspheres enabled calculation of cerebral blood flow during perfusion and recovery. Hemodynamics, intracranial pressure, cerebrovascular resistance, and oxygen consumption were also monitored. Behavioral scores were obtained for 7 days after surgery. RESULTS: Cerebral blood flow decreased significantly ( P < .002) during cooling in all groups: it was significantly higher throughout selective cerebral perfusion in the 20 degrees C to 25 degrees C versus the 10 degrees C to 15 degrees C group ( P = .0001) and remained higher during recovery ( P = .0001). Oxygen consumption decreased significantly with cooling ( P = .0001), remained low during perfusion, and rebounded with rewarming but was significantly lower at 10 degrees C to 15 degrees C than at 20 degrees C to 25 degrees C throughout selective cerebral perfusion ( P = .003) and after CPB was discontinued ( P = .001). Postoperative behavioral scores were significantly better after selective cerebral perfusion at 10 degrees C to 15 degrees C than at 20 degrees C to 25 degrees C ( P = .001). CONCLUSIONS: This study suggests that selective cerebral perfusion at 10 degrees C to 15 degrees C provides better cerebral protection than selective cerebral perfusion at 20 degrees C to 25 degrees C, even though oxygen consumption remains low for hours after selective cerebral perfusion at 10 degrees C to 15 degrees C. Prompt return of metabolism to baseline levels after hypothermic circulatory arrest/selective cerebral perfusion does not necessarily predict superior behavioral outcome.

Animals↗