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[Technique and pathophysiology of isolated hypoxic perfusion of the abdomen].

Isolated hypoxic perfusion (IHP) is a commonly used technique in the treatment of abdominal malignancies. During a phase II-study the pathophysiology of this technique was explored in patients with advanced pancreatic cancer. Twenty perfusions of the abdomen were performed in 17 patients. Under general anesthesia, femoral vessels were dissected and two balloon catheters were inserted into aorta and vena cava cranial the celiac trunk and the hepatic veins. After instillation of 40 mg of Mitomycin C (MMC) into the running perfusion system, the perfusion was maintained for further 20 minutes. Blood samples were taken in 5-minute intervals to determine pH value, blood gases as well as concentrations of electrolytes, lactate and MMC in the arterial blood. Simultaneously, blood samples were taken from the perfusion blood via a side-port of the extracorporeal perfusion system. Additionally, perfusion pressures, arterial and central venous pressure, heart rate, and the pressure in the aorta distal the balloon catheter were registered continuously. All 20 perfusions had been undertaken without perioperative mortality. After inflating the balloon catheters, blood pressure and heart rate increased rapidly. Within 5 minutes of perfusion an increase in pCO2 and the concentrations of K+ and lactate in the perfusate were registered, while pH and pO2 decreased. Fifteen minutes after instillation of MMC, concentrations of MMC in arterial and perfusion blood were equal. Twenty-four hours after the perfusion all parameters had returned to normal values. IHP was well feasible in 20 consecutive perfusions without major technical problems. A distinct but tolerable combined acidosis resulted from IHP. Despite the exact positioning and control of the balloon catheters a complete isolation was not possible.

Acid-Base Equilibrium↗

[Utility of SPECT lung perfusion scans in assessing early changes in pulmonary function of patients with lung cancer after radiotherapy].

BACKGROUND & OBJECTIVE: Radiation-induced lung injury is commonly following radiotherapy (RT)for tumors in,and around the thorax. Lung function is usually assessed by pulmonary function tests (PFTs), but RT-induced regional changes of pulmonary function cannot be accurately evaluated by PFTs. Lung perfusion scintigraphy compared with other radiographic methods can well assess the regional pulmonary physiological function,and 3-dimension conformal radiotherapy (3D-CRT) planning system can quantitatively calculate irradiation dosage. This study was to assess early changes in the pulmonary function of patients with lung cancer receiving thoracic 3D-CRT by lung perfusion scintigraphy. METHODS: Nineteen patients receiving thoracic 3D-CRT for lung cancer were studied. Single photon emission computed tomography (SPECT) lung perfusion scan,and X-ray or CT scan before RT, and after 40-50 Gy radiation were performed. Pre-RT SPECT lung perfusion images were classified by comparing lung perfusion defect with area of radiological abnormality before RT. Grade 0: no lung perfusion defect in the area of radiological abnormality. Grade 1: the size of radiological abnormality is similar to the area of lung perfusion defect. Grade 2: the area of lung perfusion defect is bigger than that of radiological abnormality,and extend to 1 pulmonary lobe. Grade 3: the area of lung perfusion defect exceed 1 pulmonary lobe. The radiation field with more than 20 Gy was drawn as a region of interest (ROI). The proportion of radioactive count within this ROI to total lung count in one slice was calculated to assess changes in pulmonary function after RT. Student's t test was used for statistical analyses. RESULTS: All patients had lung perfusion defect, 9 patients with grade 1 damage, 5 patients with grade 2 damage, and 5 patients with grade 3 damage. All tumors in the 19 patients were reduced with variant degree after 40-50 Gy radiation in CT or X-ray images. The mean radioactive proportions of ROI in 19 patients were (53.7+/-29.8)% before radiation,and (57.6+/-22.6)% during RT, the difference wasn't significant (P=0.280). The relatively decreased post-RT lung perfusion was observed in 6 patients, whereas the relatively increased post-RT lung perfusion was observed in 13 patients. CONCLUSION: SPECT lung perfusion scans is a simple, convenient, and useful method for assessing pre-RT regional lung function,and monitoring the changes in regional lung function after irradiation.

Adult↗

Risk stratification of patients with angina pectoris by stress 99mTc-tetrofosmin myocardial perfusion imaging.

UNLABELLED: Angina pectoris is a major symptom associated with myocardial ischemia. The aim of this study was to find whether stress myocardial perfusion imaging can independently predict mortality in patients with angina. METHODS: We studied 455 patients with stable angina pectoris by exercise or dobutamine stress (99m)Tc-tetrofosmin myocardial perfusion tomographic imaging. An abnormal finding was defined as a reversible or fixed perfusion abnormality. The endpoint during follow-up was death from any cause. RESULTS: Mean age was 60+/-10 y. There were 266 men (58% of the patients). Myocardial perfusion was normal in 137 patients (30%). Perfusion abnormalities were reversible in 167 patients and fixed in 151 patients. During a mean follow-up of 6+/-1.7 y, 93 patients (20%) died. The annual mortality rate was 1.5% in patients with normal perfusion and 4.5% in patients with abnormal perfusion. Patients with a multivessel distribution of perfusion abnormalities had a higher annual death rate than patients with abnormalities in a single-vessel distribution (5.1% vs. 3.7%). In a multivariate analysis model, independent predictors of death were age (risk ratio, 1.05; 95% confidence interval [CI], 1.03-1.08), the male sex (risk ratio, 2.1; CI, 1.3-3.4), diabetes (risk ratio, 2.2; CI, 1.4-3.5), heart failure (risk ratio, 2.7; CI, 1.6-4.5), smoking (risk ratio, 1.7; CI, 1.1-2.6), reversible perfusion abnormalities (risk ratio, 1.9; CI, 1.1-2.8), and fixed perfusion abnormalities (risk ratio, 2; CI, 1.2-3.1). CONCLUSION: Stress 99mTc-tetrofosmin myocardial perfusion imaging provides independent information for predicting mortality in patients with stable angina pectoris. Both reversible and fixed defects are associated with an increased risk of death. The extent of stress perfusion abnormalities is a major determinant of mortality. Patients with normal perfusion have a low mortality rate during long-term follow-up.

Adult↗

Effect of 3-methylcholanthrene pretreatment on glucuronidation and sulfation in perfused rat liver.

The metabolism of p-nitro[14C]phenol (PNP) was studied in perfused rat liver. Metabolites were identified in perfusate and bile. The perfusion system containing 0.5 mM PNP, at the start, converted the phenol within 2 hr to p-nitrophenyl glucuronide (PNPGA), 31.4% in perfusate and 21% in bile; p-nitrophenyl sulfate (PNPS), 22% in perfusate; and p-nitrophenyl glucoside (PNPG), between 2 and 4% perfusate. Biliary excretion of PNPS and PNPG accounted for less than 2% of PNP. An apparent maximal rate of PNPGA synthesis by the perfused liver, estimated from the rates of appearance of PNPGA in perfusate and bile, corresponded well to the glucuronyl-transferase activities determined in "native" liver homogenates. Sulfation of PNP in the perfused liver exhibited two apparent maximal rates of synthesis, as determined from the rates of appearance of metabolite in the perfusate. A slower rate (R1) occurred when PNP concentration was between 0.13 and 0.5 mM, and a faster rate (R2) when PNP was approximately between 0.025 and 0.13 mM in the perfusate. Possible significance of these findings is discussed. Pretreatment of rats with 3-methylcholanthrene (3MC) increased the apparent maximal rate of PNPGA production by the perfused liver by a factor of 1.7, and biliary excretion of PNPGA by a factor of 1.5. The latter increase was attributed to the increased rate of synthesis of the glucuronide rather than to an increase in the biliary transport maximum, since the 3MC treatment produced no significant effect on the biliary excretion of performed PNPGA added to the perfusate. The 3MC pretreatment increased 1.5-fold the rate of sulfation of PNP, as judged by the increase in R2.

Animals↗

[The experimental study on long-term cardiac preservation: the efficacy of low-flow continuous perfusion with fluorocarbon].

We compared the effect of simple immersion and continuous perfusion on long-term cardiac preservation, and evaluated the effectiveness of perfusion with oxygenated fluorocarbon solution. The isolated rabbit hearts were preserved for 24 hours at 4 degrees C using the following five preservation techniques: (1) simple immersion with Collins M solution (Group I), (2) perfusion with oxygenated Collins M solution at a flow rate of 10 ml/hr (Group II), (3) perfusion with the same solution as in Group II at a flow rate of 20 ml/hr (Group III), (4) perfusion with oxygenated Collins M solution containing 10% fluorocarbon at a flow rate of 10 ml/hr (Group IV), (5) perfusion with the same solution as in Group IV at a flow rate of 20 ml/hr (Group V). The hearts of Group I showed a significant decrease of myocardial ATP and an increase of myocardial lactate during preservation compared to the hearts of perfusion groups. Assessment of isovolumic left ventricular function following 24-hour preservation using a support animal showed a significant decrease of Max dp/dt and increase of end-diastolic pressure in the hearts of Group I. Perfusion with fluorocarbon (Group IV and V) significantly increased oxygen consumption compared to Group II and III in association with minimum accumulation of myocardial lactate, indicating that aerobic metabolism during preservation is better maintained in the fluorocarbon-perfused hearts. Moreover, CPK release and myocardial water gain during preservation were significantly less, and left ventricular function following preservation was significantly better in these hearts. Increasing the flow rate from 10 ml/hr to 20 ml/hr resulted in sustained increase in perfusion pressure (1.80 +/- 0.53 to 3.70 +/- 0.34 mmHg) and myocardial water content (79.2 +/- 0.4 to 87.2 +/- 0.3%) during preservation in the hearts of Group III, but it did not further improve left ventricular function despite significant enhancement of myocardial oxygen uptake in both Group III and V. These results suggest that hypothermic low-flow continuous perfusion with oxygenated Collins M solution is superior to simple immersion with the same solution for long-term cardiac preservation, and that the addition of fluorocarbon to the perfusate enhances the efficacy of such a perfusion.

Animals↗

The carbon dioxide anion radical adduct in the perfused rat liver: relationship to halocarbon-induced toxicity.

CCl4 has been shown previously to be metabolized to the trichloromethyl radical (.CCl3) and to a novel oxygen-containing carbon dioxide anion radical (.CO2-) in the perfused rat liver and in vivo. Since the role of free radicals in CCl4-induced hepatotoxicity is unclear, these studies were designed to determine if a relationship between .CO2- formation and halocarbon-induced hepatotoxicity exists. CCl4 or bromotrichloromethane (CBrCl3) was infused into livers from control or phenobarbital-treated rats perfused with either nitrogen- or oxygen-saturated Krebs-Henseleit bicarbonate buffer. Samples of effluent perfusate and chloroform/methanol extracts of liver were analyzed by ESR spectroscopy for free radical adducts following infusion of halocarbon and the spin trap, phenyl-t-butylnitrone (PBN). Hyperfine coupling constants and 13C-isotope effects observed in the ESR spectra of organic extracts of liver demonstrated the presence of the PBN radical adduct of .CCl3 from both halocarbons. Radical adducts in aqueous extracts of liver and effluent perfusate had hyperfine coupling constants and 13C-isotope effects identical to those of PBN/.CO2- generated chemically from formate. The PBN/.CO2- radical adduct was also observed in urine following the intragastric administration of CBrCl3 and PBN. Detection of PBN/.CO2- adducts in the effluent perfusate was decreased 3- to 4-fold by DIDS (0.2 mM), an inhibitor of the plasma membrane anion transport system. The rate of formation of PBN/.CO2- was decreased 2- to 3-fold following inhibition of cytochrome P-450-dependent monooxygenases by metyrapone (0.5 mM) and was increased about 2-fold by induction of cytochrome P-450 by phenobarbital pretreatment. Toxicity of halocarbons in the perfused liver was assessed by measuring the release of lactate dehydrogenase (LDH) into the effluent perfusate in livers from phenobarbital-treated rats under conditions identical to those employed to detect radical adducts (i.e., during the infusion of CCl4 or CBrCl3 into livers perfused with either nitrogen- or oxygen-saturated perfusate). Under all conditions studied, PBN/.CO2- was detected in the effluent perfusate within 2-4 min. Metabolism of halocarbons to PBN/.CO2- was 6- to 8-fold faster during perfusion with nitrogen-saturated rather than with oxygen-saturated perfusate. Concomitantly, liver damage detected from LDH release occurred much sooner during halocarbon infusion in the presence of nitrogen-saturated rather than oxygen-saturated perfusate. A good correlation between the rate of formation of PBN/.CO2- and the time of onset of LDH release following halocarbon infusion was observed.(ABSTRACT TRUNCATED AT 400 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Reduced cholestatic potency of taurolithocholate during backward perfusion of the rat liver.

Rat livers perfused backward are less susceptible to taurolithocholate (TLC) cholestasis than livers perfused forward. To understand this phenomenon, the uptake, metabolism, and excretion of TLC were studied in rat livers perfused forward and backward with TLC. Bolus injections of [3H]TLC were administered 20 minutes after the onset of unlabeled TLC infusion. Biliary bile acids were measured enzymatically and bile acid species were separated and quantified by thin-layer chromatography. Determination of radioactivity in each spot yielded the percentage distribution of various biliary bile acid metabolites. After perfusion, livers were examined by light and transmission electron microscopy. TLC infusion at 32 nmoles/minute/gm of liver reduced bile flow by 80% or more within 30 minutes of forward perfusion but not at all during backward perfusion. TLC uptake was over 95% regardless of perfusion direction. Although the distribution of biliary metabolites of TLC was the same during forward and backward perfusion, maximal rate of total biliary bile acid excretion was four-fold higher and total recovery of radioactivity in bile was six-fold higher during backward perfusion. Less than 6% of excreted radioactivity was in the form of unmetabolized TLC. Severe cholestasis induced by forward TLC perfusion was associated with extensive structural distortion of bile canalicular membranes almost exclusively in the periportal zone but with little hepatocellular necrosis. Livers perfused backward manifested no cholestasis. They showed cell necrosis in the pericentral zone which became extensive (10%) by 60 minutes, but the canalicular changes occurred only in a small proportion of canaliculi in the pericentral region. Bile canalicular membrane changes developed extensively only when very high doses of TLC were perfused backward. Even then, bile flow fell only 60%. We conclude: the lesser susceptibility to TLC cholestasis of livers perfused backward is in part related to the greater biotransformation and consequent excretion of TLC by pericentral hepatocytes. TLC-induced cholestasis is associated more closely with bile canalicular membrane changes than with extent of hepatocellular necrosis. The greater reduction of bile flow with periportal than with pericentral canalicular change is compatible with current concepts of biliary microanatomy which postulate a flow of bile from pericentral through periportal regions of the lobule into the bile ductules.

Animals↗

Cytosolic and nuclear estrogen receptors in the isolated perfused rat liver.

The isolated perfused rat liver was investigated as a potential model to analyze binding of 17 beta-[3H]estradiol (E2) to cytosolic and nuclear estrogen receptors. Viability of the isolated perfused liver was monitored by measuring leakage of cytosolic enzymes into the perfusate. These studies indicated that the liver remained viable for at least a 90-min perfusion period although significant decreases in cytosolic estrogen receptor concentrations occurred during this perfusion period. Estrogen receptor loss was minimized by supplementing the red blood cell-free perfusion medium with 5 micrograms of insulin per ml. Uptake of [3H]E2 by hepatic cytosolic estrogen receptors of the isolated perfused liver was rapid as measured by partial purification of radiolabeled ligand receptor complexes after varying times of perfusion. Peak liver concentrations of receptor-bound E2 were achieved 15 min after the onset of perfusion when using livers from either male or female rats. After 15 min, radiolabeled cytosolic ligand receptor complexes decreased rapidly, reaching lowest concentrations at 60 min. Radiolabeled salt-extractable nuclear-binding sites increased up to 30 min and then decreased slightly between 30 and 90 min. Both 4S and 5S forms of nuclear binding sites were detected in the isolated perfused livers as evaluated by sedimentation analysis on 5 to 20% sucrose density gradients. Concentrations of radiolabeled cytosolic and nuclear receptors were greater in females than males at all perfusion periods examined when the initial concentration of [3H]E2 was 4 nm. Sex differences in receptor uptake were not as great when higher concentrations of [3H]E2 were added to the perfusion medium. These studies suggest that the isolated perfused liver is a suitable model to investigate short-term uptake of estrogens by cytosolic and nuclear receptors.

Animals↗

Relationship of brain blood flow and oxygen consumption to perfusion flow rate during profoundly hypothermic cardiopulmonary bypass. An experimental study.

A study was made of the relation of brain blood flow and oxygen consumption to changes in perfusion flow rate during cardiopulmonary bypass at 20 degrees C in nine cynomolgus monkeys. Four perfusion flow rates varying from 0.25 to 1.75 L X min-1 X m-2 were randomly instituted, each for a 10 minute period. At the end of each period, brain arteriovenous oxygen content difference was measured and 15 mu radioactive microspheres were injected into the arterial perfusion line. The brain was then removed and section into anatomic regions and radioactivity was counted. Regional and total brain blood flows were calculated, as was whole brain oxygen consumption. Brain perfusion continued in all areas at all perfusion flow rates. Whole brain blood flow decreased (p less than 0.0001) as perfusion flow rate was reduced (45 +/- 6.5, 41 +/- 7.9, and 23 +/- 2.8 ml X min-1 X 100 gm-1 at 1.5, 1.0, and 0.5 L X min-1 X m-2, respectively). The proportion of the total perfusion delivered to the brain increased (p = 0.003) with decreasing perfusion flow rates (5.4% +/- 0.78%, 7.1% +/- 1.24%, and 8.2% +/- 1.11% at 1.5, 1.0, and 0.5 L X min-1 X m-2, respectively). Brain blood flow resistance remained unchanged (p = 0.4) while that of the remaining body increased (p less than 0.0001). There was a greater reduction of blood flow in the cortical white matter (p = 0.01) than in other regions of the brain. Brain oxygen consumption was the same (p = 0.5) at all perfusion flow rates, related to an increasing percent oxygen extraction with decreasing perfusion flow rate (p less than 0.0001). The data indicate that all areas of the brain remain perfused, even at low perfusion flow rates, during profoundly hypothermic cardiopulmonary bypass, and that brain oxygen consumption is maintained in part by increased oxygen extraction and in part by redistribution of the perfusate from the remaining body to the brain.

Animals↗

[Absorption of amino acids from the perfused ovine rumen].

The experiments with extracoroporeal perfusion of sheep rumen were performed [Leng et al., 1977]. Bovine plasma, diluted in a 1:1ratio with an isotonic solution of sodium chloride, was used for four perfusions, and autologous blood was used for two perfusions in the course of 150 minutes. After 60 minutes perfusion 20 g enzymatic casein hydrolyzate were applied to the rumen. The levels of free amino acids in the perfusate were recorded after 60 minutes' perfusion [the first phase of perfusion] and at the end of the experiment [the second phase]. The levels of lysine, aspartic acid and glutamic acid increased after perfusions with bovine plasma during the first phase, the levels of glutamic acid, phenylalanine, and in one case of alanine, increased after perfusions with autologus blood. Simultaneously the level of valine decreased after perfusions with bovine plasma, and after perfusions with blood the levels of arginine and valine, and/or lysine, dropped. During the second phase of perfusion, the levels of all the observed amino acids except methionine [bovine plasma], and/or orginine and methionine [blood] rose in the perfusate. The experiments showed that the level of amino acids in the rumen content presented a decisive factor affecting amino acid absorption from the rumen into the blood. Transformation of the amino acids during their passage through the remen wall may be assumed, and glutamic acid is one of the chief products of this process.

Amino Acids↗

Perfusion MRI and SPECT of brain after treatment for childhood acute lymphoblastic leukemia.

BACKGROUND: Treatment of childhood leukemia may cause perfusion defects in the brain observed by SPECT. Perfusion MRI is a novel method to study brain perfusion which has not been used previously in this setting. This study was performed to compare SPECT with perfusion MRI in patients with acute lymphoblastic leukemia (ALL) after treatment. PROCEDURE: Nineteen children or young adults underwent perfusion MRI at the cessation of treatment (n = 9) or 4-8 years after the treatment (n = 10). Seventeen of them also underwent SPECT at the time of MRI (within 0-3 days, n = 14) or a couple of months later (1.5-6 months, n = 3). SPECT images and relative cerebral blood volume (CBV) and cerebral blood flow (CBF) maps from perfusion MRI were analyzed visually. Relative CBV ratios of gray matter to white matter and thalamus to white matter were also calculated from the perfusion MRI. RESULTS: Perfusion MRI did not show any focal perfusion defects, while small defects were observed by SPECT in five of 17 children (29%) in the basal, frontal or temporal areas on the left. No significant differences were observed by perfusion MRI in the relative CBV ratios in the different treatment groups. Time since treatment, age at diagnosis, brain irradiation, or findings in conventional MRI or SPECT did not have any effect on the relative perfusion values either. CONCLUSIONS: SPECT may show small perfusion defects after treatment for childhood leukemia which are not visible by perfusion MRI. The clinical significance or prognosis of these defects is not known.

Adolescent↗

Skin capillary appearance and skin microvascular perfusion due to topical application of analgesia cream.

Local topical analgesia changes basal skin perfusion and its regulation. In particular, the response induced by local heating, which in nontreated skin comprises a rapidly increased perfusion followed by a normalization within 30 s, is altered to a delayed and persistent perfusion increase. The response dependency to the analgesia cream application time, that is, the intradermal penetration of the analgesics and in which vascular plexa the response occurs, is not known. The aim of this study was to assess changes in the appearance of superficial skin capillaries and skin microvascular perfusion changes due to different application periods of topical analgesia cream (EMLA). Twelve subjects were treated with EMLA and placebo applied to the volar side of each forearm, respectively. The treatment areas were assigned different application times (20 min, 40 min, 1 h, 2 h, and 3 h). The areas were cleared from the creams and shortly thereafter provoked during 9 s with a probe heated to 45 degrees C. To assess capillary number density and skin perfusion, capillary microscopy, and Laser Doppler perfusion imaging (LDPI), respectively, were used. The number density of physiologically active capillary was significantly decreased with longer application times of EMLA (P < 0.005). The LDPI-signal showed a persistent perfusion increase after provocation associated with increasing application time of the cream. This perfusion pattern was not seen after 20 min of treatment, but was present in 9 of 12 subjects after 3 h of treatment. No significant relationship between changes in the capillary number density and the LDF measurement was found. In conclusion, a longer application time and therefore a higher intradermal concentration and a deeper penetration of the analgesics was associated with a delayed and persistent perfusion increase after local heating. There was a discrepancy between changes in capillary number density and skin perfusion, indicating that the perfusion increase does not occur in the capillaries but in the deeper lying vessels. Hence, the contribution of the capillary perfusion to the LDF-signal is smaller than previously anticipated. Capillary number density and presumably their perfusion were decreased with longer application times.

Administration, Topical↗

Retrograde abdominal visceral perfusion: is it beneficial?

BACKGROUND: It is proposed that retrograde abdominal perfusion be used in combination with retrograde cerebral perfusion to provide total body visceral protection during aortic reconstruction; however, its physiologic effects remain unknown. METHODS: We compared the effect of superior vena caval perfusion alone with that of combined superior and inferior vena caval perfusion on the liver and kidney in 6 mongrel dogs. Organ blood flow was measured using ultrasonic flow probes on the hepatic artery, the portal vein, and the renal artery. Regional tissue blood flow to the liver and the kidney was assessed using colored microspheres and pH probes. Anesthetized dogs were placed on total cardiopulmonary bypass. After cooling to 20 degrees C, retrograde perfusion was begun with 30 minutes of superior vena caval perfusion followed by another 30 minutes of bicaval perfusion, or vice versa. RESULTS: Very little renal blood flow was measured with either method of retrograde perfusion. Although the liver received more blood flow in comparison to the kidney, there was no significant difference between superior vena caval perfusion alone and bicaval perfusion. The addition of inferior vena caval perfusion results in portal hypertension, hepatic congestion, ascites, and bowel edema. CONCLUSIONS: In the canine model, bicaval perfusion does not provide superior protection to the liver and kidneys when compared with superior vena caval perfusion alone.

Animals↗

Comparative effects of topical perfusions of pentylenetetrazol in the mesencephalon and cerebral cortex of cats.

Push-pull perfusions of pentylenetetrazol (PTZ) were carried out in the mesencephalon and cerebral cortex (orbitofrontal, motor, and suprasylvian) of "encéphale isolé" cats, while EEG recordings from motor cortices and EMG of facial muscles were obtained. There were significant differences between perfusions in the mesencephalic reticular formation (MRF) and in the cerebral cortex: (i) EEG spikes not accompanied by muscular contractions occurred during perfusion of cerebral cortex (motor cortex included), but never with perfusions in MRF. (ii) In some instances muscular tonic and clonic contractions occurred in the absence of EEG spikes when perfusing the mesencephalon, but never with cortical perfusions. (iii) Both MRF and cortical perfusions induced EEG spikes accompanied by myoclonic seizures; however, muscular seizures were practically of the same amplitude in both sides after perfusion of the MRF and were predominant in the contralateral side after cortical perfusions. In addition, significantly less perfusion time (total dose) of PTZ was needed to induce such events in the MRF than in the cerebral cortex. (iv) Generalized seizures induced by cortical perfusions showed a clear predominance of contractions in the muscles contralateral to the perfusion site, whereas perfusions in the MRF induced generalized seizures indistinguishable from those produced by i.v. administration of PTZ. Results suggest that PTZ generalized seizures, closely resembling the so called "primary generalized seizures," result from activation of the MRF, whereas PTZ acting in the cerebral cortex produces a model of focal convulsions that may become secondarily generalized.

Administration, Topical↗

The functional integrity of a normothermic perfusion system using artificial blood in pig liver.

BACKGROUND: We have reported already that we succeeded in developing a normothermic liver perfusion system consisting of purely artificial products such as artificial blood. The aim of this study was to ascertain the metabolic functional integrity of the liver perfused in this system. MATERIALS AND METHODS: A liver graft from a female pig weighing 20 kg was harvested in the usual manner. The perfusion solution consisted of artificial blood, L-15 medium, distilled water, bovine serum albumin, NaHCO3, NaOH, KCl, human regular insulin, 50% glucose solution, and dexamethasone. The isolated liver was perfused with this oxygenated perfusate through the portal vein at a rate of 300 ml/min for 9 h. We analyzed the changes of amino acids, ammonia, and urea concentrations in five livers, which showed high oxygen consumption (over 8 ml-O2/min during perfusion). RESULTS: Although urea did not exist in the perfusate at first, an extremely high level of the urea concentration appeared during the perfusion. On the other hand, the ammonia concentration was only slightly elevated during the perfusion. Arginine vanished from the perfusate with increases of citrulline and ornithine. Taurine was elevated with the disappearance of methionine. Alanine, glutamine, serine, histidine, and threonine concentrations decreased with an increase of the glucose concentration. Numerous liver cells exhibited PAS-positive cytoplasmic glycogen deposits not exhibited before perfusion. The ratios of branched-chain amino acids/aromatic amino acids were elevated during the perfusion. CONCLUSION: Normothermic liver perfusion using artificial blood could sufficiently maintain the functional integrity of the liver.

Ammonia↗

Optimizing radiation treatment plans for lung cancer using lung perfusion information.

PURPOSE: To study the impact of incorporation of lung perfusion information in the optimization of radical radiotherapy (RT) treatment plans for patients with medically inoperable non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The treatment plans for a virtual phantom and for five NSCLC patients with typical defects of pre-RT lung perfusion were optimized to minimize geometrically determined parameters as the mean lung dose (MLD), the lung volume receiving more than 20 Gy (V20), and the functional equivalent of the MLD, using perfusion-weighted dose-volume histograms. For the patients the (perfusion-weighted) optimized plans were compared to the clinically applied treatment plans. RESULTS: The feasibility of perfusion-weighted optimization was demonstrated in the phantom. Using perfusion information resulted in an increase of the weights of those beams that were directed through the hypo-perfused lung regions both for the phantom and for the studied patients. The automatically optimized dose distributions were improved with respect to lung toxicity compared with the clinical treatment plans. For patients with one hypo-perfused hemi-thorax, the estimated gain in post-RT lung perfusion was 6% of the prescribed dose compared to the geometrically optimized plan. For patients with smaller perfusion defects, perfusion-weighted optimization resulted in the same plan as the geometrically optimized plan. CONCLUSION: Perfusion-weighted optimization resulted in clinically well applicable treatment plans, which cause less radiation damage to functioning lung for patients with large perfusion defects.

Carcinoma, Non-Small-Cell Lung↗

Myocardial perfusion imaging using a non-contrast agent MR imaging technique.

INTRODUCTION: A MR imaging (MRI) method has been developed to determine quantitatively myocardial perfusion (P) in the rat heart in vivo. This method has the potential to non-invasively measure cardiac perfusion without the use of a contrast agent by exploiting the endogenous contrast from flowing blood itself. METHOD AND RESULTS: Principle of the technique is the arterial spin labeling of endogenous water protons within the short axis imaging slice. Arterial spin labeling techniques are based on a model that uses inflow effects to relate intrinsic changes in longitudinal relaxation (T1) to tissue perfusion. Perfusion is determined from the difference between a slice selective and a global inversion recovery experiment. Perfusion was determined at rest and during hyperemia induced by intravenous adenosine (3 mg/(kg min)). The MR perfusion values were compared with perfusion data obtained in the same animal using the colored microspheres (MS) technique as the gold standard. The MR perfusion (mean +/- SEM) was 3.3 +/- 0.2 ml/min/g at rest and 4.6 +/- 0.6 ml/min/g during adenosine. Perfusion values obtained by colored MS were 3.4 +/- 0.2 and 4.7 +/- 0.8 ml/min/g at rest and during vasodilation, respectively. Adenosine decreased mean arterial pressure (MAP) from 120 to 65 mmHg which implies a reduction of coronary resistance (CR) to about 50% of baseline. CONCLUSION: Our study shows that quantitative mapping of perfusion may be performed non-invasively by MRI. The MR perfusion data are in excellent correlation with data obtained by the well-established colored MS technique. Determination of perfusion reserve confirms that coronary perfusion is highly dependent on blood pressure due to changes in CR.

Animals↗

Direct evidence that coronary perfusion affects diastolic myocardial mechanical properties in canine heart.

OBJECTIVE: The effect of coronary perfusion on left ventricular chamber distensibility is only indirect evidence that perfusion alters the mechanical properties of the myocardium. The aim of this study was to demonstrate explicitly the effects of coronary perfusion on these mechanical properties. METHODS: The effects of different levels of coronary perfusion were studied both on in-plane stress-strain relations and on transverse stiffness in an isolated, perfused canine interventricular septal preparation. Additionally, to determine the vascular compartment responsible for the mechanical effects of perfusion on tissue properties, we examined the in-plane stress-strain responses and transverse stiffness after embolisation of the vasculature with 15 microns microspheres. RESULTS: The data show a clear dependence of tissue stress-strain properties on perfusion. The in-plane stress-strain relations were shifted to the left and transverse stiffness increased linearly as septal artery perfusion pressure increased. The dependence of both the in-plane stress-strain relations and transverse stiffness on perfusion was significantly decreased following embolisation. CONCLUSIONS: Myocardial tissue stiffness is directly related to perfusion. The linear relationship between transverse stiffness and perfusion makes it easier to assess the effects of perfusion on tissue stiffness than with in-plane stress-strain relations. Perfusion of capillaries and/or venules is largely responsible for these alterations in myocardial stiffness.

Animals↗