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PubMed2004

Quantitative perfusion map of malignant liver tumors, created from dynamic computed tomography data.

RATIONALE AND OBJECTIVES: To apply perfusion computed tomography (CT) technique to variable malignant liver tumors, and to define the usefulness of quantitative color mapping. MATERIALS AND METHODS: Perfusion CT images were created for 36 malignant liver tumors in 28 patients (age, 66.4 +/- 10.1 years; range, 48-85) with metastatic liver tumors (n = 17; nine colorectal carcinomas, eight other malignant tumors) and hepatocellular carcinomas (n = 11). A single-slice dynamic CT was performed after an intravenous bolus injection of 40 mL of contrast material (320 mgI/mL) with 8 mL/sec. The parameters were calculated pixel-by-pixel using maximum slope method, and quantitative maps of arterial and portal perfusion were created. In four patients who underwent transcatheter arterial chemoembolization, perfusion CT was performed before and after transcatheter arterial chemoembolization. RESULTS: In all patients, liver tumors were shown as hypervascular lesions on arterial perfusion CT. The average arterial perfusion value of the metastatic tumors from the colorectal carcinomas was 0.67 +/- 0.33 mL/min/mL, and that of hepatocellular carcinomas was 0.94 +/- 0.26 mL/min/mL (P = .03). The other metastatic tumors from various primary tumors showed a wide range (0.19-1.45 mL/min/mL) of arterial perfusion. Arterial perfusion of the liver tumors was obviously decreased after successful transcatheter arterial chemoembolization. In 12 of 15 tumors, in which portal perfusion CT images could be created, region-of-interest analysis showed no portal perfusion in the tumors. In two cases, decreased portal perfusion in the segments, which malignant tumors involved, was demonstrated. CONCLUSION: Perfusion CT can provide quantitative information about arterial and portal perfusion of liver tumors, combined with good anatomic detail in one image. This technique has a potential to evaluate the angiogenesis of liver tumors, to show secondary changes in perfusion, such as decreased portal perfusion in apparently normal liver adjacent to metastases, and to monitor the therapeutic response in vivo.

Aged↗
PubMed2002

Effects of indomethacin on responses of regional kidney perfusion to vasoactive agents in rabbits.

1. To determine whether differential release of products of arachidonic acid metabolism, via the cyclo-oxygenase pathway, underlies the diversity of responses of regional kidney perfusion to vasoactive agents, we tested the effects of intravenous indomethacin on responses to renal arterial bolus doses of vasoactive agents in pentobarbitone-anaesthetized rabbits. 2. Total renal blood flow (RBF) and regional kidney perfusion were determined by transit time ultrasound flowmetry and laser-Doppler flowmetry, respectively. 3. Responses of regional kidney blood flow to vasoactive agents were diverse: noradrenaline reduced cortical but not medullary perfusion, [Phe 2,Ile 3,Orn 8]-vasopressin reduced medullary perfusion more than cortical perfusion, endothelin-1 and angiotensin II increased medullary perfusion in the face of reduced cortical perfusion, while acetylcholine, bradykinin and the nitric oxide donor methylamine hexamethylene methylamine (MAHMA) NONOate all increased both cortical and medullary perfusion. 4. Indomethacin administration was followed by reductions in total RBF (17 +/- 6%), cortical perfusion (13 +/- 5%) and medullary perfusion (40 +/- 8%). Angiotensin II- and endothelin-1-induced increases in medullary perfusion were abolished by indomethacin, but indomethacin had no significant effects on responses of regional kidney perfusion to acetylcholine, bradykinin, MAHMA NONOate, noradrenaline and [Phe 2,Ile 3,Orn 8]-vasopressin. 5. Our results suggest that vasodilator cyclo-oxygenase products contribute to the maintenance of resting renal vascular tone, particularly in vascular elements controlling medullary perfusion. Cyclo-oxygenase products also appear to mediate endothelin-1- and angiotensin II-induced increases in medullary perfusion. However, regionally specific engagement of cyclo-oxygenase-dependent arachidonic acid metabolism does not appear to contribute to the differential effects of noradrenaline and [Phe 2,Ile 3,Orn 8]-vasopressin on cortical and medullary perfusion.

Animals↗
PubMed1999

Tl-201 myocardial perfusion SPECT: role of nitrate-augmented redistribution.

PURPOSE: TI-201 myocardial perfusion SPECT is commonly used to assess myocardial perfusion and viability. Nitrate-augmented redistribution with repeated injection facilitates the detection of reversible segments compared with standard redistribution. In this study, we investigated the potential of nitrate augmentation to improve myocardial perfusion and viability assessment without repeated injection and we also compared nitrate-augmented redistribution with delayed redistribution. METHODS: Eighteen patients underwent a stress-redistribution TI-201 SPECT study. Immediately after redistribution SPECT, each patient was administered 0.6 mg glyceryl trinitrate and nitrate-augmented redistribution SPECT acquired 30 minutes later. Each patient then returned the next day and was injected with a booster dose of TI-201 30 minutes before the delayed redistribution SPECT acquisition. For each SPECT study, the myocardium was divided into 11 segments, and perfusion to each segment was scored on a four-point scale by consensus. An overall cardiac perfusion score was derived by summing the perfusion score for each segment. RESULTS: Reduced stress perfusion was identified in 150 segments: 23 (15.3%) had improved perfusion after redistribution; 60 (40%) segments had improved perfusion after nitrate-augmented redistribution; 52 (34.7%) segments with reduced stress perfusion had improved perfusion after delayed redistribution. The cardiac perfusion score after stress was 15.9+/-5.5 (means+/-SD). The score increased to 17.4+/-5.4 after redistribution. The perfusion score improved to 19.7+/-5.8 (P < 0.05 versus redistribution) after nitrate augmentation. The cardiac perfusion score, 19.2+/-6.4, did not improve further after delayed redistribution. CONCLUSIONS: TI-201 SPECT with nitrate-augmented redistribution is as good or better than delayed redistribution with repeated injection for myocardial perfusion and viability assessment. TI-201 SPECT with nitrate-augmented redistribution has significant logistical and economic advantages over traditional delayed redistribution with TI-201 repeated injection.

Coronary Circulation↗
PubMed2003

Preoperative risk stratification using stress myocardial perfusion scintigraphy with electrocardiographic gating.

UNLABELLED: This study was designed to assess the prognostic value of stress myocardial perfusion SPECT with electrocardiographic (ECG) gating in patients undergoing noncardiac surgical treatment. METHODS: The study included 481 consecutive patients who underwent noncardiac surgery and had been referred for preoperative myocardial perfusion scintigraphy. Myocardial scintigraphy used (99m)Tc-labeled perfusion agents and dipyridamole stress with ECG gating, permitting qualitative and quantitative analyses of both myocardial perfusion and cardiac function. Reconstructed perfusion images were analyzed qualitatively and semiquantitatively. The Quantitative Gated SPECT (QGS) program was used for gated SPECT analysis to calculate global left ventricular ejection fraction and estimate regional wall motion. We assessed the relationships between perioperative cardiac events and various predictors, including clinical risk factors, radionuclide perfusion, and functional variables. RESULTS: Univariate analysis indicated that age (P < 0.001), diabetes mellitus (P < 0.01), history of heart failure (P < 0.05) or perfusion imaging (P < 0.0001), and QGS analysis (P < 0.0001) yielded significant risk stratification. According to multivariate analysis, age, diabetes mellitus, perfusion imaging, and QGS analysis were independent predictors of perioperative cardiac events. The event rate was correlated with quantitative scintigraphic indices of perfusion images (rest perfusion and ischemic scores) and QGS analysis (global ejection fraction and the number of hypokinetic segments). Although QGS functional data offered no significant incremental prognostic value in patients with abnormal perfusion, it classified patients with normal perfusion into 2 risk groups (P < 0.0001). A combination of clinical risk factors, scintigraphic perfusion results, and functional data allowed further detailed risk stratification. CONCLUSION: Stress myocardial perfusion SPECT with ECG gating has an incremental prognostic value over conventional nongated stress perfusion imaging in predicting perioperative cardiac events.

Aged↗
PubMed2004

The value of myocardial contrast echocardiography compared with SPECT in detecting myocardial perfusion abnormalities in patients with anterior acute myocardial infarction.

BACKGROUND: Microvasculature damage after myocardial infarction (MI), known as "no-reflow" phenomenon, may occur in some patients with acute MI in spite of invasive treatment and opened infarct-related coronary artery. There are several non-invasive and invasive methods used for the coronary flow assessment at the tissue level. AIM: To compare the value of intravenous contrast echocardiography (MCE) in detecting myocardial perfusion defects in patients with acute MI with (99m)Tc MIBI SPECT study. METHODS: Sixteen patients (11 males, 5 females, mean age 55.4+/-10.2 years) underwent primary coronary angioplasty or facilitated angioplasty (with reduced dose of a fibrinolytic drug and glycoprotein IIb/IIIa inhibitor) (PCI) for acute anterior MI. TIMI grade flow, TIMI Myocardial Perfusion Grade (TMPG), corrected TIMI frame count (cTFC), wall motion score index (WMSI) and segmental perfusion by myocardial contrast echocardiography (MCE) were estimated in real time before and immediately after PCI. MCE was repeated on the third day after PCI. All patients underwent (99m)Tc MIBI SPECT study (SPECT) while at rest on the third day after PCI. The area at risk was defined as the number of segments with no perfusion before angioplasty. Reflow was defined as an increase in contrast score in the same segments after angioplasty. RESULTS: Baseline MCE showed 95 segments with perfusion defects. Immediately after PCI, 77 segments were found with perfusion defect; in 10 patients improvement of myocardial perfusion was observed whereas in 6 patients perfusion defect remained unchanged. On the third day further improvement was observed in 8 patients. The number of segments with perfusion defect decreased to 53. SPECT detected perfusion defect in 54 segments. The agreement between MCE and SPECT for detecting perfusion abnormality was 98% (kappa 0.94). CONCLUSIONS: MCE is a safe technique for detecting myocardial perfusion in patients with acute MI. MCE proves that both primary and facilitated angioplasty improve myocardial perfusion in two thirds of patients with acute MI. Serial MCE allows identification of patients with both early and late improvement of myocardial perfusion. There is a very strong correlation between MCE and SPECT in the assessment of perfusion defects.

Aged↗
PubMed2004

Construction and validation of a microprocessor controlled extracorporal circuit in rats for the optimization of isolated limb perfusion.

Although a few experimental approaches to isolated limb perfusion (ILP) are described in the literature, none of these animal models mimics the clinical perfusion techniques adequately to improve the technique of ILP on the basis of valid preclinical data. Therefore, we developed an ILP setup in rats allowing online monitoring of essential perfusion parameters such as temperature (in perfusate, various tissues, and rectum), pH (perfusate), perfusion pressure, and O(2) concentration (in perfusate, tissue), by a tailor-made data acquisition system. This setup permits close supervision of vital parameters during ILP. Various interdependencies, concerning the flow rate and the pressure of perfusate as well as tissue oxygenation were registered. For the measurement of pO(2) values in the perfusate and in different regions of the perfused hind limb, a novel type of microoptode based on quenching of a fluorescent dye was devised. Stable normothermic (37 degrees C) perfusion conditions were maintained at a constant perfusion pressure in the range of 40-60 mm Hg by administration of the spasmo lytic moxaverine (0.5 mg/mL of perfusate as initial dose) at a perfusate flow rate of 0.5 mL/min for 60 min. At the end of an ILP, there were no signs of tissue damage, neither concerning laboratory data (K(+), myoglobin, creatine kinase, lactic dehydrogenase) nor histopathological criteria. The reported ILP model is not only well suited to investigate the effects of hyperthermia but also to assess the efficacy of new antineoplastic approaches, when nude rats, bearing human tumours in the hind limbs, are used.

Animals↗
PubMed1996

An optimized model for rat liver perfusion studies.

Conditions which influence the viability, integrity, and extraction efficiency of the isolated perfused rat liver were examined to establish optimal conditions for subsequent work in reperfusion injury studies including the choice of buffer, use of oncotic agents, hematocrit, perfusion flow rate, and pressure. Rat livers were perfused with MOPS-buffered Ringer solution with or without erythrocytes. Perfusates were collected and analyzed for blood gases, electrolytes, enzymes, radioactivity in MID studies, and lignocaine in extraction studies. Liver tissue was sampled for histological examinations, and wet:dry weight of the liver was also determined. MOPS-buffered Ringer solution was found to be superior to Krebs bicarbonate buffer, in terms of pH control and buffering capacity, especially during any prolonged period of liver perfusion. A pH of 7. 2 is chosen for perfusion since this is the physiological pH of the portal blood. The presence of albumin was important as an oncotic agent, particularly when erythrocytes were used in the perfusate. Perfusion pressure, resistance, and vascular volume are flow-dependent and the inclusion of erythrocytes in the perfusate substantially altered the flow characteristics for perfusion pressure and resistance but not vascular volume. Lignocaine extraction was relatively flow-independent. Perfusion injury as defined by enzyme release and tissue fine structure was closely related to the supply of O2. The optimal conditions for liver perfusion depend upon an adequate supply of oxygen. This can be achieved by using either erythrocyte-free perfusate at a flow rate greater than 6 ml/min/g liver or a 20% erythrocyte-containing perfusate at 2 ml/min/g.

Animals↗
PubMed1988

Determination of adenosine in fetal perfusates of human placental cotyledons using fluorescence derivatization and reversed-phase high-performance liquid chromatography.

A simple, sensitive HPLC method using fluorescence detection was developed for determination of adenosine in fetal venous perfusates of dual-perfused cotyledons from human term placentas. Maternal and fetal circuits of in vitro placental cotyledons were perfused with physiological salt solution containing dextrose and dextran (Earle's medium). Conditions were established for optimal formation of fluorescent 1,N6-ethenoadenosine from adenosine and chloroacetaldehyde in Earle's medium and for optimal resolution of 1,N6-ethenoadenosine by reversed-phase HPLC of the reaction mixture. The yield of 1,N6-ethenoadenosine was enhanced by dilution and acidification of the sample matrix. Perfusate samples in autosampler vials were diluted 40% with water and reacted with chloroacetaldehyde for 40 min at 100 degrees C; replicate 100-microliters injections were made automatically from each reaction mixture for HPLC analysis with fluorescence detection on a column packed with 3 microns octadecylsilica (Hypersil). Calibration curves were prepared similarly from 4-100 nM adenosine in Earle's medium. Alternatively, perfusate samples were diluted twofold with dilute phosphoric acid to give a final pH of 5.4 before reaction with chloroacetaldehyde, and replicate 50-microliters injections were made automatically for HPLC; calibration curves were prepared from 2-400 nM adenosine in Earle's medium. 1,N6-Ethenoadenosine was well resolved from Earle's-derived artifactual peaks on chromatography with either a linear or a concave gradient of methanol in ammonium phosphate buffer. Total run times were 15 and 19 min, respectively. Sensitivity of measurement of adenosine was 2-4 nM. Derivatization of adenosine using the acidified reaction mixture gave a limit of detection of 100 fmol of adenosine per injection. Application of the method to analysis of adenosine in fetal venous perfusates of eight dual-perfused cotyledons, each from a different placenta, gave a range of 3.5-52 nM adenosine. Ischemia, imposed by cessation of maternal perfusion, caused a two- to sixfold increase in fetal venous perfusate adenosine concomitant with an increase in fetoplacental perfusion pressure; perfusion pressure and perfusate adenosine returned to baseline levels on reperfusion of the maternal circuit. This facile method of determination of perfusate adenosine should allow investigation of the role of placental adenosine release in regulation of fetoplacental vascular resistance and should be applicable to study of adenosine released by other isolated perfused organs.

Acetaldehyde↗
PubMed1986

Alterations in biochemical functions during hyperthermic isolation-perfusion of the human liver.

Hyperthermia (42-42.5 degrees) was applied to the liver of eight patients with cancer in the liver by a technique of isolation-perfusion. Hepatic functional integrity was assessed during perfusion through measurement of multiple perfusate constituents. Data from seven perfusions were available for analysis. During perfusion there was an increase in perfusate lactate, pyruvate, glucose, urea, potassium, alkaline phosphatase, SGOT, and LDH. All increases in these constituents were significant (P less than 0.05) except for potassium. Lactate accumulated throughout the perfusion from an initial level of 3.8 +/- 1.0 mM to 7.6 +/- 3.5 mM at 4 hr. Pyruvate increased over the first 3 hr of perfusion from 0.14 +/- 0.06 mM to 0.80 +/- 0.37 mM before declining to 0.54 +/- 0.24 mM at 4 hr. The L/P (lactate/pyruvate) ratio decreased during perfusion to less than 10 in the first 2 hr, but rose to within normal limits by the end of perfusion. The decreases in L/P ratios were significant (P less than 0.05). Initially there was a rapid rise in perfusate glucose concentrations from 4.5 +/- 0.8 mM to 20.7 +/- 5.4 mM at 2 hr with nonsignificant changes thereafter. Urea levels increased from 0.64 +/- 0.22 mM to 1.92 +/- 0.76 mM. Perfusate potassium increased from the initial level of 7.0 +/- 1.0 mM during perfusion to 8.3 +/- 1.7 mM at 2 hr before declining. SGOT, LDH, and alkaline phosphatase increased during perfusion from 21 +/- 15, 142 +/- 48, and 16 +/- 6 to 176 +/- 22, 472 +/- 53 and 52 +/- 42, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Acute phase response to Salmonella in a pig liver perfusion model.

Livers from 7- to 14-day old pigs were maintained on a perfusion apparatus for 3 h. The perfused livers maintained physiologic and immunologic functions during perfusion. The perfused livers retained 78-94% of a non-recirculating inoculum of approximately 1-5 x 10(8) Salmonella choleraesuis (Scs), and cleared 94.9 +/- 1.7% of the retained (Scs) during the 3-h perfusion period. When the acute phase response (APR) was induced in liver donor pigs 24 h before liver perfusion, the perfused livers had diminished capability to retain, and greatly diminished capability to clear Scs. When sterile, filtered, and concentrated liver perfusate (LP) from previous, LPS-perfused livers was added to the perfusion fluid (PF) at 50 min of Scs perfusion (passive APR), Scs clearance was inhibited. When sterile, filtered LP from previously Scs perfused livers was added to the system, liver clearance was abolished, and Scs always grew in such livers during the 3 h perfusion period. The LP of livers perfused with Scs enhanced growth of Scs in an in vitro assay. These observations suggest that products of the acute phase response favor growth of Scs in vitro and in vivo.

Acute-Phase Reaction↗
PubMed2005

A novel protocol of retrograde cerebral perfusion with intermittent pressure augmentation for brain protection.

OBJECTIVES: We examined a novel protocol of retrograde cerebral perfusion with intermittent pressure augmentation to improve the clinical usefulness of this procedure, in a canine model, because a high retrograde cerebral perfusion pressure may be required to open cerebral vessels. METHODS: Eighteen dogs (25.2 +/- 4.1 kg) were randomly divided into the following 3 groups: circulatory arrest group (circulatory arrest alone), conventional-retrograde cerebral perfusion group (conventional retrograde cerebral perfusion at 25 mm Hg), and intermittent-retrograde cerebral perfusion group (retrograde cerebral perfusion at 15 mm Hg with intermittent pressure augmentation to 45 mm Hg). The animals were cooled down to 26 degrees C under cardiopulmonary bypass and underwent 60 minutes of circulatory arrest with or without retrograde cerebral perfusion in accordance with the protocol described. They were weaned from cardiopulmonary bypass after rewarming and observed for 12 hours after the procedures. The retinal vessels were observed as a means of noninvasive direct visualization of the cerebral vascular system. The level of Tau proteins in the cerebrospinal fluid was measured as a marker of neuronal damage. RESULTS: While the retinal vessels were fully distended with blood (100%) at a retrograde cerebral perfusion pressure of 45 mm Hg in the intermittent-retrograde cerebral perfusion group, full distension of the retinal vessels was not observed in the conventional-retrograde cerebral perfusion group (67%). The level of Tau proteins, measured 12 hours after the operation, was lower in the intermittent-retrograde cerebral perfusion group (247 +/- 70 pg/mL) than in the circulatory arrest group (1313 +/- 463 pg/mL; P < .05) or the conventional-retrograde cerebral perfusion group (1449 +/- 693 pg/mL; P < .05). Histopathologic examination revealed that the most effective brain protection was obtained in the intermittent-retrograde cerebral perfusion group (P < .05). CONCLUSIONS: Intermittent-retrograde cerebral perfusion effectively opens up cerebral vessels to allow adequate blood supply to the brain, thereby minimizing brain damage. This novel method may protect the cerebral system effectively from ischemia during circulatory arrest.

Animals↗
PubMed2003

A liver perfusion model for studies of selective adherence and transient halting of portal blood leukocytes in sinusoids.

Portal blood leukocytes play an important, but still poorly defined, role in the immune processes of the liver. In our previous studies, we showed that certain leukocyte subsets are selectively halted in the liver. These cells marginate in sinusoids and, together with resident Kupffer and endothelial sinusoidal cells, participate in antiviral and antitumor processes. The molecular mechanisms of margination and cooperation with resident sinusoidal cells require clarification. However, in vivo harvesting of portal blood leukocytes is associated with cumbersome cannulation of portal and hepatic veins and manipulation of the liver, causing major disturbances in splanchnic blood flow and liver blood supply, totally distorting sinusoidal blood perfusion and leukocyte margination. To overcome these difficulties, we have developed an in situ normothermic rat liver perfusion model permitting quantitative observations of blood leukocyte extraction in sinusoids. First, liver was flushed through the portal vein and the effluent leukocytes, named liver-associated leukocytes (LAL1), were collected from hepatic veins. Then, the liver was perfused for 60 min with 50 ml of blood using a semiclosed perfusion system. Upon completion of perfusion, the liver portal vasculature was flushed again to retrieve the leukocytes extracted from the perfusing blood (LAL2). These cells were characterized with respect to their phenotype and cytotoxicity. The mean leukocyte count of the washout before perfusion was 1.04+/-0.2x10(6)/g of liver tissue and 0.9+/-0.1x10(6)/g after 60 min of perfusion, indicating retention by the perfused liver, the live leukocyte extracting capacity. To further evaluate the efficiency of perfusion, FITC-labelled leukocytes were added to the perfusing leukocyte-free blood. Around 95% of the postperfusion washout LALs were FITC(+). Heat-killed leukocytes did not marginate in sinusoids. Preincubation of leukocytes with substances able to lower adhesion capacity, such as lidocaine, trypsin and AAGM1, significantly decreased the postperfusion LAL2 washout population. The numbers of extracted postperfusion LAL2 CD5(+), CD4(+), CD8(+), CD56(+) and class II(+) subsets did not differ statistically from those of preperfusion LAL1. Moreover, the cytotoxicity of LAL2 and LAL1 against CC531 and K562 remained at a similar level. Thus, perfused liver also retained its selective leukocyte extraction capacity. This model shows that the process of selective margination of portal blood cell subsets in the liver can be studied in an artificially perfused liver subject to physiological blood flow parameters, temperature, oxygenation and minimal ischemic time before connection to the perfusion device. Furthermore, it is suitable for studies of the selective recruitment of blood cells in sinusoids in a wide large of situations including liver tumors, infections, rejection after transplantation, graft vs. host disease, as well as in the investigation of the effect of drugs on these processes.

Animals↗
PubMed1997

Neurophysiologic monitoring to assure delivery of retrograde cerebral perfusion.

BACKGROUND: Patients undergoing complex aortic procedures performed with deep hypothermia and circulatory arrest have a significant risk of an adverse neurologic event when the arrest period is prolonged. Retrograde cerebral perfusion appears to improve cerebral protection, although collapsed cortical veins or functional jugular venous valves may restrict flow at the frequently recommended maximum pressure of 25 mm Hg. Therefore, the purpose of this study was to demonstrate the benefit of multimodality neurophysiologic monitoring in assuring delivery of retrograde cerebral perfusion. METHODS: Electroencephalography, cerebral blood flow velocity, and regional cerebral venous oxygen saturation were used to quantify the intraoperative neurophysiologic changes accompanying retrograde cerebral perfusion. The magnitude of changes was compared with those previously observed during arrest without retrograde cerebral perfusion. RESULTS: Thirty patients underwent complex aortic procedures necessitating circulatory arrest, 22 with retrograde cerebral perfusion. The mean retrograde perfusion pressure of 40 mm Hg (30 to 49 mm Hg, 95% confidence interval) and flow rate of 1.2 L/min (0.9 to 1.6 L/min) necessary to achieve documented retrograde cerebral perfusion was much higher than previously recommended. During both retrograde cerebral perfusion and rewarming, cerebral oximetric monitoring guided adjustments in perfusion parameters to limit the rate of desaturation to 0.4% per minute (0.3% to 0.6%). With retrograde cerebral perfusion there was a rapid (1) recovery of electroencephalographic activity during rewarming (21 minutes [range 16 to 26 minutes]) and (2) return of consciousness after the operation (81% [58% to 95%, 95% confidence interval] awake by 12 hours). There was no transcranial Doppler evidence of cerebral edema with retrograde cerebral perfusion. Two neurologic complications occurred in the 22 patients managed with retrograde cerebral perfusion and one in the eight patients managed with arrest only. CONCLUSIONS: Multimodality neurologic monitoring assured optimal brain cooling and bihemispheric delivery of retrograde cerebral perfusion. Necessary retrograde pressure and flow were often higher than values previously reported. Avoidance of profound cerebral venous oxygen desaturation during retrograde cerebral perfusion and rewarming was associated with rapid recovery of neurologic function.

Adult↗
PubMed2003

Decrease in core liver temperature with 10 degrees C by in situ hypothermic perfusion under total hepatic vascular exclusion reduces liver ischemia and reperfusion injury during partial hepatectomy in pigs.

OBJECTIVE: We attempted to assess liver ischemia/reperfusion injury under a mild decrease in core liver temperature of 10 degrees C by in situ hypothermic perfusion during ischemia. METHODS: Liver ischemia was induced in pigs by total hepatic vascular exclusion with concomitant in situ perfusion with hypothermic (4 degrees C) Ringer-glucose (cold perfused group, core liver temperature maintained at 28 degrees C), with normothermic (38 degrees C) Ringer-glucose (warm perfused group) or without in situ perfusion (control group). RESULTS: In the cold perfused, warm perfused, and control groups, 24-hour survival was 5/5, 0/5, and 3/5, respectively. Hemodynamic parameters in the cold perfused group remained stable, whereas pigs in both other groups required circulatory support. Plasma AST and interleukin-6 levels were lower in the cold perfused group than in both other groups. Hepatocellular function was best preserved in the cold perfused group as indicated by complete recovery of bile production during reperfusion and no loss of indocyanine green clearance capacity. In both other groups, bile production and indocyanine green clearance capacity were reduced significantly. The hyaluronic acid uptake capacity of pigs in the cold perfused group or control group did not differ, indicating preserved sinusoidal endothelial cell function. Histopathologic injury scores during reperfusion were significantly lower in the cold perfused group when compared to both other groups. CONCLUSIONS: A mild decrease in core liver temperature of 10 degrees C by in situ hypothermic liver perfusion during ischemia protects the liver from ischemia/reperfusion injury. This protection appears to be related to cooling of the liver rather than to the washout of blood during perfusion.

Animals↗
PubMed1969

Influence of amino acid supply on ribosomes and protein synthesis of perfused rat liver.

1. The livers of rats were perfused in situ with medium containing mixtures of amino acids in multiples of their concentration in normal rat plasma. The incorporation of labelled amino acid into protein of the liver and of the perfusing medium increased with increasing amino acid concentration. During 60min. perfusions, labelling of liver protein reached a plateau, and labelling of medium protein was inhibited when the initial concentration of the amino acid mixture was more than ten times the normal plasma value. 2. Examination of polysome profiles derived from livers perfused without amino acids in the medium showed that the number of large aggregates was decreased and the number of small aggregates, particularly monomers and dimers, was increased with time of perfusion. The addition of amino acids to the perfusion medium reversed this polysome shift to an extent that was dependent on the initial concentration of amino acids. Polysome profiles derived from livers perfused for 60min. with ten times the normal plasma concentration of amino acids were essentially the same as the polysome profiles of normal non-perfused livers. 3. The ability of ribosome preparations from perfused livers to incorporate amino acids into protein in vitro decreased with increasing time of perfusion when no amino acids were added to the medium, but increased as the concentration of amino acids in the perfusion medium was increased. 4. The ability of cell sap from perfused livers to support protein synthesis in vitro was not influenced by the amino acid concentration of the perfusion medium. 5. Livers were perfused for 60min. with medium containing amino acid mixtures at ten times the normal plasma concentration but deficient in one amino acid. Maximal incorporation of labelled amino acid into liver protein, the stability of the polysome profile and the ability of ribosome preparations to incorporate amino acids into protein were found to depend on the presence of 11 amino acids: arginine, asparagine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, threonine, tryptophan and valine. A mixture of these 11 amino acids, at ten times their normal plasma concentration, stimulated the incorporation of labelled amino acid into liver protein, stabilized the polysome profile and increased the ability of ribosome preparations to incorporate amino acids into protein to the same extent as the complete mixture. 6. It is concluded that the availability of certain amino acids plays an important role in the control of protein synthesis, possibly by stimulating the ability of ribosomes to become, and to remain, attached to messenger RNA.

Amino Acids↗
PubMed1971

Sodium transport by perfused giant axons of Loligo.

The sodium efflux from perfused squid giant axons has been studied using radioactive sodium, and the sufficient conditions for the maintenance of a potassium- and ouabain-sensitive sodium efflux have been established. The following were found.1. Axons extruded and then perfused with their own axoplasm had a sodium efflux which was sensitive to cyanide, potassium and ouabain and was thus similar to the efflux from intact axons.2. A method for replacing natural axoplasm into fibres previously perfused with artificial axoplasm was developed and used to establish an artificial perfusate that was not irreversibly toxic.3. Short perfusion (5 min) with a variety of artificial perfusates was then found to give fibres which had potassium- and ouabain-sensitive sodium effluxes when ATP was present in the perfusate.4. In the absence of ATP the sodium efflux was small and relatively insensitive to both external potassium and to ouabain.5. With ADP in the perfusate, fibres gave a sodium efflux which was ouabain-sensitive but was little affected by the removal of external potassium from the sodium-rich sea water bathing the fibres.6. The perfused fibres differed from intact fibres in having large ouabain-insensitive sodium effluxes.7. After very long perfusions (40-90 min), with the simple media containing ATP, the rate constant for sodium efflux from the fibres tended to be large and was relatively insensitive to potassium or to ouabain.8. Fibres refilled with natural axoplasm after long perfusion showed increased sensitivity to external potassium; refilled with dispersed axoplasm the sodium efflux tended to become very large.9. After very long perfusions with artificial axoplasms containing ATP, a potassium- and ouabain-sensitive sodium efflux was found to persist provided that dextran was present and the total osmotic pressure and the hydrostatic pressure of the perfusate were controlled. Under these conditions the sodium efflux resembled that from briefly perfused fibres. The necessary and sufficient conditions for the maintenance of sodium transport by perfused giant axons are discussed.

Adenosine Diphosphate↗
PubMed2002

Reduced liver uptake of arterially infused melphalan during retrograde rat liver perfusion with unaffected liver tumor uptake.

Isolated hepatic perfusion (IHP) with melphalan is used for patients with nonresectable metastases confined to the liver. To improve the efficacy of IHP and to reduce the toxicity to the liver, reversion (retrograde perfusion) of the bloodstream through the liver in a rat model was studied. For liver tumor induction male WAG/Rij rats were inoculated with CC531 cells, a colorectal tumor cell line. After 11 to 12 days the tumor-bearing rat livers were perfused by single-pass perfusion through either the portal (orthograde) or caval vein (retrograde) for different time periods. During perfusion melphalan (160 Schultze) was infused in the hepatic artery. Melphalan concentrations were measured by high-performance liquid chromatography. A rapid extraction of melphalan by the liver occurred in the first 5 min, reaching steady state after 10 to 20 min for both perfusion directions. The melphalan concentration of the outflow perfusate was significantly higher in the retrograde perfusion compared with the orthograde perfusion. The melphalan content of the tumor tissue was unaffected by perfusion direction at any time point. To the contrary, the melphalan uptake in liver tissue was strongly influenced: the melphalan content after 40-min retrograde perfusion was 12% of that after orthograde perfusion. The average tumor/liver concentration ratio was 6 for orthograde perfusion and 30 for retrograde perfusion. In conclusion, retrograde IHP with continuous melphalan infusion in the hepatic artery provides a high tumor uptake of melphalan with potentially reduced liver toxicity compared with orthograde IHP.

Animals↗
PubMed1996

Effects of permanent dual chamber pacing on myocardial perfusion in symptomatic hypertrophic cardiomyopathy.

OBJECTIVE: Angina and the presence of myocardial ischaemia are common in hypertrophic cardiomyopathy. Dual chamber pacing results in clinical improvement in these patients. This study evaluates the effects of permanent dual chamber pacing on absolute regional myocardial perfusion and perfusion reserve. SETTING: University hospital. PATIENTS AND DESIGN: Six patients with hypertrophic cardiomyopathy and severe symptoms of angina received a dual chamber pacemaker. Absolute myocardial regional perfusion and perfusion reserve (dipyridamole 0.56 mg/kg) were measured by dynamic positron emission tomography with 13N-ammonia both during sinus rhythm and 3 months after pacemaker insertion. Results were compared with those from 28 healthy volunteers. RESULTS: Pacing resulted in a reduction of anginal complaints and a reduction in intraventricular pressure gradient from 65 (SD 30) mm Hg to 19 (10) mm Hg. During sinus rhythm, baseline perfusion was higher in patients with hypertrophic cardiomyopathy than controls (184 (31) v 106 (26) ml/min/100 g, P < 0.01), and perfusion reserve was lower (1.6 (0.4) v 2.8 (1.0), P < 0.05). During pacing myocardial perfusion decreased to 130 (27) ml/min/100 g (P < 0.05), with variable responses in terms of perfusion reserve. Pacing caused a redistribution of myocardial stress perfusion and perfusion reserve. The coefficient of regional variation of myocardial stress perfusion decreased from 19.7 (7.0)% to 14.6 (3.9)% during pacing (12.9 (3.8)% in controls, P < 0.01). The coefficient of regional variation of perfusion reserve decreased from 16.7 (6.6)% to 11.4 (2.6)% during pacing (9.8 (4.1)% in controls, P < 0.01). CONCLUSIONS: Pacing caused a decrease of resting left ventricular myocardial blood flow and blood flow during pharmacologically induced coronary vasodilatation. Although global perfusion reserve remained unchanged, myocardial perfusion reserve became more homogeneously distributed.

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