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PubMed2004

Efficacy assessment of cerebral arterial bypass surgery using statistical parametric mapping and probabilistic brain atlas on basal/acetazolamide brain perfusion SPECT.

UNLABELLED: The efficacy of cerebral arterial bypass surgery was assessed on brain perfusion SPECT using statistical parametric mapping (SPM) and a probabilistic brain atlas. METHODS: Fifteen patients with ischemia in the internal carotid artery (ICA) territory and 21 age-matched healthy volunteers were enrolled. (99m)Tc-HMPAO basal/acetazolamide brain perfusion SPECT was performed 2 wk before and after bypass surgery and also on a healthy control group. Using SPM analysis, group comparisons were made between pre- and postoperative SPECT for each basal/acetazolamide image, and improvements of perfusion and perfusion reserve were assessed. The number of significant voxels on the SPM analysis was defined as the extent of ischemia. With the use of the probabilistic brain atlas, the counts for the cerebral lobes and the ICA territory were automatically calculated for each image and compared. RESULTS: The group comparisons by SPM between patients and healthy volunteers showed a significant improvement in general perfusion status in the ICA territory. The improvement in perfusion reserve was more extensive than the improvement in perfusion. The extent of ischemia was also significantly decreased after surgery (1,693 +/- 2,604 to 371 +/- 523 voxels in basal images, P = 0.060; 11,879 +/- 6,449 to 5,997 +/- 3,864 voxels in acetazolamide images, P = 0.005). In the analysis using the probabilistic brain atlas, the preoperatively decreased perfusion was normalized after surgery, but a residual decrease in the perfusion reserve was also observed in the ICA territory. The counts in the volume of interest of the ICA territory were significantly improved (38.5 +/- 4.1 to 41.5 +/- 2.7 in basal images, P = 0.024; 34.2 +/- 4.4 to 38.8 +/- 2.9 in acetazolamide images, P = 0.003). One patient showing a decrease in perfusion had a perioperative cerebral infarct. CONCLUSION: Using SPM and a probabilistic brain atlas, the perfusion, the perfusion reserve, and changes in both after cerebral arterial bypass surgery were effectively assessed and correlated well with physiologic reasoning.

Acetazolamide↗
PubMed2005

[Study of post-infarction coronary perfusion using quantitative analysis of myocardial echocardiography with intravenous injection of contrast].

INTRODUCTION AND OBJECTIVES: After a myocardial infarction, damage to the microcirculation indicates a worse prognosis. We compared the usefulness of the quantitative analysis of myocardial contrast echocardiography with intravenous injection of contrast (MCE-iv) with intracoronary injection (MCE-ic) for analyzing coronary perfusion. PATIENTS AND METHOD: We studied 42 patients with a first ST-elevation myocardial infarction, single-vessel disease and a patent artery (TIMI 3, stenosis < 50%). Myocardial perfusion in segments in the infarct-related area was quantified (normalized scale 0-1) with MCE-ic (bolus of Levovist, real-time imaging, perfusion considered normal if > 0.75) and MCE-iv (perfusion of SonoVue, single-image capture in 1 out of each 6 cycles with trigger set at end-systole, perfusion considered normal if > 0.9). Perfusion was considered abnormal if 2 or more segments showed altered perfusion. RESULTS: Quantification with MCE-iv took 5 +/- 1 minutes. No side effects were observed. MCE-ic was normal in 141 segments (80%) out of 176 segments included in the infarcted area, whereas 35 segments (20%) showed abnormal perfusion. MCE-ic was normal in 31 patients (74%) and was altered in 11 cases (26%). Normal perfusion with MCE-iv had a sensitivity of 91%, a specificity of 84% and a kappa index of 0.67 for predicting normal perfusion with MCE-ic (r = 0.86; P < .0001 between the two techniques). CONCLUSIONS: In comparison with MCE-ic, quantitative analysis of single images captured during intravenous perfusion of contrast is an easy, rapid and valid method for analyzing postinfarction coronary perfusion.

Cardiac Catheterization↗
PubMed2005

Clinical evaluation of a new concept: resting myocardial perfusion heterogeneity quantified by markovian analysis of PET identifies coronary microvascular dysfunction and early atherosclerosis in 1,034 subjects.

UNLABELLED: Coronary endothelial dysfunction is an early marker of coronary artery disease (CAD) but its noninvasive assessment is limited. We tested the hypothesis that diffuse patchy heterogeneous resting myocardial perfusion by noninvasive cardiac PET, quantified objectively by Markovian homogeneity analysis, or its improvement during dipyridamole stress, is a predictor of even mild stress perfusion abnormalities, consistent with coronary microvascular dysfunction as an early marker of CAD. METHODS: Rest-dipyridamole PET with (82)Rb was performed on 1,034 consecutive subjects for possible CAD or follow-up, for second opinion on revascularization procedures, or for screening because of risk factors and on 50 healthy control subjects. Objective, automated software quantified myocardial PET perfusion images for (i) patchy diffuse perfusion heterogeneity by Markovian homogeneity analysis separately from, independently of, and around significant localized regional perfusion defects; (ii) size and severity of localized regional perfusion defects caused by flow-limiting stenosis; and (iii) the graded base-to-apex longitudinal perfusion gradient due to early diffuse CAD without flow-limiting stenosis. History of vascular risk factors was obtained for all subjects. RESULTS: Resting myocardial perfusion heterogeneity with a homogeneity index outside 1 SD of healthy reference subjects and its improvement with dipyridamole correlated closely with CAD documented by stress-induced regional myocardial perfusion abnormalities outside 1 SD independently of other risk factors by multivariate logistic regression analysis (P < 0.001), by multivariate linear regression analysis (P < 0.001), and by chi(2) analysis (P < 0.001). The relative odds ratios of having stress-induced myocardial perfusion abnormalities for a resting homogeneity index outside 1 SD of healthy reference subjects was highly predictive and substantially greater than for standard risk factors. CONCLUSION: Patchy heterogeneous resting myocardial perfusion by noninvasive cardiac PET quantified objectively using Markovian homogeneity analysis, and its improvement after dipyridamole, are powerful independent predictors of even mild stress-induced perfusion abnormalities, more than standard risk factors, consistent with coronary microvascular dysfunction as an early marker of preclinical CAD for potential preventive treatment.

Age Distribution↗
PubMed1990

Gamma scintigraphic analysis of the distribution of perfusion of blood in the equine foot during black walnut (Juglans nigra)-induced laminitis.

Twelve horses, with acute laminitis (primarily in the forefeet) at 12 hours after intragastric dosing with an aqueous extract of black walnut (Juglans nigra) heart-wood, were studied. The distribution of perfusion of blood to the foot and to outlined regions within the foot was quantified, using gamma scintigraphy of regionally infused 99mTc-labeled macroaggregated albumin, before and 12 hours after extract administration. Horses 1 to 3 were not studied further. Perfusion was quantified again for horses 4 to 12 at 84 hours after extract administration. At the onset of acute laminitis, horses 7 to 12 were administered a single dose of prazosin (0.025 mg/kg of body weight, IV) immediately after scintigraphy of the right forelimb and before scintigraphy of the left forelimb. When compared with baseline images, perfusion to the forefoot of horses after the development of acute laminitis was quantitatively decreased vs perfusion to the entire distal portion of the forelimb. Also with the onset of laminitis, perfusion also decreased to the dorsal laminar and coronary corium regions vs the distal portion of the forelimb. The acute laminitis-associated deficit in perfusion to the dorsal laminitis-associated deficit in perfusion deficit in perfusion to either the coronary corium or the entire forefoot. Equivalent deficits in the distribution of perfusion were not detected in forelimbs from horses with acute laminitis and which had been treated with prazosin. When compared with baseline images, perfusion to the dorsal lamina was increased in relation to perfusion to the distal portion of the limb at postdosing hour 84. Prazosin treatment did not influence that increase in perfusion to the dorsal lamina.

Animals↗
PubMed1979

Comparison of bubble and membrane oxygenators in short and long perfusions.

Eighty patients had cardiopulmonary bypass (CPB), half having short (109 +/- 11 minutes) perfusions and half having long (188 +/- 14 min) perfusions. Twenty patients in each group were perfused with bubble oxygenators (Bentley, Harvey, or Galen) and 20 with membrane oxygenators (Modulung or Teflo). Hemodilution to a hematocrit value of 22.5% +/- 1.4% and hypothermia to 28 degrees +/- 2 degrees C were used in all patients. Complete hemograms, sequential multiple analyzer 18 tests, coagulation profiles, blood gases and pH, three immunoglobulins, and two complement fraction proteins were sampled as follows: three times before perfusion, one to ten times during perfusion, 1 hour immediately after perfusion, and 4, 24, and 48 hours postoperatively. Data in concentration terms were compared statistically and reported as mean and standard error for each subset. Additionally, rates of gain or loss were calculated in terms of quantity per liter of blood pumped per minute. During perfusion for both duration sets, use of a membrane oxygenator resulted in greater pump flows (4.55 +/- 0.15 L/min versus 3.75 +/- 0.11 L/min), lower total peripheral resistances (1,125 +/- 63 dynes.sec.cm-5 versus 1,652 +/- 115 dynes.sec.cm-5), and greater urinary outputs (9.4 +/- 1.1 ml/min versus 2.2 +/- 0.6 ml/min) than in the bubble oxygenator subsets. Comparisons of measured and calculated data in the immediate postperfusion interval showed no differences between bubble and membrane oxygenator subsets for short perfusions. In long perfusions, the membrane subset had lower plasma hemoglobin and white cell concentrations and generation rates, smaller (3 to 8 1/2 times) losses of IgG, IgM, C3 and shed blood necessitating less transfusion, and greater C4 losses. The membrane oxygenator systems used were more complex and costly and offered no advantages for short perfusion in adults. In anticipated long perfusions or where bleeding may be a problem, a membrane oxygenator appears more efficacious than bubble systems. For perfusions of less than 2 hours, membrane oxygenators had no biochemical or hematologic advantage over the bubble devices used in this study.

Blood Cell Count↗
PubMed1997

[Examination of myocardial perfusion with positron emission tomography: a clinically useful and valid method?].

Positron emission tomography (PET) of the heart has gained widespread scientific and clinical acceptance with regard to 2 indications: 1. the detection of perfusion abnormalities by qualitative and semiquantitative analyses of perfusion images at rest and during physical or pharmacological stress using well validated perfusion tracers such as N-13 ammonia, Rb-82 rubidiumchloride, or O-15 labeled water, 2. Viability imaging of myocardial regions with reduced contractility by combining perfusion measurements with substrate metabolism as assessed from F-18 deoxyglucose utilization. This overview summarizes the use of PET as a perfusion imaging method. With a sensitivity > 90% in combination with a high specificity, PET is today the best available nuclear imaging technique for the diagnosis of coronary artery disease (CAD). The short half-life of the perfusion tracers in combination with highly sophisticated hard- and software enables rapid PET studies with high patient throughput. The high diagnostic accuracy and the methological advantages as compared to conventional scintigraphy allows to use PET perfusion imaging for detection of subtle changes of the perfusion reserve for detection of CAD in high risk but asymptomatic patients as well as in patients with proven CAD undergoing various treatment forms such as risk factor reduction or coronary revascularization. In patients following orthotopic heart transplantation, evolving transplant vasculopathy can be detected at an early stage. Quantitative PET imaging at rest allows for detection of myocardial viability since cellular survival is based on maintenance of a minimal perfusion and structural changes correlate to the degree of perfusion reduction. Furthermore, quantitative assessment of the myocardial perfusion reserve detects the magnitude and competence of collaterals in regions with occluded epicardial arteries and thus, imaging of several coronary distribution territories in one noninvasive study. The cost of PET in combination with the cost of a cyclotron facility together with the demanding methological problems have limited the availability of PET to a few but sophisticated centers. Therefore, quantitative PET investigations have been performed predominantly for scientific purposes and the cost-effectiveness of PET in the everyday clinical setting is not yet finally proven. However, the unique possibilities of PET to study noninvasively and quantitatively myocardial perfusion and metabolism as well as cardiac innervation and pharmacokinetics of cardiac drugs have established cardiac PET as a scientific tool of highest quality for the future.

Coronary Circulation↗
PubMed1999

Brief ex vivo perfusion with heparinized and/or citrated whole blood enhances tolerance of free muscle flaps to prolonged ischemia.

This study investigated the use of heparinized and/or citrated whole blood as a perfusate for enhancing muscle tolerance to warm ischemia. Unilateral cutaneous trunci muscle flaps were harvested from Sprague-Dawley rats and stored for 10 hr at 22-24 degrees C prior to transplantation to the groin. One group served as a non-perfused control. In three experimental groups, the flaps were hand-perfused ex vivo with 1.0 ml of heparinized, citrated, or heparinized and citrated autogenous whole blood at physiological pressures. Perfusion was administered over a 10-min period 5 hr into the ischemic period. Flaps were revascularized on the femoral vessels and then harvested 48 hr following revascularization. Tissue injury was assessed by calculation of flap weight change (indicator of tissue edema), histochemical evaluation of muscle dehydrogenase activity (nitroblue tetrazolium assay), and light microscopy. All perfused groups had significantly higher muscle dehydrogenase activity compared with non-perfused controls (P < 0.005). Perfusion with combined heparin-citrated blood was significantly more protective than perfusion with either anticoagulant alone (P < 0.025). The only statistically significant reduction in percent flap edema was seen in the combined heparin-citrate perfusion of flaps compared with nonperfused controls (P < 0.05). Histologic evaluation confirmed a reduction in tissue edema in the perfused flaps. We conclude that mid-ischemic perfusion with heparinized and/or citrated blood limits the deleterious effects of extended warm ischemia.

Analysis of Variance↗
PubMed1992

Effects of normal and sickle erythrocytes on prostacyclin release by perfused human umbilical cord veins.

We compared the effects of normal (AA) and sickle (SS) erythrocytes (RBC) on endothelial cell release of prostacyclin by perfused human umbilical cord veins. Two equal-length segments of fresh umbilical cords were perfused first with serum-free Dulbecco's modified Eagle's medium (DMEM) to establish the basal prostacyclin production rate for each segment; then one segment was perfused with SS RBC and/or plasma, while the other segment was simultaneously perfused with AA RBC and/or plasma. Aliquots of perfusate were removed at intervals for measurement of the stable prostacyclin metabolite 6-keto-prostaglandin F1 alpha (6-keto-PGF). Basal prostacyclin production by segments from the same cord was very similar, but it varied considerably among segments from different cords. Therefore, the ratio of prostacyclin release with RBC and/or plasma to basal prostacyclin release for each segment was used to compare prostacyclin release among segments from different cords. Mean prostacyclin release was significantly higher from segments perfused with SS RBC in autologous plasma than from segments perfused with AA RBC in autologous plasma at 15, 30, and 60 min. However, no significant differences in mean prostacyclin production were observed between segments perfused with SS vs. AA RBC in DMEM or between segments perfused with SS vs. AA plasma alone. No significant correlations were observed between prostacyclin production and either the viscosity of SS and AA RBC in autologous plasma or DMEM or the adhesiveness of SS and AA RBC to cultured human umbilical vein endothelial cells. We conclude that SS RBC in autologous plasma cause increased prostacyclin release from perfused human umbilical cord veins. The perfused human umbilical cord vein system may be a useful model for comparing the response of vascular endothelium to SS and AA RBC and plasma under controlled-flow conditions.

6-Ketoprostaglandin F1 alpha↗
PubMed1998

Measurement of perfusion rate in human melanoma xenografts by contrast-enhanced magnetic resonance imaging.

Reliable methods based on MRI for measurement of the perfusion rate in human tumors are highly warranted. Tumors of two amelanotic human melanoma xenograft lines were subjected to dynamic 1H MRI after i.v. administration of gadopentetate dimeglumine (Gd-DTPA). The aim was to investigate to what extent different perfusion parameters determined from the Gd-DTPA kinetics, i.e., the initial uptake rate, the maximal uptake, the decay rate, and the perfusion rate calculated by use of the Kety equation, can be used as a reliable estimate of tumor perfusion rate. Each parameter was calculated in dual; one calculation was based on relative signal intensity increase (RSII) in T1-weighted MR images and the other on Gd-DTPA concentration determined from the images. The perfusion parameters were compared with the perfusion rates determined from measurement of tumor uptake of 86Rb or [14C]iodoantipyrine. The results showed that reliable estimates of tumor perfusion rate can be achieved from analysis of Gd-DTPA kinetics by use of the Kety equation. Gd-DTPA kinetics based on concentration might be used to achieve reliable estimates of absolute tumor perfusion rate, whereas reliable estimates of the relative perfusion rate might also be achieved from Gd-DTPA kinetics based on RSII. The initial uptake rate, the maximal uptake, and the decay rate of Gd-DTPA, however, are not reliable estimates of tumor perfusion rate, mainly because these parameters are highly influenced by the tumor extracellular volume fraction in addition to the perfusion rate.

Animals↗
PubMed1998

Hypothermic oscillating liver perfusion stimulates ATP synthesis prior to transplantation.

BACKGROUND: ATP and glycogen depletion often have been demonstrated during cold storage of the liver prior to transplantation. Suppression of events that lead to metabolic depression and to lipid peroxidation could contribute to improvement of liver preservation. A new method of liver preservation for transplantation is therefore suggested, an oscillating oxygenated hypothermic liver perfusion. METHODS: Biochemical analysis of liver tissue samples and perfusate after 10 h of perfusion by the presented oscillating perfusion model were compared with results after continuous liver perfusion for 10 h as well as with data derived from cold-stored livers over a period of 10 h. Particular reference was made to nucleotide metabolites, glycogen content, lipid peroxidation, glutathione content, glycolytic metabolites, and enzyme release before and after preservation. RESULTS: Glycogen depletion occurred to the same degree in hypothermic storage and machine perfusion (oscillating as well as continuous perfusion), but the energy charge was significantly increased after oxygenated perfusion, whereas cold storage resulted in a significant energy charge depletion. In addition, perfusion by an oscillating technique yielded superior energy charge loading compared to the continuous perfusion technique and diminished the other hand lipid peroxidation. CONCLUSIONS: Hypothermic oscillating oxygenated perfusion could be important for the improvement of the quality of energy-depleted organs prior to transplantation.

Adenosine↗
PubMed2006

The "push-to-low" approach for optimization of high-density perfusion cultures of animal cells.

High product titer is considered a strategic advantage of fed-batch over perfusion cultivation mode. The titer difference has been experimentally demonstrated and reported in the literature. However, the related theoretical aspects and strategies for optimization of perfusion processes with respect to their fed-batch counterparts have not been thoroughly explored. The present paper introduces a unified framework for comparison of fed-batch and perfusion cultures, and proposes directions for improvement of the latter. The comparison is based on the concept of "equivalent specific perfusion rate", a variable that conveniently bridges various cultivation modes. The analysis shows that development of economically competitive perfusion processes for production of stable proteins depends on our ability to dramatically reduce the dilution rate while keeping high cell density, i.e., operating at low specific perfusion rates. Under these conditions, titer increases significantly, approaching the range of fed-batch titers. However, as dilution rate is decreased, a limit is reached below which performance declines due to poor growth and viability, specific productivity, or product instability. To overcome these limitations, a strategy referred to as "push-to-low" optimization has been developed. This approach involves an iterative stepwise decrease of the specific perfusion rate, and is most suitable for production of stable proteins where increased residence time does not compromise apparent specific productivity or product quality. The push-to-low approach was successfully applied to the production of monoclonal antibody against tumor necrosis factor (TNF). The experimental results followed closely the theoretical prediction, providing a multifold increase in titer. Despite the medium improvement, reduction of the specific growth rate along with increased apoptosis was observed at low specific perfusion rates. This phenomenon could not be explained with limitation or inhibition by the known nutrients and metabolites. Even further improvement would be possible if the cause of apoptosis were understood. In general, a strategic target in the optimization of perfusion processes should be the decrease of the cell-specific perfusion rate to below 0.05 nL/cell/day, resulting in high, batch-like titers. The potential for high titer, combined with high volumetric productivity, stable performance over many months, and superior product/harvest quality, make perfusion processes an attractive alternative to fed-batch production, even in the case of stable proteins.

Animals↗
PubMed1992

Portal circulation and the function of hepatocytes during ex vivo perfusion of the rat liver preserved for six hours after core cooling.

Portal circulation and the function of hepatocytes during isolated organ perfusion were compared between the rat liver perfused immediately after extirpation and the liver perfused after core cooling and six hours of preservation. Nine rat livers were extirpated after core cooling, preserved for six hours in University of Wisconsin (UW) solution at 4 degrees C and then were connected to a perfusion chamber (hypothermic preservation group: 6-hr HP group). Six rat livers were immediately connected to the perfusion chamber after extirpation (control group). During 60 minutes of isolated liver perfusion, both portal circulation and the function of hepatocytes were determined every 10 minutes. Portal vein resistance increased and portal blood flow decreased during the first 20 minutes of perfusion and then stabilized in both groups. Portal vein resistance was significantly higher and portal blood flow was significantly lower for the first 10 minutes of perfusion in the 6-hr HP group, compared to the control group. The function of hepatocytes, determined by the rate of elimination of ammonia, oxygen consumption, and glucose availability were depressed in the 6-hr HP group, compared to the control groups during isolated liver perfusion. However, there was no statistically significant difference of portal perfusion and the function of hepatocytes between the two groups at the end of perfusion. The results of the present study indicate that the rat liver can be preserved in a satisfactory condition for six hours by the use of hypothermic preservation, coupled with core cooling.

Ammonia↗
PubMed1981

Effects of pulsatile and non-pulsatile perfusion on the isolated canine heart.

Isolated canine hearts with a critical stenosis on one coronary artery were perfused for 2 h with blood from supporting dogs using a new roller pump system that can deliver pulsatile or non-pulsatile flow perfusion. Non-pulsatile perfusion caused a decrease in coronary venous oxygen tension of 22% (P less than 0.05) accompanied by increasing carbon dioxide tension of 50% (P less than 0.02). With pulsatile flow coronary venous oxygen and carbon dioxide tensions remained stable. Non-pulsatile perfusion decreased the coronary arteriovenous oxygen difference by 35% (P less than 0.02), coronary blood flow by 40% (P less than 0.02), and myocardial oxygen consumption by 54% (P less than 0.01) whereas pulsatile flow did not change any of these variables. Subendocardial blood flow distal to the stenosis fell by 0.15 +/- 0.04 ml/min per gram myocardium (mean +/- S.E.M.) (P less than 0.01) during linear perfusion. The endocardial/epicardial-flow ratio was less than one and decreased further during fibrillation period indicating underperfusion of the endocardial muscle region. With pulsatile flow subendocardial flow remained unaltered during the two hours of fibrillation. Edema formation was 24% in hearts subjected to non-pulsatile flow but only 14% in hearts perfused by pulsatile perfusion (P less than 0.05). Accordingly, the ischemic area involved 40% of the left ventricle during non-pulsatile flow but 25% of the left ventricle in hearts perfused by pulsatile perfusion (P less than 0.05). The results indicate that pulsatile flow perfusion may prevent severe hemodynamic, hematologic, and metabolic alterations in fibrillating isolated canine hearts. It is suggested that pulsatile perfusion may be useful for fibrillating hearts during open heart surgery.

Animals↗
PubMed1986

Apparent loss of calcium-activated potassium current in internally perfused snail neurons is due to accumulation of free intracellular calcium.

Internal perfusion of Helix neurons with a solution containing potassium aspartate, MgCl2, ATP, and HEPES causes the calcium-activated potassium current (IK(Ca)) evoked by depolarizing voltage steps to decrease with time. When internal free Ca++ is strongly buffered to 10(-7) M by including 0.5 mM EGTA and 0.225 mM CaCl2 in the internal solution, IK(Ca) remains constant for up to 3 hours of perfusion. In cells where IK(Ca) is small at the start of perfusion, perfusion with the strongly buffered 10(-7) M free Ca++ solution produces increases in IK(Ca) which ultimately saturate. In cells perfused with solutions buffered to 10(-6) M free Ca++, IK(Ca) is low and does not change with perfusion. These results lead us to conclude that IK(Ca) is stable in perfused Helix neurons and that the apparent loss of IK(Ca) seen initially with perfusion is due to accumulation of cytoplasmic calcium. Since the calcium current (ICa) provides the Ca++ which activates IK(Ca) during a depolarizing pulse, ICa is also stable in perfused cells when free intracellular Ca++ is buffered. Perfusion with 1 microM calmodulin (CaM) produces no effect on IK(Ca) with either 10(-7) or 10(-6) M free internal calcium. Inhibiting endogenous CaM by including 50 microM trifluoperazine (TFP) in both the bath and the internal perfusion solution also produces no effect on IK(Ca) with 10(-7) M free internal calcium. It is concluded that CaM plays no role in IK(Ca) activation.

Animals↗
PubMed2003

[Arterial back table pressure perfusion prevents ischemic biliary lesions after orthotopic liver transplantation].

INTRODUCTION: Ischemic biliary lesions are a threatening complication following orthotopic liver transplantation. Their exact pathophysiological mechanism is unknown so far, but insufficient perfusion of biliary arterial vessels might be responsible for the development of these lesions. This might be changed by improved perfusion techniques. We performed a controlled study of cases since February 2000. MATERIALS AND METHODS: We used arterial back table pressure perfusion to achieve reliable perfusion of the capillary system of the biliary tract, which may be impaired by the high viscosity of University of Wisconsin solution. In this study, 190 orthotopic liver transplantations performed between September 1997 and July 2002 were investigated with regard to ischemic biliary lesions. RESULTS: One hundred thirty-one grafts were preserved by in situ standard perfusion including portal perfusion,whereas additional arterial back table pressure perfusion was performed in 59 cases. Donor-related factors, recipient age, indications for transplantation, transplantation techniques, and ischemia times were comparable between groups. Twenty-one (16%) of the patients in the standard perfusion group and only one of the those receiving arterial back table pressure perfusion developed ischemic biliary lesions. This difference was highly significant (P=0.004). Maximal aspartate aminotransferase and alanine aminotransferase levels in the first 3 days were significantly lower in the arterial back table pressure perfusion group (P>0.05). CONCLUSION: Arterial back table pressure perfusion is an easy and reliable method for preventing ischemic biliary lesions in orthotopic liver transplantation. It should, therefore, be the standard technique in liver procurement.

Adenosine↗
PubMed2006

Prognostic value of stress 99mTc-tetrofosmin myocardial perfusion imaging in predicting all-cause mortality: a 6-year follow-up study.

PURPOSE: The aim of this study was to ascertain whether stress myocardial perfusion imaging can independently predict long-term mortality. METHODS: We studied 1,386 patients with known or suspected coronary artery disease by means of stress 99mTc-tetrofosmin myocardial perfusion tomography. The end point during follow-up was death from any cause. Mortality rates were compared with that in a reference population using calculated age- and gender-specific data in the general population. RESULTS: Mean age was 60+/-11 years. There were 608 (44%) women. Perfusion abnormalities were fixed in 416 (30%) patients and reversible in 445 (32%) patients. During a mean follow-up of 6+/-1.9 years, 290 (21%) patients died. The annual mortality was 1.7% in patients with normal perfusion and 5.2% in patients with abnormal perfusion. Patients with multivessel distribution of perfusion abnormalities had the highest annual mortality (6.2%). The annual mortality in the reference population was 3.2%. In a multivariate analysis model, predictors of death were age [risk ratio (RR)=1.06, 95% CI 1.04-1.07], male gender (RR=2, CI 1.6-2.6), history of heart failure (RR=2.3, CI 1.8-3.1), diabetes mellitus (RR=2.1, CI 1.6-2.7), smoking (RR=1.8, CI 1.4-2.3), reversible perfusion defects (RR=1.8, CI 1.4-2.5) and fixed perfusion defects (RR=1.7, CI 1.3-2.1). CONCLUSION: Myocardial perfusion abnormalities on stress 99mTc-tetrofosmin tomography are independently associated with long-term risk of death. The extent of perfusion abnormalities is a major determinant of mortality. The presence of normal perfusion is associated with a lower mortality compared with the general population.

Coronary Artery Disease↗
PubMed2000

Hyperosmotic perfusion of the beating rat heart and the role of the Na+/K+/2Cl- co-transporter and the Na+/H+ exchanger.

The aim of the present study was to investigate the role of the Na+/K+/2Cl- co-transporter and the Na+/H+ exchanger on contractile function and electrolyte regulation during hyperosmotic perfusion of the heart. Langendorff perfused rat hearts were subjected to hyperosmolal perfusion in 10-min intervals. Perfusates were made hyperosmotic by adding mannitol to the buffer (370, 450 and 600 mOsmol/kg H2O). Cardiac contractile function was monitored with a balloon in the left ventricle (LV) coupled to a pressure transducer. Cardiac effluent was sampled repeatedly throughout and after hyperosmotic perfusion and analysed for content of Na+, K+, and Cl-. All three hyperosmotic perfusates initially reduced LV developed pressure (LVDP), but for 370 and 450 mOsmol/kg H2O, LVDP recovered to baseline within 4 min of perfusion. With 600 mOsmol/kg H2O, LVDP recovered slowly and was 50% below baseline after 10 min of hyperosmotic perfusion. Inhibition of the Na+/H+ exchanger with 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and 3-methylsulfonyl-4-piperidinobenzoyl-guanidine methanesulfonate (HOE 694) abolished the recovery of LVDP to the 600 mOsmol/kg H2O perfusate, whereas inhibition of the Na+/K+/2Cl- co-transporter had no impact on LVDP. Potassium was taken up by the heart during hyperosmotic perfusion and this uptake was significantly reduced with inhibition of the Na+/H+ exchanger. Intracellular pH was assessed with 31p magnetic resonance spectroscopy and hyperosmolality induced a significant alkalosis that was dependent upon the Na+/H+ exchanger. The rat heart responds to moderate elevations in osmolality with a transient reduction in contractile function, whereas an elevation of 300 mOsmol/kg H2O persistently reduces contractile function. The Na+/H+ exchanger, but not the Na+/K+/2Cl- co-transporter, is of importance in contractile recovery and electrolyte regulation during hyperosmotic perfusion in the rat heart.

Animals↗
PubMed1988

Inadequate subendocardial oxygen delivery during perfluorocarbon perfusion in a canine model of ischemia.

Perfusion of the coronary artery distal to an occlusion was performed in 16 canine preparations to compare the mechanical perfusion of autologous blood to the perfluorocarbon fluosol DA, 20% emulsion (FDA-20). Both substances were perfused under similar conditions (30, 60, and 80 ml/min) and regional electrograms, contractility, and coronary perfusion were measured relative to native coronary perfusion. Autologous blood (60 and 80 ml/min) produced a significant increase in regional (epicardial, midmyocardial, and endocardial) and transmural flow, but not in the endocardial/epicardial perfusion ratio. No other significant changes were observed during autologous blood perfusion. In contrast, FDA-20 perfusion resulted in significant ST depression (-1.8 +/- 0.2, -1.7 +/- 0.2, and -1.3 +/- 0.3 mm) at 30, 60, and 80 ml/min, respectively. FDA-20 also induced a significant decrease in distal diastolic coronary pressure and resistance, a significant decrease in the endocardial/epicardial perfusion ratio at all three perfusion rates, and a significant reduction in delivery of O2 to the subendocardium. These results indicate that autologous blood perfusion of the distal coronary artery during occlusion preserves myocardial function to a better degree than does FDA-20.

Animals↗