Comparativecost-effectivenessanalyses of cardiacmagneticresonanceimaging versus invasive coronary angiography combined with fractional flow reserve testing to diagnose ischemia in coronary artery disease

Introduction: According to guidelines, patients with coronary artery disease (CAD) should undergo revascularization if myocardial ischemia is present. While coronary angiography (CXA) allows the morphological assessment of CAD, the fractional flow reserve (FFR) has proved to be a complementary invasive test to assess the functional significance of CAD, i.e. to detect ischemia. Perfusion Cardiac Magnetic Resonance (CMR) has turned out to be a robust non-invasive technique to assess myocardial ischemia. The objective: is to compare the cost-effectiveness ratio - defined as the costs per patient correctly diagnosed - of two algorithms used to diagnose hemodynamically significant CAD in relation to the pretest likelihood of CAD: 1) aCMRto assess ischemia before referring positive patients to CXA (CMR + CXA), 2) a CXA in all patients combined with a FFR test in patients with angiographically positive stenoses (CXA + FFR). Methods: The costs, evaluated from the health care system perspective in the Swiss, German, the United Kingdom (UK) and the United States (US) contexts, included public prices of the different tests considered as outpatient procedures, complications' costs and costs induced by diagnosis errors (false negative). The effectiveness criterion wasthe ability to accurately identify apatient with significantCAD.Test performancesused in the model were based on the clinical literature. Using a mathematical model, we compared the cost-effectiveness ratio for both algorithms for hypothetical patient cohorts with different pretest likelihood of CAD. Results: The cost-effectiveness ratio decreased hyperbolically with increasing pretest likelihood of CAD for both strategies. CMR + CXA and CXA + FFR were equally costeffective at a pretest likelihood of CAD of 62% in Switzerland, 67% in Germany, 83% in the UK and 84% in the US with costs of CHF 5'794, Euros 1'472, £ 2'685 and $ 2'126 per patient correctly diagnosed. Below these thresholds, CMR + CXA showed lower costs per patient correctly diagnosed than CXA + FFR. Implications for the health care system/professionals/patients/society These results facilitate decision making for the clinical use of new generations of imaging procedures to detect ischemia. They show to what extent the cost-effectiveness to diagnose CAD depends on the prevalence of the disease.

Intrauterine growth restriction and absent or reverse end-diastolic blood flow in umbilical artery (Doppler class II or III): A retrospective study of short- and long-term fetal morbidity and mortality.

OBJECTIVE: Absent or reverse end-diastolic flow (Doppler II/III) in umbilical artery is correlated with poor perinatal outcome, particularly in intrauterine growth restricted (IUGR) fetuses. The optimal timing of delivery is still controversial. We studied the short- and long-term morbidity and mortality among these children associated with our defined management. STUDY DESIGN: Sixty-nine IUGR fetuses with umbilical Doppler II/III were divided into three groups; Group 1, severe early IUGR, no therapeutic intervention (n = 7); Group 2, fetuses with pathological biophysical profile, immediate delivery (n = 35); Group 3, fetuses for which expectant management had been decided (n = 27). RESULTS: In Group 1, stillbirth was observed after a mean delay of 6.3 days. Group 2 delivered at an average of 31.6 weeks and two died in the neonatal period (6%). In Group 3 after a mean delay of 8 days, average gestational age at delivery was 31.7 weeks; two intra uterine and four perinatal deaths were observed (22%). Long-term follow-up revealed no sequelae in 25/31 (81%) and 15/18 (83%), and major handicap occurred in 1 (3%) and 2 patients (11%), respectively, for Groups 2 and 3. CONCLUSION: Fetal mortality was observed in 22% of this high risk group. After a mean period of follow-up of 5 years, 82% of infants showed no sequelae. According to our management, IUGR associated with umbilical Doppler II or III does not show any benefit from an expectant management in term of long-term morbidity.

Computational fluid dynamics of the right ventricular outflow tract and of the pulmonary artery: a bench model of flow dynamics.

OBJECTIVES: The reconstruction of the right ventricular outflow tract (RVOT) with valved conduits remains a challenge. The reoperation rate at 5 years can be as high as 25% and depends on age, type of conduit, conduit diameter and principal heart malformation. The aim of this study is to provide a bench model with computer fluid dynamics to analyse the haemodynamics of the RVOT, pulmonary artery, its bifurcation, and left and right pulmonary arteries that in the future may serve as a tool for analysis and prediction of outcome following RVOT reconstruction. METHODS: Pressure, flow and diameter at the RVOT, pulmonary artery, bifurcation of the pulmonary artery, and left and right pulmonary arteries were measured in five normal pigs with a mean weight of 24.6 ± 0.89 kg. Data obtained were used for a 3D computer fluid-dynamics simulation of flow conditions, focusing on the pressure, flow and shear stress profile of the pulmonary trunk to the level of the left and right pulmonary arteries. RESULTS: Three inlet steady flow profiles were obtained at 0.2, 0.29 and 0.36 m/s that correspond to the flow rates of 1.5, 2.0 and 2.5 l/min flow at the RVOT. The flow velocity profile was constant at the RVOT down to the bifurcation and decreased at the left and right pulmonary arteries. In all three inlet velocity profiles, low sheer stress and low-velocity areas were detected along the left wall of the pulmonary artery, at the pulmonary artery bifurcation and at the ostia of both pulmonary arteries. CONCLUSIONS: This computed fluid real-time model provides us with a realistic picture of fluid dynamics in the pulmonary tract area. Deep shear stress areas correspond to a turbulent flow profile that is a predictive factor for the development of vessel wall arteriosclerosis. We believe that this bench model may be a useful tool for further evaluation of RVOT pathology following surgical reconstructions.

Superior venous drainage in the "LifeBox": a portable extracorporeal oxygenator with a self-expanding venous cannula.

BACKGROUND: In an experimental setting, the performance of the LifeBox, a new portable extracorporeal membrane oxygenator (ECMO) system suitable for patient transport, is presented. Standard rectilinear percutaneous cannulae are normally employed for this purpose, but have limited flow and pressure delivery due to their rigid structure. Therefore, we aimed to determine the potential for flow increase by using self-expanding venous cannulae. METHODS: Veno-arterial bypass was established in three pigs (40.6+/-5.1 kg). The venous line of the cardiopulmonary bypass was established by cannulation of the external jugular vein. The arterial side of the circulation was secured by cannulation of the common carotid artery. Two different venous cannulae (SmartCanula 18/36F 430mm and Biomedicus 19F) were examined for their functional integrity when used in conjunction with the centrifugal pump (500-3000 RPM) of the LifeBox system. RESULTS: At 1500, 2000, 2500, and 3000 RPM, the blood flow increased steadily for each cannula, but remained higher in the self-expanding cannula. That is, the 19F rectilinear cannula achieved a blood flow of 0.93+/-0.14, 1.47+/-0.37, 1.9+/-0.68, and 1.5+/-0.9 l/min, respectively, and the 18/36F self-expanding cannula achieved 1.1+/-0.1, 1.9+/-0.33, 2.8+/-0.39 and 3.66+/-0.52 l/min. However, when tested for venous line pressure, the standard venous cannula achieved -29+/-10.7mmHg while the self-expanding cannula achieved -13.6 +/-4.3mmHg at 1500 RMP. As the RPM increased from 2500 to 3000, the venous line pressure accounted for -141.9+/-20 and -98+/-7.3mmHg for the 19F rectilinear cannula and -30.6+/-6.4 and -45+/-11.6mmHg for the self-expanding cannula. CONCLUSION: The self-expanding cannula exhibited superior venous drainage ability when compared to the performance of the standard rectilinear cannula with the use of the LifeBox. The flow rate achieved was approximately 40% greater than the standard drainage device, with a maximal pump flow recorded at 4.3l/min.

Superior diagnostic performance of perfusion-cardiovascular magnetic resonance versus SPECT to detect coronary artery disease: The secondary endpoints of the multicenter multivendor MR-IMPACT II (Magnetic Resonance Imaging for Myocardial Perfusion Assessment in Coronary Artery Disease Trial).

ABSTRACT: BACKGROUND: Perfusion-cardiovascular magnetic resonance (CMR) is generally accepted as an alternative to SPECT to assess myocardial ischemia non-invasively. However its performance vs gated-SPECT and in sub-populations is not fully established. The goal was to compare in a multicenter setting the diagnostic performance of perfusion-CMR and gated-SPECT for the detection of CAD in various populations using conventional x-ray coronary angiography (CXA) as the standard of reference. METHODS: In 33 centers (in US and Europe) 533 patients, eligible for CXA or SPECT, were enrolled in this multivendor trial. SPECT and CXA were performed within 4 weeks before or after CMR in all patients. Prevalence of CAD in the sample was 49% and 515 patients received MR contrast medium. Drop-out rates for CMR and SPECT were 5.6% and 3.7%, respectively (ns). The study was powered for the primary endpoint of non-inferiority of CMR vs SPECT for both, sensitivity and specificity for the detection of CAD (using a single-threshold reading), the results for the primary endpoint were reported elsewhere. In this article secondary endpoints are presented, i.e. the diagnostic performance of CMR versus SPECT in subpopulations such as multi-vessel disease (MVD), in men, in women, and in patients without prior myocardial infarction (MI). For diagnostic performance assessment the area under the receiver-operator-characteristics-curve (AUC) was calculated. Readers were blinded versus clinical data, CXA, and imaging results. RESULTS: The diagnostic performance (= area under ROC = AUC) of CMR was superior to SPECT (p = 0.0004, n = 425) and to gated-SPECT (p = 0.018, n = 253). CMR performed better than SPECT in MVD (p = 0.003 vs all SPECT, p = 0.04 vs gated-SPECT), in men (p = 0.004, n = 313) and in women (p = 0.03, n = 112) as well as in the non-infarct patients (p = 0.005, n = 186 in 1-3 vessel disease and p = 0.015, n = 140 in MVD). CONCLUSION: In this large multicenter, multivendor study the diagnostic performance of perfusion-CMR to detect CAD was superior to perfusion SPECT in the entire population and in sub-groups. Perfusion-CMR can be recommended as an alternative for SPECT imaging. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT00977093.

Prevalence and clinical importance of mesenteric venous thrombosis in the swiss inflammatory bowel disease cohort.

OBJECTIVE. The purpose of this study was to evaluate the prevalence of mesenteric venous thrombosis (MVT) in the Swiss Inflammatory Bowel Disease Cohort Study and to correlate MVT with clinical outcome. MATERIALS AND METHODS. Abdominal portal phase CT was used to examine patients with inflammatory bowel disease (IBD). Two experienced abdominal radiologists retrospectively analyzed the images, focusing on the superior and inferior mesenteric vein branches and looking for signs of acute or chronic thrombosis. The location of abnormalities was registered. The presence of MVT was correlated with IBD-related radiologic signs and complications. RESULTS. The cases of 160 patients with IBD (89 women, 71 men; Crohn disease [CD], 121 patients; ulcerative colitis [UC], 39 patients; median age at diagnosis, 27 years for patients with CD, 32 years for patients with UC) were analyzed. MVT was detected in 43 patients with IBD (26.8%). One of these patients had acute MVT; 38, chronic MVT; and four, both. The prevalence of MVT did not differ between CD (35/121 [28.9%]) and UC (8/39 [20.5%]) (p = 0.303). The location of thrombosis was different between CD and UC (CD, jejunal or ileal veins only [p = 0.005]; UC, rectocolic veins only [p = 0.001]). Almost all (41/43) cases of thrombosis were peripheral. MVT in CD patients was more frequently associated with bowel wall thickening (p = 0.013), mesenteric fat hypertrophy (p = 0.005), ascites (p = 0.002), and mesenteric lymph node enlargement (p = 0.036) and was associated with higher rate of bowel stenosis (p < 0.001) and more intestinal IBD-related surgery (p = 0.016) in the outcome. Statistical analyses for patients with UC were not relevant because of the limited population (n = 8). CONCLUSION. MVT is frequently found in patients with IBD. Among patients with CD, MVT is associated with bowel stenosis and CD-related intestinal surgery.

Heterogeneous T-cell response to MAGE-A10(254-262): high avidity-specific cytolytic T lymphocytes show superior antitumor activity.

MAGE-encoded antigens, which are expressed by tumors of many histological types but not in normal tissues, are suitable candidates for vaccine-based immunotherapy of cancers. Thus far, however, T-cell responses to MAGE antigens have been detected only occasionally in cancer patients. In contrast, by using HLA/peptide fluorescent tetramers, we have observed recently that CD8(+) T cells specific for peptide MAGE-A10(254-262) can be detected frequently in peptide-stimulated peripheral blood mononuclear cells from HLA-A2-expressing melanoma patients and healthy donors. On the basis of these results, antitumoral vaccination trials using peptide MAGE-A10(254-262) have been implemented recently. In the present study, we have characterized MAGE-A10(254-262)-specific CD8(+) T cells in polyclonal cultures and at the clonal level. The results indicate that the repertoire of MAGE-A10(254-262)-specific CD8(+) T cells is diverse both in terms of clonal composition, efficiency of peptide recognition, and tumor-specific lytic activity. Importantly, only CD8(+) T cells able to recognize the antigenic peptide with high efficiency are able to lyse MAGE-A10-expressing tumor cells. Under defined experimental conditions, the tetramer staining intensity exhibited by MAGE-A10(254-262)-specific CD8(+) T cells correlates with efficiency of peptide recognition so that "high" and "low" avidity cells can be separated by FACS. Altogether, the data reported here provide evidence for functional diversity of MAGE-A10(254-262)-specific T cells and will be instrumental for the monitoring of peptide MAGE-A10(254-262)-based clinical trials.

Prevalence and clinical importance of mesenteric venous thrombosis in the Swiss Inflammatory Bowel Disease Cohort

OBJECTIVE: The purpose of this study was to evaluate the prevalence of mesenteric venous thrombosis (MVT) in the Swiss Inflammatory Bowel Disease Cohort Study and to correlate MVT with clinical outcome. MATERIALS AND METHODS: Abdominal portal phase CT was used to examine patients with inflammatory bowel disease (IBD). Two experienced abdominal radiologists retrospectively analyzed the images, focusing on the superior and inferior mesenteric vein branches and looking for signs of acute or chronic thrombosis. The location of abnormalities was registered. The presence of MVT was correlated with IBD-related radiologic signs and complications. RESULTS: The cases of 160 patients with IBD (89 women, 71 men; Crohn disease [CD], 121 patients; ulcerative colitis [UC], 39 patients; median age at diagnosis, 27 years for patients with CD, 32 years for patients with UC) were analyzed. MVT was detected in 43 patients with IBD (26.8%). One of these patients had acute MVT; 38, chronic MVT; and four, both. The prevalence of MVT did not differ between CD (35/121 [28.9%]) and UC (8/39 [20.5%]) (p = 0.303). The location of thrombosis was different between CD and UC (CD, jejunal or ileal veins only [p = 0.005]; UC, rectocolic veins only [p = 0.001]). Almost all (41/43) cases of thrombosis were peripheral. MVT in CD patients was more frequently associated with bowel wall thickening (p = 0.013), mesenteric fat hypertrophy (p = 0.005), ascites (p = 0.002), and mesenteric lymph node enlargement (p = 0.036) and was associated with higher rate of bowel stenosis (p < 0.001) and more intestinal IBD-related surgery (p = 0.016) in the outcome. Statistical analyses for patients with UC were not relevant because of the limited population (n = 8). CONCLUSION: MVT is frequently found in patients with IBD. Among patients with CD, MVT is associated with bowel stenosis and CD-related intestinal surgery.

Is intra-operative blood flow predictive for early failure of radiocephalic arteriovenous fistula?

BACKGROUND: For over 50 years, radiocephalic wrist arteriovenous fistulae (RCAVF) have been the primary and best vascular access for haemodialysis. Nevertheless, early failure due to thrombosis or non-maturation is a major complication resulting in their abandonment. This prospective study was designed to investigate the predictive value of intra-operative blood flow on early failure of primary RCAVF before the first effective dialysis. METHODS: We enrolled patients undergoing creation of primary RCAVF for haemodialysis based on the pre-operative ultrasound vascular mapping discussed in a multidisciplinary approach. Intra-operative blood flow measurement was systematically performed once the anastomosis had been completed using a transit-time ultrasonic flowmeter. During the follow-up, blood flow was estimated by colour flow ultrasound at various intervals. Any events related to the RCAVF were recorded. RESULTS: Autogenous RCAVFs (n = 58) in 58 patients were constructed and followed up for an average of 30 days. Thrombosis and non-maturation occurred in eight (14%) and four (7%) patients, respectively. The intra-operative blood flow in functioning RCAVFs was significantly higher compared to non-functioning RCAVFs (230 vs 98 mL/min; P = 0.007), as well as 1 week (753 vs 228 mL/min; P = 0.0008) and 4 weeks (915 vs 245 mL/min, P < 0.0001) later. Blood flow volume measurements with a cut-off value of 120 mL/min had a sensitivity of 67%, specificity of 75% and positive predictive value of 91%. CONCLUSIONS: Blood flow <120 mL has a good predictive value for early failure in RCAVF. During the procedure, this cut-off value may be used to select appropriately which RCAVF should be investigated in the operation theatre in order to correct in real time any abnormality.

Cost evaluation of cardiac magnetic resonance imaging versus coronary angiography for the work-up of coronary artery disease

Background: CMR has recently emerged as a robust and reliable technique to assess coronary artery disease (CAD). A negative perfusion CMR test predicts low event rates of 0.3-0.5%/year. Invasive coronary angiography (CA) remains the "gold standard" for the evaluation of CAD in many countries.Objective: Assessing the costs of the two strategies in the European CMR registry for the work-up of known or suspected CAD from a health care payer perspective. Strategy 1) a CA to all patients or 2) a CA only to patients who are diagnosed positive for ischemia in a prior CMR.Method and results: Using data of the European CMR registry (20 hospitals, 11'040 consecutive patients) we calculated the proportion of patients who were diagnosed positive (20.6%), uncertain (6.5%), and negative (72.9%) after the CMR test in patients with known or suspected CAD (n=2'717). No other medical test was performed to patients who were negative for ischemia. Positive diagnosed patients had a coronary angiography. Those with uncertain diagnosis had additional tests (84.7%: stress echocardiography, 13.1%: CCT, 2.3% SPECT), these costs were added to the CMR strategy costs. Information from costs for tests in Germany and Switzerland were used. A sensibility analysis was performed for inpatient CA. For costs see figure. Results - costs.Discussion: The CMR strategy costs less than the CA strategy for the health insurance systems both, in Germany and Switzerland. While lower in costs, the CMR strategy is a non-invasive one, does not expose to radiation, and yields additional information on cardiac function, viability, valves, and great vessels. Developing the use of CMR instead of CA might imply some reduction in costs together with superior patient safety and comfort, and a better utilization of resources at the hospital level. Document introduit le : 01.12.2011

Inversion prepared coronary MR angiography: direct visualization of coronary blood flow.

PURPOSE: Visualization of coronary blood flow by means of a slice-selective inversion pre-pulse in concert with bright-blood coronary MRA. MATERIALS AND METHODS: Coronary magnetic resonance angiography (MRA) of the right coronary artery (RCA) was performed in eight healthy adult subjects on a 1.5 Tesla MR system (Gyroscan ACS-NT, Philips Medical Systems, Best, NL) using a free-breathing navigator-gated and cardiac-triggered 3D steady-state free-precession (SSFP) sequence with radial k-space sampling. Imaging was performed with and without a slice-selective inversion pre-pulse, which was positioned along the main axis of the coronary artery but perpendicular to the imaging volume. Objective image quality parameters such as SNR, CNR, maximal visible vessel length, and vessel border definition were analyzed. RESULTS: In contrast to conventional bright-blood 3D coronary MRA, the selective inversion pre-pulse provided a direct measure of coronary blood flow. In addition, CNR between the RCA and right ventricular blood pool was increased and the vessels had a tendency towards better delineation. Blood SNR and CNR between right coronary blood and epicardial fat were comparable in both sequences. CONCLUSION: The combination of a free-breathing navigator-gated and cardiac-triggered 3D SSFP sequence with a slice-selective inversion pre-pulse allows for direct and directional visualization of coronary blood flow with the additional benefit of improved contrast between coronary and right ventricular blood pool.

The effects of sevoflurane and halothane anesthesia on cerebral blood flow velocity in children.

We compared cerebral blood flow velocity during anesthesia with sevoflurane and halothane in 23 children admitted for elective surgery (age, 0.4-9.7 yr; median age, 1.9 yr; ASA physical status I-II). Inhaled induction was performed in a randomized sequence with sevoflurane or halothane. Under steady-state conditions, cerebral blood flow velocity (systolic [V(s)], mean [V(mn)], and diastolic [VD]) were measured by a blinded investigator using transcranial pulsed Doppler ultrasonography. The anesthetic was then changed. CBFV measurements were repeated after washout of the first anesthetic and after steady-state of the second (equivalent minimal alveolar concentration to first anesthetic). The resistance index was calculated. VD and V(mn) were significantly lower during sevoflurane (V(mn) 1.35 m/s) than during halothane (V(mn) 1.50 m/s; P = 0.001), whereas V(s) was unchanged. The resistance index was lower during halothane (P < 0.001). Our results indicate lower vessel resistance and higher mean velocity during halothane than during sevoflurane. IMPLICATIONS: The mean cerebral blood flow velocity is significantly decreased in children during inhaled anesthesia with sevoflurane than during halothane. This might be relevant for the choice of anesthetic in children with risk of increased intracranial pressure, neurosurgery, or craniofacial osteotomies.

Heterogeneity of human monocytes: an optimized four-color flow cytometry protocol for analysis of monocyte subsets.

Monocytes are central mediators in the development of atherosclerotic plaques. They circulate in blood and eventually migrate into tissue including the vessel wall where they give rise to macrophages and dendritic cells. The existence of monocyte subsets with distinct roles in homeostasis and inflammation suggests specialization of function. These subsets are identified based on expression of the CD14 and CD16 markers. Routinely applicable protocols remain elusive, however. Here, we present an optimized four-color flow cytometry protocol for analysis of human blood monocyte subsets using a specific PE-Cy5-conjugated monoclonal antibody (mAb) to HLA-DR, a PE-Cy7-conjugated mAb to CD14, a FITC-conjugated mAb to CD16, and PE-conjugated mAbs to additional markers relevant to monocyte function. Classical CD14(+)CD16(-) monocytes (here termed "Mo1" subset) expressed high CCR2, CD36, CD64, and CD62L, but low CX(3)CR1, whereas "nonclassical" CD14(lo)CD16(+) monocytes (Mo3) essentially showed the inverse expression pattern. CD14(+)CD16(+) monocytes (Mo2) expressed high HLA-DR, CD36, and CD64. In patients with stable coronary artery disease (n = 13), classical monocytes were decreased, whereas "nonclassical" monocytes were increased 90% compared with healthy subjects with angiographically normal coronary arteries (n = 14). Classical monocytes from CAD patients expressed higher CX(3)CR1 and CCR2 than controls. Thus, stable CAD is associated with expansion of the nonclassical monocyte subset and increased expression of inflammatory markers on monocytes. Flow cytometric analysis of monocyte subsets and marker expression may provide valuable information on vascular inflammation. This may translate into the identification of monocyte subsets as selective therapeutic targets, thus avoiding adverse events associated with indiscriminate monocyte inhibition.

A simple way to decompress the left ventricle during venoarterial bypass

OBJECTIVE: The aim of this investigation was to improve the hemodynamics during venoarterial bypass by remote decompression of the left ventricle (LV). METHODS: Venoarterial bypass was established in 5 bovine experiments (69+/-10 kg) by the transjugular insertion of a self-expanding cannula (smartcanula) with return through a carotid artery. Cardiogenic shock was simulated with ventricular fibrillation induced by an external stimulator. Left ventricular decompression was achieved by switching to transfemoral drainage of the pulmonary artery (PA) with a long self-expanding cannula. RESULTS: Initial pump flow was 4.7+/-0.9 l/min and the aortic pressure accounted for 75+/-21 mmHg. After induction of ventricular fibrillation, the pump flow dropped after 11+/-8 min to 2.5+/-0.1 l/min. Transfemoral decompression increased the pump flow to 5.6+/-0.7 l/min, while the RV pressure decreased from 27+/-9 to 3+/-5 mmHg, the PA pressure decreased from 29+/-7 to 5+/-4 mmHg, the LV pressure decreased from 29+/-6 to 7+/-2 mmHg, and the aortic pressure increased from 31+/-3 to 47+/-11 mmHg. CONCLUSIONS: Remote drainage of the pulmonary artery during venoarterial bypass allows for effective decompression of the left ventricle and provides superior hemodynamics.

Cytostatic lung perfusion results in heterogeneous spatial regional blood flow and drug distribution: evaluation of different cytostatic lung perfusion techniques in a porcine model.

OBJECTIVES: Comparison of doxorubicin uptake, leakage and spatial regional blood flow, and drug distribution was made for antegrade, retrograde, combined antegrade and retrograde isolated lung perfusion, and pulmonary artery infusion by endovascular inflow occlusion (blood flow occlusion), as opposed to intravenous administration in a porcine model. METHODS: White pigs underwent single-pass lung perfusion with doxorubicin (320 mug/mL), labeled 99mTc-microspheres, and Indian ink. Visual assessment of the ink distribution and perfusion scintigraphy of the perfused lung was performed. 99mTc activity and doxorubicin levels were measured by gamma counting and high-performance liquid chromatography on 15 tissue samples from each perfused lung at predetermined localizations. RESULTS: Overall doxorubicin uptake in the perfused lung was significantly higher (P = .001) and the plasma concentration was significantly lower (P < .0001) after all isolated lung perfusion techniques, compared with intravenous administration, without differences between them. Pulmonary artery infusion (blood flow occlusion) showed an equally high doxorubicin uptake in the perfused lung but a higher systemic leakage than surgical isolated lung perfusion (P < .0001). The geometric coefficients of variation of the doxorubicin lung tissue levels were 175%, 279%, 226%, and 151% for antegrade, retrograde, combined antegrade and retrograde isolated lung perfusion, and pulmonary artery infusion by endovascular inflow occlusion (blood flow occlusion), respectively, compared with 51% for intravenous administration (P = .09). 99mTc activity measurements of the samples paralleled the doxorubicin level measurements, indicating a trend to a more heterogeneous spatial regional blood flow and drug distribution after isolated lung perfusion and blood flow occlusion compared with intravenous administration. CONCLUSIONS: Cytostatic lung perfusion results in a high overall doxorubicin uptake, which is, however, heterogeneously distributed within the perfused lung.