Progression of Blood Pressure and Cardiovascular Outcomes in Hypertensive Patients in a Reference Center

Background: Hypertension is a public health problem, considering its high prevalence, low control rate and cardiovascular complications. Objective: Evaluate the control of blood pressure (BP) and cardiovascular outcomes in patients enrolled at the Reference Center for Hypertension and Diabetes, located in a medium-sized city in the Midwest Region of Brazil. Methods: Population-based study comparing patients enrolled in the service at the time of their admission and after an average follow-up of five years. Participants were aged ≥18 years and were regularly monitored at the Center up to 6 months before data collection. We assessed demographic variables, BP, body mass index, risk factors, and cardiovascular outcomes. Results: We studied 1,298 individuals, predominantly women (60.9%), and with mean age of 56.7±13.1 years. Over time, there was a significant increase in physical inactivity, alcohol consumption, diabetes, dyslipidemia, and excessive weight. As for cardiovascular outcomes, we observed an increase in stroke and myocardial revascularization, and a lower frequency of chronic renal failure. During follow-up, there was significant improvement in the rate of BP control (from 29.6% to 39.6%; p = 0.001) and 72 deaths, 91.7% of which were due to cardiovascular diseases. Conclusion: Despite considerable improvements in the rate of BP control during follow-up, risk factors worsened and cardiovascular outcomes increased.

Associations between alcohol consumption and selected cytokines in a Swiss population-based sample (CoLaus study).

To assess the associations between alcohol consumption and cytokine levels (interleukin-1beta - IL-1β; interleukin-6 - IL-6 and tumor necrosis factor-α - TNF-α) in a Caucasian population. Population sample of 2884 men and 3201 women aged 35-75. Alcohol consumption was categorized as nondrinkers, low (1-6 drinks/week), moderate (7-13/week) and high (14+/week). No difference in IL-1β levels was found between alcohol consumption categories. Low and moderate alcohol consumption led to lower IL-6 levels: median (interquartile range) 1.47 (0.70-3.51), 1.41 (0.70-3.32), 1.42 (0.66-3.19) and 1.70 (0.83-4.39) pg/ml for nondrinkers, low, moderate and high drinkers, respectively, p<0.01, but this association was no longer significant after multivariate adjustment. Compared to nondrinkers, moderate drinkers had the lowest odds (Odds ratio=0.86 (0.71-1.03)) of being in the highest quartile of IL-6, with a significant (p<0.05) quadratic trend. Low and moderate alcohol consumption led to lower TNF-α levels: 2.92 (1.79-4.63), 2.83 (1.84-4.48), 2.82 (1.76-4.34) and 3.15 (1.91-4.73) pg/ml for nondrinkers, low, moderate and high drinkers, respectively, p<0.02, and this difference remained borderline significant (p=0.06) after multivariate adjustment. Moderate drinkers had a lower odds (0.81 [0.68-0.98]) of being in the highest quartile of TNF-α. No specific alcoholic beverage (wine, beer or spirits) effect was found. Moderate alcohol consumption is associated with lower levels of IL-6 and (to a lesser degree) of TNF-α, irrespective of the type of alcohol consumed. No association was found between IL-1β levels and alcohol consumption.

No interaction between alcohol consumption and HDL-related genes on HDL cholesterol levels.

OBJECTIVE: To assess the relationships and possible interactions between polymorphisms related to HDL levels and alcohol consumption. METHODS: Cross-sectional population-based study including 2863 women and 2546 men aged 35-75 years (CoLaus study). Alcohol intake was assessed by the reported alcohol consumption of the last 7 days. Nineteen candidate genes known to influence HDL levels were studied. RESULTS: Alcohol consumption increased HDL cholesterol levels in both genders. After multivariate adjustment for gender, age, body mass index, smoking, hypolipidaemic drug treatment, physical activity and alcohol consumption, APOA5, CETP, LIPC and LPL gene polymorphisms were significantly (10(-5) threshold) related with HDL cholesterol levels, while no genexalcohol intake interaction was found for all SNPs studied. ABCA1 polymorphisms were related to HDL cholesterol levels on bivariate analysis but the relationship was no longer significant after multivariate analysis. CONCLUSION: Our data confirm the association of alcohol consumption and of APOA5, CETP, LIPC and LPL gene polymorphisms with HDL cholesterol levels. Conversely, no genexalcohol consumption interactions were found, suggesting that the effect of alcohol consumption on HDL cholesterol levels is not mediated via a modulation of HDL related genes.

Impact of the C2/C6 ratio of high-molecular-weight hydroxyethyl starch on pharmacokinetics and blood coagulation in pigs

Rapport de synthèse : Contexte: l'hydroxyéthylamidon (HEA) est largement utilisé comme expanseur volémique en anesthésiologie et réanimation. Cependant, cette classe de produits perturbe le system de la coagulation. Des améliorations restent possibles dans le choix de la combinaison optimale de poids moléculaire, de degré de substitution en radicaux éthyle et de localisation de ces radicaux sur le squelette glucidique des polymères, afin d'optimiser leur efficacité et leur tolérance. L'HEA de poids moléculaire élevé et faiblement substitué n'affecte pas plus la coagulation sanguine que de l'HEA de bas poids moléculaire faiblement substitué. Nous examinons in vivo l'effet d'un abaissement du rapport C2/C6 sur les caractéristiques pharmacocinétiques et l'impact sur la coagulation sanguine d'un HEA de haut poids moléculaire faiblement substitué. Matériels et méthode: nous comparons dans une étude prospective, randomisée et parallèle l'HEA 650/0.42/2.8 avec l'HEA 650/0.42/5.6 auprès de 30 cochons. Avant, pendant et jusqu'à 630 minutes après une perfusion de 30 ml/kg d'HEA, des échantillons sanguins ont été collectés pour mesurer les concentrations d'HEA, les tests de coagulation plasmatique classiques et la coagulation sanguine par thrombélastographie (TEG®, Haemoscope Corporation, Niles, II, U.S.). Les paramètres pharmacocinétiques ont été estimés en adaptant un modèle à deux compartiments. Résultats: la constante d'élimination est de 0.009 ± 0.001 (min-1) pour l'HEA 650/0.42/2.8 et 0.007 ± 0.001 (min-1) pour l'HEA 650/0.42/5.6 (p<0.001); la surface sous la courbe de concentration est de 1374 ± 340 min*g/L pour l'HEA 650/0.42/2.8 et 1697 ± 411 min*g/L pour l'HEA 650/0.42/5.6 (p=0.026). Les concentrations mesurées d'HEA ne montrent pas de différence entre l'HEA 650/0.42/2.8 et l'HEA 650/0.42/5.6. Les deux solutions d'HEA affectent de façon identique la coagulation sanguine: l'index de coagulation thrombélastographique diminue pareillement à ta fin de la perfusion d'HEA 650/0.42/2.8 et d'HEA 650/0.42/5.6 (p=0.29). De même, le temps de thromboplastine partielle activée et le temps de prothrombine augmentent de manière similaire pour l'HEA 650/0.42/2.8 et l'HEA 650/0.42/5.6 (p=0.83). Conclusion: la réduction du rapport C2/C6 de l'HEA de poids moléculaire élevé et faiblement substitué aboutit à une élimination légèrement accélérée d'HEA. Cependant, elle ne modifie pas l'effet perturbateur sur la coagulation.

Intérêt de l'éthylglucuronide comme marqueur d'abus d'alcool, aspects analytiques, diagnostiques et médico-légaux

RESUMEUne consommation excessive et chronique d'alcool est associée à une augmentation significative de la morbidité et de la mortalité. L'identification de marqueurs biologiques fiables, permettant de mettre en évidence une consommation excessive et chronique, présente donc un intérêt certain pour prévenir les conséquences néfastes de l'abus d'alcool. L'approche couramment employée consiste à mesurer les marqueurs biologiques indirects dans le sang, tels que les marqueurs hépatiques dont l'augmentation peut résulter d'une consommation chronique et excessive d'alcool. Cependant, leur valeur diagnostique est souvent limitée par leur manque de sensibilité et/ou de spécificité et leur combinaison est généralement recommandée pour améliorer le diagnostic. A ce jour, il n'existe pas de marqueur biologique permettant le diagnostic fiable d'une consommation chronique et excessive d'alcool.L'objectif principal de cette thèse était d'évaluer la pertinence de l'éthylglucuronide (EtG), un métabolite direct de l'éthanol présentant la particularité d'être incorporé dans les cheveux, comme marqueur d'une consommation chronique et excessive d'alcool. Dans un premier temps, une revue de la littérature a permis de dresser un état des lieux de l'usage de l'EtG et d'identifier les axes de réflexion. L'EtG s'est révélé être un marqueur efficace pour identifier une consommation chronique et excessive d'alcool. Cependant, l'absence de seuil de positivité fiable et une méconnaissance des facteurs influençant l'incorporation de l'EtG dans les cheveux ont été mises en évidence. Afin d'investiguer ces différents points, deux études ont été conduites : (1) une étude chez le rat pour tenter de comprendre les facteurs influençant l'incorporation de l'EtG dans les cheveux et étudier la relation entre la quantité d'alcool administrée et la concentration d'EtG mesurée dans les cheveux; et (2) une étude clinique afin de déterminer les performances diagnostiques de l'EtG comme marqueur d'une consommation excessive et chronique d'alcool. Une méthode analytique sensible et sélective par chromatographic gazeuse couplée à la spectrométrie de masse en tandem a été développée et appliquée à l'analyse de l'EtG dans les cheveux.Le sang semblait jouer un rôle majeur dans l'incorporation de l'EtG dans les poils. Son incorporation n'était pas influencée par la pigmentation. La concentration d'EtG mesurée dans les poils de rats reflétait la dose d'éthanol administrée. De plus, la mesure de l'EtG dans les cheveux humains a démontré de très bonnes performances diagnostiques pour détecter une consommation excessive et chronique d'alcool. Les performances diagnostiques de l'EtG surpassaient celles des marqueurs hépatiques usuels seuls ou combinés. L'EtG n'était pas influencé par l'âge, le sexe ou l'indice de masse corporelle. Un seuil de positivité de 25 pg/mg permettait de détecter les consommateurs à usage nocif avec une grande fiabilité. Un seuil de positivité de 9 pg/mg permettait de détecter les consommateurs à risque.SUMMARYChronic and excessive alcohol consumption is associated with a significant increase of morbidity and mortality. The identification of a reliable biomarker to detect chronic and excessive alcohol consumers would be valuable to prevent alcohol's harmful effects. The combined analysis of 2 or more hepatic biomarkers, which are known to be increased following sustained alcohol consumption, is usually applied to enhance the diagnostic performance in identifying chronic and excessive alcohol consumers. However, their diagnostic value is often limited by their lack of sensitivity and / or specificity and their combination is generally recommended to improve diagnosis. To date, there are no reliable biomarkers available for diagnosing chronic and excessive alcohol consumption.The main objective of this research was to evaluate the relevance of EtG, a direct alcohol metabolite, as a biomarker of chronic and excessive alcohol consumption, thanks to its characteristic to incorporate into hair. First, a review of literature on the use of EtG was carried out. EtG demonstrated strong potential in detecting chronic and excessive alcohol consumption. However, the lack of reliable cutoff and the unawareness of factors that affect the EtG incorporation into hair were stressed. To investigate these points, two studies have been conducted: (1) a nonclinical study in rats to determine the factors affecting the incorporation of EtG into hair as well as to investigate the relationship between the amount of alcohol administered and the EtG concentration measured in hair; and (2) a clinical study to determine the diagnostic performance of EtG as a biomarker for the identification of chronic and excessive alcohol consumers. A sensitive and specific Gas Chromatography-Mass Spectrometry coupled to tandem Mass Spectrometry method has been developed and applied to hair EtG analysis.Bloodstream seemed to play a major role in the EtG incorporation into hair. EtG incorporation into rat hair was not affected by hair pigmentation. EtG concentration in rat hair appeared to reflect the EtG concentration in blood. Besides, EtG demonstrated strong diagnostic performance in detecting both heavy alcohol consumption and at-risk alcohol consumption, and clearly outperformed diagnostic performance of hepatic biomarkers. In contrast with hepatic biomarkers, EtG was not associated with age, gender or body mass index. A reliable cutoff value of 25 pg/mg allowed to detect heavy drinkers; a reliable cutoff value of 9 pg/mg allowed to detect at-risk drinkers.

The impact of iron supplementation efficiency in female blood donors with a decreased ferritin level and no anaemia. Rationale and design of a randomised controlled trial: a study protocol.

ABSTRACT: BACKGROUND: There is no recommendation to screen ferritin level in blood donors, even though several studies have noted the high prevalence of iron deficiency after blood donation, particularly among menstruating females. Furthermore, some clinical trials have shown that non-anaemic women with unexplained fatigue may benefit from iron supplementation. Our objective is to determine the clinical effect of iron supplementation on fatigue in female blood donors without anaemia, but with a mean serum ferritin </= 30 ng/ml. METHODS/DESIGN: In a double blind randomised controlled trial, we will measure blood count and ferritin level of women under age 50 yr, who donate blood to the University Hospital of Lausanne Blood Transfusion Department, at the time of the donation and after 1 week. One hundred and forty donors with a ferritin level </= 30 ng/ml and haemoglobin level >/= 120 g/l (non-anaemic) a week after the donation will be included in the study and randomised. A one-month course of oral ferrous sulphate (80 mg/day of elemental iron) will be introduced vs. placebo. Self-reported fatigue will be measured using a visual analogue scale. Secondary outcomes are: score of fatigue (Fatigue Severity Scale), maximal aerobic power (Chester Step Test), quality of life (SF-12), and mood disorders (Prime-MD). Haemoglobin and ferritin concentration will be monitored before and after the intervention. DISCUSSION: Iron deficiency is a potential problem for all blood donors, especially menstruating women. To our knowledge, no other intervention study has yet evaluated the impact of iron supplementation on subjective symptoms after a blood donation. TRIAL REGISTRATION: NCT00689793.

Prognostic value of postoperative carcinoembryonic antigen concentration and extent of invasion of resection margins after hepatic resection for colorectal metastases.

OBJECTIVE: To evaluate the prognostic value of postoperative concentration of carcinoembryonic antigen (CEA) and extent of surgical margins after resection of liver metastases from colorectal cancer. DESIGN: Retrospective study. SETTING: Teaching hospital, Switzerland. SUBJECTS: 49 patients with hepatic metastases after primary colorectal cancer. INTERVENTIONS: Resection of hepatic metastases MAIN OUTCOME MEASURES: Assessment of prognostic value of variables by univariate and multivariate analysis. RESULTS: Median survival was 24 months (range 5-86 months). Resection margins were clear (> 1-cm) in 10, close (< 1-cm) in 25 and invaded in 9 patients. On univariate analysis, a postoperative concentration of CEA of <4ng/ml was correlated with prolonged survival (p < 0.001), but the width of the resection margin was not of prognostic importance. There was no correlation between width of resection margins and postoperative concentration of CEA (p = 0.5). On multivariate analysis, postoperative concentrations of CEA of 4 ng/ml or more were associated with increased risk of death (relative risk 7.3; 95% confidence interval (CI) 2.8-18.7, p < 0.001). CONCLUSION: Postoperative CEA offers better prognostic discrimination than the width of resection margins after resection of liver metastases from colorectal tumours. Some patients with invaded resection margins did survive for 3 years, but no patient did whose CEA concentration was 4 ng/ml or more. The definition of a potentially curative hepatic resection should include a postoperative CEA concentration of <4 ng/ml (within the reference range).

Detection of EPO doping and blood doping: the haematological module of the Athlete Biological Passport.

The increase of the body's capacity to transport oxygen is a prime target for doping athletes in all endurance sports. For this pupose, blood transfusions or erythropoiesis stimulating agents (ESA), such as erythropoietin, NESP, and CERA are used. As direct detection of such manipulations is difficult, biomarkers that are connected to the haematopoietic system (haemoglobin concentration, reticulocytes) are monitored over time (Athlete Biological Passport (ABP)) and analyzed using mathematical models to identify patterns suspicious of doping. With this information, athletes can either be sanctioned directly based on their profile or targeted with conventional doping tests. Key issues for the appropriate use of the ABP are correct targeting and use of all available information (e.g. whereabouts, cross sectional population data) in a forensic manner. Future developments of the passport include the correction of all concentration-based variables for shifts in plasma volume, which might considerably increase sensitivity. New passport markers from the genomic, proteomic, and metabolomic level might add further information, but need to be validated before integration into the passport procedure. A first assessment of blood data of federations that have implemented the passport show encouraging signs of a decreased blood-doping prevalence in their athletes, which adds scientific credibility to this innovative concept in the fight against ESA- and blood doping. Copyright © 2012 John Wiley & Sons, Ltd.

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.

Alcohol drinking and cardiovascular risk in a population with high mean alcohol consumption.

Moderate alcohol consumption has been associated with lower coronary artery disease (CAD) risk. However, data on the CAD risk associated with high alcohol consumption are conflicting. The aim of this study was to examine the impact of heavier drinking on 10-year CAD risk in a population with high mean alcohol consumption. In a population-based study of 5,769 adults (aged 35 to 75 years) without cardiovascular disease in Switzerland, 1-week alcohol consumption was categorized as 0, 1 to 6, 7 to 13, 14 to 20, 21 to 27, 28 to 34, and > or =35 drinks/week or as nondrinkers (0 drinks/week), moderate (1 to 13 drinks/week), high (14 to 34 drinks/week), and very high (> or =35 drinks/week). Blood pressure and lipids were measured, and 10-year CAD risk was calculated according to the Framingham risk score. Seventy-three percent (n = 4,214) of the participants consumed alcohol; 16% (n = 909) were high drinkers and 2% (n = 119) very high drinkers. In multivariate analysis, increasing alcohol consumption was associated with higher high-density lipoprotein cholesterol (from a mean +/- SE of 1.57 +/- 0.01 mmol/L in nondrinkers to 1.88 +/- 0.03 mmol/L in very high drinkers); triglycerides (1.17 +/- 1.01 to 1.32 +/- 1.05 mmol/L), and systolic and diastolic blood pressure (127.4 +/- 0.4 to 132.2 +/- 1.4 mm Hg and 78.7 +/- 0.3 to 81.7 +/- 0.9 mm Hg, respectively) (all p values for trend <0.001). Ten-year CAD risk increased from 4.31 +/- 0.10% to 4.90 +/- 0.37% (p = 0.03) with alcohol use, with a J-shaped relation. Increasing wine consumption was more related to high-density lipoprotein cholesterol levels, whereas beer and spirits were related to increased triglyceride levels. In conclusion, as measured by 10-year CAD risk, the protective effect of alcohol consumption disappears in very high drinkers, because the beneficial increase in high-density lipoprotein cholesterol is offset by the increases in blood pressure levels.

Red blood cell structure and dynamics explored with digital holographic microspcopy

Digital holographic microscopy (DHM) is a technique that allows obtaining, from a single recorded hologram, quantitative phase image of living cell with interferometric accuracy. Specifically the optical phase shift induced by the specimen on the transmitted wave front can be regarded as a powerful endogenous contrast agent, depending on both the thickness and the refractive index of the sample. Thanks to a decoupling procedure cell thickness and intracellular refractive index can be measured separately. Consequently, Mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC), two highly relevant clinical parameters, have been measured non-invasively at a single cell level. The DHM nanometric axial and microsecond temporal sensitivities have permitted to measure the red blood cell membrane fluctuations (CMF) on the whole cell surface. ©2009 COPYRIGHT SPIE--The International Society for Optical Engineering.

Blood transfusion and iatrogenic risks in Mexico city: anti-Trypanosoma cruzi seroprevalence in 43,048 blood donors, evaluation of parasitemia, and electrocardiogram findings in seropositive

Iatrogenous transmission of Trypanosoma cruziby blood transfusion was suggested as a potential risk by Pellegrino (1949). Seropositive blood donors in Mexico were first reported in 1978, however, limited information is available due to small sampling, the use of heterogeneous serologic assays, and geographically limited studies. A wide survey carried out in 18 out of the 32 states of Mexico, showed a national mean of 1.6% seropositive among 64,969 donors, ranging from 0.2 to 2.8%. In the present study, we have screened 43,048 voluntary blood donors in a period of five years at the Instituto Nacional de Cardiología I. Chávez, a concentration hospital located in Mexico city which serves mainly the metropolitan area and accepts from all over the country. Standardized ELISA and IIF were used to identify seropositive individuals in addition to hemoculture, PCR and standard 12 lead ECG tests that were applied to a group of seropositive patients (29/161). The result showed a seropositivity of 0.37% (161/43,048). From the group of seropositive individuals 40% (12/29) were potential carriers of T. cruzi at the donation time and 5/29 had subclinical ECG abnormalities. Parasitological tests performed in 70 erythrocyte and platelet fractions from seropositive units (70/161) showed negative results. Our findings strongly support T. cruzi screening in the transfusion medicine practice and identify subclinical heart disease among seropositive blood donors.

Benznidazole vs benznidazole in multilamellar liposomes: how different they interact with blood components?

In spite of its widespread use, benznidazole's (BNZ) toxicity and low efficacy remains as major drawbacks that impair successful treatments against Chagas disease. Previously, attempting to increase the selectivity and reduce its toxicity on infected tissues, multilamellar liposomes (MLV) composed of hydrogenated soybean phosphatidylcholine (HSPC): distearoyl-phosphatidylglycerol (DSPG): cholesterol (CHOL) 2:1:2 mol:mol loaded with BNZ (MLV-BNZ) were designed. In this work we compared different properties of MLV-BNZ with those of BNZ. Opposite to other hydrophobic drugs, the results indicated that slight changes of BNZ×s association degree to proteins and lipoproteins should not modify the percentage of unbound drug available to exert pharmacological action. On the other hand, when loaded in MLV, BNZ reduced its association to plasma proteins in 45% and became refractory to the sinking effect of blood, dropping 4.5 folds. Additionally, when loaded in MLV, BNZ had higher volume distribution (160 ± 20 vs 102 ± 15 ml/kg) and total clearance (35.23 ± 2.3 vs 21.9 ± 1.4 ml/h.kg), and lower concentration-time curve (7.23 ± 0.2 vs 9.16 ± 0.5 µg.h/ml) than BNZ. Hence, these studies showed that for MLV-BNZ, the amount of BNZ can be substantially increased, from 25 to 70%, being this formulation more rapidly cleared from circulation than free drug; also due to the lower interaction with blood components, lower side effects can be expected.

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.