Clinical implementation of deep-learning based auto-contouring tools-Experience of three French radiotherapy centers.

Deep-learning (DL)-based auto-contouring solutions have recently been proposed as a convincing alternative to decrease workload of target volumes and organs-at-risk (OAR) delineation in radiotherapy planning and improve inter-observer consistency. However, there is minimal literature of clinical implementations of such algorithms in a clinical routine. In this paper we first present an update of the state-of-the-art of DL-based solutions. We then summarize recent recommendations proposed by the European society for radiotherapy and oncology (ESTRO) to be followed before any clinical implementation of artificial intelligence-based solutions in clinic. The last section describes the methodology carried out by three French radiation oncology departments to deploy CE-marked commercial solutions. Based on the information collected, a majority of OAR are retained by the centers among those proposed by the manufacturers, validating the usefulness of DL-based models to decrease clinicians' workload. Target volumes, with the exception of lymph node areas in breast, head and neck and pelvic regions, whole breast, breast wall, prostate and seminal vesicles, are not available in the three commercial solutions at this time. No implemented workflows are currently available to continuously improve the models, but these can be adapted/retrained in some solutions during the commissioning phase to best fit local practices. In reported experiences, automatic workflows were implemented to limit human interactions and make the workflow more fluid. Recommendations published by the ESTRO group will be of importance for guiding physicists in the clinical implementation of patient specific and regular quality assurances.

[Self medication with Annona muricata L. (corossol) as an anti-cancer agent in Reunion]. / Automédication par Annona muricata L. (corossol) à visée anticancéreuse à la Réunion.

INTRODUCTION: Annona muricata L. also called soursop, graviola, guanabana and sapoty (French creole) is a fruit tree growing in tropical countries. The fruits, seeds, leaves and roots are used in traditional medicine. Potential anticancer effects encourage patients to consume this product as self medication. The object of the study was to determine the prevalence of use of graviola as an anticancer agent by patients treated for a lung cancer. METHODS: Our survey took place in two thoracic oncology day cares units of the university hospital of Reunion. All the patients treated by chemotherapy and immunotherapy for lung cancer were asked the same questions in a face to face interview over a 6-month period. RESULTS: One hundred questionnaires were collected. Sixty seven patients consumed graviola. In 53.7%, graviola was consumed as an anticancer agent and 25 patients took it regularly. Most often graviola was ingested as an infusion of boiled leaves (69.5%). The supply was exclusively local. CONCLUSIONS: A quarter of patients treated by chemotherapy for a lung cancer in Reunion consume graviola regularly as self medication. The consequences of this intake, drug interactions and side effects are unknown and would be interesting to identify.

[Multiple ground-glass opacities nodules]. / Nodules en verre dépoli et adénocarcinome EGFR muté.

INTRODUCTION: Ground-glass opacities nodules are frequently detected with the advances of radiological imaging. These can be preinvasive lesions such as atypical adenomatous hyperplasia but also invasive lesions. It leads to question in patients with lung cancer about treatment strategy and follow up. CASE REPORT: We report the case of a 72 years-old woman followed for a lung adenocarcinoma with an EGFR mutation of the right upper lobe stage IIb. The CT scan shows multiple pure ground-glass opacities in the same lobe of the primitive tumor but also in the other lobe. On the piece of lobectomy, histopathology of two ground-glass opacities showed atypical adenomatous hyperplasia. CONCLUSION: Ground-glass opacities nodules could be found in patients with an operable lung cancer. These can be multiple and match with atypical adenomatous hyperplasia but also carcinomas lesions. The radiological surveillance is still the standard. The strategy for surgical resection has to be defined especially in case of multiple lesions which can require repeated surgical resection.

Assessing allergic rhinitis in developing countries.

BACKGROUND: Allergic rhinitis (AR) affects 5% to 40% of the general population. In developing countries, AR is poorly documented and tracked due to a lack of appropriate diagnostic tools. OBJECTIVE: 1) To validate a questionnaire standardised in industrialised countries to ascertain AR, the Score For Allergic Rhinitis (SFAR), in developing countries; 2) to better understand AR prevalence previously reported from developing countries by comparing results from the SFAR and the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires. METHODS: Six African countries were selected for their climates. In each country, 70 individuals with and 30 without nasal symptoms filled out the SFAR and the ISAAC questionnaires. Skin prick tests (SPTs) for allergens were performed by the physician if necessary. RESULTS: The SFAR presented a close match with the gold standard (the physician's diagnosis of AR backed up by SPT where necessary) in terms of various performance parameters. In particular, it showed high sensitivity (0.84) and specificity (0.81). Compared to the ISAAC questionnaire, the SFAR had greater sensitivity and equal specificity. CONCLUSIONS: In the absence of a medical visit, the SFAR is a useful standardised screening instrument for the collection of information needed for the identification of AR in developing countries.

[Exposure to fine air particles and occurrence of allergic diseases: results of ISAAC-France phase 2]. / Exposition aux particules atmosphériques fines et développement des maladies allergiques de l'enfant. Résultats épidémiologiques issus de l'étude des six villes (ISAAC-2 France).

To evaluate whether fine air particles could be involved in the occurrence of atopy and allergic diseases, we performed a cross-sectional epidemiological survey involving primary schoolchildren living in six French towns with contrasted air pollution levels. Air pollution was measured during a week in the school yards and by standard air monitoring networks. Children get an examination in school looking for atopic dermatitis and bronchial hyperresponsiveness assessed by a standardized run test. Besides, parents or guardians provided past medical history and environmental data, especially on passive smoking. Overall, 5,338 children, aged 10.4 (+/-0.7) years, coming from 108 different schools and 401 different classes were included in the survey. Taking into account potential confounders, high exposure to proximity PM(2.5) was linked to a higher point prevalence of atopic dermatitis and hyperresponsiveness, to a higher cumulative prevalence of allergic asthma and a higher sensitization rate to common indoor allergens. Thus, these data suggest that chronic exposure to urban fine particles could be a risk factor for atopy, hyperresponsiveness and asthma.

Sex and gender differences in tobacco smoking among adolescents in French secondary schools.

AIM: We investigated the relationship between sex (genetic/biological) and gender (environmental/cultural) factors in relation to adolescent tobacco smoking. METHODS: A representative sample of 11,582 students from French secondary public schools participated in the study by completing a self-administered, standardised questionnaire. RESULTS: Using the WHO classification for smoking in the youth, 15.6% of the adolescents were regular smokers, 7.7% occasional smokers, 17.9% experimental smokers and 4.8% ex-smokers, with no statistically significant gender difference. Taking non-smoking as a reference, puberty had a much greater effect on the likelihood of being a regular smoker [OR = 18.0 (95% Confidence Interval: 9.6-32)] than of being an experimental/occasional smoker [OR = 3.7 (2.9-4.6)] among girls. For boys, the effect of puberty was not as great [OR = 4.7 (3.5-6.5)] for regular vs. [OR = 2.1 (1.8-2.5)] for experimental/occasional smokers). Similarly, illicit drug use had a larger effect on the likelihood of being regular smoker vs. non-smoker [OR = 15.0 (12.0-20.0) in boys and 12 (8.8-16.0) in girls] than of being experimental/occasional smoker vs. a non-smoker [OR = 4.8 (3.7-6.1) and 2.9 (2.1-3.9) respectively]. Other factors related to regular smoking were exposure to passive smoking and regular alcohol consumption. Living with both parents was a protective factor for life and regular smoking in both genders. CONCLUSIONS: Our results show that influential factors of sex-related (puberty), gender-specific (environmental tobacco smoking, alcohol consumption, drug abuse) or sex/gender (regular sexual intercourse) are related to the smoking behaviour in French adolescents.

[MR imaging features of deep pelvic endometriosis: correlation with laparoscopy]. / Caractéristiques IRM de l'endométriose profonde: corrélation aux résultats coelioscopiques.

UNLABELLED: Deep pelvic endometriosis is an invalidating disorder affecting the retrocervical region, rectosigmoid colon and urinary bladder generally requiring surgical management. MRI is the preoperative imaging modality of choice. The purpose of this paper is to describe the MR imaging features of deep pelvic endometriosis with laparoscopic correlation. METHODS: Thirty-five patients with clinical suspicion of deep pelvic endometriosis underwent pelvic MRI. Results of MRI, including morphological and signal characteristics features of the lesions were compared to laparoscopic fidings. RESULTS: Laparoscopy detected lesions of deep pelvic endometriosis of the uterosacral ligaments (n=10), torus uterinum (n=9), rectosigmoid (n=11), Douglas pouch (n=9), recto-vaginal septum (n=6), bladder (n=4) and posterior vaginal cul-de-sac (n=2). The sensitivity, specificity, positive predictive value and negative predictive value of MRI were assessed for each localization. CONCLUSION: MRI allows diagnosis of deep pelvic endometriosis of the bladder, rectosigmoid and Douglas pouch and with lower sensitivity for lesions of the uterosacral ligaments, posterior vaginal cul-de-sac and rectovaginal septum.

Reported prevalence and co-morbidity of asthma, chronic bronchitis and emphysema: a pan-European estimation.

OBJECTIVE: Comparable population-based data exist at the European level for asthma but not for chronic obstructive pulmonary disease. Data from the World Health Organization's Large Analysis and Review of European Housing and Health Status Study conducted in random samples from eight European cities were used 1) to describe the prevalence of chronic bronchitis and emphysema (CBE) and asthma according to socio-demography, addictions, physical activities and body mass index; and 2) to identify the co-morbidities of these respiratory diseases. DESIGN: A total of 6915 adults filled out a standardised questionnaire on health outcomes, including major respiratory diseases and individual characteristics. RESULTS: Data showed that in the year preceding the survey, 3.3% of individuals had been diagnosed or treated for asthma and 6.2% for CBE. One per cent suffered simultaneously from both. Large variations were observed between cities. Physical activities and never smoking were inversely associated with CBE, independently of socio-cultural differences between the eight cities. Furthermore, both asthma and CBE were significantly related to several non-respiratory diseases, after adjustment for potential confounders. CONCLUSION: Population-based data from eight European cities show that there is a link between chronic respiratory diseases and various non-respiratory co-morbidities that needs further investigation.

[The LTD laryngeal tube: a new single-use airway device]. / Le tube laryngé à usage unique LTD: un nouveau dispositif supralaryngé.

OBJECTIVES: Clinical study of a new supraglottic single use airway device, the LTD with evaluation of insertion, efficiency during intermittent positive pressure ventilation and side effects. STUDY DESIGN: Prospective, open clinical study. PATIENTS AND METHODS: Fifty adult patients [33 years (26-55)] were scheduled for elective surgery (orthopaedic, plastic or maxillo-facial) under general anaesthesia less than two hours in dorsal position. No patient presented clinical sign of difficult airway management or risk of regurgitation. We studied easiness and delay for insertion, oro-pharyngeal leak pressure, peak airway pressure with positive pressure ventilation and side effects during the first 24 hours. RESULTS: Insertion was successful in 94%. Median insertion time was 38 s (32-45). Difficulties of insertions were found in 25%. Oro-pharyngeal leak pressure, always superior than peak pressure [18 cmH2O (15-21)] increased from 26 cmH2O (22-32.5) to 34 cmH2O (29-40) at the end of the surgery. No case of gastric inflation, regurgitation or SpO2<95% were noticed. Moderate sore throat incidence was 6% in recovery room, 15% at the sixth hour and absent at the 24th hour. CONCLUSION: The learning curve was low< or =10. Insertion is easy. The quality of airway protection allows secure positive pressure ventilation. Postoperative side effects are minor and transient.

C4-substituted isoquinolines: synthesis and cytotoxic action.

A facile synthesis of the C4-substituted isoquinolines 5a-c and 6a-c is described. Commercially available 4-bromoisoquinoline is converted to the alpha,beta-unsaturated esters 8 and 10 on treatment with the appropriate acrylate ester under Heck reaction conditions. The saturated amides 5a-c were obtained from the reaction of ester 9 with the requisite primary amine. Similarly the unsaturated analogues 6a-c were prepared by reacting ester 10 with the appropriate amine. The cytotoxicity of the target molecules was evaluated in two tumour cell lines in vitro. Two compounds, 6b and 6c, showed sufficient activity in the human non-small cell lung cancer line NSCLC-N16-L16 to be worthy of further study.

[Diagnosis of flat epithelial atypia (FEA) after stereotactic vacuum-assisted biopsy (VAB) of the breast: What is the best management: systematic surgery for all or follow-up?]. / Lésions de métaplasie cylindriques atypiques (MCA) diagnostiquées par macrobiopsies assistées par aspiration: opportunité d'une exérèse chirurgicale?

OBJECTIVE: FEA lesions group two histological types: columnar cell hyperplasia with atypia (CCHA) and columnar cell change with atypia (CCA). The increasing use of VAB has resulted in increased detection of isolated FEA lesions. The aim of this study was to define the best management possible for these patients: which cases may not need excision? MATERIAL AND METHODS: From our database of 780 VABs carried out from 2000 to 2004, 59 patients with FEA were diagnosed. Cases in which no surgery was performed or all features were not available were excluded, thus excluding 19 cases. Forty patients with FEA were included. We reviewed clinical and mammographic characteristics, histological biopsy, and the corresponding surgically excised tissue features. RESULTS: VAB yielded 25 cases of CCHA and 15 cases of CCA. Surgery revealed seven ductal carcinoma cases (four invasive, three in situ); nine benign lesions, and 24 with atypia (19 FEA and six atypical ductal hyperplasia). We found two features related to the risk of cancer: the presence and the size of hyperplasia. All carcinomas were found within the CCHA lesions. No cancer was yielded when size was less than 10 mm within CCA lesions and lesions that were totally removed. CONCLUSION: We recommend surgical excision when CCHA greater than 10 mm is found on the VAB or it is incompletely removed. CCA lesions or CCHA less than 10 mm or totally removed may obviate systematic surgery.

Questionnaire on health systems and national resources for control of respiratory health in low-income countries.

BACKGROUND: Due to increased exposure to risk factors such as ageing and tobacco smoking, chronic respiratory diseases (CRDs) have become a major cause of morbidity and mortality worldwide. Data on CRDs and their management in developing countries (DC) are nevertheless sparse and not comparable. OBJECTIVE: To implement and validate a standardised self-administered questionnaire to be proposed to health authorities to assess the resources of their health system for dealing with respiratory diseases. METHODS: The questionnaire concerned social security, description of the health system, human resources available within the system, initial training and continuing education of health personnel, existence of a list of essential drugs, vaccine coverage and specific resources involved in CRD and tobacco control. RESULTS: The validity of the criteria of the questionnaire was tested in Reunion Island, where health data are accessible and reliable, and was found to be satisfactory. Its acceptability and relevance were deemed appropriate in Tunisia and in Mozambique. CONCLUSION: The self-administered questionnaire is a simple, reliable and cheap tool. Although designed for the study of respiratory diseases, it can easily be transposed and adapted to other pathologies.

In utero and perinatal complications preceding asthma.

BACKGROUND: It has been suggested that pregnancy and early life may influence the development of asthma in the offspring, but published studies have not carefully controlled for potential biases. METHODS: In a large British birth cohort of 4065 natural children of 2583 mothers, we investigated whether in utero and perinatal influences contribute to the development and the severity of asthma in childhood, allowing for possible confounders of the relationship, and considering the nonindependence of familial data. RESULTS: Child asthma (10.1%) was more frequently reported by mothers when there had been health complications during pregnancy (prevalence =14.3%; adjusted odds ratio [ORadj] =2.01; 95% confidence interval, 1.52-2.67), labor, or delivery (19.3%, ORadj =1.35, 1.01-1.81); child illness or health complications during the first week of life (22.6%, ORadj =1.35, 1.01-1.82); and birth weight of < 2.5 kg (7.0%, ORadj =1.57, 1.10-2.25). Specific causes of health complications during pregnancy which significantly related to asthma were early or threatened labor (ICD: 644) (4.8%, ORadj =1.58, 1.03-2.40) and the malposition or malpresentation of the fetus (ICD: 652) (1.6%, ORadj =3.63, 1.47-8.91). CONCLUSION: The results provide further evidence that in utero and perinatal factors may increase the risk of developing asthma.

Phase I study of cinchonine, a multidrug resistance reversing agent, combined with the CHVP regimen in relapsed and refractory lymphoproliferative syndromes.

Overexpression of P-glycoprotein (P-gp) in cancer cells reduces intracellular accumulation of various anticancer drugs including anthracyclines and vinca alkaloids. This multidrug resistance (MDR) phenotype can be reversed in vitro by a number of non-cytotoxic drugs. We have identified the quinine's isomer cinchonine as a potent MDR reversing agent, both in vitro and in animal models. Here, we report an open phase I dose escalation trial in patients with refractory or relapsed malignant lymphoid diseases. Cinchonine dihydrochloride was administered by continuous i.v. infusion for 48 h and escalated over five dose levels ranging from 15 to 35 mg/kg/d. Cinchonine infusion started 24 h before i.v. doxorubicin (25 mg/m2), vinblastine (6 mg/m2), cyclophosphamide (600 mg/m2) and methylprednisolone (1 mg/kg/d) (CHVP regimen) and lasted for 24 h after chemotherapy infusion. Thirty-four patients received 87 cycles of CHVP/cinchonine. The MTD of cinchonine administered by continuous i.v. infusion was 30 mg/kg/d. Prolonged cardiac repolarization was the main dose-limiting toxicity. No ventricular arrhythmia including 'torsade de pointes' was observed. An MDR reversing activity was identified in the serum from every patient and correlated with cinchonine serum level. When infused at 30 mg/kg/d, cinchonine demonstrated a limited influence on doxorubicin pharmacokinetic. We conclude that i.v. infusion of cinchonine might be started 12 h before MDR-related chemotherapy infusion and requires continuous cardiac monitoring but no reduction of cytotoxic drug doses.

Predictors of short-term mortality in critically ill patients with solid malignancies.

UNLABELLED: Admission of cancer patients with serious medical complications to the ICU remains controversial primarily because of the high short-term mortality rates in these patients. However, the cancer patient population is heterogeneous regarding age, underlying conditions, and curability of their disease, suggesting that large variations may occur in the effectiveness of intensive care within this subgroup of critically ill patients. OBJECTIVES: To identify factors predicting 30-day mortality in patients with solid tumors admitted to a medical ICU. PATIENTS AND METHODS: We conducted a retrospective study in 120 consecutive cancer patients (excluding patients with hematological malignancies) admitted to the medical ICU of a 650-bed university hospital between January 1990 and July 1997. Medical history, physical and laboratory test findings at admission, and therapeutic interventions within the first 24 h in the ICU were recorded. The study endpoint was vital status 30 days after ICU admission. Stepwise logistic regression was used to identify independent prognostic factors. RESULTS: The observed 30-day mortality rate was 58.7 % (n = 68), with most deaths (92 %) occurring in the ICU. Univariate predictors of 30-day mortality were either protective [prior surgery for the cancer (p = 0.01) and complete remission (p = 0.01)] or associated with higher mortality [Knaus scale C or D (p = 0.02), shock (p = 0.04), need for vasopressors (p = 0.0006) or for mechanical ventilation (p = 0.0001), SAPS II score greater than 36 (p = 0.0001), LOD score greater than 6 (p = 0.0001), and ODIN score > 2 (p = 0.0001)]. Three variables were independent predictors: previous surgery for the cancer (OR 0.20, 95 % CI 0.07-0.58), LOD score > 6 (OR 1.26, 95 % CI 1.09-1.44), and need for mechanical ventilation (OR 3.55, 95 % CI; 1.26-6.7). Variables previously thought to be indicative of a poor prognosis (i. e., advanced age, metastatic or progressive disease, neutropenia or bone marrow transplantation) were not predictive of outcome. CONCLUSION: When transfer to an ICU is considered an option by patients and physicians, 30-day mortality is better estimated by an evaluation of acute organ dysfunction than by the characteristics of the underlying malignancy.

Effects of amiodarone on cardiac function and mitochondrial oxidative phosphorylation during ischemia and reperfusion.

This study was carried out in order to determine if the efficiency of amiodarone, a class III antiarrhythmic agent, is associated with changes in mitochondrial oxidative phosphorylation. A population of 30 rats were treated with amiodarone (100 mg/kg/day) for 5 days. A second population receiving only vehicle was used as control. The hearts were perfused according to the working mode. After 15 min of normoxic perfusion, the left main coronary artery was ligated and the ligation was maintained for 20 min. The ligation was removed and reperfusion continued for a further 30 min. The electrocardiogram was monitored continuously. At the end of perfusion, the ischemic and non ischemic areas were visually separated and mitochondria were harvested from each area. Their oxidative and energy metabolism were assessed with palmitoylcarnitine as substrate in 2 respiration media differing in their free calcium concentration (0 or 0.34 microm). In normoxic conditions, amiodarone treatment increased the cardiac metabolic efficiency (mechanical work to oxygen consumption ratio). The local ischemia decreased the aortic and coronary flows without modifying the cardiac metabolic efficiency. Amiodarone treatment maintained the aortic flow at a significantly higher value; the duration of severe arrhythmias was significantly decreased by the drug. The reperfusion of the ischemic area allowed the partial recovery of fluid dynamics. The coronary flow was restored to 89% of the pre ischemic value. Conversely, the aortic flow never exceeded that measured at the end of ischemia, partly due to the important development of severe arrhythmias. The recovery of aortic flow and metabolic efficiency during reperfusion was improved by amiodarone treatment; ventricular tachycardia and fibrillation duration were reduced. In the mitochondria issued from the normoxic area, the energy metabolism was not altered by the amiodarone treatment, but the presence of calcium in the respiration medium modified the oxidative phosphorylation. The divalent cation slightly decreased the state III respiration rate and increased noticeably the state IV respiration rate. This was associated with an important mitochondrial AMP production and maintenance of ADP in the respiration medium. This energy wasting was reported to decrease the mitochondrial metabolic efficiency. After an ischemia-reperfusion sequence, mitochondrial oxidation phosphorylation was reduced and amiodarone treatment amplified this decrease. This was presumably due to an increased mitochondrial calcium accumulation. Thus, the beneficial properties of amiodarone during reperfusion are supposed to be due to a protection against the deleterious effect of excess matrix calcium on mitochondrial energy metabolism.

[Postoperative antero-external tibial compartment syndrome: co-responsibility of the operating table]. / Syndrome postopératoire des loges tibiales antéro-externes: coresponsabilité de la table opératoire.

A 26-year-old, ASA1 patient underwent maxillofacial surgery under general anaesthesia, of 12-hour duration in the supine position. Postoperatively he developed rhabdomyolysis and acute renal failure. In the subsequent days, a bilateral leg compartment syndrome occurred with anterior tibial motor nerve injury requiring fasciotomies and excision of necrotic muscles. Several aetiological factors may have contributed to this accident: a long-lasting procedure, controlled hypotension and inappropriate position of the lower limbs. A laboratory study showed that the hardness of some new operating tables could be responsible for this complication. Some prophylactic measures are therefore required before the use of such devices.

Building a virtual reality temporal bone dissection simulator.

The temporal bone is one of seven bones that comprise the human skull, and has an intimate relationship with many vital structures. Anatomically, its three-dimensional relationships make it one of the most challenging areas for surgeons to understand and master. In addition, the temporal bone contains minute structures that are among the most sophisticated and delicate in the human body. These structures include the cochlea and vestibular organs, which are responsible for hearing and balance; the middle ear, including the ossicles, which conduct acoustic energy to the cochlea; and the facial nerve, which is responsible for controlling the muscles of facial expression, and contributes to the sensation of taste. Additionally, the temporal bone forms a major portion of the skull base, and has intimate relationships to vital structures including the carotid artery, jugular vein, cerebral cortex, brainstem, and cranial nerves. Surgical procedures performed on the temporal bone include: procedures to eradicate chronic and acute infections; procedures to remove malignant and benign tumors within the temporal bone, from the skull base, or from the posterior cranial fossa; procedures to restore the hearing mechanism; procedures to eliminate balance disorders; and procedures to correct congenital anomalies. For surgeons-in-training, and even surgeons-in-practice, mastery of the anatomy of the temporal bone and the many complex approaches necessary to treat patients takes years of focused endeavor. This is typically accomplished through the dissection of human cadaver temporal bones, which are scarce, and require a dedicated laboratory facility. Efforts are currently underway to develop a realistic simulator for temporal bone procedures. Users immersed in the simulator will interact with a three-dimensional temporal bone, derived from patient-specific data, using a haptic interface to simulate traditional surgical procedures. Feedback from experts in otologic surgery will be built into the system for additional instruction. This presentation will include an overview of the application being developed, a report of its current state of development, and plans for the future.

Myocardial ischemia and in vitro mitochondrial metabolic efficiency.

The purpose of this study was to evaluate the oxidative capacities and the rate of energy synthesis in isolated mitochondria extracted from normal and post-ischemic myocardium. Isolated rat hearts were perfused according to the working mode with a Krebs Heinseleit buffer containing glucose (11 mM), insulin (10 IU/l) and caprylic acid (25 microM). After a 15 min perfusion in normoxic conditions, the hearts were subjected to a 20 min local zero-flow ischemia followed by a 20 min reperfusion. During the perfusion, the aortic and coronary flows, the aortic pressure and the electrocardiogram were monitored. At the end of the reperfusion period, the non-ischemic and ischemic zones (NIZ and IZ, respectively) were separated and the mitochondria were harvested from each zone. The oxygen uptake and the rate of energy production of the NIZ and IZ mitochondria were then assessed with palmitoylcarnitine as substrate in 2 buffers differing in their free calcium concentration (0.041 and 0.150 microM). Ischemia provoked a 50% reduction of coronary and aortic flows. The reperfusion of the IZ allowed the partial recovery of coronary flow, but the aortic flow decreased beneath its ischemic value because of the occurrence of severe arrhythmias, stunning and probably hibernation. The IZ mitochondria displayed a lower rate of oxygen consumption, whatever the buffer free calcium concentration. Conversely, their rate of energy production was increased, indicating that their metabolic efficiency was improved as compared to NIZ mitochondria. This might be due to the mitochondrial calcium overload persisting during reperfusion, to the activation of the inner membrane Na+/Ca2+ exchange and to a significant mitochondrial swelling. On the other hand, the presence of an elevated free calcium concentration in the respiration buffer provoked some energy wasting characterized by a constant AMP production. This was attributed to some accumulation of acetate and the activation of the energy-consuming acetylCoA synthetase. In conclusion, ischemia and reperfusion did not alter the membrane integrity of the mitochondria but improved their metabolic efficiency. Nevertheless, these in vitro results can not reflect the mitochondrial function in the reperfused myocardium. The mitochondrial calcium overload reported to last during reperfusion in the cardiomyocytes might mimic the free calcium-induced reduction of metabolic efficiency observed in vitro in the present study. The resulting energy wasting might be responsible for the contractile abnormalities noticed in the reperfused myocardium.