Prognostic implications of preoperative aerobic capacity and exercise oscillatory ventilation after liver transplantation.

Our aim was to determine preoperative aerobic capacity (oxygen uptake [V'O2 ]) and prevalence of exercise oscillatory ventilation (EOV), underlying clinical characteristics of patients with EOV, and significance of reduced aerobic capacity and EOV in predicting mortality after liver transplantation. We prospectively studied 263 patients who underwent elective liver transplantation. Patients were followed up for 1 year. Despite minor impairment of resting cardiopulmonary function, preoperative aerobic capacity was reduced (peak V'O2 : 64 ± 19% predicted). EOV occurred in 10% of patients. Model for End-Stage Liver Disease score tended to be higher in patients with EOV compared to patients without, but failed to reach significance (p = 0.09). EOV patients had lower peak V'O2 and higher ventilatory drive. EOV was more frequent in nonsurvivors than in survivors (30% vs. 9%, p = 0.01) and was independently associated with posttransplant all-cause 1-year mortality. Reduced peak V'O2 best predicted the primary composite endpoint defined as 1-year mortality and/or prolonged hospitalization and early in-hospital mortality. Multivariate analysis revealed EOV (χ(2), 3.96; p = 0.04) and V'O2 (χ(2), 4.28; p = 0.04) as independent predictors of mortality and so-called primary composite endpoint, respectively. EOV and reduced peak V'O2 may identify high-risk candidates for liver transplantation, which would motivate a more aggressive treatment when detected.

[Functional exercise testing in idiopathic inflammatory myopathies with pulmonary involvement]. / Intérêt de l'épreuve fonctionnelle d'exercice au cours des myopathies inflammatoires avec atteinte pulmonaire.

INTRODUCTION: Dyspnoea occurring during inflammatory myopathy associated with interstitial lung disease (ILD) can be ascribed to several physiopathological pathways. The purpose of this study was to analyse cardiopulmonary exercise testing (CPET) abnormalities in these patients in order to precise mechanisms responsible for decreased aerobic capacity. METHODS: Ten patients (52 +/- 12 years) were diagnosed as having inflammatory myopathy with interstitial lung disease. Exercise dyspnoea was found in 9 patients. All of them had a restrictive pattern associated to and impairment of the transfer factor for carbon monoxide. CPET was performed with a bicycle ergometer using a standard protocol of incremental increasing work load. RESULTS: Two patients had a normal exercise capacity while eight patients had abnormal VO2 associated with hyperventilation, abnormal gas exchange, as well as and abnormal dead space. Five patients also exhibited decreased oxygen pulse (<80% expected value) at peak exercise; 4 out of 5 had persistence of ventilatory reserve. In addition DeltaFC/DeltaVO2 was increased (>50) in 7 cases. CONCLUSION: CPET provides useful information in the understanding of mechanisms of dyspnoea and might be an effective tool in treatment decision making: in patients with inflammatory myopathy and associated ILD abnormal oxygen pulse may reflect cardiac disorder or muscular abnormalities (inflammatory or steroid myopathy).

Case Report: Bothrops lanceolatus Snakebite Surgical Management-Relevance of Fasciotomy.

Bothrops lanceolatus is an endemic Crotalidae species in Martinique, where approximately 30 cases of envenoming are managed yearly. Envenoming characteristics from Bothrops species include local tissue damage, systemic bleeding, and hemodynamic alterations. We hereby report a case of severe envenomation following B. lanceolatus snakebite to the right calf. Severe local manifestations developed progressively up to the lower limb despite adequate antivenom therapy. Systemic manifestations of venom also occurred, resulting in intensive care therapy. Surgery exploration revealed soft tissue necrosis, friability of the deep fascia, and myonecrosis. The patient needed multiple debridement procedures and fasciotomy of all leg compartments and anterior compartment of the thigh. Diagnosis of necrotizing fasciitis was confirmed by positive Aeromonas hydrophila blood cultures. This clinical case illustrates that major soft tissue infection, including necrotizing fasciitis may occur after snakebite. Abnormal coagulation tests should not delay surgical management, as severe envenoming is a life-threatening condition.

Elevated alveolar nitric oxide is linked to poor aerobic capacity and chronotropic incompetence in liver transplant candidates.

BACKGROUND & AIMS: Increased nitric oxide is involved in abnormal hemodynamic parameters and respiratory function of cirrhotic patients. We aimed to quantify partitioning exhaled nitric oxide measurements in exhaled air in liver transplantation (LT) candidates and evaluate their relationships with chronotropic incompetence and aerobic capacity. METHODS: We compared exhaled nitric oxide (NO) measurements, heart rate response and peak oxygen uptake during incremental exercise in liver transplantation candidates to those of controls. RESULTS: As opposed to healthy control subjects, LT candidates displayed elevated alveolar NO, blunted chronotropic response and reduced V'O2 at maximal exercise. In LT candidates, median peak V'O2 was 18.7 ml kg-1 min-1 (interquartile range (IQR) 16.2; 21.8), corresponding to 65% (IQR 57; 72) of the predicted value. Compared with controls, LT candidates had increased levels of alveolar NO (median (IQR) 2.0 (1.2; 2.2) versus 3.1 (2.3; 4.5), p < 0.001). In controls, no relations were found between alveolar NO and V'O2 peak or heart rate reserve whereas in cirrhotic patients, negative correlations and negative slopes were found between alveolar NO and V'O2 peak and heart rate reserve decrease. CONCLUSIONS: Increasing alveolar NO could be a specific pathophysiological condition limiting aerobic capacity in LT candidates.

Cytokine profile of human septic shock serum inducing cardiomyocyte contractile dysfunction.

This study was designed to measure nitrite/nitrate and cytokine levels of serum obtained from septic shock patients and to describe potential depressant effects of human septic serum on rat cardiomyocytes. Serum was prepared from 10 non-septic patients and 10 patients with documented septic shock. Adult rat ventricular myocytes were exposed to 20 % serum in the medium. Cardiomyocyte contractility was assessed by measuring shortening fraction and shortening velocity. Serum levels of nitrite/nitrate, a marker of nitric oxide final metabolites, and cytokines (tumor necrosis factor (TNF)-alpha, interleukin (IL) 1beta, 6, 10, 8 and 12p70) were measured. Compared with serum from non-septic patients, serum of septic shock patients induced rapid reduction of the extent and velocity of shortening in isolated cardiomyocytes. Nitrite/nitrate, TNF-alpha, IL-1beta and IL-12p70 concentrations of tested serum for cardiomyocyte studies were not increased in septic serum compared with controls. In contrast, septic serum that induced a depression of in vitro contractility, had increased levels of IL-6, IL-8 and IL-10. We can conclude that the depression of in vitro contractility induced by septic serum is not directly dependent on elevated levels of nitric oxide metabolites, TNF-alpha or IL-1beta. Our results support the view that other cytokines, including IL-6, IL-8 and IL-10, are potent circulating mediators of myocardial depression in cardiomyocytes.

[Activation of cardiac caspases: a double-edged weapon implicated in cardiac dysfunction]. / L'activation des caspases dans les cellules cardiaques: une arme a double tranchant impliquée dans la dysfonction cardiaque.

Low dead cell levels detected in various cardiac pathologies led to consider cardiac apoptosis as epiphenomena without repercussion on heart function. However, apoptosis prevention, and more specifically caspase inhibition, has been associated with major myocardial contractile performance improvement. This review describes specifically caspase involvement in myocardial dysfunction and highlights typical cardiomyocyte apoptosis signaling features. Thus caspase neutralization may represent a promising therapeutic strategy in heart disease treatments.

[Cardiopulmonary exercise testing in exercise-induced pulmonary hypertension]. / Intérêt de l'épreuve fonctionnelle d'exercice dans la détection de l'hypertension pulmonaire d'exercice.

OBJECTIVE: To determine the accuracy of cardiopulmonary exercise-testing (CPET) in detecting exercise-induced pulmonary hypertension. BACKGROUND: CPET plays a key role in the investigation of exertional breathlessness. Exercise-induced pulmonary hypertension has been recently demonstrated to be a cause of exertional dyspnea. However, the features of CPET associated with the condition are still unknown. METHODS: We prospectively studied CPET and exercise echo-cardiography characteristics in 39 patients complaining of exertional breathlessness. Patients could be divided into 3 groups as follows: 1) control subjects having normal pulmonary arterial pressure at rest [pulmonary arterial systolic pressure < 35 mmHg] and at peak exercise [pulmonary arterial systolic pressure < 45 mmHg]; 2) patients having exercise-induced PH; 3) patients having resting PH. Results from CPET have been analyzed within each group. RESULTS: Patients developing exercise-induced PH revealed an increased VD/VT ratio and CO2 gradient (P[a-ET]CO2) at peak exercise compared to controls (VD/VT at 0.38 +/- 0.1 vs 0.29 +/- 0.11 and P[a-ET]CO2 at 4,6 +/- 3,1 vs 1 +/- 3,8 mmHg). VD/VT and P[a-ET]CO2 were increased in patients with resting PH. A VD/VT ratio at peak exercise higher than 0.34 was 72.7% sensitive and 71% specific in predicting exercise-induced PH. Positive and negative predictive values were 72.7% and 70.1% respectively. CONCLUSION: Patients with exercise-induced PH did not decrease or may increase dead space during exercise. Therefore CPET may be a useful tool in selecting patients who need to undergo further exercise haemodynamic investigations.

[Measurement of daily physical activity in patients with cystic fibrosis]. / Evaluation de l'activité physique quotidienne de patients adultes atteints de mucoviscidose.

BACKGROUND: Cystic fibrosis (CF) patients often have a good level of daily activity contrasting with the impairment of pulmonary functions. The aim of this prospective study was to measure physical daily activity (PDA) in CF-patients and compare it with rest pulmonary functions and exercise tolerance. MATERIAL AND METHODS: Fifteen CF-patients and 9 control subjects have been recruted. PDA was measured during 7 days using an accelerometer: Global-PDA (daily mean counts per day), percentage of inactivity (1 to 2 METS), light activity (2 to 3 METS), and moderate-to-hard activity (greater than 3 METS). Spirometry (FEV1, Vital Capacity) and clinical exercice testing (VO2, workload) were also performed. RESULTS: Global-PDA of CF-patients was lower than control subjects (p < 0.05). Light activity (15.5 +/- 3.3% vs 13.4 +/- 2.4%) and inactivity (81.2 +/- 9% vs 79.9 +/- 3.1%) were similar in both groups. Only moderate-to-hard activity was greater in control subjects than in CF-patients (6.7 +/- 1.6% vs 3.3 +/- 3.4%; p < 0.05). There were correlations between Global-PDA and moderate-to-hard activity (r = 0.94), FEV1 (r = 0.72), Vital Capacity (r = 0.77), workload peak (r = 0.88), and VO2peak (r = 0.70). CONCLUSION: CF-patients have a lower PDA than control subjects because of a lower moderate-to-hard activity (>3 METS). In clinical practice, interviewing a CF-patient on his "run-life" PDA (<3 METS) has poor relationship with his real "moderate-to-hard activity", and this is a confusing factor for clinicians.

[Exercise performance of patients with alveolar proteinosis]. / Comportement a l'exercice des patients atteints de protéinose alvéolaire.

INTRODUCTION: Cardiopulmonary exercise testing (CPET) is used to evaluate the severity of interstitial lung diseases, particularly when lung function is normal. The aim of this study was to analyse exercise capacity of patients with alveolar proteinosis. METHODS: We studied 7 patients undergoing alveolar proteinosis (aged 38 +/- 5 years), Three patients complained of exertional dyspnoea, 2 had a reduced vital capacity and 5 had a DLCO of less than 75% predicted. CPET was performed on a bicycle ergometer using a standard incremental protocol. RESULTS: CPET was symptom limited for all patients.. At peak exercise, VO2 was severely reduced (19.5 +/- 5.2 ml/kg/min, 58 +/- 9%). All patients developed hyperventilation. Ventilatory reserve was 42 +/- 11% of MMV, and dead space ratio (Vd/Vt) reached 0.29 +/- 0.05. Cardio-circulatory adaptation was normal (maximum heart rate 83 +/- 9%; VO2/heart rate 70 +/- 10%). Six patients exhibited gas exchange abnormalities at peak exercise (including 4 patients having a normal vital capacity): P(A-a)O2 56 +/- 18mm Hg; PaO2 65 +/- 18 mm Hg. CONCLUSION: Patients undergoing alveolar proteinosis have severe impairment of aerobic capacity and gas exchange on exercise. CPET appears to be useful for therapeutic management.

Antithrombin reduces mesenteric venular leukocyte interactions and small intestine injury in endotoxemic rats.

We examined the hypothesis that recombinant human antithrombin would reduce mesenteric venule leukocyte adhesion and small intestine injury in endotoxemic rats. Endotoxemic (endotoxin 10 mg/kg, intravenously) rats were treated either with saline or recombinant human antithrombin (250 and 500 U/kg). In some rats, indomethacin (100 mg/kg, intraperitoneally) was injected 60 min prior to endotoxin and recominant human antithrombin (500 U/kg) treatment. Compared to controls, intravital videomicroscopy of the mesentric venule showed an increase of leukocyte rolling (55+/-17 versus 70+/-19 leukocytes/min; P < 0.05) and firm adhesion (1.1+/-0.3 versus 5.8+/-0.8 leukocytes/100 microm; P < 0.05) in endotoxemic rats. Recombinant human antithrombin attenuated endotoxin-induced venular endothelium leukocyte adhesive cascade. The beneficial effects of recombinant human antithrombin on leukocyte adhesion were inhibited by indomethacin (100 mg/kg, intraperitoneally) in endotoxemic rats. Endotoxin treatment increased fluorescein isothiocyanate (FITC)-labeled dextran 4,000 (FD4) gut lumen to plasma ratio and wet weight/dry weight ratio. Recombinant human antithrombin (500 U/kg) attenuated endotoxin-induced gut injury. These observations suggest that recombinant human antithrombin reduces endothelium-leukocyte interactions in endotoxemic rats by interacting with local prostacyclin production.

Massive arsenic poisoning--effect of hemodialysis and dimercaprol on arsenic kinetics.

In massive arsenic poisoning, the use of hemodialysis and dimercaprol (BAL) therapy is still controversial. Hemodialysis is thought of value only for supportive care. BAL therapy has been criticized because of its delayed action, its own toxicity and its possible influence on arsenic clearance during hemodialysis. We studied arsenic kinetics during an acute suicidal intoxication (10 g of sodium arsenate). Treatment included gastric lavage, oral charcoal and supportive measures. Hemodialysis was performed immediately and repeated the next day. BAL therapy was prescribed only on the second day. Cardiovascular collapse, anuria and hepatic disturbance recovered in a few days and the patient could be discharged on the 15th day. Instantaneous serum arsenic hemodialysis clearance was 85 +/- 75 ml/min without previous BAL injection and 87.5 +/- 75 ml/min with a previous 250 mg BAL injection (difference not significant) indicating that BAL did not impede arsenic dialysis. The calculated total hemodialysis clearance of arsenic was higher than mean serum hemodialysis clearance indicating that erythrocyte bound arsenic is also eliminated during dialysis. We propose to consider early hemodialysis as an elimination measure in massive arsenic poisoning and to choose BAL as a chelator when dialysis is required.

Inhaled NO preadministration modulates local and remote ischemia-reperfusion organ injury in a rat model.

Inhaled nitric oxide (iNO) has been shown to have a protective effect in lung ischemia-reperfusion (I/R)-induced injuries. We studied the role of iNO (10 parts/million for 4 h) administered before I/R. In an isolated perfused lung preparation, iNO decreased the extravascular albumin accumulation from 2,059 +/- 522 to 615 +/- 105 microl and prevented the increase in lung wet-to-dry weight ratio. To study the mechanisms of this prevention, we evaluated the role of nitric oxide (NO) transport and lung exposure with matched experiments by using either lungs or blood of animals exposed to iNO and blood or lungs of naive animals. iNO-exposed blood with naive lungs did not limit the extravascular albumin accumulation (2,561 +/- 397 microl), but iNO-exposed lungs showed a leak not significantly different from the group in which both lungs and blood were iNO exposed (855 +/- 224 vs. 615 +/- 105 microl). An improvement in heart I/R left ventricular developed pressure in the animals exposed to iNO showed that blood-transported NO was, however, sufficient to trigger remote organ endothelium and reduce the consequences of a delayed injury. In conclusion, preventive iNO reduces the consequences of lung I/R injuries by a mechanism based on tissue or endothelium triggering.

In vivo application of intestinal pH measurement using 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF) fluorescence imaging.

Measurement of gastrointestinal intramucosal pH (pHim) has been recognized as an important factor in the detection of hypoxia-induced dysfunctions. However, current pH measurement techniques are limited in terms of time and spatial resolutions. A major advance in accurate pH measurement was the development of the ratiometric fluorescent indicator dye, 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF). This study aimed to set up and validate a fluorescence imaging technique to measure in vivo the intramucosal pH (pHim) of the intestine. The intestine was inserted into an optical chamber placed under a microscope. Animals were injected intravenously with the pH-sensitive fluorescent dye BCECF. Fluorescence was visualized by illuminating the intestine alternately at 490 and 470 nm. The emitted fluorescence was directed to an intensified camera. The ratio of emitted fluorescence at excitation wavelengths of 490 and 470 nm was measured, corrected and converted to pHim by constructing a calibration curve. The pHim controls were performed with a pH microelectrode and were correlated with venous blood gas sampling. Results show that pHim is determined with an accuracy of +/- 0.07 pH units and a response time of 1 min. In conclusion pHim mapping of rat intestine can be obtained by fluorescence imaging using BCECF. This technology could be easily adapted for endoscopic pH measurements.

Pedicle musculocutaneous flap transplantation: prediction of final outcome by transcutaneous oxygen measurements in hyperbaric oxygen.

In pedicle musculocutaneous flaps, a local circulatory insufficiency with a total or subtotal ischemia may occur and jeopardize the result of the reconstructive surgery. Transcutaneous oxygen pressure (PtcO2) monitoring has been shown to reflect tissue perfusion and has been advocated to predict the final outcome of ischemic flaps. Unfortunately, under normal atmospheric conditions, this test is not sufficiently discriminative. We evaluate the effect of hyperbaric oxygen conditions on the efficiency of this test. Fifteen patients with pedicle musculocutaneous flap were evaluated by clinical examination and transcutaneous oxygen tension measurements. The final outcome was healing in 7 and failure in 8. In order to determine the predictive value of transcutaneous oxygen tension, measurements were done immediately after the surgical procedure. In ambient air, neither the absolute value of transcutaneous oxygen tension (2.6 +/- 3.6 versus 11.7 +/- 12.6 torr; N.S.) nor the difference or the ratio between the transcutaneous oxygen tension of the flap and the subclavicular reference shows any significant difference according to the outcome (failure or success). The same is true in normobaric oxygen. In hyperbaric oxygen, however, there is a significant difference in transcutaneous oxygen tension between the two groups (12 +/- 12 versus 378 +/- 385 torr; p < 0.01). A transcutaneous oxygen tension higher than 50 torr in hyperbaric oxygen (2.5 atm abs) is the best cutoff value to discriminate success from failure.

Effects of breathing air at 4 atm abs: evidence for a change in strategy.

The effect of breathing air at 4 atm abs on two tasks was investigated. For the recognition memory task, subjects learned a list of symbols in anticipation of a recognition test. The second task was a speed test in which subjects were instructed to detect all occurrences of a given target. A signal detection analysis of performance to the recognition test showed that sensitivity index was invariant, but the criterion (beta) became stricter under hyperbaric pressure. For the speed test, the results showed that under pressure the error rate increased progressively with time while the working speed remained constant. It is argued that strategic variables may be particularly sensitive to the hyperbaric environment.

[Anaerobic infections of the soft tissues]. / Les infections anaérobies des tissus mous.

Anaerobic soft tissue infections are still life threatening infections. Although their frequency is actually moderate; they remain severe because physicians are often insufficiently aware of them. Although the classification between myonecrosis and necrotizing fasciitis is still valid, these infections share so many points in common that they can be considered together. Their origin is often traumatic or surgical but may also be secondary to an ulcer or a small wound in a high-risk patient: arteriosclerotic, diabetic. Hypoxia, traumatic muscle crush, heavy bacterial contamination as well as incorrect antibiotic prophylaxis are the major reasons for their occurrence. Management consists of antibiotics adapted to both anaerobic and associated aerobic bacteria, large and early surgical debridement, but with conservative excision, and intensive hyperbaric oxygen therapy. Strict prevention measures must be applied to avoid their occurrence.

[The role of exercise testing in the management of systemic sarcoidosis]. / Intérêt de l'épreuve d'effort métabolique dans la prise en charge d'une sarcoïdose systémique.

INTRODUCTION: Patients suffering from sarcoidosis sometimes report dyspnoea of effort. The restrictive or obstructive ventilatory problems contribute to this disability, but the systemic manifestations of sarcoidosis should be considered as other possible causes of the dyspnoea. CASE REPORT: We report a case of systemic sarcoidosis in a 29 year old man from the Ivory Coast. The disorder presented in December 1999 with generalised symptoms and grade II dyspnoea (Sadoul). Investigations confirmed pulmonary, mediastinal, hepatic, lachrymal and salivary involvement. Lung function tests at rest showed a combined restrictive and obstructive ventilatory defect. The initial exercise test showed evidence of severe limitation of aerobic metabolism with impaired oxygen uptake without limitation of ventilation. The absence of cardiac involvement, confirmed by echocardiography and myocardial isotope scanning, suggested that the dyspnoea was, at least in part, secondary to a "peripheral" muscular abnormality. After 3 months treatment with oral corticosteroids, the clinical and physiological parameters improved. Exercise testing confirmed an improvement in maximum work rate and oxygen uptake. The relative stability of the functional measurements and the subsequent development of myalgia prompted a biopsy of the quadriceps that showed granulomata within the muscle tissue, confirming a sarcoid myopathy. A combination of steroids and methotrexate allowed the patient to increase his exercise capacity without any major change in the resting lung function tests. CONCLUSIONS: This case report underlines the role of exercise testing in determining the cause of dyspnoea. In this patient it contributed to the diagnosis of sarcoid myopathy and lead to modification of his treatment.

[Carbon monoxide poisoning]. / L'intoxication au monoxyde de carbone.

Carbon monoxide (CO) poisoning still represents a frequent and severe casualty in France. Aside from the well-known effect of CO on hemoglobin, the role of CO binding to other hemoproteins like myoglobin and cytochrome a3 has been more recently recognized. Moreover, in addition to these hypoxic injuries, the reoxygenation phase may itself induce toxic effects by a mechanism close to the ischemia-reperfusion phenomenon. Clinical manifestations include neurologic disturbances, cardiac arrhythmia, respiratory and circulatory failures which usually disappear with removal from toxic atmosphere and administration of oxygen. However, long term neurologic manifestations may occur and lead to important functional impairment and disability. Hyperbaric oxygen is actually the treatment of choice to avoid the occurrence of delayed sequelae. HBO is advocated in every patient who remains comatose on hospital admission, who has lost consciousness during toxic exposure or with persisting neurologic abnormalities. CO poisoned pregnant women should also undergo HBO.

[Indications for hyperbaric oxygen therapy. Organization of the treatment unit. Training of personnel]. / Les indications de l'oxygénothérapie hyperbare. Organisation d'une unité de traitement. Formation des personnels.

Pathophysiologic mechanisms involved in the application of HBO therapy are poorly understood that may limit its clinical use. However, useful indications are well standardized in the setting of critical care medicine, CO poisoning, decompression sickness, gas gangrene and soft tissue anaerobic infections, crush syndrome, burns, sudden deafness... HBO therapy is also indicated in the management of chronic limb ischemia, diabetic foot lesion, osteomyelitis, osteoradionecrosis. These clinical indications have been evaluated in a Consensus Conference on Hyperbaric Medicine that has classified its application according to its efficiency. Indications were classified as strongly recommended (positively affects the patient's survival), recommended (does not influence the patient's survival but is important for the prevention of serious disorders) and optional (regarded as a additional treatment modality). Clinical application of HBO therapy requires specific equipment including a multiplace hyperbaric chamber and specific educational program and training for personnel employed in the clinical hyperbaric center. Lastly, HBO therapy is related to accurate rules defining its indications as well as its evaluation that are minimal prerequisites for safety and clinical results.

[Role of microcirculation in multiorgan failure of infectious origin]. / Rôle de la microcirculation dans la défaillance multiviscérale d'origine infectieuse.

The normal host response to infection is a complex process which serves to localize and control bacterial invasion and to initiate repair of injured tissue. This inflammatory process is accompanied by activation of circulating and fixed phagocytic cells and generation of pro-inflammatory and anti-inflammatory mediators. Sepsis results when the prerequisite inflammatory response to infection becomes generalized, and thereby extends to involve otherwise normal tissue which is remote from the initial site of injury or infection. Sepsis is typically associated to cardiovascular alterations that have been characterized by increases in oxygen delivery to the tissues. Paradoxically, the host's systemic inflammatory response syndrome may simultaneously disturb the ability to adequately match tissue oxygen needs and availability at a time when tissue oxygen needs are typically increased. Depressed tissue oxygen availability relative to augmented needs may result from dysfunction at all of the central, regional, and microregional levels of the circulation. Significant dysregulation in the process by which oxygen availability is usually matched to changing tissue oxygen needs is typical associated with changes the microvascular blood flow behavior, vascular reactivity and endothelial and leukocyte activation. Specific tools developed to explore the microcirculation have been applied in the setting of both human and animal models sepsis. Abnormalities observed in the septic microvasculature are characterized by reductions in cutaneous and skeletal muscle blood flow and in mucosal intestinal ischemia and hypoxia. Regarding the skeletal muscle organ system, microvascular abnormalities were further characterized by an impairment of blood flow to increase in response to oxygen need increase. Also, microvascular abnormalities in the intestine were associated with evidence of endothelial and leukocyte activation leading to epithelial dysfunction. Thus, sepsis appears to be associated with early onset microvascular dysfunction. The relationship between microvascular dysfunction and endothelial and leukocyte activation leading to organ failure has been suggested by numerous studies.