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.

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.

Simplified open repair for anterior chest wall deformities. Analysis of results in 205 patients.

INTRODUCTION: Pectus deformities are the most frequently seen congenital thoracic wall anomalies. The cause of these conditions is thought to be abnormal elongation of the rib cartilages. We here report our clinical experience and the results of a sternochondroplasty procedure based on the subperichondrial resection of the elongated cartilages. HYPOTHESIS: This technique is a valuable surgical strategy to treat the wide variety of pectus deformities. PATIENTS AND METHODS: During the period from October 2001 through September 2009, 205 adult patients (171 men and 34 women) underwent pectus excavatum (181), carinatum (19) or arcuatum (5) repair. The patients' pre and postoperative data were collected using a computerized database, and the results were assessed with a minimum 2-year follow-up. RESULTS: The postoperative morbidity rate was minimal and the mortality was nil. The surgeon graded cosmetic results as excellent (72.5%), good (25%) or fair (2.5%), while patients reported better results. Patients with pectus excavatum were found to have much more patent foramen ovale (PFO) than the normal adult population, which occluded after the procedure in 61% of patients, and significant improvement was found in exercise cardiopulmonary function and exercise tolerance at the 1-year follow-up. DISCUSSION: Our sternochondroplasty technique based on the subperichondrial resection of the elongated cartilages allows satisfactory repair of both pectus excavatum and sternal prominence. It is a safe procedure that might improve the effectiveness of surgical therapy in patients with pectus deformities.

[Prognostic value of clinical exercise testing in idiopathic pulmonary fibrosis]. / Intérêt pronostique de l'exploration fonctionnelle à l'exercice (EFX) au cours de la fibrose pulmonaire idiopathique.

Current guidelines for referring patients with idiopathic pulmonary fibrosis (IPF) for lung transplantation, based on resting parameters, are insufficient to predict 3-year mortality. The aim of this study was to determine the prognostic value of cardio-pulmonary exercise testing (CPET) in patients with IPF. A multicentre retrospective study of 3-year outcome was made on 63 adult patients with IPF who underwent CPET with blood gas analysis. Demographic data, resting pulmonary function and CPET parameters were collected to perform a univariate survival analysis. To estimate prognosis at 3 years, a multivariate logistic regression analysis by Kaplan-Meier curves and log-rank tests was performed. Forty-four patients (70%) were alive without lung transplant at the end of the 3-year follow-up: 19 patients (30%) were dead (n=14) or transplanted (n=5). Univariate analysis indicated that: at rest lower TLC, FVC, DLCO and PaCO(2), higher alveolo-arterial gradient for oxygen [P(A-a)O(2)] and pH; at ventilatory threshold (VT) higher VE/VO(2) and VE/VCO(2) and at peak exercise higher VE/VO(2) and VE/VCO(2), higher pH and ΔP(A-a)O(2)/ΔVO(2) (mmHg/L), lower VO(2) peak, PaO(2) and VO(2)/FC were associated with a significantly lower survival at 3 years. The multivariate logistic regression analysis showed that CPT (<65%) and VE/VO(2) at VT (>45) were independently associated with a lower survival at 3 years. Restriction and hyperventilation at ventilatory threshold are major prognostic factors in the course of IPF. CPET with blood gas analysis may have a prognostic value in these patients and initial evaluation of these parameters can help to predict disease progression.

[Cardiopulmonary exercise testing in patients with pectus excavatum]. / Exploration fonctionnelle à l'exercice des patients présentant un pectus excavatum.

The functional consequences of physiologic impairments due to pectus excavatum (PE) are not known. This study was conducted to determine the exercise performance in patients with this condition. This prospective study included all patients presenting for PE during a 5-year period. Patients had a chest CT scan to measure the PE severity index, resting pulmonary function tests, cardiopulmonary exercise testing (CPET) with gas exchange analysis and echocardiography. Thirty-two patients were included, with a mean age of 25.9 years. The mean PE severity index was 3.72 ± 0.87. The maximal oxygen uptake (VO(2-max)) was 78.6 ± 22.1% predicted. Only four out of the 32 patients had a normal CPET. In the remaining patients, we observed three main patterns of limitation: 18 patients had a marked limitation in increasing their tidal volume (41 ± 5% of FVC at VO(2-max) versus 51 ± 7.5%); five patients had abnormal gas exchange with increased P(A-a)O(2) at VO(2-max) (47 ± 23 mmHg versus 20 ± 7.5 mmHg) associated with a patent foramen ovale without elevation of right pressure. The five last patients had cardiovascular impairment with a decreased oxygen pulse at VO(2-max) (57 ± 9% versus 90 ± 20%). They exhibited the most severe limitation (VO(2-max) = 55 ± 10%; P = 0.003). CPET abnormalities were predicted by neither PE index severity nor the results of resting pulmonary function tests. PE is associated with abnormal CPET, including impairments in ventilatory, cardiovascular responses and/or gas exchange, which may be of importance in disease management.

[Prognostic value of clinical exercise testing in adult patients with cystic fibrosis]. / Intérêt pronostique de l'épreuve fonctionnelle d'exercice au cours de la mucoviscidose de l'adulte.

BACKGROUND: Current guidelines for referring cystic fibrosis (CF) patients for lung transplantation, based on resting parameters, are insufficient to predict 3-year mortality. The aim of this study was to determine the prognostic value of cardiopulmonary exercise testing (CPET) in adult CF patients. METHODS: A multicenter retrospective study on 3-year outcomes was made on 51 adult CF patients who underwent CPET with blood gas analysis. Demographic data, resting pulmonary function and CPET parameters were collected to perform a univariate survival analysis by Kaplan-Meier curves and log-rank tests. To estimate prognosis, a multivariate logistic regression analysis was performed. RESULTS: The survival log-rank analysis indicated that lower FEV(1), lower body mass index (BMI), diabetes mellitus, lower work rate and higher alveolar-arterial gradient for oxygen (P[A-a]O(2)) at peak exercise were associated with a significantly higher risk of death. The logistic regression analysis showed that BMI (<19.8) and P(A-a)O(2) peak (>43 mmHg) were independently associated with a lower chance of survival. CONCLUSION: CPET with blood gas analysis may have a prognostic value in adult CF patients. Further larger prospective clinical studies are warranted to confirm these preliminary results.

Cytokine concentrations in exhaled breath condensates in systemic sclerosis.

BACKGROUND: Pulmonary fibrosis in systemic sclerosis (SSc) involves inflammatory processes in the lower respiratory tract. Analysis of exhaled breath condensate (EBC) is a non-invasive method for studying inflammatory mediators, such as cytokines, which are of interest from both physiological and therapeutic perspectives. The aim of this study was to assess and compare cytokine concentrations in the EBC of SSc patients and controls. MATERIAL AND METHODS: EBC was collected from 19 SSc patients and 19 controls. We used a multiplex assay test kit to assay interleukin (IL)-2, -4, -6, -10, tumour necrosis factor-alpha, and interferon-gamma in samples concentrated by lyophilization. RESULTS: Cytokine concentrations in EBC were higher in SSc patients than in controls. The stepwise analyses showed that IL-4 was the biomarker which contributed most to the discrimination between controls and patients (Wilk's Lambda = 0.55, p < 0.001). We observed significant negative correlations of EBC cytokines with total lung capacity and diffusion capacity of the lung for carbon monoxide. CONCLUSIONS: These findings suggest that EBC sampling permits the non-invasive study of inflammation in SSc patients, and may be correlated with the severity of interstitial lung disease.

[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).

[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.

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.

Positional hyperventilation-induced hypoxaemia in pectus excavatum.

The presented case is of a young male (aged 19 yrs) with a pectus excavatum who showed significant exercise intolerance, despite normal pulmonary function at rest, including carbon monoxide diffusing capacity. Clinical exercise testing led to a strong suspicion of a right-to-left shunt due to an abnormally wide alveolo-arterial oxygen gradient (26.4 kPa) at peak oxygen uptake, with severe arterial hypoxaemia (arterial oxygen tension 12.54 kPa). A right-to-left shunt was confirmed by transoesophageal echocardiography demonstrating a permeable foramen ovale, despite normal right heart pressures. The right-to-left venous flow was mainly dependent on the upright body position and the deep inspiration. Indeed, i.v. dobutamine infusion to selectively affect cardiac output and hyperventilation induced by tidal volume expansion at constant breathing rate in the supine position did not result in arterial oxygen desaturation or shunting. Closure of the foramen ovale through atrial umbrella placement dramatically improved clinical and physiological abnormalities. This observation demonstrates that a hyperventilatory manoeuvre in the upright position is able to detect a permeable foramen ovale favouring flow in the inferior vena cava in the direction of the abnormal pre-existing atrial channel in a patient with a pectus excavatum.

[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.

[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.

[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.

[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.

Maximal lactate steady state does not correspond to a complete physiological steady state.

The purpose of this study was to verify whether the maximal lactate steady state (MLSS) corresponds to a physiological steady state. Eight male trained subjects performed a 30-min test on a cycle ergometer at a constant power corresponding to their own MLSS which had been previously determined. No significant variation was observed between the 10th and the 30th min for arterial lactate concentration, redox state, arterial oxygen pressure, arterial oxygen saturation, bicarbonates concentration, base excess, hematocrit, hemoglobin concentration, plasma volume, oxygen uptake, carbon dioxide output, gas exchange ratio, minute ventilation, ventilatory equivalents for oxygen and carbon dioxide, and arterial systolic blood pressure values. However, arterial carbon dioxide pressure and pH values were significantly different between the 10th and the 30th min (p < 0.01). Respiratory rate values and heart rate significantly increased (p < 0.01). These results indicate that MLSS does not correspond to a complete physiological steady state.

Differential effects of caspase inhibitors on endotoxin-induced myocardial dysfunction and heart apoptosis.

Endotoxin is one of the major factors causing myocardial depression and death during sepsis in humans. Recently, it was reported that endotoxin may induce cardiomyocyte apoptosis. Also, multiple caspase activation has been implicated in endotoxin-induced apoptosis in several organ systems. In this study, we investigated whether endotoxin would increase myocardial caspase activities and evaluated the effects of in vivo administration (3 mg/kg) of the broad-spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone(z-VAD.fmk), the caspase-3-like inhibitor benzyloxycarbonyl-Asp-Glu-Val-Asp-chloromethylketone (z-DEVD.cmk), and the caspase-1-like inhibitor acetyl-Tyr-Val-Ala-Asp-chloromethylketone (Ac-YVAD. fmk), on endotoxin-induced myocardial dysfunction and apoptosis. Endotoxin administration (10 mg/kg iv) induced myocardial contractile dysfunction that was associated with caspase activity increases and nuclear apoptosis. Broad-spectrum z-VAD.fmk and z-DEVD.cmk improved endotoxin-induced myocardial dysfunction and reduced caspase activation and nuclear apoptosis when given immediately and 2 h after endotoxin. In contrast, no effects of Ac-YVAD.fmk were observed on myocardial function and caspase-induced apoptosis. Administration of caspase inhibitors 4 h after endotoxin treatment was not able to protect the rat heart from myocardial dysfunction and nuclear apoptosis. These observations provide evidence that in our model, caspase activation plays a role in endotoxin-induced myocardial apoptosis. Caspase inhibition strategy may represent a therapeutic approach to endotoxin-induced myocardial dysfunction.