A Comparative Study on Platelet-Rich Plasma From Elderly Individuals and Young Adults to Treat Pressure Ulcers in Mice.

OBJECTIVE: The aim of the present study was to compare the therapeutic effects of activated platelet-rich plasma (PRP) prepared from elderly individuals and young adults to treat pressure ulcers (PUs), and to accumulate a theoretical basis for allogeneic PRP treatment of PUs in elderly patients. MATERIALS AND METHODS: Whole blood was extracted from elderly individuals aged >65 y and young adult volunteers for PRP preparation, and platelet concentrations in whole blood and PRP were compared. Growth factors released from activated PRP were assayed using the enzyme-linked immunosorbent assay. C57BL/6 mice were divided into three groups: the control saline, elderly-PRP (Group A), and young adult-PRP (Group B). Ischemia-reperfusion injury-induced PUs were established on the backs of mice. PUs were photographed on days 0, 5, and 10 to assess their sizes. Specimens were collected on day 10 and subjected to hematoxylin and eosin and Masson's staining. Immunohistochemical staining for CD31 was conducted to evaluate vascular formation, and cell invasion was assessed using a Transwell assay. The action of PRP on transforming growth factor-beta (TGF-ß)-dependent fibroblast activity and epithelial-mesenchymal transition was analyzed using immunofluorescence and Western blotting in vitro. RESULTS: The platelet concentrations in whole blood and PRP of young adults were significantly higher than that in elderly individuals. The two PRP treatment groups had similar platelet enrichment coefficients of PRP. After activation, PRP from young adults produced significantly higher levels of platelet-derived growth factor, TGF-ß, and vascular endothelial growth factor than PRP from elderly individuals (P < 0.05). The concentrations of platelet-derived growth factor, TGF-ß, and vascular endothelial growth factor were positively correlated with the platelet concentrations in whole blood and PRP. The effects of PRP in regulating the expressions of TGF-ß, α-smooth muscle actin, vimentin, and E-cadherin were observed in vivo and in vitro. The two PRP treatment groups exhibited better wound healing than the control group, as evidenced by more re-epithelialization, higher collagen content, skin fibrosis, and more blood vessel formation over time. Group B exhibited better wound healing than Group A (P < 0.05). CONCLUSION: PRP exhibits potent wound healing ability in PU therapy, and PRP from young adults is seemingly superior to that from elderly individuals because of a higher concentration of platelets and increased production of growth factors.

Primary Ciliary Body Marginal Zone Lymphoma Presenting as Hemorrhagic Hypopyon.

PURPOSE: Our purpose is to report a patient with primary unilateral ciliary body marginal zone lymphoma who initially presented with hemorrhagic hypopyon. METHODS: Retrospective review of the clinical, imaging, and immunohistopathological features of the case was performed. RESULTS: A 59-year-old man was referred with right anterior uveitis of unknown etiology which was unresponsive to systemic treatment. Slit-lamp biomicroscopy showed normotensive hemorrhagic hypopyon in that eye. Anterior segment ultrasound biomicroscopy revealed an iridociliary mass lesion. Because an anterior chamber paracentesis was noncontributory, a diagnostic cyclectomy was performed. Histopathological evaluation showed that the neoplastic cells were positive for CD20, lambda light chain, and BCL 2. BCL 6, CD10, CD5, SOX11, kappa, and Cyclin D1 stains were negative. The final diagnosis was extranodal marginal zone lymphoma of the ciliary body. CONCLUSIONS: Although rare, ciliary lymphoma may be a cause of intractable anterior uveitis. Repeat biopsies could be carried out when there is a high level of clinical suspicion.

Systemic Loss of C-terminal Src Kinase Expression Elicits Spontaneous Suppurative Inflammation in Conditional Knockout Mice.

C-terminal Src kinase (Csk) is one of the critical negative regulators of the Src family of kinases. The Src family of kinases are nonreceptor tyrosine kinases that regulate inflammation, cell proliferation, motility, and adhesion. To investigate potential histologic lesions associated with systemic loss of Csk gene activity in adult mice, conditional Csk-knockout mice were examined. Cre-mediated systemic excision of Csk induced by tamoxifen treatment resulted in multiorgan inflammation. Specifically, induction of Csk gene excision with three days of tamoxifen treatment resulted in greater than 90% gene excision. Strikingly, these mice developed enteritis that ranged from minimal and suppurative to severe, fibrinonecrosuppurative and hemorrhagic. Other inflammatory lesions included suppurative pneumonia, gastritis, and myocarditis, and increased numbers of inflammatory cells within the hepatic parenchyma. When tamoxifen treatment was reduced from three days to one day in an effort to lower the level of Csk gene excision and limit lesion development, the mice developed severe suppurative to pyogranulomatous pneumonia and minimal to mild suppurative enteritis. Lesions observed secondary to Csk gene excision suggest important roles for Csk in downregulating the proinflammatory activity of the Src family of kinases and limiting neutrophil-mediated inflammation.

Human Exoproteome in Acute Apical Abscesses.

INTRODUCTION: An acute apical abscess is a severe response of the host to massive invasion of the periapical tissues by bacteria from infected root canals. Although many studies have investigated the microbiota involved in the process, information on the host factors released during abscess formation is scarce. The purpose of this study was to describe the human exoproteome in samples from acute apical abscesses. METHODS: Fourteen pus samples were obtained by aspiration from patients with an acute apical abscess. Samples were subjected to protein digestion, and the tryptic peptides were analyzed using a mass spectrometer and ion trap instrument. The human proteins identified in this analysis were classified into different functional categories. RESULTS: A total of 303 proteins were identified. Most of these proteins were involved in cellular and metabolic processes. Immune system proteins were also very frequent and included immunoglobulins, S100 proteins, complement proteins, and heat shock proteins. Polymorphonuclear neutrophil proteins were also commonly detected, including myeloperoxidases, defensins, elastases, and gelatinases. Iron-sequestering proteins including transferrin and lactoferrin/lactotransferrin were found in many samples. CONCLUSIONS: The human exoproteome included a wide variety of proteins related to cellular processes, metabolism, and immune response. Proteins involved in different mechanisms against infection, tissue damage, and protection against tissue damage were identified. Knowledge of the presence and function of these proteins using proteomics provides an insight into the complex host-pathogen relationship, the host antimicrobial strategies to fight infections, and the disease pathogenesis.

[DETERMINATION OF A FATTY ACIDS CONTENT IN BILIARY LIPIDS AS A PROGNOSTIC FACTOR FOR THE COMPLICATIONS OCCURRENCE IN PATIENTS AFTER OPERATIONS FOR AN ACUTE CHOLECYSTITIS IN A HIGH OPERATIVE­ANESTHESIOLOGICAL RISK].

Investigation was conducted with objective to establish a prognostic significance of the fatty acids content in biliary lipids for the complications occurrence in patients, operated on for an acute cholecystitis, while presence of high operative­anesthesiological risk. A fatty acids content in biliary lipids was analyzed in 64 patients in presence of moderate (grade ІІ) and severe (grade ІІІ) course of the disease. Coefficients К1 and К2 for prognostication of postoperative purulent­inflammatory complications occurrence were elaborated, their threshold level (К1=0.59, К2=1.8) was established. There was established, that excess of the threshold meaning of К1 and К2 in a bile of patients, suffering an acute cholecystitis while presence of high operative­anesthesiological risk, constitutes a prognostic criterion for the postoperative purulent­inflammatory complications occurrence

High extracellular levels of potassium and trace metals in human brain abscess.

Brain abscesses frequently cause symptoms such as seizures, delirium, paresis and sensory deficits that could reflect brain edema, increased intracranial pressure, or tissue destruction. However, it is also possible that pus constituents could disturb neuronal function in the surrounding brain tissue. In pus from 16 human brain abscesses, extracellular potassium ([K(+)]o) was 10.6 ± 4.8 mmol/L (mean ± SD; maximum value 22.0 mmol/L). In cerebrospinal fluid (CSF), [K(+)]o was 2.7 ± 0.6 mmol/L (N = 14; difference from pus p < 0.001), which is similar to previous control values for [K(+)]o in CSF and brain parenchyma. Zinc and iron were >40-fold higher in pus than in CSF; calcium, copper, manganese, and chromium were also higher, whereas sodium and magnesium were similar. Pus from 10 extracerebral abscesses (empyemas) also had higher [K(+)]o, zinc, iron, calcium, copper, manganese, and chromium than did CSF. Brain abscess [K(+)]o was significantly higher than serum potassium (3.8 ± 0.5 mmol/L; p = 0.0001), indicating that the elevated abscess [K(+)]o originated from damaged cells (e.g. brain cells and leukocytes), not from serum. High [K(+)]o could depolarize neurons, high levels of zinc could inhibit glutamate and GABA receptors, and high levels of iron and copper could cause oxidative damage, all of which could contribute to neuronal dysfunction in brain abscess patients.

[Features of coagulative blood potential disorder in acute constitutional inflammatory response of septic tubo-ovarian formations].

BACKGROUND: There are no any systemized studies of relationship between the coagulative haemostasis' disorders and metabolic and cytokine status in patients with septic tuboovarial formations. OBJECTIVE: The aim of the present work was to study the mechanisms of blood coagulation disorders and their relationships with changes of cytokine status and acute phase of inflammatory response in septic tubo-ovarian formations in women. METHODS: 32 patients with purulent tubovarial formations and 30 healthy women were examined. RESULTS: Shortening of activated partial thromboplastin, prothrombin and thrombin clotting time, increasing the duration of XIIa-kallikrehin-dependent fibrinolysis, as well as the elevation of paracoagulation products in blood plasma were observed. IL-1ß (p =0.000023), TNF-α (p <0.001), C-reactive protein (p <0.001), haptoglobin (p <0.001) and fibrinogen (p <0.001) levels were higher in peripheral blood of patients in comparison with healthy women. Accumulation of lipid hydroperoxides (p <0. 001) and malonic dialdehyde (p <0.001) occurred in the blood plasma of patients. Serum albumin (p <0.001) and transferring (p <0.001) levels were lesser in patients with purulent tubo ovarial formations in comparison with healthy women. CONCLUSION: The obtained results showing an initiating role of cytokine and oxidative metabolic status changes in blood coagulation potential's and fibrinolysis activity's disorders developing. This biochemical signs may be used as objective criteria which may serve to determine the risk of thrombosis in case of acute inflammatory response in women with purulent inflammation.

[The role of interleukin 1-beta in pathogenesis and treatment of recurrent suppurative rhinosinusitis].

The objective of the present work was to study specific immunogenetic characteristics of 1-beta interleukin (IL 1-beta) production and estimate the possibility of using recombinant IL 1-beta for the treatment of recurrent suppurative rhinosinusitis. It was shown that the low production of IL 1-beta attributable to the combination of genotypes +3953>T *C/*C and -511C>T *C/*TAND *t/*t is associated with a relapse of suppurative rhinosinusitis. The patients presenting with this disorder are in need of dispensary examination and repeated administration of recombinant IL 1 beta (betaleukin) during the period of exacerbation of suppurative rhinosinusitis.

[Metabolic correction of the lipid-transport system in experimental diffuse purulent peritonitis].

The research was performed in 55 male chinchilla rabbits. For the first time the effect of metabolic preparations "citoflavin" and "neoton" of the protein-lipid spectrum of blood was studied in experimental diffuse purulent peritonitis. The development of diffuse purulent peritonitis caused negative changes in blood lipid-transport system which resulted in a decreased blood protein level and high density lipoproteins (HDL) and growth of triglycerides. In the HDL phospholipid spectrum the pathological changes are characterized by an increased lisophosphotide content and compensatory growth of the level of poliglycerophosphatides. A comparative analysis has shown that both preparations possess unidirectional action which is more pronounced in "citoflavin" than in "neoton".

[Structural changes in heart at experimental widespread purulent peritonitis].

Structural changes in the heart are studied at an experimental widespread purulent peritonitis. It was established that in 6 hours after initiation of peritonitis in a myocardium the severe disorders of blood circulation, interstitial edema, the phenomena of kariopyknosis, development of systemic toxic damages specifying in high speed at this disease were observed. One of the mechanism of their development is a energy deficiency. The proof of this is destructive changes of cardiomyocytes mitochondria. The comparative analysis of use of metabolic preparations "Citoflavin", containing amber acid, and "Neoton", containing phosphocreatine, for the purpose of pharmacological support of cardiac activity at an experimental widespread purulent peritonitis has revealed high efficiency of the preparation "Citoflavin". It caused more intensive decrease of inflammatory changes in a myocardium, preventing of cardiomyocytes necrobiosis, contribution to preservation of normal structure and growth of quantity of mitochondria.

Abscess penetration of cefpirome: concentrations and simulated pharmacokinetic profiles in pus.

PURPOSE: Abscess patients frequently receive antibiotic therapy when incision cannot be performed or in addition to incision. However, antibiotic concentrations in human abscesses are widely unknown. METHODS: Pharmacokinetics of cefpirome in 12 human abscesses located in different body regions was studied. Cefpirome (2 g) was administered as an intravenous short infusion, and concentrations were measured in plasma over an 8-h period and in abscesses at incision. A pharmacokinetic two-stage model was applied. RESULTS: At abscess incision performed 158 ± 112 min after the start of the infusion, the cefpirome concentrations in the abscess fluid varied markedly, ranging from ≤0.1 (limit of quantification) to 47 (mean 8.4 ± 14.1 ) mg/L. Cefpirome was detectable in nine of 12 abscesses. Maximum concentrations were calculated to be 183 ± 106 mg/L in plasma and 12 ± 16 mg/L in the abscess. A cefpirome concentration of 2 mg/L, which is the minimum concentration inhibiting growth of 90% of the most relevant bacterial pathogens, was exceeded spontaneously in six of 12 abscesses after a single dose. Cefpirome concentrations in the abscess did not correlate with either the pH or the ratio of surface area to volume of the abscesses, nor with plasma pharmacokinetics. CONCLUSIONS: Cefpirome may be useful to treat abscess patients because it was detectable in most abscesses after a single dose. However, the penetration of cefpirome into abscesses is extremely variable and cannot be predicted by measuring other available covariates.

Altered BRCA1 and BRCA2 responses and mutation of BRCA1 gene in mice exposed chronically and transgenerationally to aqueous extract of betel nut (AEBN).

The Brca1 and Brca2 tumor suppressor genes are involved in the maintenance of genomic integrity as they facilitate error free DNA repair. This study was designed to understand the role of Brca1 and Brca2 in betel nut (BN) induced chronic and transgenerational carcinogenesis in mice. Young male and female Swiss Albino mice were chronically as well as transgenerationally exposed to aqueous extract of betel nut (AEBN) in drinking water (2 mg ml(-1)) for up to 24 weeks. In chronically exposed mice, the levels of Brca1 and Brca2 proteins were elevated to approximately 1.4-fold over the age matched controls after 2 weeks of exposure to AEBN, followed by a decline below the controls. In transgenerationally exposed mice, both Brca1 and Brca2 proteins remained below the controls from the onset of AEBN exposure and rapidly declined further, indicating a loss of tumor suppressor protection. Nucleotide sequencing of exon 11 of Brca1 and exon 27 of Brca2 did not reveal mutation in liver nodules of chronically exposed mice, while a G → C mutation Brca1 was observed in liver nodules as well as in solid tumors developing in transgenerationally exposed mice. Thus, the genomic instability arising due to the lowering in the levels of Brca1 and Brca2 proteins and mutation in exon 11 of Brca1 gene contributed to the increased risk of cancer in mice exposed transgenerationally to AEBN.

The role of Stenotrophomonas maltophilia in refractory chronic rhinosinusitis.

BACKGROUND: Stenotrophomonas maltophilia is a multidrug-resistant Gram-negative bacillus that has been implicated in serious nosocomial infections. This microbe has also been isolated from sinus cultures in refractory chronic rhinosinusitis (CRS). The goal of this study was to elucidate the implications of S. maltophilia-positive cultures in the setting of CRS. The objectives of the study were (1) to define clinical and microbiological characteristics and (2) to assess management strategy and overall outcomes of S. maltophilia-positive sinus cultures in CRS patients. METHODS: A retrospective review was performed of 101 patients over a 5-year period. RESULTS: The mean age was 56.9 years with a female/male ratio of 1.1:1. Previous sinus surgery had been performed in 90.1% of patients. Greater than 97% of patients had been given antibiotics in the previous 6 months. The most common presenting symptom was discolored nasal drainage (76.2%) with endoscopic evidence of pus or crusting in 83.2% of cases. Monotherapy with trimethoprim sulfamethoxazole (TMX) or fluoroquinolones was used in 41 and 26%, respectively. This intervention resulted in overall symptom and endoscopic improvement in 70% of cases. CONCLUSION: The presence of S. maltophilia isolates on culture are associated with clinically relevant symptoms and endoscopic findings in patients with refractory CRS. Despite its multidrug-resistant nature, monotherapy with TMX or fluoroquinolones appears to be effective in providing patients with bacterial infection with symptom relief in a majority of cases.

Research on serum and saliva concentration of some bivalent cations in patient with suppurations of the oro-maxillo-facial area.

UNLABELLED: Bivalent cations, such as calcium, magnesium, zinc, copper and manganese play important roles in some physiological and pathological processes on the human body. AIM: To determine possible modifications in serum and saliva concentration of total-Ca2+, total-Mg2+, Zn2+ and Cu2+ in patients with suppurative infections of the oro-maxillo-facial area and eventually their significance for the mentioned pathology. MATERIAL AND METHOD: Study included 47 patients with suppurative infections of the oro-maxillo-facial area, hospitalised during 2006-2008 in the oro-maxillo-facial clinic of "Sfântul Spiridon" Hospital Iasi and 43 healthy control volunteers. RESULTS: Results revealed decreased serum Zn2+ (0.94 +/- 0.21 vs. 1.39 +/- 0.14 mg/L, p < 0.01), decreased serum Zn2+/Cu2+ ratio and increased serum and saliva total-Mg2+ concentration (27.34 +/- 2.61 mg/mL in patients vs. 23.83 +/- 1.61 mg/L in healthy controls- serum, p < 0.05 and 3.79 +/- 0.41 mg/mL in patients vs. 3.21 +/- 0.40 mg/mL in healthy controls - saliva, p < 0.05) in patients with suppurative infections of the oro-maxillo-facial area vs. healthy controls. There were no statistically significant differences in total-Ca2+ concentrations in saliva and serum. Our data are in agreement with medical literature revealing zinc deficiency as a predisposition factor to infection. CONCLUSION: We consider that a significant increase in total-Mg2+ saliva concentration, as well as a decrease in Zn2+/Cu2+ serum ratio could be considered a marker for predisposition to oro-maxillar suppurations.

Inflammatory sites as a source of plasma neopterin: measurement of high levels of neopterin and markers of oxidative stress in pus drained from human abscesses.

OBJECTIVES: Plasma neopterin is a clinical marker of inflammation. Interferon-gamma triggers 7,8-dihydroneopterin and its oxidation product, neopterin, to be released from macrophages. 7,8-dihydroneopterin is a potent antioxidant which can protect macrophages from oxidative damage in vitro. This study examined whether 7,8-dihydroneopterin/neopterin levels reach sufficient concentrations in human pus to provide antioxidant activity and be the source of plasma neopterin. DESIGN AND METHODS: Pus was removed by needle aspiration from 19 patients and examined for total neopterin, protein-bound DOPA, dityrosine, alpha-tocopherol, lipid oxidation and protein carbonyls. RESULTS: Total neopterin was detected between 50 nM and 1.2 microM, with an average concentration of 0.51 microM. Significant quantities of oxidized proteins and lipids were detected. alpha-Tocopherol concentrations positively correlate with total neopterin levels. CONCLUSIONS: Total neopterin levels found in the pus was up to 100 times higher than that reported in plasma, suggesting plasma neopterin originates from inflammatory sites. The concentration of total neopterin suggests that 7,8-dihydroneopterin could act as an antioxidant during inflammation.

[Regional lymphotropic antibiotic therapy as a part of comprehensive treatment of children with purulent-inflammatory diseases of maxillofacial region].

126 children (aged 3-14 years) with severe purulent-inflammatory maxillofacial lesions underwent complex treatment: lymhotropic method of antibiotic (cefamabol) therapy was used in 64 of them. Clinical, microbiological and pharmacokinetic investigations have shown the method of lymphotropic regional antibiotic therapy to be effective and feasible to treat purulent-inflammatory maxillofacial lesions in children.

Pleural fluid interleukin-8 and C-reactive protein for discriminating complicated non-purulent from uncomplicated parapneumonic effusions.

BACKGROUND AND OBJECTIVE: This study was designed to test the hypothesis that measurement of IL-8 and CRP in pleural fluid could improve the identification of patients with non-purulent parapneumonic effusions that ultimately require chest tube drainage. METHODS: We assessed IL-8, CRP and three classical parameters (pH, glucose and LDH) in the pleural fluid of 100 patients with parapneumonic effusions. Forty-nine of these patients had non-purulent complicated effusions (complicated parapneumonic pleural effusion, CPPE), and 51 had uncomplicated parapneumonic pleural effusions (UPPE). Receiver-operating characteristic curves were used to assess the sensitivity and specificity of pleural fluid biochemical parameters for differentiating among the two patient groups. IL-8 production was determined using a commercially available ELISA kit, and CRP was measured by immunoassay. RESULTS: At a cutoff value of 1000 pg/mL, IL-8 differentiated CPPE from UPPE with a sensitivity of 84% and a specificity of 82%. Likewise, CRP levels were higher in CPPE than in UPPE, and showed 72% sensitivity and 71% specificity at a cutoff value of 80 mg/L. We found that all five pleural fluid tests showed similar diagnostic accuracies when evaluated by receiver-operating characteristic analysis. However, multivariate analysis indicated that the size of the effusion, as well as pleural fluid pH and IL-8 concentration, were the best discriminatory parameters, with likelihood ratios of 6.4, 4.4 and 3.9, respectively. CONCLUSIONS: Pleural fluid IL-8 is an accurate marker for the identification of non-purulent CPPE.

Significance of diffusion-weighted imaging and apparent diffusion coefficient maps for the evaluation of pyogenic ventriculitis.

OBJECTIVE: The aim of this study is to assess the significance of an apparent diffusion coefficient (ADC) modality for the diagnosis and follow-up evaluation of ventriculitis. PATIENTS AND METHODS: Twelve patients with ventriculitis were enrolled in this study. Diffusion-weighted (DW) magnetic resonance images (MRI) and ADC maps of the periventricular white matter, intraventricular collections detected in the third or lateral ventricles and normal cerebrospinal fluid (CSF) were obtained. The images and ADC data from each lesion were correlated and then compared amongst the different lesions. CSF studies were performed via external ventricular drain (EVD) catheters or lumbar punctures performed on the same day as ADC mapping. Linear regression was used to analyze relationships among pleocytosis, glucose, chloride, protein content of pus, and ADC counting. RESULTS: A total of 24 ADC values for intraventricular pus and CSF findings were obtained from 12 patients and analyzed. The DW MRI showed marked hyperintensity in purulent lesions, and the corresponding ADC maps revealed prominent hypointensity and decreased ADC values in dependent CSF compared with non-dependent CSF and normal white matter. Dependent CSF is defined as the CSF which is mixed with purulent discharge which is located at the lower portion of the ventricle by gravity. The correlations between ADC counting and pleocytosis, and also protein content were strong: r(2)=-0.84, r(2)=-0.62, respectively (p<0.001). CONCLUSION: A decreased ADC value and increased signal intensity of dependent intraventricular fluid by DW MRI suggests the presence of material with restricted water diffusion in the ventricular space. This is seen in pyogenic ventriculitis when water diffusion is restricted in suppurative fluid. ADC counting is negatively correlated with pleocytosis and the protein content of CSF. Therefore, the ADC value might be a useful non-invasive method for the follow-up evaluation of ventriculitis as well as the diagnosis of it.

Distinct cardiodynamic and molecular characteristics during early and late stages of sepsis-induced myocardial dysfunction.

We hypothesized that progressive decline in myocardial performance would correlate with upregulation of markers for apoptotic mechanisms following increased duration of polymicrobial sepsis in the rat. Male Sprague-Dawley rats (350-400 g) were randomized into sham, 1-, 3- and 7-day sepsis groups. Each septic rat received 200 mg/kg cecal inoculum intraperitoneally (i.p). The post-mortem analysis showed a severely inflamed peritoneum with the presence of pus in all septic animals that was directly proportional to the duration of sepsis. We observed 10, 33 and 42% mortality in the 1-, 3- and 7-day sepsis groups, respectively. Septic animals at 3 and 7 days exhibited an increased wet lung/total body weight and heart weight/total body weight. A significant increase in total cardiac troponin I (cTnI) and C Reactive Protein (CRP) and endothelin-1 (ET-1) was also observed with an increased duration of sepsis. Myocardial ET-1 concentration in the 7-day post-sepsis group was significantly elevated compared to the sham and 1-day post-sepsis groups. Sepsis also produced a significant decrease in the mean arterial pressure in the 7-day post-sepsis group and tachycardia in the 1-, 3-, and 7-day post-sepsis groups compared to the sham group. A significant prolongation of the left ventricular isovolumic relaxation rate constant, tau, and left ventricular end-diastolic pressure in the 1-, 3- and 7-day post-sepsis groups compared to the sham group was observed. In addition, a significant decrease in the rates of left ventricular relaxation (-dP/dt) and contraction (+dP/dt) in the 3- and 7-day post-sepsis groups compared to the sham and 1-day post-sepsis group was observed. Sepsis produced a significant upregulation in the expression of myocardial TRADD, cytosolic active caspase-3, the Bax/Bcl(2) ratio, and the mitochondrial release of cytochrome C in the 3- and 7-day post-sepsis groups. We observed a progressive increase in the number of TUNEL positive nuclei, cytosolic caspase-3 activation and co-localization of PARP in the nuclei at 1, 3 and 7 days post-sepsis. These data suggest that the progression of sepsis from 1 day to 3-7 days produce distinct cardiodynamic characteristics with a more profound effect during later stages. The sepsis-induced decline in myocardial performance correlates with the induction of myocardial apoptosis.