Pancreatic stone protein is highly increased during posttraumatic sepsis and activates neutrophil granulocytes

OBJECTIVES: The level of pancreatic stone protein/regenerating protein (PSP/reg), a secretory protein produced in the pancreas, increases dramatically during pancreatic disease. However, after stress (e.g., anesthesia), PSP/reg levels are increased transiently in animals without pancreatic injury. Therefore, we aimed to determine whether PSP/reg is an acute-phase protein after nonpancreatic trauma. PATIENTS: Eighty-three polytraumatic patients without pancreatic damage. MEASUREMENTS AND MAIN RESULTS: We compared serum PSP/reg levels from polytraumatic patients without pancreatic damage with those in healthy controls (n = 38). C-reactive protein, interleukin-6, procalcitonin, and leukocyte numbers were also compared. The expression of CD62L and CD11b on neutrophils after exposure to PSP/reg was analyzed by flow cytometry. Thirty-three patients (39%) developed sepsis, 32 (38%) had local infections, and 18 (21%) had no infections. At admission, PSP/reg serum levels (10.2 [6.2-14.5] ng/mL; median [interquartile range]) were comparable with those in healthy controls (10.4 [7.5-12.3] ng/mL). During hospital stay, PSP/reg levels were elevated significantly in patients with sepsis (146.4 ng/mL) and in patients with infections (111.4 ng/mL) compared with patients without infections (22.8 ng/mL). Furthermore, binding of fluorescein isothiocyanate-labeled recombinant PSP/reg to human neutrophils was demonstrated. Recombinant PSP/reg elicited a dose-dependent shedding of L-selectin (CD62L) and upregulation of beta2-integrin (CD11b) in neutrophils, which indicates that PSP/reg activates neutrophils. CONCLUSIONS: We conclude that PSP/reg is up-regulated in blood after trauma, and the PSP/reg level is related to the severity of inflammation. Furthermore, PSP/reg binds to and activates neutrophils. Therefore, PSP/reg might be an acute-phase protein that could serve as a marker for posttraumatic complications.

Effect of two bioabsorbable barrier membranes on bone regeneration of standardized defects in calvarial bone: a comparative histomorphometric study in pigs

BACKGROUND: The effect of two different bioabsorbable collagen membranes on bone regeneration was assessed in standardized, membrane-protected calvarial defects in pigs. METHODS: Two standardized defect types (6 x 6 x 6 mm and 9 x 9 x 9 mm) were produced in the calvaria of pigs: empty defects without a membrane (group 1; eight defects per size); defects filled with deproteinized bovine bone mineral (DBBM) without a membrane (group 2; eight defects per size); defects filled with DBBM and covered by a collagen membrane (group 3; eight defects per size); and defects filled with DBBM and covered by a cross-linked collagen membrane (CCM) (group 4; eight defects per size). Sacrifice took place 16 weeks after surgery, and the following parameters were analyzed: descriptive histology; semiquantitative histology (SQH), assessing bone regeneration in the whole defect area; and histomorphometric analysis of the percentage of bone and DBBM in the regenerated area at three different depth levels of the defect. RESULTS: Using SQH, both membrane types resulted in significantly better bone regeneration compared to groups 1 and 2, irrespective of the defect size (P <0.005), with no difference between the two membranes. In the histomorphometric analysis, the layer immediately below the surface exhibited a significantly higher percentage of bone in groups 3 (27%) and 4 (36%) versus the two other groups for the 9 x 9 x 9-mm defects. No such differences were apparent for the 6 x 6 x 6-mm defects or the other two depth levels (bottom and middle layer) for either defect size. CONCLUSIONS: The two collagen membranes tested significantly enhanced bone regeneration, especially in the superficial level of the calvarial bone defects. The prototype CCM did not provide any further advantage in the present animal model.

Potential clinical utility of polymerase chain reaction in microbiological testing for sepsis

OBJECTIVES: To evaluate the potential improvement of antimicrobial treatment by utilizing a new multiplex polymerase chain reaction (PCR) assay that identifies sepsis-relevant microorganisms in blood. DESIGN: Prospective, observational international multicentered trial. SETTING: University hospitals in Germany (n = 2), Spain (n = 1), and the United States (n = 1), and one Italian tertiary general hospital. PATIENTS: 436 sepsis patients with 467 episodes of antimicrobial treatment. METHODS: Whole blood for PCR and blood culture (BC) analysis was sampled independently for each episode. The potential impact of reporting microorganisms by PCR on adequacy and timeliness of antimicrobial therapy was analyzed. The number of gainable days on early adequate antimicrobial treatment attributable to PCR findings was assessed. MEASUREMENTS AND MAIN RESULTS: Sepsis criteria, days on antimicrobial therapy, antimicrobial substances administered, and microorganisms identified by PCR and BC susceptibility tests. RESULTS: BC diagnosed 117 clinically relevant microorganisms; PCR identified 154. Ninety-nine episodes were BC positive (BC+); 131 episodes were PCR positive (PCR+). Overall, 127.8 days of clinically inadequate empirical antibiotic treatment in the 99 BC+ episodes were observed. Utilization of PCR-aided diagnostics calculates to a potential reduction of 106.5 clinically inadequate treatment days. The ratio of gainable early adequate treatment days to number of PCR tests done is 22.8 days/100 tests overall (confidence interval 15-31) and 36.4 days/100 tests in the intensive care and surgical ward populations (confidence interval 22-51). CONCLUSIONS: Rapid PCR identification of microorganisms may contribute to a reduction of early inadequate antibiotic treatment in sepsis.

Rivastigmine for the prevention of postoperative delirium in elderly patients undergoing elective cardiac surgery--a randomized controlled trial

OBJECTIVE: Cardiac surgery is frequently followed by postoperative delirium, which is associated with increased 1-year mortality, late cognitive deficits, and higher costs. Currently, there are no recommendations for pharmacologic prevention of postoperative delirium. Impaired cholinergic transmission is believed to play an important role in the development of delirium. We tested the hypothesis that prophylactic short-term administration of oral rivastigmine, a cholinesterase inhibitor, reduces the incidence of delirium in elderly patients during the first 6 days after elective cardiac surgery. DESIGN:: Double-blind, randomized, placebo-controlled trial. SETTING: One Swiss University Hospital. PATIENTS: One hundred twenty patients aged 65 or older undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTION: Patients were randomly assigned to receive either placebo or 3 doses of 1.5 mg of oral rivastigmine per day starting the evening before surgery and continuing until the evening of the sixth postoperative day. MEASUREMENTS AND MAIN RESULTS: The primary predefined outcome was delirium diagnosed with the Confusion Assessment Method within 6 days postoperatively. Secondary outcome measures were the results of daily Mini-Mental State Examinations and clock drawing tests, and the use of a rescue treatment consisting of haloperidol and/or lorazepam in patients with delirium. Delirium developed in 17 of 57 (30%) and 18 of 56 (32%) patients in the placebo and rivastigmine groups, respectively (p = 0.8). There was no treatment effect on the time course of Mini-Mental State Examinations and clock drawing tests (p = 0.4 and p = 0.8, respectively). There was no significant difference in the number of patients receiving haloperidol (18 of 57 and 17 of 56, p = 0.9) or lorazepam (38 of 57 and 35 of 56, p = 0.6) in the placebo and rivastigmine groups, respectively. CONCLUSION: This negative or, because of methodologic issues, possibly failed trial does not support short-term prophylactic administration of oral rivastigmine to prevent postoperative delirium in elderly patients undergoing elective cardiac surgery with cardiopulmonary bypass.

Increased splanchnic oxygen extraction because of routine nursing procedures

OBJECTIVE: Multiple organ failure is a common complication of acute circulatory and respiratory failure. We hypothesized that therapeutic interventions used routinely in intensive care can interfere with the perfusion of the gut and the liver, and thereby increase the risk of mismatch between oxygen supply and demand. DESIGN: Prospective, observational study. SETTING: Interdisciplinary intensive care unit (ICU) of a university hospital. PATIENTS: Thirty-six patients on mechanical ventilation with acute respiratory or circulatory failure or severe infection were included. INTERVENTIONS: Insertion of a hepatic venous catheter. MEASUREMENTS AND MAIN RESULTS: Daily nursing procedures were recorded. A decrease of >or=5% in hepatic venous oxygen saturation (Sho2) was considered relevant. Observation time was 64 (29-104) hours (median [interquartile range]). The ICU stay was 11 (8-15) days, and hospital mortality was 35%. The number of periods with procedures/patient was 170 (98-268), the number of procedure-related decreases in Sho2 was 29 (13-41), and the number of decreases in Sho2 unrelated to procedures was 9 (4-19). Accordingly, procedure-related Sho2 decreases occurred 11 (7-17) times per day. Median Sho2 decrease during the procedures was 7 (5-10)%, and median increase in the gradient between mixed and hepatic venous oxygen saturation was 6 (4-9)%. Procedures that caused most Sho2 decreases were airway suctioning, assessment of level of sedation, and changing patients' position. Sho2 decreases were associated with small but significant increases in heart rate and intravascular pressures. Maximal Sequential Organ Failure Assessment scores in the ICU correlated with the number of Sho2 decreases (r: .56; p < 0.001) and with the number of procedure-related Sho2 decreases (r: .60; p < 0.001). CONCLUSIONS: Patients are exposed to repeated episodes of impaired splanchnic perfusion during routine nursing procedures. More research is needed to examine the correlation, if any, between nursing procedures and hepatic venous desaturation.

Better conduct of clinical trials: the control group in critical care trials

OBJECTIVE: To review trial design issues related to control groups. DESIGN: Review of the literature with specific reference to critical care trials. MAIN RESULTS AND CONCLUSIONS: Performing randomized controlled trials in the critical care setting presents specific problems: studies include patients with rapidly lethal conditions, the majority of intensive care patients suffer from syndromes rather than from well-definable diseases, the severity of such syndromes cannot be precisely assessed, and the treatment consists of interacting therapies. Interactions between physiology, pathophysiology, and therapies are at best marginally understood and may have a major impact on study design and interpretation of results. Selection of the right control group is crucial for the interpretation and clinical implementation of results. Studies comparing new interventions with current ones or different levels of current treatments have the problem of the necessity of defining "usual care." Usual care controls without any constraints typically include substantial heterogeneity. Constraints in the usual therapy may help to reduce some variation. Inclusion of unrestricted usual care groups may help to enhance safety. Practice misalignment is a novel problem in which patients receive a treatment that is the direct opposite of usual care, and occurs when fixed-dose interventions are used in situations where care is normally titrated. Practice misalignment should be considered in the design and interpretation of studies on titrated therapies.

Classification of the taxon 2 and taxon 3 complex of Bisgaard within Gallibacterium and description of Gallibacterium melopsittaci sp. nov., Gallibacterium trehalosifermentans sp. nov. and Gallibacterium salpingitidis sp. nov

This investigation was based on 23 isolates from several European countries collected over the past 30 years, and included characterization of all isolates. Published data on amplified fragment length polymorphism typing of isolates representing all biovars as well as protein profiles were used to select strains that were then further characterized by polyamine profiling and sequencing of 16S rRNA, infB, rpoB and recN genes. Comparison of 16S rRNA gene sequences revealed a monophyletic group within the avian 16S rRNA group of the Pasteurellaceae, which currently includes the genera Avibacterium, Gallibacterium and Volucribacter. Five monophyletic subgroups related to Gallibacterium anatis were recognized by 16S rRNA, rpoB, infB and recN gene sequence comparisons. Whole-genome similarity between strains of the five subgroups and the type strain of G. anatis calculated from recN sequences allowed us to classify them within the genus Gallibacterium. In addition, phenotypic data including biochemical traits, protein profiling and polyamine patterns clearly indicated that these taxa are related. Major phenotypic diversity was observed for 16S rRNA gene sequence groups. Furthermore, comparison of whole-genome similarities, phenotypic data and published data on amplified fragment length polymorphism and protein profiling revealed that each of the five groups present unique properties that allow the proposal of three novel species of Gallibacterium, for which we propose the names Gallibacterium melopsittaci sp. nov. (type strain F450(T) =CCUG 36331(T) =CCM 7538(T)), Gallibacterium trehalosifermentans sp. nov. (type strain 52/S3/90(T) =CCUG 55631(T) =CCM 7539(T)) and Gallibacterium salpingitidis sp. nov. (type strain F150(T) =CCUG 15564(T) =CCUG 36325(T) =NCTC 11414(T)), a novel genomospecies 3 of Gallibacterium and an unnamed taxon (group V). An emended description of the genus Gallibacterium is also presented.

Modeling the stratospheric warming following the Mt. Pinatubo eruption: uncertainties in aerosol extinctions

In terms of atmospheric impact, the volcanic eruption of Mt. Pinatubo (1991) is the best characterized large eruption on record. We investigate here the model-derived stratospheric warming following the Pinatubo eruption as derived from SAGE II extinction data including recent improvements in the processing algorithm. This method, termed SAGE_4λ, makes use of the four wavelengths (385, 452, 525 and 1024 nm) of the SAGE II data when available, and uses a data-filling procedure in the opacity-induced "gap" regions. Using SAGE_4λ, we derived aerosol size distributions that properly reproduce extinction coefficients also at much longer wavelengths. This provides a good basis for calculating the absorption of terrestrial infrared radiation and the resulting stratospheric heating. However, we also show that the use of this data set in a global chemistry–climate model (CCM) still leads to stronger aerosol-induced stratospheric heating than observed, with temperatures partly even higher than the already too high values found by many models in recent general circulation model (GCM) and CCM intercomparisons. This suggests that the overestimation of the stratospheric warming after the Pinatubo eruption may not be ascribed to an insufficient observational database but instead to using outdated data sets, to deficiencies in the implementation of the forcing data, or to radiative or dynamical model artifacts. Conversely, the SAGE_4λ approach reduces the infrared absorption in the tropical tropopause region, resulting in a significantly better agreement with the post-volcanic temperature record at these altitudes.

A global historical ozone data set and prominent features of stratospheric variability prior to 1979

We present a vertically resolved zonal mean monthly mean global ozone data set spanning the period 1901 to 2007, called HISTOZ.1.0. It is based on a new approach that combines information from an ensemble of chemistry climate model (CCM) simulations with historical total column ozone information. The CCM simulations incorporate important external drivers of stratospheric chemistry and dynamics (in particular solar and volcanic effects, greenhouse gases and ozone depleting substances, sea surface temperatures, and the quasi-biennial oscillation). The historical total column ozone observations include ground-based measurements from the 1920s onward and satellite observations from 1970 to 1976. An off-line data assimilation approach is used to combine model simulations, observations, and information on the observation error. The period starting in 1979 was used for validation with existing ozone data sets and therefore only ground-based measurements were assimilated. Results demonstrate considerable skill from the CCM simulations alone. Assimilating observations provides additional skill for total column ozone. With respect to the vertical ozone distribution, assimilating observations increases on average the correlation with a reference data set, but does not decrease the mean squared error. Analyses of HISTOZ.1.0 with respect to the effects of El Niño–Southern Oscillation (ENSO) and of the 11 yr solar cycle on stratospheric ozone from 1934 to 1979 qualitatively confirm previous studies that focussed on the post-1979 period. The ENSO signature exhibits a much clearer imprint of a change in strength of the Brewer–Dobson circulation compared to the post-1979 period. The imprint of the 11 yr solar cycle is slightly weaker in the earlier period. Furthermore, the total column ozone increase from the 1950s to around 1970 at northern mid-latitudes is briefly discussed. Indications for contributions of a tropospheric ozone increase, greenhouse gases, and changes in atmospheric circulation are found. Finally, the paper points at several possible future improvements of HISTOZ.1.0.

Climate and chemistry effects of a regional scale nuclear conflict

Previous studies have highlighted the severity of detrimental effects for life on earth after an assumed regionally limited nuclear war. These effects are caused by climatic, chemical and radiative changes persisting for up to one decade. However, so far only a very limited number of climate model simulations have been performed, giving rise to the question how realistic previous computations have been. This study uses the coupled chemistry climate model (CCM) SOCOL, which belongs to a different family of CCMs than previously used, to investigate the consequences of such a hypothetical nuclear conflict. In accordance with previous studies, the present work assumes a scenario of a nuclear conflict between India and Pakistan, each applying 50 warheads with an individual blasting power of 15 kt ("Hiroshima size") against the major population centers, resulting in the emission of tiny soot particles, which are generated in the firestorms expected in the aftermath of the detonations. Substantial uncertainties related to the calculation of likely soot emissions, particularly concerning assumptions of target fuel loading and targeting of weapons, have been addressed by simulating several scenarios, with soot emissions ranging from 1 to 12 Tg. Their high absorptivity with respect to solar radiation leads to a rapid self-lofting of the soot particles into the strato- and mesosphere within a few days after emission, where they remain for several years. Consequently, the model suggests earth's surface temperatures to drop by several degrees Celsius due to the shielding of solar irradiance by the soot, indicating a major global cooling. In addition, there is a substantial reduction of precipitation lasting 5 to 10 yr after the conflict, depending on the magnitude of the initial soot release. Extreme cold spells associated with an increase in sea ice formation are found during Northern Hemisphere winter, which expose the continental land masses of North America and Eurasia to a cooling of several degrees. In the stratosphere, the strong heating leads to an acceleration of catalytic ozone loss and, consequently, to enhancements of UV radiation at the ground. In contrast to surface temperature and precipitation changes, which show a linear dependence to the soot burden, there is a saturation effect with respect to stratospheric ozone chemistry. Soot emissions of 5 Tg lead to an ozone column reduction of almost 50% in northern high latitudes, while emitting 12 Tg only increases ozone loss by a further 10%. In summary, this study, though using a different chemistry climate model, corroborates the previous investigations with respect to the atmospheric impacts. In addition to these persistent effects, the present study draws attention to episodically cold phases, which would likely add to the severity of human harm worldwide. The best insurance against such a catastrophic development would be the delegitimization of nuclear weapons.

A cellular cleavage pathway for the Moloney murine leukemia virus precursor protein, Pr65$\rm\sp{gag}$: Identification of a new viral protein containing CAp30 and NCp10 sequences

The origin and structure of P55$\sp{\rm gag},$ a gag encoded polyprotein lacking the nucleocapsid protein, NCp10, have been explored. Evidence shows that P55$\sp{\rm gag}$ is formed by non-viral proteolytic cleavage of the Moloney murine leukemia virus (MoMuLV)gag precursor protein, Pr65$\sp{\rm gag}.$ P55$\sp{\rm gag}$ is produced in cells infected by a viral protease deletion mutant and by a recombinant murine sarcoma virus known to lack the protease gene, implying that a cellular protease is responsible for the cleavage. Structural and immunological studies show that the protein cleavage site is upstream of the CAp30-NCp10 viral proteolytic junction, implying that P55$\sp{\rm gag}$ lacks the carboxy-terminal residues of CAp30. During the course of studying P55$\sp{\rm gag},$ another protein was discovered, which I named nucleocapsid-related protein(NCRP). NCRP possesses the portion of CAp30 that is lacking in P55$\sp{\rm gag}.$ NCRP possesses antigenic epitopes present in CAp30 and NCp10. NCRP was observed in virus lysates and in nuclear lysates of MoMuLV infected cells; it was not detected in the cytoplasmic fractions of MoMuLV infected cells. Our results indicated that NCRP originates from Pr65$\sp{\rm gag},$ resulting from the same cellular proteolytic cleavage event that produces the viral cellular protein P55$\sp{\rm gag}.$ P55$\sp{\rm gag}$- and NCRP-like proteins also were observed in AKV murine leukemia virus (AKV MuLV) and feline leukemia virus (FeLV) infected cells and in their respective virus particles. The site of cleavage that yields P55$\sp{\rm gag}$ and NCRP is within the carboxy terminus of CAp30, likely within a motif highly conserved among mammalian type C retroviruses. This new motif, called the capsid conserved motif (CCM), overlaps a region containing both a possible bipartite nuclear targeting sequence and a region homologous with the U1 small nuclear ribonucleoprotein 70-kD protein. This domain, when intact, may act as a nuclear targeting sequence for the gag precursor proteins Pr65$\sp{\rm gag}$ and CAp30. Nuclei of cells infected with MoMuLV were examined for the presence of gag proteins. Both Pr65$\sp{\rm gag}$ and CAp30 were detected in the nuclear fraction of MoMuLV, AKV MuLV and FeLV infected cells. P55$\sp{\rm gag}$ was never detected in the nucleus of MoMuLV, AKV MuLV and FeLV infected cells or in their respective virus particles. I propose that NCRP may be involved in sequestering viral genomic RNA for the purposes of encapsidation and intracellular viral genomic RNA dimerization. ^

Volcanic forcing for climate modeling: a new microphysics-based data set covering years 1600–present

As the understanding and representation of the impacts of volcanic eruptions on climate have improved in the last decades, uncertainties in the stratospheric aerosol forcing from large eruptions are now linked not only to visible optical depth estimates on a global scale but also to details on the size, latitude and altitude distributions of the stratospheric aerosols. Based on our understanding of these uncertainties, we propose a new model-based approach to generating a volcanic forcing for general circulation model (GCM) and chemistry–climate model (CCM) simulations. This new volcanic forcing, covering the 1600–present period, uses an aerosol microphysical model to provide a realistic, physically consistent treatment of the stratospheric sulfate aerosols. Twenty-six eruptions were modeled individually using the latest available ice cores aerosol mass estimates and historical data on the latitude and date of eruptions. The evolution of aerosol spatial and size distribution after the sulfur dioxide discharge are hence characterized for each volcanic eruption. Large variations are seen in hemispheric partitioning and size distributions in relation to location/date of eruptions and injected SO2 masses. Results for recent eruptions show reasonable agreement with observations. By providing these new estimates of spatial distributions of shortwave and long-wave radiative perturbations, this volcanic forcing may help to better constrain the climate model responses to volcanic eruptions in the 1600–present period. The final data set consists of 3-D values (with constant longitude) of spectrally resolved extinction coefficients, single scattering albedos and asymmetry factors calculated for different wavelength bands upon request. Surface area densities for heterogeneous chemistry are also provided.

Influence of inspiration to expiration ratio on cyclic recruitment and derecruitment of atelectasis in a saline lavage model of acute respiratory distress syndrome*

OBJECTIVE Cyclic recruitment and derecruitment of atelectasis can occur during mechanical ventilation, especially in injured lungs. Experimentally, cyclic recruitment and derecruitment can be quantified by respiration-dependent changes in PaO2 (ΔPaO2), reflecting the varying intrapulmonary shunt fraction within the respiratory cycle. This study investigated the effect of inspiration to expiration ratio upon ΔPaO2 and Horowitz index. DESIGN Prospective randomized study. SETTING Laboratory investigation. SUBJECTS Piglets, average weight 30 ± 2 kg. INTERVENTIONS At respiratory rate 6 breaths/min, end-inspiratory pressure (Pendinsp) 40 cm H2O, positive end-expiratory pressure 5 cm H2O, and FIO2 1.0, measurements were performed at randomly set inspiration to expiration ratios during baseline healthy and mild surfactant depletion injury. Lung damage was titrated by repetitive surfactant washout to induce maximal cyclic recruitment and derecruitment as measured by multifrequency phase fluorimetry. Regional ventilation distribution was evaluated by electrical impedance tomography. Step changes in airway pressure from 5 to 40 cm H2O and vice versa were performed after lavage to calculate PO2-based recruitment and derecruitment time constants (TAU). MEASUREMENTS AND MAIN RESULTS In baseline healthy, cyclic recruitment and derecruitment could not be provoked, whereas in model acute respiratory distress syndrome, the highest ΔPaO2 were routinely detected at an inspiration to expiration ratio of 1:4 (range, 52-277 torr [6.9-36.9 kPa]). Shorter expiration time reduced cyclic recruitment and derecruitment significantly (158 ± 85 torr [21.1 ± 11.3 kPa] [inspiration to expiration ratio, 1:4]; 25 ± 12 torr [3.3 ± 1.6 kPa] [inspiration to expiration ratio, 4:1]; p < 0.0001), whereas the PaO2/FIO2 ratio increased (267 ± 50 [inspiration to expiration ratio, 1:4]; 424 ± 53 [inspiration to expiration ratio, 4:1]; p < 0.0001). Correspondingly, regional ventilation redistributed toward dependent lung regions (p < 0.0001). Recruitment was much faster (TAU: fast 1.6 s [78%]; slow 9.2 s) than derecruitment (TAU: fast 3.1 s [87%]; slow 17.7 s) (p = 0.0078). CONCLUSIONS Inverse ratio ventilation minimizes cyclic recruitment and derecruitment of atelectasis in an experimental model of surfactant-depleted pigs. Time constants for recruitment and derecruitment, and regional ventilation distribution, reflect these findings and highlight the time dependency of cyclic recruitment and derecruitment.

Cirrhotic cardiomyopathy: A cardiologist’s perspective

Cardiac dysfunction is frequently observed in patients with cirrhosis, and has long been linked to the direct toxic effect of alcohol. Cirrhotic cardiomyopathy (CCM) has recently been identified as an entity regardless of the cirrhosis etiology. Increased cardiac output due to hyperdynamic circulation is a pathophysiological hallmark of the disease. The underlying mechanisms involved in pathogenesis of CCM are complex and involve various neurohumoral and cellular pathways, including the impaired β-receptor and calcium signaling, altered cardiomyocyte membrane physiology, elevated sympathetic nervous tone and increased activity of vasodilatory pathways predominantly through the actions of nitric oxide, carbon monoxide and endocannabinoids. The main clinical features of CCM include attenuated systolic contractility in response to physiologic or pharmacologic strain, diastolic dysfunction, electrical conductance abnormalities and chronotropic incompetence. Particularly the diastolic dysfunction with impaired ventricular relaxation and ventricular filling is a prominent feature of CCM. The underlying mechanism of diastolic dysfunction in cirrhosis is likely due to the increased myocardial wall stiffness caused by myocardial hypertrophy, fibrosis and subendothelial edema, subsequently resulting in high filling pressures of the left ventricle and atrium. Currently, no specific treatment exists for CCM. The liver transplantation is the only established effective therapy for patients with end-stage liver disease and associated cardiac failure. Liver transplantation has been shown to reverse systolic and diastolic dysfunction and the prolonged QT interval after transplantation. Here, we review the pathophysiological basis and clinical features of cirrhotic cardiomyopathy, and discuss currently available limited therapeutic options.