86 Haemodynamic effects of the enteral administration of tranexamic acid in an experimental model of haemorrhagic shock

Aim Systemic proteolysis has been proposed as part of the complex pathologic events occurring during haemorrhagic shock (HS). Hypoperfusion may increase permeability of the gut mucosa, promoting intestinal proteases translocation into the circulation and multiorgan failure ('autodigestion hypothesis'). 1 The interruption of this cascade of events may improve systemic perfusion and organ functions. Method The present study investigated the effects of the enteral administration of a protease inhibitor, i.e. tranexamic acid (TXA), on hemodynamics in a porcine model of controlled severe acute bleeding, fluid resuscitation and blood transfusion. Six animals underwent HS without any treatment while five animals were treated with enteral TXA. Results Baseline measurements were similar in both HS and TXA groups. Both groups showed a significant reduction in mean arterial pressure (MAP) after bleeding compared to baseline values, however at the end of the fluid resuscitation MAP was significantly higher in the TXA group (62.67±13.17 vs 92.20±22.35 mmHg, p Conclusion In this experimental model of HS the enteral administration of TXA was associated with a global improvement in hemodynamics; however, only small benefits were observed on mixed venous saturation and lactate levels. Reference . Schmid-Schonbein GW. 2008landis award lecture. Inflammation and the autodigestion hypothesis. Microcirculation 2009;16(4):289–306. Conflict of interest None Funding Non

Thromboembolic event rate in paroxysmal and persistent atrial fibrillation: Data from the GISSI-AF trial

BACKGROUND: Few data on the thromboembolic (TE) risk of paroxysmal and persistent atrial fibrillation (AF) are available. This study aimed to assess the incidence of TE events in paroxysmal and persistent AF. METHODS: We performed a subset post hoc analysis of 771 patients with paroxysmal and 463 with persistent AF enrolled in the multicenter, prospective, randomized, double-blind, placebo-controlled GISSI-AF trial - comparing the efficacy of valsartan versus placebo in preventing AF recurrences – where the choice of antithrombotic treatment was left to the judgment of the referring physician. TE and major outcome events were centrally validated. AF recurrences were detected by frequent clinic visits and a transtelephonic monitoring device with weekly and symptomatic transmissions. RESULTS: Eighty-five percent of patients had a history of hypertension, and the 7.7% had heart failure, left ventricular dysfunction, or both. The mean CHADS(2) score was 1.41±0.84. TE and major bleeding events were observed at a low incidence among the overall population at 1-year follow-up (0.97% and 0.81%, respectively). The univariate and multivariable analyses revealed no statistically significant differences in the incidence of TE, major bleeding events or mortality in paroxysmal and persistent AF patients. TE events were more common among women than men (p=0.02). The follow-up examination showed under- or overtreatment with warfarin in many patients, according to guideline suggestions. Warfarin was more frequently prescribed to patients with persistent AF (p<0.0001) and patients with AF recurrences (p<0.0001). AF recurrences were noninvasively detected in 632 (51.2%) patients. In patients without AF recurrences, the TE event rate was 0.5% versus 1.74%, 1.28%, and 1.18% for those with only symptomatic, only asymptomatic or both symptomatic and asymptomatic AF recurrences, respectively, but the difference was not statistically significant, even after adjusting for warfarin treatment and the CHADS(2) score (HR 2.93; CI 95%; 0.8-10.9; p=0.11). CONCLUSIONS: TE and major bleeding events showed a very low incidence in the GISSI-AF trial population, despite under- or overtreatment with warfarin in many patients. TE events had a similar rate in paroxysmal and persistent AF. TRIAL REGISTRATION: Trial registration number: NCT0037627

Effect of mild hypercapnia on outcome and histological injury in a porcine post cardiac arrest model

Aim of the study: To evaluate in an established porcine post cardiac arrest model the effect of a mild hypercapnic ventilatory strategy on outcome. Methods: The left anterior descending coronary artery was occluded in 14 pigs and ventricular fibrillation induced and left untreated for 12 min. Cardiopulmonary resuscitation was performed for 5 min prior to defibrillation. After resuscitation, pigs were assigned to either normocapnic (end-tidal carbon dioxide (EtCO2) target: 35-40 mmHg) or hypercapnic ventilation (EtCO2 45-50 mmHg). Hemodynamics was invasively measured and EtCO2 was monitored with an infrared capnometer. Blood gas analysis, serum neuron-specific enolase (NSE) and high sensitive cardiac troponin T (hs-cTnT) were assessed. Survival and functional recovery were evaluated up to 96 h. Results: Twelve pigs were successfully resuscitated and eight survived up to 96 h, with animals in the hypercapnic group showing trend towards a longer survival. EtCO2 and arterial partial pressure of CO2 were higher in the hypercapnic group compared to the normocapnic one (p <0.01), during the 4-hour intervention. Hypercapnia was associated with higher mean arterial pressure compared to normocapnia (p <0.05). No significant differences were observed in hs-cTnT and in NSE between groups, although the values tended to be lower in the hypercapnic one. Neuronal degeneration was lesser in the frontal cortex of hypercapnic animals compared to the normocapnic ones (p <0.05). Neurological recovery was equivalent in the two groups. Conclusion: Mild hypercapnia after resuscitation was associated with better arterial pressure and lesser neuronal degeneration in this model. Nevertheless, no corresponding improvements in neurological recovery were observed.Peer reviewe

LUCAS Versus Manual Chest Compression During Ambulance Transport : A Hemodynamic Study in a Porcine Model of Cardiac Arrest

Background-Mechanical chest compression (CC) is currently suggested to deliver sustained high-quality CC in a moving ambulance. This study compared the hemodynamic support provided by a mechanical piston device or manual CC during ambulance transport in a porcine model of cardiopulmonary resuscitation. Methods and Results-In a simulated urban ambulance transport, 16 pigs in cardiac arrest were randomized to 18 minutes of mechanical CC with the LUCAS (n=8) or manual CC (n=8). ECG, arterial and right atrial pressure, together with end-tidal CO2 and transthoracic impedance curve were continuously recorded. Arterial lactate was assessed during cardiopulmonary resuscitation and after resuscitation. During the initial 3 minutes of cardiopulmonary resuscitation, the ambulance was stationary, while then proceeded along a predefined itinerary. When the ambulance was stationary, CC-generated hemodynamics were equivalent in the 2 groups. However, during ambulance transport, arterial and coronary perfusion pressure, and end-tidal CO(2 )were significantly higher with mechanical CC compared with manual CC (coronary perfusion pressure: 43 +/- 4 versus 18 +/- 4 mmHg; end-tidal CO2: 31 +/- 2 versus 19 +/- 2 mmHg, P Conclusions-This model adds evidence in favor of the use of mechanical devices to provide ongoing high-quality CC and tissue perfusion during ambulance transport.Peer reviewe

Insulin treatment and clinical outcomes in patients with diabetes and heart failure with preserved ejection fraction

Aims: Insulin causes sodium retention and hypoglycaemia and its use is associated with worse outcomes in heart failure (HF) with reduced ejection fraction. We have investigated whether this is also the case in HF with preserved ejection fraction (HFpEF). Methods and results: We examined the association between diabetes/diabetes treatments and the risk of the primary composite of cardiovascular death or HF hospitalization, as well as other outcomes in adjusted analyses in CHARM-Preserved (left ventricular ejection fraction ≥ 45%), I-Preserve and TOPCAT (Americas) pooled. Of 8466 patients, 2653 (31%) had diabetes, including 979 (37%) receiving insulin. Patients receiving insulin were younger, had a higher body mass index, prevalence of ischaemic aetiology, N-terminal pro-B-type natriuretic peptide and use of diuretics, worse New York Heart Association class and signs and symptoms, and worse quality of life and renal function, compared to patients with diabetes not on insulin. Among the 1398 patients with echocardiographic data, insulin use was associated with higher left ventricular end-diastolic pressure and more diastolic dysfunction than in other participants. The primary outcome occurred at a rate of 6.3 per 100 patient-years in patients without diabetes, and 10.2 and 17.1 per 100 patient-years in diabetes patients without and with insulin use, respectively [fully adjusted hazard ratio (aHR) insulin-treated diabetes vs. other diabetes: 1.41, 95% confidence interval (CI) 1.23-1.63, P &lt; 0.001]. The adjusted HR is 1.67 (95% CI 1.20-2.32, p = 0.002) for sudden death (insulin-treated diabetes vs. other diabetes). Conclusions: Insulin use is associated with poor outcomes in HFpEF. Although we cannot conclude a causal association, the safety of insulin and alternative glucose-lowering treatments in HF needs to be evaluated in clinical trials

NT-proBNP for Risk Prediction in Heart Failure:Identification of Optimal Cutoffs Across Body Mass Index Categories

OBJECTIVES The goal of this study was to assess the predictive power of N-terminal pro–B-type natriuretic peptide (NT-proBNP) and the decision cutoffs in heart failure (HF) across body mass index (BMI) categories. BACKGROUND  Concentrations of NT-proBNP predict outcome in HF. Although the influence of BMI to reduce levels of NT-proBNP is known, the impact of obesity on prognostic value remains uncertain. METHODS Individual data from the BIOS (Biomarkers In Heart Failure Outpatient Study) consortium were analyzed. Patients with stable HF were classified as underweight (BMI = 40 kg/m(2)) obese. The prognostic rote of NT-proBNP was tested for the endpoints of all-cause and cardiac death. RESULTS The study population included 12,763 patients (mean age 66 +/- 12 years; 25% women; mean left ventricular ejection fraction 33% 113%). Most patients were overweight (n = 5,176), followed by normal weight (n = 4,299), mildly obese (n = 2,157), moderately obese (n = 612), severely obese (n = 314), and underweight (n = 205). NT-proBNP inversely correlated with BMI (beta = -0.174 for 1 kg/m(2); P < 0.001). Adding NT-proBNP to clinical models improved risk prediction across BMI categories, with the exception of severely obese patients. The best cutoffs of NT-proBNP for 5-year all-cause death prediction were lower as BMI increased (3,785 ng/L, 2,193 ng/L, 1,554 ng/L, 1,045 ng/L, 755 ng/L, and 879 ng/L, for underweight, normal weight, overweight, and mildly, moderately, and severely obese patients, respectively) and were higher in women than in men. CONCLUSIONS NT-proBNP maintains its independent prognostic value up to 40 kg/m(2) BMI, and tower optimal risk-prediction cutoffs are observed in overweight and obese patients

Histone Deacetylase Inhibition Enhances Self Renewal and Cardioprotection by Human Cord Blood-Derived CD34+ Cells

Abstract BACKGROUND: Use of peripheral blood- or bone marrow-derived progenitors for ischemic heart repair is a feasible option to induce neo-vascularization in ischemic tissues. These cells, named Endothelial Progenitors Cells (EPCs), have been extensively characterized phenotypically and functionally. The clinical efficacy of cardiac repair by EPCs cells remains, however, limited, due to cell autonomous defects as a consequence of risk factors. The devise of "enhancement" strategies has been therefore sought to improve repair ability of these cells and increase the clinical benefit. PRINCIPAL FINDINGS: Pharmacologic inhibition of histone deacetylases (HDACs) is known to enhance hematopoietic stem cells engraftment by improvement of self renewal and inhibition of differentiation in the presence of mitogenic stimuli in vitro. In the present study cord blood-derived CD34(+) were pre-conditioned with the HDAC inhibitor Valproic Acid. This treatment affected stem cell growth and gene expression, and improved ischemic myocardium protection in an immunodeficient mouse model of myocardial infarction. CONCLUSIONS: Our results show that HDAC blockade leads to phenotype changes in CD34(+) cells with enhanced self renewal and cardioprotection

Risk stratification according to insulin type: reply

No abstract available