Effects of ramipril on ventricular arrhythmia after myocardial infarction in rabbits

BACKGROUND:

Ventricular arrhythmia (VA) is one of the most common complications of myocardial infarction (MI), and ventricular tachycardia and fibrillation are the main causes for sudden cardiac death. This study aimed to explore the effect of ramipril on the occurrence of VA and its mechanism after MI in rabbits.

METHODS:

Twenty-four New Zealand rabbits purchased from the Wuhan Laboratory Animal Research Center were divided into three groups: sham-operated (SHAM) group (n=8), MI group (n=8) and MI with ramipril (RAM) group (n=8). Rabbits in the SHAM group received a median sternotomy without ligation of the left ventricular coronary artery. Rabbits in the MI and RAM groups received a median sternotomy followed by ligation of the left coronary artery. The successful anterior MI was confirmed by elevation of the ST segment with more than 0.2 mV in lead II and III. After MI, rabbits in the RAM group were fed with intragastric ramipril (1 mg/kg per day) for 12 weeks. Before and 12 weeks after MI in the three groups, ventricular tachycardia or fibrillation (VT/VF) episodes and MAP in cadiocytes of the epicardium, mid-myocardium and endocardium were recorded by a multichannel physiograph. Student''s t test and ANOVA were used for statistical analysis.

RESULTS:

VT/VF episodes were decreased more markedly in the RAM group than in the MI group after 12 weeks (2.6±0.8 vs. 12.4±2.9, P<0.05). Twelve weeks after MI, the duration of repolarization for 90% (APD₉₀) of three-tier ventricular myocytes in the MI group was longer than that before MI (258.2±21.1 vs. 230.1±23.2, 278.0±23.8 vs. 245.8±25.4, 242.6±22.7 vs. 227.0±21.7, P<0.05). However, the APD₉₀ was not significantly different at 12 weeks before and after MI in the RAM group (P>0.05). Moreover, the transmural dispersion of repolarization (TDR) was increased more markedly 12 weeks after MI in the MI group than in the SHAM and RAM groups (36.2±10.2 vs. 18.7±6.2, 24.9±8.7, P<0.05). But the TDR was not significantly different between the RAM and SHAM groups (18.7±6.2 vs. 24.9±8.7, P>0.05).

CONCLUSION:

Ramipril may reduce the incidence of malignant ventricular arrhythmia via improvement of transmembrance repolarization heterogeneity after MI.KEY WORDS: Myocardial infarction, Ventricular arrhythmia, Monophasic action potential duration, Transmural dispersion of repolarization, Ramipril, Rabbits     

Thyroid hormone alterations in trauma patients requiring massive transfusion: An observational study

BACKGROUND:

Although non-thyroidal illness syndrome (NTIS) is considered a negative prognostic factor, the alterations in free triiodothyronine (fT3) levels in trauma patients requiring massive transfusion have not been reported.

METHODS:

A prospective observational study comparing 2 groups of trauma patients was conducted. Group M comprised trauma patients requiring massive transfusions (>10 units of packed red blood cells) within 24 hours of emergency admission. Group C comprised patients with an injury severity score >9 but not requiring massive transfusions. Levels of fT3, free thyroxine (fT4), and thyroid-stimulating hormone (TSH) were evaluated on admission and on days 1, 2, and 7 after admission. The clinical backgrounds and variables measured including total transfusion amounts were compared and the inter-group prognosis was evaluated. Results are presented as mean±standard deviation.

RESULTS:

Nineteen patients were enrolled in each group. In both groups, 32 were men, and the mean age was 50±24 years. In group C one patient died from respiratory failure. The initial fT3 levels in group M (1.95±0.37 pg/mL) were significantly lower than those in group C (2.49±0.72 pg/mL; P<0.01) and remained low until 1 week after admission. Initial inter-group fT4 and TSH levels were not significantly different. TSH levels at 1 week (1.99±1.64 µIU/mL) were higher than at admission (1.48±0.5 µIU/mL) in group C (P<0.05).

CONCLUSION:

Typical NTIS was observed in trauma patients requiring massive transfusions. When initial resuscitation achieved circulatory stabilization, prognosis was not strongly associated with NTIS.KEY WORDS: Non-thyroidal illness syndrome, Massive transfusion, Trauma, Free triiodothyronine, Thyroid hormone     

Racemic ketamine in adult head injury patients: use in endotracheal suctioning

Introduction

Endotracheal suctioning (ETS) is essential for patient care in an ICU but may represent a cause of cerebral secondary injury. Ketamine has been historically contraindicated for its use in head injury patients, since an increase of intracranial pressure (ICP) was reported; nevertheless, its use was recently suggested in neurosurgical patients. In this prospective observational study we investigated the effect of ETS on ICP, cerebral perfusion pressure (CPP), jugular oxygen saturation (SjO₂) and cerebral blood flow velocity (mVMCA) before and after the administration of ketamine.

Methods

In the control phase, ETS was performed on patients sedated with propofol and remifentanil in continuous infusion. If a cough was present, patients were assigned to the intervention phase, and 100 γ/kg/min of racemic ketamine for 10 minutes was added before ETS.

Results

In the control group ETS stimulated the cough reflex, with a median cough score of 2 (interquartile range (IQR) 1 to 2). Furthermore, it caused an increase in mean arterial pressure (MAP) (from 89.0 ± 11.6 to 96.4 ± 13.1 mmHg; P <0.001), ICP (from 11.0 ± 6.7 to 18.5 ± 8.9 mmHg; P <0.001), SjO₂ (from 82.3 ± 7.5 to 89.1 ± 5.4; P = 0.01) and mVMCA (from 76.8 ± 20.4 to 90.2 ± 30.2 cm/sec; P = 0.04). CPP did not vary with ETS. In the intervention group, no significant variation of MAP, CPP, mVMCA, and SjO₂ were observed in any step; after ETS, ICP increased if compared with baseline (15.1 ± 9.4 vs. 11.0 ± 6.4 mmHg; P <0.05). Cough score was significantly reduced in comparison with controls (P <0.0001).

Conclusions

Ketamine did not induce any significant variation in cerebral and systemic parameters. After ETS, it maintained cerebral hemodynamics without changes in CPP, mVMCA and SjO₂, and prevented cough reflex. Nevertheless, ketamine was not completely effective when used to control ICP increase after administration of 100 γ/kg/min for 10 minutes.     

Elevated plasma thrombomodulin and angiopoietin-2 predict the development of acute kidney injury in patients with acute myocardial infarction

Introduction

Acute kidney injury (AKI) following acute myocardial infarction (AMI) is associated with unfavorable prognosis. Endothelial activation and injury were found to play a critical role in the development of both AKI and AMI. This pilot study aimed to determine whether the plasma markers of endothelial injury and activation could serve as independent predictors for AKI in patients with AMI.

Methods

This prospective study was conducted from March 2010 to July 2012 and enrolled consecutive 132 patients with AMI receiving percutaneous coronary intervention (PCI). Plasma levels of thrombomodulin (TM), von Willebrand factor (vWF), angiopoietin (Ang)-1, Ang-2, Tie-2, and vascular endothelial growth factor (VEGF) were measured on day 1 of AMI. AKI was defined as elevation of serum creatinine of more than 0.3 mg/dL within 48 hours.

Results

In total, 13 out of 132 (9.8%) patients with AMI developed AKI within 48 hours. Compared with patients without AKI, patients with AKI had increased plasma levels of Ang-2 (6338.28 ± 5862.77 versus 2412.03 ± 1256.58 pg/mL, P = 0.033) and sTM (7.6 ± 2.26 versus 5.34 ± 2.0 ng/mL, P < 0.001), and lower estimated glomerular filtration rate (eGFR) (46.5 ± 20.2 versus 92.5 ± 25.5 mL/min/1.73 m², P < 0.001). Furthermore, the areas under the receiver operating curves demonstrated that plasma thrombomodulin (TM) and Ang-2 levels on day 1 of AMI had modest discriminative powers for predicting AKI development following AMI (0.796, P <0.001; 0.833, P <0.001; respectively).

Conclusions

Endothelial activation, quantified by plasma levels of TM and Ang-2 may play an important role in development of AKI in patients with AMI.     

PKCα signaling pathway involves in TNF-α-induced IP3R1 expression in human mesangial cells

BACKGROUND:

This study aimed to explore the effects of TNF-α on the expression of IP₃R1 mRNA and protein in human mesangial cells (HMCs), and to elucidate the mechanism of TNF-α relating to IP₃R1 expression in the occurrence of hepatorenal syndrome (HRS).

METHODS:

HMCs were stimulated by tumor (TNF-α) with 100 ng/mL for different hours (2, 4, 8, and 24 hours). The expression changes of IP₃R1 mRNA and protein were detected by quantitative real-time polymerase chain reaction and immunoblotting. Several inhibitors including D609, {"type":"entrez-nucleotide","attrs":{"text":"U73122","term_id":"4098075","term_text":"U73122"}}U73122, PP1, safingol, rottlerin and non-radioactive protein kinase C (PKC) were used to examine the mechanism of signal transduction of TNF-α-regulated IP₃R1 in HMCs.

RESULTS:

The levels of IP₃R1 mRNA at 2 hours after TNF-α exposure were significantly enhanced and peaked at 8 hours in HMCs (P<0.01), then descended at 24 hours (P<0.01). The levels of IP₃R1 protein at 4 hours after TNF-α exposure were obviously increased and peaked at 24 hours after TNF-α exposure (P<0.01). Compared to the control group, safingol (PKCα inhibitor) and D609 (phosphatidylcholine-specific phospholipase C inhibitor) significantly blocked the TNF-αinduced expression of IP₃R1 mRNA (3.30±0.81 vs. 1.95±0.13, P<0.05; 2.10±0.49, P<0.01) and IP₃R1 protein (3.09±0.13 vs. 1.86+0.39, P<0.01; 1.98±0.02, P<0.01). TNF-α promoted PKCα activation with maximal PKCα phosphorylation that occurred 8 hours after stimulation measured by non-radioactive PKC assay, and the effect was markedly attenuated by pretreatment with D609 or safingol.

CONCLUSION:

TNF-α increased the expression of IP₃R1 and this was mediated, at least in part, through the PC-PLC/PKCα signaling pathways in HMCs.KEY WORDS: TNF-α, Hepatorenal syndrome, Human mesangial cells, Protein kinase C, Phosphatidylcholine-specific phospholipase C     

An Internet-Based Diabetes Management Platform Improves Team Care and Outcomes in an Urban Latino Population

OBJECTIVE

To compare usual diabetes care (UDC) to a comprehensive diabetes care intervention condition (IC) involving an Internet-based “diabetes dashboard” management tool used by clinicians.

RESEARCH DESIGN AND METHODS

We used a parallel-group randomized design. Diabetes nurses, diabetes dietitians, and providers used the diabetes dashboard as a clinical decision support system to deliver a five-visit, 6-month intervention to 199 poorly controlled (HbA_1c >7.5% [58 mmol/mol]) Latino type 2 diabetic (T2D) patients (mean age 55 years, 60% female) at urban community health centers. We compared this intervention to an established, in-house UDC program (n = 200) for its impact on blood glucose control and psychosocial outcomes.

RESULTS

Recruitment and retention rates were 79.0 and 88.5%, respectively. Compared with UDC, more IC patients reached HbA_1c targets of <7% (53 mmol/mol; 15.8 vs. 7.0%, respectively, P < 0.01) and <8% (64 mmol/mol; 45.2 vs. 25.3%, respectively, P < 0.001). In multiple linear regression adjusting for baseline HbA_1c, adjusted mean ± SE HbA_1c at follow-up was significantly lower in the IC compared with the UDC group (P < 0.001; IC 8.4 ± 0.10%; UDC 9.2 ± 0.10%). The results showed lower diabetes distress at follow-up for IC patients (40.4 ± 2.1) as compared with UDC patients (48.3 ± 2.0) (P < 0.01), and also lower social distress (32.2 ± 1.3 vs. 27.2 ± 1.4, P < 0.01). There was a similar, statistically significant (P < 0.01) improvement for both groups in the proportion of patients moving from depressed status at baseline to nondepressed at follow-up (41.8 vs. 40%; no significance between groups).

CONCLUSIONS

The diabetes dashboard intervention significantly improved diabetes-related outcomes among Latinos with poorly controlled T2D compared with a similar diabetes team condition without access to the diabetes dashboard.     

The biological effects of higher and lower positive end-expiratory pressure in pulmonary and extrapulmonary acute lung injury with intra-abdominal hypertension

Introduction

Mechanical ventilation with high positive end-expiratory pressure (PEEP) has been used in patients with acute respiratory distress syndrome (ARDS) and intra-abdominal hypertension (IAH), but the role of PEEP in minimizing lung injury remains controversial. We hypothesized that in the presence of acute lung injury (ALI) with IAH: 1) higher PEEP levels improve pulmonary morphofunction and minimize lung injury; and 2) the biological effects of higher PEEP are more effective in extrapulmonary (exp) than pulmonary (p) ALI.

Methods

In 48 adult male Wistar rats, ALIp and ALIexp were induced by Escherichia coli lipopolysaccharide intratracheally and intraperitoneally, respectively. After 24 hours, animals were anesthetized and mechanically ventilated (tidal volume of 6 mL/kg). IAH (15 mmHg) was induced and rats randomly assigned to PEEP of 5 (PEEP5), 7 (PEEP7) or 10 (PEEP10) cmH₂O for 1 hour.

Results

In both ALIp and ALIexp, higher PEEP levels improved oxygenation. PEEP10 increased alveolar hyperinflation and epithelial cell damage compared to PEEP5, independent of ALI etiology. In ALIp, PEEP7 and PEEP10 increased lung elastance compared to PEEP5 (4.3 ± 0.7 and 4.3 ± 0.9 versus 3.1 ± 0.3 cmH₂O/mL, respectively, P <0.01), without changes in alveolar collapse, interleukin-6, caspase-3, type III procollagen, receptor for advanced glycation end-products, and vascular cell adhesion molecule-1 expressions. Moreover, PEEP10 increased diaphragmatic injury compared to PEEP5. In ALIexp, PEEP7 decreased lung elastance and alveolar collapse compared to PEEP5 (2.3 ± 0.5 versus 3.6 ± 0.7 cmH₂O/mL, P <0.02, and 27.2 (24.7 to 36.8) versus 44.2 (39.7 to 56.9)%, P <0.05, respectively), while PEEP7 and PEEP10 increased interleukin-6 and type III procollagen expressions, as well as type II epithelial cell damage compared to PEEP5.

Conclusions

In the current models of ALI with IAH, in contrast to our primary hypothesis, higher PEEP is more effective in ALIp than ALIexp as demonstrated by the activation of biological markers. Therefore, higher PEEP should be used cautiously in the presence of IAH and ALI, mainly in ALIexp.     

Susceptibility to ventilator induced lung injury is increased in senescent rats

Introduction

The principal mechanisms of ventilator induced lung injury (VILI) have been investigated in numerous animal studies. However, prospective data on the effect of old age on VILI are limited. Under the hypothesis that susceptibility to VILI is increased in old age, we investigated the pulmonary and extrapulmonary effects of mechanical ventilation with high tidal volume (VT) in old compared to young adult animals.

Interventions

Old (19.1 ± 3.0 months) and young adult (4.4 ± 1.3 months) male Wistar rats were anesthetized and mechanically ventilated (positive end-expiratory pressure 5 cmH2O, fraction of inspired oxygen 0.4, respiratory rate 40/minute) with a tidal volume (VT) of either 8, 16 or 24 ml/kg for four hours.Respiratory and hemodynamic variables, including cardiac output, and markers of systemic inflammation were recorded throughout the ventilation period. Lung histology and wet-to-dry weight ratio, injury markers in lung lavage and respiratory system pressure-volume curves were assessed post mortem. Basic pulmonary characteristics were assessed in non-ventilated animals.

Results

Compared to young adult animals, high VT (24 ml/kg body weight) caused more lung injury in old animals as indicated by decreased oxygenation (arterial oxygen tension (PaO2): 208 ± 3 vs. 131 ± 20 mmHg; P <0.05), increased lung wet-to-dry-weight ratio (5.61 ± 0.29 vs. 7.52 ± 0.27; P <0.05), lung lavage protein (206 ± 52 mg/l vs. 1,432 ± 101; P <0.05) and cytokine (IL-6: 856 ± 448 vs. 3,283 ± 943 pg/ml; P <0.05) concentration. In addition, old animals ventilated with high VT had more systemic inflammation than young animals (IL-1β: 149 ± 44 vs. 272 ± 36 pg/ml; P <0.05 - young vs. old, respectively).

Conclusions

Ventilation with unphysiologically large tidal volumes is associated with more lung injury in old compared to young rats. Aggravated pulmonary and systemic inflammation is a key finding in old animals developing VILI.     

Increased Skeletal Muscle Capillarization After Aerobic Exercise Training and Weight Loss Improves Insulin Sensitivity in Adults With IGT

OBJECTIVE

Transcapillary transport of insulin is one determinant of glucose uptake by skeletal muscle; thus, a reduction in capillary density (CD) may worsen insulin sensitivity. Skeletal muscle CD is lower in older adults with impaired glucose tolerance (IGT) compared with those with normal glucose tolerance and may be modifiable through aerobic exercise training and weight loss (AEX+WL). We tested the hypothesis that 6-month AEX+WL would increase CD to improve insulin sensitivity and glucose tolerance in older adults with IGT.

RESEARCH DESIGN AND METHODS

Sixteen sedentary, overweight-obese (BMI 27–35 kg/m²), older (63 ± 2 years) men and women with IGT underwent hyperinsulinemic-euglycemic clamps to measure insulin sensitivity, oral glucose tolerance tests, exercise and body composition testing, and vastus lateralis muscle biopsies to determine CD before and after 6-month AEX+WL.

RESULTS

Insulin sensitivity (M) and 120-min postprandial glucose (G₁₂₀) correlated with CD at baseline (r = 0.58 and r = −0.60, respectively, P < 0.05). AEX+WL increased maximal oxygen consumption (VO_2max) 18% (P = 0.02) and reduced weight and fat mass 8% (P < 0.02). CD increased 15% (264 ± 11 vs. 304 ± 14 capillaries/mm², P = 0.01), M increased 21% (42.4 ± 4.0 vs. 51.4 ± 4.3 µmol/kg FFM/min, P < 0.05), and G₁₂₀ decreased 16% (9.35 ± 0.5 vs. 7.85 ± 0.5 mmol/L, P = 0.008) after AEX+WL. Regression analyses showed that the AEX+WL-induced increase in CD independently predicted the increase in M (r = 0.74, P < 0.01) as well as the decrease in G₁₂₀ (r = −0.55, P < 0.05).

CONCLUSIONS

Six-month AEX+WL increases skeletal muscle CD in older adults with IGT. This represents one mechanism by which AEX+WL improves insulin sensitivity in older adults with IGT.     

High-frequency oscillation and tracheal gas insufflation in patients with severe acute respiratory distress syndrome and traumatic brain injury: an interventional physiological study

Introduction

In acute respiratory distress syndrome (ARDS), combined high-frequency oscillation (HFO) and tracheal gas insufflation (TGI) improves gas exchange compared with conventional mechanical ventilation (CMV). We evaluated the effect of HFO-TGI on PaO₂/fractional inspired O₂ (FiO₂) and PaCO₂, systemic hemodynamics, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) in patients with traumatic brain injury (TBI) and concurrent severe ARDS.

Methods

We studied 13 TBI/ARDS patients requiring anesthesia, hyperosmolar therapy, and ventilation with moderate-to-high CMV-tidal volumes for ICP control. Patients had PaO₂/FiO₂ <100 mm Hg at end-expiratory pressure ≥10 cm H₂O. Patients received consecutive, daily, 12-hour rescue sessions of HFO-TGI interspersed with 12-hour periods of CMV. HFO-TGI was discontinued when the post-HFO-TGI PaO₂/FiO₂ exceeded 100 mm Hg for >12 hours. Arterial/central-venous blood gases, hemodynamics, and ICP were recorded before, during (every 4 hours), and after HFO-TGI, and were analyzed by using repeated measures analysis of variance. Respiratory mechanics were assessed before and after HFO-TGI.

Results

Each patient received three to four HFO-TGI sessions (total sessions, n = 43). Pre-HFO-TGI PaO₂/FiO₂ (mean ± standard deviation (SD): 83.2 ± 15.5 mm Hg) increased on average by approximately 130% to163% during HFO-TGI (P < 0.01) and remained improved by approximately 73% after HFO-TGI (P < 0.01). Pre-HFO-TGI CMV plateau pressure (30.4 ± 4.5 cm H₂O) and respiratory compliance (37.8 ± 9.2 ml/cm H₂O), respectively, improved on average by approximately 7.5% and 20% after HFO-TGI (P < 0.01 for both). During HFO-TGI, systemic hemodynamics remained unchanged. Transient improvements were observed after 4 hours of HFO-TGI versus pre-HFO-TGI CMV in PaCO₂ (37.7 ± 9.9 versus 41.2 ± 10.8 mm Hg; P < 0.01), ICP (17.2 ± 5.4 versus 19.7 ± 5.9 mm Hg; P < 0.05), and CPP (77.2 ± 14.6 versus 71.9 ± 14.8 mm Hg; P < 0.05).

Conclusions

In TBI/ARDS patients, HFO-TGI may improve oxygenation and respiratory mechanics, without adversely affecting PaCO₂, hemodynamics, or ICP. These findings support the use of HFO-TGI as a rescue ventilatory strategy in patients with severe TBI and imminent oxygenation failure due to severe ARDS.     

Relationships between genetic polymorphisms of triggering receptor expressed on myeloid cells-1 and septic shock in a Chinese Han population

BACKGROUND: Triggering receptor expressed on myeloid cells-1(TREM-1) is a cell surface receptor expressed on neutrophils and monocytes. TREM-1 acts to amplify infl ammation and serves as a critical mediator of infl ammatory response in the context of sepsis. To date, the predisposition of TREM-1 gene polymorphisms to septic shock has not been reported. This study was designed to investigate whether TREM-1 genomic variations are associated with the development of septic shock.METHODS: We genotyped two TREM-1 single nucleotide polymorphisms(SNPs, rs2234237 and rs2234246) and evaluated the relationships between these SNPs and septic shock on susceptibility and prognosis.RESULTS: TREM-1 rs2234246 A allele in the promoter region was signifi cantly associated with the susceptibility of septic shock in recessive model(AA, OR=3.10, 95%CI 1.15 to 8.32, P=0.02), and in codominant model(AG, OR=0.72, 95%CI 0.43–1.19, P=0.02; AA, OR=2.71, 95%CI 1.00–7.42; P=0.03). However, in three inherited models(dominant model, recessive model, and codominant model), none of the assayed loci was signif icantly associated with the prognosis of septic shock. The nonsurvivor group demonstrated higher plasma IL-6 levels(99.7±34.7 pg/mL vs. 61.2±26.5 pg/mL, P0.01) than the survivor group. Plasma concentrations of IL-6 among the three genotypes of rs2234246 were AA 99.4±48.9 pg/m L, AG 85.4±43 pg/m L, and GG 65.3±30.7 pg/m L(P0.01). The plasma concentrations of IL-6 in patients with AA genotypes were signifi cantly higher than those in patients with GG genotypes(P0.01).CONCLUSION: TREM-1 genetic polymorphisms rs2234246 may be significantly correlated only with susceptibility to septic shock in the Chinese Han population.     

Veno-venous extracorporeal CO2 removal for the treatment of severe respiratory acidosis: pathophysiological and technical considerations

Introduction

While non-invasive ventilation aimed at avoiding intubation has become the modality of choice to treat mild to moderate acute respiratory acidosis, many severely acidotic patients (pH <7.20) still need intubation. Extracorporeal veno-venous CO₂ removal (ECCO₂R) could prove to be an alternative. The present animal study tested in a systematic fashion technical requirements for successful ECCO₂R in terms of cannula size, blood and sweep gas flow.

Methods

ECCO₂R with a 0.98 m² surface oxygenator was performed in six acidotic (pH <7.20) pigs using either a 14.5 French (Fr) or a 19Fr catheter, with sweep gas flow rates of 8 and 16 L/minute, respectively. During each experiment the blood flow was incrementally increased to a maximum of 400 mL/minute (14.5Fr catheter) and 1000 mL/minute (19Fr catheter).

Results

Amelioration of severe respiratory acidosis was only feasible when blood flow rates of 750 to 1000 mL/minute (19Fr catheter) were used. Maximal CO₂-elimination was 146.1 ± 22.6 mL/minute, while pH increased from 7.13 ± 0.08 to 7.41 ± 0.07 (blood flow of 1000 mL/minute; sweep gas flow 16 L/minute). Accordingly, a sweep gas flow of 8 L/minute resulted in a maximal CO₂-elimination rate of 138.0 ± 16.9 mL/minute. The 14.5Fr catheter allowed a maximum CO₂ elimination rate of 77.9 mL/minute, which did not result in the normalization of pH.

Conclusions

Veno-venous ECCO₂R may serve as a treatment option for severe respiratory acidosis. In this porcine model, ECCO₂R was most effective when using blood flow rates ranging between 750 and 1000 mL/minute, while an increase in sweep gas flow from 8 to 16 L/minute had less impact on ECCO₂R in this setting.     

Parenteral diclofenac infusion significantly decreases brain-tissue oxygen tension in patients with poor-grade aneurysmal subarachnoid hemorrhage

Introduction

Diclofenac, a nonsteroidal antiinflammatory drug, is commonly used as antipyretic therapy in intensive care. The purpose of this study was to investigate the effects of parenteral diclofenac infusion on brain homeostasis, including brain-tissue oxygen tension (P_btO₂) and brain metabolism after aneurysmal subarachnoid hemorrhage (aSAH).

Methods

We conducted a prospective, observational study with retrospective analysis of 21 consecutive aSAH patients with multimodal neuromonitoring. Cerebral perfusion pressure (CPP), mean arterial pressure (MAP), intracranial pressure (ICP), body temperature, and P_btO₂ were analyzed after parenteral diclofenac infusion administered over a 34-minute period (20 to 45 IQR). Data are given as mean ± standard error of mean and median with interquartile range (IQR), as appropriate. Time-series data were analyzed by using a general linear model extended by generalized estimation equations (GEEs).

Results

One-hundred twenty-three interventions were analyzed. Body temperature decreased from 38.3°C ± 0.05°C by 0.8°C ± 0.06°C (P < 0.001). A 10% decrease in MAP and CPP (P < 0.001) necessitated an increase of vasopressors in 26% (n = 32), colloids in 33% (n = 41), and crystalloids in 5% (n = 7) of interventions. P_btO₂ decreased by 13% from a baseline value of 28.1 ± 2.2 mm Hg, resulting in brain-tissue hypoxia (P_btO₂ <20 mm Hg) in 38% (n = 8) of patients and 35% (n = 43) of interventions. P_btO₂ <30 mm Hg before intervention was associated with brain-tissue hypoxia after parenteral diclofenac infusion (likelihood ratio, 40; AUC, 93%; 95% confidence interval (CI), 87% to 99%; P < 0.001). Cerebral metabolism showed no significant changes after parenteral diclofenac infusion.

Conclusions

Parenteral diclofenac infusion after aSAH effectively reduces body temperature, but may lead to CPP decrease and brain-tissue hypoxia, which were both associated with poor outcome after aSAH.     

The relationship between platelet endothelial cell adhesion molecule-1 and paraquat-induced lung injury in rabbits

BACKGROUND:

Platelet endothelial cell adhesion molecule-1 (PECAM-1), also known as CD31, is mainly distributed in vascular endothelial cells. Studies have shown that PECAM-1 is a very significant indicator of angiogenesis, and has been used as an indicator for vascular endothelial cells. The present study aimed to explore the relationship between the expression of PECAM-1 and the degree of acute lung injury (ALI) and fibrosis in paraquat (PQ) induced lung injury in rabbits.

METHODS:

Thirty-six adult New Zealand rabbits were randomly divided into three groups (12 rabbits in each group) according to PQ dosage: 8 mg/kg (group A), 16 mg/kg (group B), and 32 mg/kg (group C). After PQ infusion, the rabbits were monitored for 7 days and then euthanized. The lungs were removed for histological evaluation. Masson staining was used to determine the degree of lung fibrosis (LF), and semi-quantitative immune-histochemistry analysis to determine the expression of PECAM-1. Pearson’s product-moment correlation analysis was performed to evaluate the relationship between the expression of PECAM-1 and the extent of lung injuries expressed by ALI score and degree of LF.

RESULTS:

Rabbits in the three groups showed apparent poisoning. The rabbits survived longer in group A than in groups B and C (6.47±0.99 days vs. 6.09±1.04 days vs. 4.77±2.04 days) (P<0.05). ALI score was lower in group A than in groups B and C (8.33±1.03 vs. 9.83±1.17 vs. 11.50±1.38) (P<0.05), and there was statistically significant difference between group B and group C (P=0.03). LF was slighter in group A than in groups B and C (31.09%±2.05 % vs. 34.37%±1.62 % vs. 36.54%±0.44%) (P<0.05), and there was statistically significant difference between group B and group C (P=0.026). The PEACAM-1 expression was higher in group A than in groups B and C (20.31%±0.70% vs. 19.34%±0.68% vs. 18.37%±0.46%) (P<0.05), and there was statistically significant difference between group B and group C (P=0.017). Pearson’s correlation analysis showed that the expression of PECAM-1 was negatively correlated to both ALI score (Coe=–0.732, P=0.001) and degree of LF (Coe=–0.779, P<0.001).

CONCLUSIONS:

The PECAM-1 expression significantly decreases in New Zealand rabbits after PQ poisoning, and the decrease is dose-dependent. The PECAM-1 expression is negatively correlated with ALI score and LF, showing a significant role in the development of lung injuries induced by PQ.KEY WORDS: Platelet endothelial cell adhesion molecule-1, Paraquat, Acute lung injury, Lung fibrosis     

Baseline Adiponectin Levels Do Not Influence the Response to Pioglitazone in ACT NOW

OBJECTIVE

Plasma adiponectin levels are reduced in type 2 diabetes mellitus (T2DM) and other insulin-resistant states. We examined whether plasma adiponectin levels at baseline and after pioglitazone treatment in impaired glucose tolerance (IGT) subjects were associated with improved insulin sensitivity (S_I) and glucose tolerance status.

RESEARCH DESIGN AND METHODS

A total of 602 high-risk IGT subjects in ACT NOW were randomized to receive pioglitazone or placebo with a median follow-up of 2.4 years.

RESULTS

Pioglitazone reduced IGT conversion to diabetes by 72% in association with improved β-cell function by 64% (insulin secretion/insulin resistance index) and increased tissue sensitivity by 88% (Matsuda index). In pioglitazone-treated subjects, plasma adiponectin concentration increased threefold from 13 ± 0.5 to 38 ± 2.5 μg/mL (P < 0.001) and was strongly correlated with the improvement in S_I (r = 0.436, P < 0.001) and modestly correlated with glucose area under the curve during oral glucose tolerance test (r = 0.238, P < 0.005) and insulin secretion/insulin resistance index (r = 0.306, P < 0.005). The increase in adiponectin was a strong predictor of reversion to normal glucose tolerance and prevention of T2DM. In the placebo group, plasma adiponectin did not change and was not correlated with changes in glucose levels. There was an inverse association between baseline plasma adiponectin concentration and progression to diabetes in the placebo group but not in the pioglitazone group.

CONCLUSIONS

Baseline adiponectin does not predict the response to pioglitazone. The increase in plasma adiponectin concentration after pioglitazone therapy in IGT subjects is strongly related to improved glucose tolerance status and enhanced tissue sensitivity to insulin.     

Effects of hypothermia on the liver in a swine model of cardiopulmonary resuscitation

BACKGROUND:

The study aimed to explore the effects of hypothermia state induced by 4 ºC normal saline (NS) on liver biochemistry, enzymology and morphology after restoration of spontaneous circulation (ROSC) by cardiopulmonary resuscitation (CPR) in swine.

METHODS:

After 4 minutes of ventricular fibrillation (VF), standard CPR was carried out. Then the survivors were divided into two groups: low temperature group and normal temperature group. The low temperature (LT) group (n=5) received continuously 4 ºC NS at the speed of 1.33 mL/kg per minute for 22 minutes, then at the speed lowering to 10 mL/kg per hour. The normal temperature (NT) group (n=5) received NS with normal room temperature at the same speed of the LT group. Hemodynamic status and oxygen metabolism were monitored and the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were measured in blood samples obtained at baseline and at 10 minutes, 2 hours and 4 hours after ROSC. At 24 hours after ROSC, the animals were killed and the liver was removed to determine the Na⁺-K⁺-ATPase and Ca²⁺-ATPase enzyme activities and histological changes under a light or electron microscope.

RESULTS:

Core temperature was decreased in the LT group (P<0.05), while HR, MAP and CPP were not significantly decreased (P>0.05) compared with the NT group (P>0.05). The oxygen extraction ratio was lower in the LT group than in the NT group (P<0.05). The serum levels of ALT, AST and LDH increased in both groups but not significantly in the LT group. The enzyme activity of liver ATP was much higher in the LT group (Na⁺-K⁺-ATP enzyme: 8.64±3.32 U vs. 3.28±0.71 U; Ca²⁺-ATP enzyme: 10.92±2.12 U vs. 2.75±0.78 U, P<0.05). The LT group showed less cellular edema, inflammation and few damaged mitochondria as compared with the NT group.

CONCLUSION:

These data suggested that infusing 4 ºC NS continuously after ROSC could quickly lower the core body temperature, while maintaining a stable hemodynamic state and balancing oxygen metabolism, which protect the liver in terms of biochemistry, enzymology and histology after CPR.KEY WORDS: Therapeutic hypothermia, Cardiac arrest, Liver, Hemodynamics     

Thromboxane Mediation of Cardiopulmonary Effects of Embolism

Humoral factors released from platelets during pulmonary embolism may be the cause of several attendant cardiopulmonary abnormalities. This study examines the role of thromboxanes (Tx) after experimental embolism induced with 0.5 g/kg autologous clot in four groups of five dogs: (a) untreated embolized controls; (b) pretreatment with the Tx synthetase inhibitor, imidazole 25 mg/kg · h i.v., starting 30 min before embolization; (c) pretreatment with the cyclooxygenase inhibitor indomethacin, 5 mg/kg, 12 h per os and 1 mg/kg, 1 h i.v. before the experiment; (d) treatment with prostacyclin (PGI₂) 100 ηg/kg · min i.v. for 1 h, 1 h after embolization. Within 30 min, embolization led to increases of 6-keto-PGF_1α, the stable hydrolysis product of PGI₂, from 0.11±0.08 ηg/ml (mean±SD) to 0.33±0.10 ηg/ml (P < 0.005) and TxB₂, the stable product of TxA₂, from 0.10±0.04 ηg/ml to 0.38±0.06 ηg/ml (P < 0.001). Increases were observed in total dead space (V_D/V_T) from 0.46±0.03 to 0.61±0.08 (P < 0.025, physiologic shunting (_S/_T) from 16±4% to 38±9% (P < 0.01), pulmonary vascular resistance (PVR) from 2.27±0.59 mm Hg·min/liter to 9.21±1.90 mm Hg·min/liter (P < 0.005) and mean pulmonary arterial pressure from 14±6 mm Hg to 34±1 mm Hg (P < 0.001). Cardiac index (CI) fell from 139±11 ml/kg·min to 95±17 ml/kg·min in 4 h (P < 0.025). Imidazole pretreatment prevented a rise of TxB₂, but not 6-keto-PGF_1α; indomethacin blocked both. Both agents maintained V_D/V_T at base line and limited increases in _S/_T and PVR. CI was higher after imidazole pretreatment compared with controls (P < 0.025). Indomethacin led to intermediate levels of CI. PGI₂ lowered TxB₂ (P < 0.025), V_D/V_T (P < 0.025), _S/_T (P < 0.025) and PVR (P < 0.05) within 30 min. During PGI₂ infusion, CI was higher than controls. Concentrations of TxB₂ correlated with V_D/V_T, r = 0.79 and _S/_T, r = 0.69 (P < 0.001). Treatment of three dogs with the imidazole derivative ketoconazole, 10 mg/kg IV, 30 min after 0.75 g/kg autologous clot resulted in a lowering of physiologic dead space, but no other improvement of cardiopulmonary function. These results show that a number of cardiopulmonary abnormalities induced by pulmonary embolism are related directly or indirectly to platelet secretions and that V_D/V_T is closely allied to TxA₂ levels.     

Expressions of SOCS-1 and SOCS-3 in the myocardium of patients with sudden cardiac death

BACKGROUND:

As the regulators of cytokines, suppressors of cytokine signaling (SOCS) play an important role in the inflammation reaction. Some studies found that SOCS-1 and SOCS-3 were involved in the pathogenesis of some inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease. But the expressions of SOCS in coronary heart disease have not yet been reported. This study aimed to investigate the expression and clinical significance of SOCS-1 and SOCS-3 in the myocardium of patients with sudden cardiac death (SCD).

METHODS:

Myocardial autopsy specimens were collected from 24 patients at the Forensic Medicine Department of Sun Yat-Sen University, Guangzhou, China between 2005 and 2006. Of them, 9 patients had autopsy findings consistent with coronary atherosclerosis (non-myocardial infarction) leading to SCD (non-MI group), 7 died of acute myocardial infaction (MI group), and 8 died from traffic accidents and trauma (control group). The expressions of SOCS-1 mRNA and SOCS-3 mRNA in the myocardium of the non-MI, MI and control groups were detected using RT-PCR. The levels of SOCS-1 and SOCS-3 proteins were detected using immunohistochemistry. Statistical analyses were performed using SPSS version 13.0 software and the data were analyzed by ANOVA.

RESULTS:

The expressions of SOCS-1 mRNA and SOCS-3 mRNA in the non-MI and MI groups were significantly higher than those in the control group[(0.788±0.101), (0.741±0.111) vs. (0.436±0.044), (P<0.01); (0.841±0.092), (0.776±0.070) vs. (0.454±0.076), (P<0.01)] respectively. The antibody-positive cells of SOCS-1 protein in the myocardium of the non-MI and MI groups were significantly higher than those in the myocardium of the control group[(320.00±48.48), (347.14±70.88) vs. (42.50±10.35), (P<0.01)] respectively. The antibody-positive cells of SOCS-3 protein in the myocardium of the non-MI and MI groups were significantly higher than those in the myocardium of the control group[(381.11±59.25) vs. (40.00±10.69), (P<0.01)] and[(332.86±111.91) vs. (40.00±10.69), (P=0.001)].

CONCLUSION:

The expressions of SOCS-1 and SOCS-3 in the myocardium of patients with SCD from coronary heart disease are significantly increased and contribute to the pathogenesis of SCD.KEY WORDS: Sudden cardiac death, Myocardial infarction, Suppressor of cytokine signaling-1, Suppressor of cytokine signaling-3