Effects of α-methylnorepinephrine on cardiac function and myocardium at early stage of resuscitation in rabbits

BACKGROUND:

Recent studies have shown that α2-adrenergic agonists can reduce postresuscitation myocardial injury. This study was undertaken to observe changes of hemodynamics, myocardial injury markers cTnT and cardiac morphology by establishing a cardiopulmonary resuscitation model with rabbits, and to detect whether α-methyl norepinephrine (α-MNE) can reduce the myocardial injury after CPR and improve cardiac function.

METHODS:

Eighteen health rabbits, weighing 2.5-3.5 kg, both male and female, were provided by the Lanzhou Institute of Veterinary Medicine. After setting up a rabbit model of cardiopulmonary resuscitation, 18 rabbits were randomly divided into three groups. The rabbits in group A as an operation-control group were subjected to anesthesia, endotracheal intubation, and surgery without induction of ventricular fibrillation. The rabbits in group B as an epinephrine group were administered with 30 μg/kg epinephrineduring CPR. The rabbits in group C as a MNE group were administered with 100 μg/kg a-MNE during CPR. The left ventricular end-diastolic pressure (LVEDP), left ventricular pressure rise and fall rate (±dp/dt) and serum concentrations of BNP were measured. Statistical package of SPSS 10.0 was used for data analysis and significant differences between means were evaluated by ANOVA.

RESULTS:

Compared to group A, the LVEDP of other two groups increased respectively (P<0.01 all), and peak±dp/dt decreased in the other two groups (P<0.01). The increase of LVEDP was lower in group C than in group B (P<0.05), whereas peak±dp/dt was higher in group C than in group B (P<0.05) at the same stage. Compared to group A, the cTnT of the remaining two groups increased, respectively (P<0.01), and peaked at 30 minutes. cTnT was less elevated in group C than in group B (P<0.05) during the same period. In groups B and C, myocardial injury was seen under a light microscope, but the injury in group C was lighter than that in group B.

CONCLUSION:

Methylnorepinephrine can lessen myocardial dysfunction after CPR.KEY WORDS: Cardiopulmonary resuscitation;, α2-adrenergic agonist;, Post-resuscitation myocardial dysfunction     

Effects of hyperbaric oxygen on intestinal mucosa apoptosis caused by ischemia-reperfusion injury in rats

BACKGROUND:

Hyperbaric oxygen (HBO) is an effective adjuvant therapy for ischemia- reperfusion (I/R) injury of the brain, small intestine and testis in addition to crushing injury. Studies have shown that HBO increases the activity of villi of the ileum 30 minutes after I/R injury. The present study aimed to observe the effect of HBO on apoptosis of epithelial cells in the small intestine during different periods of I/R and to elucidate the potential mechanisms.

METHODS:

Rats were subjected to 60-minute ischemia by clamping the superior mesenteric artery and 60-minute reperfusion by removal of clamping. The rats were randomly divided into four groups: I/R group, HBO precondition or HBO treatment before ischemia (HBO-P), HBO treatment during ischemia period (HBO-I), and HBO treatment during reperfusion (HBO-R). After 60-minute reperfusion, samples of the small intestine were prepared to measure the level of ATP by using the colorimetric method and immunochemical expression of caspase-3. The levels of TNF-α in intestinal tissue were measured using the enzyme-linked immunosorbent assay method (Elisa).

RESULTS:

TNF-α levels were significantly lower in the HBO-I group than in the HBO-P (P<0.05), HBO-R and I/R groups; there was no significant difference between the HBO-R and I/R groups (P>0.05). The expression of caspas-3 was significantly lower in the HBO-I group than in the HBO-P group (P<0.05); it was also significantly lower in the HBO-P group than in the I/R and HBO-R groups (P<0.05). ATP level was significantly lower in the HBO-I group than in the HBO-P group (P<0.05), and also it was significantly lower in the HBO-P group than in the I/R and HBO-R groups (P<0.05).

CONCLUSIONS:

There is an association between HBO, small intestinal I/R injury, and mucosa apoptosis. HBO maintains ATP and aerobic metabolism, inhibites TNF-α production, and thus prevents intestinal mucosa from apoptosis. Best results can be obtained when HBO is administered to patients in the period of ischemia, and no side effects are produced when HBO is given during the period of reperfusion.KEY WORDS: Hyperbaric oxygen, Ischemia-reperfusion injury, Apoptosis     

Effects of pulmonary stretch reflex on lung injury in rabbits with acute respiratory distress syndrome

BACKGROUND:

Pulmonary stretch reflex plays an important role in regulation of respiratory movement. This study aimed to evaluate the effect of pulmonary stretch reflex on lung injury in rabbits with acute respiratory distress syndrome (ARDS).

METHODS:

ARDS rabbits were given intratracheal infusion of hydrochloric acid and ventilated with neurally adjusted ventilatory assistance (NAVA) with a tidal volume (V_T) of 6 mL/kg and the electrical activity of diaphragm (EAdi)-determined positive end expiratory pressure. After isolation of the bilateral vagus nerve trunk, the rabbits were randomized into two groups: sham operation (SHAM) group (n=5) and bilateral vagotomy (VAG) group (n=5). Gas exchange and respiratory mechanics were detected at baseline, after lung injury and 1, 2, and 3 hours after ventilation respectively. Pulmonary permeability index, pathological changes and inflammatory response were also measured.

RESULTS:

Compared with the SHAM group, PaO₂/FiO₂ in the VAG group decreased significantly 2 and 3 hours after ventilation (P<0.05). There was no significant difference in PaCO₂ between the SHAM and VAG groups (P>0.05), and the VAG group had a high V_T, peak pressure (Ppeak), and mean pressure (Pm) compared with the SHAM group 1, 2, 3 hours after ventilation (P<0.05). Compared to the SHAM group, dead space fraction (V_D/V_T) and respiratory system elastance (Ers) in the VAG group increased (P<0.05) and static pulmonary compliance (Cst) decreased markedly (P<0.05) after ventilation for 3 hours. Lung wet/dry weight ratio (W/D) (8.4±1.2 vs. 6.6±1.0), lung injury score (6.3±1.8 vs. 3.8±1.3), tumor necrosis factor-α (TNF-α) (779±372 pg/mL vs. 355±130 pg/mL) and interleukin-8 (IL-8) (169±21 pg/mL vs. 118±17 pg/mL) increased significantly in the VAG group compared with the SHAM group (P<0.05).

CONCLUSION:

Lung injury is aggravated after bilateral vagotomy, demonstrating that pulmonary stretch reflex may have protective effect on the lung.KEY WORDS: Pulmonary stretch reflex, Vagus nerve, Lung injury, Acute respiratory distress syndrome, Electrical activity of diaphragm, Mechanical ventilation     

Effect of exogenous phosphocreatine on cardiomycytic apoptosis and expression of Bcl-2 and Bax after cardiopulmonary resuscitation in rats

BACKGROUND:

Ischemia-reperfusion injury in the myocardium after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) is an important pathologic basis of post-cardiac arrest of syndrome (PCAS), and apoptosis is one of the major mechanisms in myocardial ischemia-reperfusion injury. To lessen myocardial ischemia-reperfusion injury after cardiac arrest and CPR, it is important to reduce energy consumption and to increase energy supply in the myocardium. This study aimed to observe changes of cell apoptosis and expression of Bcl-2 and Bax protein on the myocardium after CPR in rats, and the protective effects of different doses of exogenous phosphocreatine (creatine phosphate, CP) on them.

METHODS:

A total of 32 male adult Sprague-Dawley rats were randomly divided into 4 groups: control group (group A), CPR group (group B), low-dose CP group (group C, CP 0.5 g/kg at beginning of CPR and 1.0 g/kg at 2 hours after CPR) and high-dose CP group (group D, CP 1.0 g/kg at beginning of CPR and 2.0 g/kg at 2 hours after CPR). Cardiac arrest was induced by asphyxiation and CPR started at 7 minutes after asphyxiation in groups B, C and D. Myocardium samples were taken at 24 hours after CPR. Cardiomycytic apoptosis was detected by the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. The expression of Bcl-2 and Bax protein was measured by immunohistochemistry.

RESULTS:

Cardiomyocytic apoptosis index (AI) and expression of Bcl-2 and Bax protein increased more significantly in groups B, C and D than in group A (P<0.01), but Bcl-2/Bax ratio significantly decreased (P<0.01). Cardiomyocytic AI and expression of Bcl-2 and Bax protein decreased more significantly in groups C and D than in group B (P<0.01), but Bcl-2/Bax ratio increased more significantly (P<0.01). Cardiomyocytic AI and expression of Bcl-2 and Bax protein decreased more significantly in group D than in group C (P<0.05), but Bcl-2/Bax ratio increased more significantly (P<0.05).

CONCLUSION:

Exogenous phosphocreatine, especially at a large dose, could inhibit cardiomyocytic apoptosis and alleviate myocardial injury after CPR in rats.KEY WORDS: Cardiopulmonary resuscitation, Phosphocreatine, Apoptosis, Bcl-2, Bax, TUNEL     

The Effect of Silymarin on Mesenteric Ischemia-Reperfusion Injury

Objective

To examine the effect of silymarin (SM), a mixture of flavonoids and polyphenols extracted from Silybum marianum, on mesenteric ischemia-reperfusion (I-R) injury in a rat model.

Materials and Methods

Fifty rats were randomly divided into 5 groups (n = 10). Group 1 was sham operated, while groups 2-5 were subjected to mesenteric I-R lasting 1 h. Group 2 received isotonic sodium chloride, group 3 received SM (100 mg/kg/day) for 7 days before I-R, group 4 received SM for 7 days after I-R, and group 5 received SM for 7 days both before and after I-R. The rats were sacrificed by exsanguination in groups 1-3 at the 24th hour and groups 4 and 5 were sacrificed on the 7th day of reperfusion. Blood and intestinal specimens were taken for biochemical and pathological evaluations.

Results

Serum superoxide dismutase (SOD) and heat shock protein 70 levels were significantly higher in group 2 (5.24 ± 1.76 U/l and 261.4 ± 16.8 ng/ml) compared to the sham group (2.08 ± 1.76 U/l and 189.9 ± 28.7 ng/ml) (p < 0.001 and p < 0.0001, respectively). However, SOD activity and the extent and severity of the histopathological lesions were significantly less in groups 3 [3.11 ± 1.18 U/l, 1.0 (range 0.0-2.0)], 4 [2.15 ± 0.87 U/l, 1.0 (range 1.0-3.0)], and 5 [1.80 ± 0.61 U/l, 0.5 (range 0.0-2.0)], treated with SM, than in group 2 [5.24 ± 1.76 U/l, 2.0 (range 2.0-3.0)] (p = 0.002, p < 0.001, and p = 0.0001; p < 0.001, p = 0.007, and p = 0.0001, respectively). Also, TNF-α levels were lower in the SM-supplemented groups compared to group 2. Serum thiobarbituric acid-reactive substance concentrations were low in the pre-/posttreatment groups treated with SM compared to group 2. No statistical difference was observed for protein carbonyls between the groups.

Conclusion

Our findings suggest that SM therapy may attenuate the oxidative and intestinal damage induced by I-R injuries.Key Words: Silymarin, Ileum, Ischemia-reperfusion injury, Oxidant stress, Histopathology     

BASEBALL PLAYERS WITH ULNAR COLLATERAL LIGAMENT TEARS DEMONSTRATE DECREASED ROTATOR CUFF STRENGTH COMPARED TO HEALTHY CONTROLS

Background

Ulnar Collateral Ligament (UCL) tears are common in baseball players. Alterations in rotator cuff strength are believed to be associated with injury to the shoulder and/or elbow in baseball players.

Hypothesis/Purpose

Baseball players diagnosed with a UCL tear will demonstrate decreased internal (IR) and external rotation (ER) force as an indication of isometric muscular strength in the throwing arm compared to IR and ER force of the throwing arm in healthy baseball players. The purpose of this study was to examine isometric IR and ER strength of the shoulder in baseball players with UCL tears at the time of injury compared to healthy baseball players.

Study Design

Case‐control study design

Methods

Thirty‐three of the participants were diagnosed with a UCL tear and thirty‐three were healthy, age‐ and positioned‐matched controls. All of the participants played baseball at either the high school or collegiate level and volunteered for the study. Isometric rotator cuff strength measurements for internal (IR) and external rotation (ER) were performed with the arm held to the side at 0 ° of shoulder abduction. All measurements were taken bilaterally and the means of the throwing and non‐throwing arms for IR and ER in the UCL group were compared to the means of the throwing and non‐throwing arms in the healthy group. One‐way ANOVAs were used to calculate differences between groups (p < 0.05).

Results

Baseball players with UCL tears demonstrated significant rotator cuff strength deficits on their throwing arm IR (p < .001) and ER (p < .001) compared to throwing arm IR and ER in the Healthy (UCL IR = 131.3 ± 31.6 N; Healthy IR = 174.9 ± 20.7 N) (UCL ER = 86.4 ± 18.3 N; Healthy ER = 122.3 ± 18.3 N). On the non‐throwing arm, the UCL group was weaker in both IR (135.0 ± 31.1 N; p < .001) and ER (93.4 ± 22.8 N; p < .001) than IR (172.1 ± 24.1 N) and ER (122.3 ± 19.1 N) in the Healthy group.

Conclusion

Participants with a UCL tear exhibit lower force values as an indication of isometric rotator cuff strength in both the throwing and non‐throwing arms than a healthy cohort.

Level of Evidence

Level 4     

Potential role of a disintegrin and metalloproteinase-17 (ADAM17) in age-associated ventricular remodeling of rats

Excessive tumor necrosis factor-α (TNF-α) could enhance cell death and aggravate left ventricular remodeling and myocardial dysfunction. A disintegrin and metalloproteinase-17 (ADAM17), an important maturation regulator of TNF-α, might be involved in the aging-associated ventricular remodeling. The present study observed myocardial ADAM17 expression in young and aged rats and explored the association between cardiac structure/function and expression of ADAM17 in 6 month-old (n = 10, young group) and 24 month-old SD rats (n = 10, old group). The body, heart weight and heart weight/body weight ratio of rats in the old group were all significantly increased compared to that in the young group (P < 0.05). The left ventricular systolic end-diameter and end-diastolic diameters were significantly enlarged in the old group compared to the young group (P < 0.05), while the systolic function index including the left ventricular ejection fraction and left ventricular fractional shortening were similar between the two groups. The peak mitral flow velocity (E)/peak mitral annulus velocity (E′) ratio was significantly higher in the old group than in the young group (P < 0.05). Histological examination showed more damage of cardiomyocytes, interstitial collagen deposition and inflammatory cell infiltration in the old group. Immunohistochemistry examination showed that myocardial TNF-α expression was mainly located in cardiomyocytes and was significantly higher in the old group than in the young group (P < 0.05). The protein expression of myocardial ADAM17 detected by western blot was significantly higher in the old group than in the young group (P < 0.05), while TIMP-3 expression was similar between the two groups. The present study suggested that ADAM17 and inflammation might play an important role in aging-related myocardial remodeling through regulating TNF-α.

Excessive tumor necrosis factor-α (TNF-α) could enhance cell death and aggravate left ventricular remodeling and myocardial dysfunction.     

Complement Localization and Mediation of Ischemic Injury in Baboon Myocardium

We sought to determine whether the third component of complement (C3) is localized in ischemic baboon myocardium after coronary artery ligation. Furthermore, we assessed the effects of prior C3 depletion on myocardial necrosis. We studied seven control baboons (group I) and seven C3-depleted (group II) baboons that were killed 24 h after ligation of the anterior descending coronary artery. Multiple tissue samples were obtained from infarct, intermediate, and normal myocardial sites as defined by serial unipolar epicardial ECG mapping. In group I baboons, myocardial creatine kinase content from infarct sites was reduced as compared with normal sites (12.6±0.92 [SE] vs. 24.4±0.75 IU/mg protein, P < 0.001). The intermediate sites from group I contained more creatine kinase (19.0±1.25 IU/mg protein) than infarct sites (P < 0.001), but less (P < 0.025) than normal sites. In group II, intermediate sites showed no significant reduction in creatine kinase from normal sites and there was significantly less creatine kinase depletion in infarct sites when compared with group I animals (33.7±4.6 and 51.4±1.8% depletion, respectively, P < 0.001). In all seven group I baboons, uniform C3 localization was observed in infarct sites by direct immunofluorescence but appeared in mosaic patterns in intermediate sites. C3 was not demonstrated in any normal sites, nor in any site from group II baboons. Additional studies on baboons killed at earlier times after ligation indicated that C3 was localized focally on swollen myocytes in infarct sites as early as 4 h after coronary ligation. These results strongly implicate the active participation of the complement system of inflammatory proteins in the pathogenesis of myocardial tissue injury following coronary occlusion.     

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     

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.     

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.     

At-risk but viable myocardium in a large animal model of non ST-segment elevation acute coronary syndrome: cardiovascular magnetic resonance with ex vivo validation

Background

Patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) have varying degrees of salvageable myocardium at risk of irreversible injury. We hypothesized that a novel model of NSTE-ACS produces acute myocardial injury, measured by increased T2 cardiovascular magnetic resonance (CMR), without significant necrosis by late gadolinium enhancement (LGE).

Methods

In a canine model, partial coronary stenosis was created and electrodes placed on the epicardium. Myocardial T2, an indicator of at-risk myocardium, was measured pre- and post-tachycardic pacing.

Results

Serum troponin-I (TnI) was not detectable in unoperated sham animals but averaged 1.97 ± 0.72 ng/mL in model animals. Coronary stenosis and pacing produced significantly higher T2 in the affected vs. the remote myocardium (53.2 ± 4.9 vs. 43.6 ± 2.8 ms, p < 0.01) with no evident injury by LGE. Microscopy revealed no significant irreversible cellular injury. Relative respiration rate (RRR) of affected vs. remote myocardial tissue was significantly lower in model vs. sham animals (0.72 ± 0.07 vs. 1.04 ± 0.07, p < 0.001). Lower RRR corresponded to higher final TnI levels (R² = 0.83, p = 0.004) and changes in CaMKIID and mitochondrial gene expression.

Conclusions

A large animal NSTE-ACS model with mild TnI elevation and without ST elevation, similar to the human syndrome, demonstrates signs of acute myocardial injury by T2-CMR without significant irreversible damage. Reduced tissue respiration and associated adaptations of critical metabolic pathways correspond to increased myocardial injury by serum biomarkers in this model. T2-CMR as a biomarker of at-risk but salvageable myocardium warrants further consideration in preclinical and clinical studies of NSTE-ACS.     

Clinical and procedural predictors of no-reflow in patients with acute myocardial infarction after primary percutaneous coronary intervention

BACKGROUND:

The treatment of acute myocardial infarction (AMI) is thought to restore antegrade blood flow in the infarct-related artery (IRA) and minimize ischemic damage to the myocardium as soon as possible. The present study aimed to identify possible clinical predictors for no-reflow in patients with AMI after primary percutaneous coronary intervention (PCI).

METHODS:

A total of 312 consecutive patients with AMI who had been treated from January 2008 to December 2010 at the Cardiology Department of East Hospital, Tongji University School of Medicine were enrolled in this study. Inclusion criteria were: (i) patients underwent successfully primary PCI within 12 hours after the appearance of symptoms; or (ii) patients with ischemic chest pain for more than 12 hours after a successful primary PCI within 24 hours after appearance of symptoms. Exculsion criteria were: (i) coronary artery spasm; (ii) diameter stenosis of the culprit lesion was <50% and coronary blood flow was normal; (iii) patients with severe left main coronary or multivessel disease, who had to require emergency revascularization. According to thrombolysis in myocardial infarction (TIMI), the patients were divided into a reflow group and a no-reflow group. The clinical data, angiography findings and surgical data were compared between the two groups. Univariate and multivariate logistic regressions were used to determine the predictors for no-reflow.

RESULTS:

Fifty-four (17.3%) of the patients developed NR phenomenon after primary PCI. Univariate analysis showed that age, time from onset to reperfusion, systolic blood pressure (SBP) on admission, Killip class of myocardial infarction, intra-aortic balloon pump (IABP) use before primary PCI, TIMI flow grade before primary PCI, type of occlusion, thrombus burden on baseline angiography, target lesion length, reference luminal diameter and method of reperfusion were correlated with no-reflow (P<0.05 for all). Multiple logistic regression analysis identified that age >65 years [OR=1.470, 95% confidence interval (CI) 1.460–1.490, P=0.007], long time from onset to reperfusion >6 hours (OR=1.270, 95%CI 1.160–1.400, P=0.001), low SBP on admission <100 mmHg (OR=1.910, 95%CI 1.018–3.896, P=0.004), IABP use before PCI (OR= 1.949, 95%CI 1.168–3.253, P=0.011), low (≤1) TIMI flow grade before primary PCI (OR=1.100, 95%CI 1.080–1.250, P<0.001), high thrombus burden (OR=1.600, 95%CI 1.470–2.760, P=0.030), and long target lesion (OR=1.948, 95%CI 1.908–1.990, P=0.019) on angiography were independent predictors of no-reflow.

CONCLUSION:

The occurrence of no-reflow after primary PCI for acute myocardial infarction can predict clinical, angiographic and procedural features.KEY WORDS: Acute myocardial infarction, No-reflow phenomenon, Percutaneous coronary intervention, Thrombus     

Effects of bone marrow-derived mesenchymal stem cells engraftment on vascular endothelial cell growth factor in lung tissue and plasma at early stage of smoke inhalation injury

BACKGROUND:

This study was undertaken to determine the effect of mesenchymal stem cells (MSCs) engraftment on vascular endothelial cell growth factor (VEGF) in lung tissue, plasma and extravascular lung water at early stage of smoke inhalation injury.

METHODS:

A rabbit smoke inhalation injury model was established using a home-made smoke inhalation injury generator, and rabbits were divided into two groups randomly: a control group (S group, n=32) and a MSCs treatment group (M group, n=32). 10 ml PBS was injected via the ear marginal vein immediately at injury into the S group. Third generation MSCs with a concentration of 1×10⁷/10 ml PBS were injected via the ear marginal vein immediately at injury into the M group. VEGF in peripheral blood and lung tissue were measured at 0 (baseline), 2, 4 and 6 hours after injection respectively and analyzed. The right lungs of rabbits were taken to measure lung water mass fraction.

RESULTS:

In the lung tissue, VEGF decreased gradually in the S group (P<0.05) and significantly decreased in the M group (P<0.05), but it increased more significantly than the values at the corresponding time points (P<0.05). In peripheral blood, VEGF increased gradually in the S group (P<0.05) and markedly increased in the M group (P<0.05), but it decreased more significantly than the values at corresponding time points (P<0.05).

CONCLUSION:

MSCs engraftment to smoke inhalation injury could increase VEGF in lung tissue, decrease VEGF in plasma and reduce extravascular lung water, indicating its protective effect on smoke inhalation injury.KEY WORDS: Mesenchymal stem cells, Smoke inhalation injury, Vascular endothelial cell growth factor, Extravascular lung water, Rabbit     

The protective effects of a phosphodiesterase 5 inhibitor,sildenafil, on postresuscitation cardiac dysfunction of cardiac arrest: metabolic evidence from microdialysis

Introduction

Recent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion injury. The aim of this study was to determine, by obtaining metabolic evidence from microdialysis, if sildenafil could reduce the severity of postresuscitation myocardial dysfunction and lead to cardioprotection through beneficial effects on energy metabolism.

Methods

Twenty-four male piglets were randomly divided into three groups: sildenafil (n = 8), saline (SA; n = 8) and sham operation (n = 8). Sildenafil pretreatment consisted of 0.5 mg/kg sildenafil administered once intraperitoneally 30 minutes prior to ventricular fibrillation (VF). The myocardial interstitial fluid (ISF) concentrations of glucose, lactate, pyruvate, glutamate and glycerol were determined by microdialysis before VF. Afterward, the piglets were subjected to 8 minutes of untreated VF followed by 15 minutes of open-chest cardiopulmonary resuscitation. ISF was collected continuously, and the experiment was terminated 24 hours after resuscitation.

Results

After 8 minutes of untreated VF, the sildenafil group exhibited higher glucose and pyruvate concentrations of ISF and lower lactate and glutamate levels in comparison with the SA group, and these data reached statistical significance (P < 0.05). Advanced cardiac life support was delivered to both groups, with a 24-hour survival rate showing a promising trend in the sildenafil group (7 of 8 versus 3 of 8 survivors, P < 0.05). Compared with the SA group, the sildenafil group had a better outcome in terms of hemodynamic and oxygen metabolism parameters (P < 0.05). Myocardial tissue analysis revealed a dramatic increase in the contents of ATP, ADP and phosphocreatine in the sildenafil group versus the SA group at 24 hours after return of spontaneous circulation (ROSC; P = 0.03, P = 0.02 and P = 0.02, respectively). Furthermore, 24 hours after ROSC, the sildenafil group had marked elevations in activity of left ventricular Na⁺-K⁺-ATPase and Ca²⁺-ATPase compared with the SA group (P = 0.03, P = 0.04, respectively).

Conclusions

Sildenafil could reduce the severity of postresuscitation myocardial dysfunction, and it produced better clearance of metabolic waste in the ISF. This work might provide insights into the development of a novel strategy to treat postresuscitation myocardial dysfunction.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0641-7) contains supplementary material, which is available to authorized users.     

Insulin Resistance and Inflammation in Hypogonadotropic Hypogonadism and Their Reduction After Testosterone Replacement in Men With Type 2 Diabetes

OBJECTIVE

One-third of men with type 2 diabetes have hypogonadotropic hypogonadism (HH). We conducted a randomized placebo-controlled trial to evaluate the effect of testosterone replacement on insulin resistance in men with type 2 diabetes and HH.

RESEARCH DESIGN AND METHODS

A total of 94 men with type 2 diabetes were recruited into the study; 50 men were eugonadal, while 44 men had HH. Insulin sensitivity was calculated from the glucose infusion rate (GIR) during hyperinsulinemic-euglycemic clamp. Lean body mass and fat mass were measured by DEXA and MRI. Subcutaneous fat samples were taken to assess insulin signaling genes. Men with HH were randomized to receive intramuscular testosterone (250 mg) or placebo (1 mL saline) every 2 weeks for 24 weeks.

RESULTS

Men with HH had higher subcutaneous and visceral fat mass than eugonadal men. GIR was 36% lower in men with HH. GIR increased by 32% after 24 weeks of testosterone therapy but did not change after placebo (P = 0.03 for comparison). There was a decrease in subcutaneous fat mass (−3.3 kg) and increase in lean mass (3.4 kg) after testosterone treatment (P < 0.01) compared with placebo. Visceral and hepatic fat did not change. The expression of insulin signaling genes (IR-β, IRS-1, AKT-2, and GLUT4) in adipose tissue was significantly lower in men with HH and was upregulated after testosterone treatment. Testosterone treatment also caused a significant fall in circulating concentrations of free fatty acids, C-reactive protein, interleukin-1β, tumor necrosis factor-α, and leptin (P < 0.05 for all).

CONCLUSIONS

Testosterone treatment in men with type 2 diabetes and HH increases insulin sensitivity, increases lean mass, and decreases subcutaneous fat.     

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     

Protective effect of glutamine in critical patients with acute liver injury

BACKGROUND:

Glutamine (Gln) supplementation is known to decrease oxidative stress and inflammatory response, enhance resistance to infectious pathogens, shorten hospital stay, and decrease medical costs of patients. This study was undertaken to evaluate the relationship between the effect of early parenteral glutamine (Gln) supplement on acute liver injury (ALI) and heat shock protein 70 (HSP-70) expression in critical patients.

METHODS:

Forty-four patients who had been admitted to the emergency intensive care unit (EICU) of Nanjing First Hospital Affiliated to Nanjing Medical University were randomly divided into a control group (n=22) and a Gln group (n=22). The patients of the two groups received enteral and parenteral nutrition. In addition, parenteral Gln 0.4 g/kg per day was given for 7 days in the Gln group. Serum HSP-70 and Gln were measured at admission and at 7 days after admission. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBiL), serum levels of HSP-70 and Gln, mechanical ventilation (MV) time, ICU stay, peripheral blood of TNF-α, IL-6, CD3, CD4 and CD4/CD8 levels were also measured in the two groups.

RESULTS:

In the Gln group, the levels of serum HSP-70 and Gln were significantly higher after Gln treatment than those before the treatment (P<0.01). HSP-70 level was positively correlated with the Gln level in the Gln group after administration of parenteral Gln (P<0.01). The levels of serum ALT, AST, TBiL and TNF-α, IL-6 were lower in the Gln group than in the non-Gln group (P<0.01). MV time and ICU stay were significantly different between the two groups (P<0.05). The levels of CD3, CD4 and CD4/CD8 were significantly higher in the Gln group than in the control group after treatment (P<0.05).

CONCLUSION:

Parenteral Gln significantly increases the level of serum HSP70 in critically ill patients. The enhanced expression of HSP70 is correlated with improved outcomes of Gln-treated patients with acute liver injury.KEY WORDS: Glutamine, Heat shock protein, Critically ill patients, Acute liver injury