Milrinone Administered Before Ischemia or Just After Reperfusion, Attenuates Myocardial Stunning in Anesthetized Swine

Purpose We assessed the dose or timing effect of milrinone administered against myocardial stunning in 37 anesthetized open-chest swine. Methods All swine were subjected to 12-min ischemia followed by reperfusion to produce myocardial stunning. Group A (n = 12) received saline in place of milrinone both before and after ischemia. Group B (n = 9) and C (n = 9) received intravenous milrinone at a rate of 5 μg/kg/min for 10 min followed by 0.5 μg/kg/min for 10 min and 10 μg/kg/min for 10 min followed by 1 μg/kg/min for 10 min, respectively, until 30 min before coronary occlusion. Group D (n = 7) received the same dose of milrinone as group B starting 1 min after reperfusion. Myocardial contractility was assessed by percentage segment shortening (%SS). Results Five swine in group A and two swine in groups B and C each had ventricular fibrillation or tachycardia after reperfusion, and were thus excluded from further analysis. The percentage changes of %SS from the baseline 90 min after reperfusion in groups B, C, and D were 78 ± 9%, 82 ± 13%, and 79 ± 7%, respectively, which were significantly higher than those in group A (43 ± 13%). Conclusion We conclude that milrinone administered before ischemia or just after reperfusion attenuates myocardial stunning.     

Masked nocturnal hypertension—a novel marker of risk in type 2 diabetes

Aims/hypothesis  This study was designed to evaluate the prevalence of masked nocturnal hypertension (MNHT) and its impact on arterial stiffness and central blood pressure in patients with type 2 diabetes. Methods  Middle-aged patients (n = 414) with type 2 diabetes underwent clinic and ambulatory BP measurements and applanation tonometry. Results  MNHT (clinic BP < 130/80 mmHg and night-time BP ≥ 120/70 mmHg) was found in 7.2% of patients (n = 30). Compared with patients with both clinical and nocturnal normotension (n = 70), patients with MNHT had higher aortic pulse wave velocity (PWV) (10.2 ± 1.8 m/s vs 9.4 ± 1.7 m/s; p = 0.03) and higher central BP (117.6 ± 13.9/74.0 ± 9.1 mmHg vs 110.4 ± 16.4/69.7 ± 9.6 mmHg, p = 0.04). In patients with clinical normotension, night-time systolic BP correlated significantly with PWV. Conclusions/interpretation  Thirty per cent of patients with clinical normotension had nocturnal hypertension. This was accompanied by increased arterial stiffness and higher central BP. We conclude that in clinically normotensive patients with type 2 diabetes, ambulatory BP measurement may help clinicians to identify patients with increased cardiovascular risk.     

Long-term Follow-up of Patients Undergoing Postconditioning During ST-Elevation Myocardial Infarction

Reperfusion injury may offset the optimal salvage of myocardium achieved during primary coronary angioplasty. Thus, coronary reperfusion must be combined with cardioprotective adjunctive therapies in order to optimize myocardial salvage and minimize infarct size. Forty-three patients with their first ST-elevation myocardial infarction were randomized to myocardial postconditioning or standard of care at the time of primary coronary angioplasty. Postconditioning was performed immediately upon crossing the lesion with the guide wire and consisted of four cycles of 30 s occlusion followed by 30 s of reperfusion. End-points included infarct size, myocardial perfusion grade (MPG), left-ventricular ejection fraction (LVEF), and long-term clinical events (death and heart failure). Despite similar ischemic times (≅4.5 h) (p = 0.9) a reduction in infarct size was observed among patients treated with the postconditioning protocol. Peak creatine phosphokinase (CPK), as well as its myocardial band (MB) fraction, was significantly lower in the postconditioning group when compared with the control group (CPK—control, 2,444 ± 1,928 IU/L vs. PC, 2,182 ± 1,717 IU/L; CPK-MB—control, 242 ± 40 IU/L vs. PC, 195 ± 33 IU/L; p = 0.64 and p < 0.01, respectively). EF in the postconditioning group was improved when compared with the control group (control, 43% ± 15 vs. PC, 52% ± 9; p = 0.05). After a mean follow-up of 3.4 years, a 6-point absolute difference in LVEF was still evident in the postconditioning group (p = 0.18). MPG was better among patients treated with the postconditioning protocol compared with control (2.5 ± 0.5 vs. 2.1 ± 0.6; p = 0.02). Due to the small sample size no significant differences in clinical events were detected (p value for death = 0.9; p value for heart failure = 0.2). A simple postconditioning protocol applied at the onset of mechanical reperfusion, resulted in reduction of infarct size, better epicardial and myocardial flow, and improvement in left ventricular function. The beneficial effects of postconditioning on cardiac function persist beyond 3 years.     

A prospective randomised comparison of large-tip cryoablation and 8-mm-tip radiofrequency catheter ablation of atrial flutter

Purpose  Although radiofrequency (RF) energy is routinely used for tricuspid isthmus (TI) ablation, it is often associated with discomfort. The paucity of studies comparing the feasibility and efficacy of cryo- versus RF energy for TI-ablation urged us to conduct a prospective, randomised trial. Methods  Forty patients with atrial flutter (AFl) were randomised to RF- or cryoenergy for TI-ablation. Perceived pain was scored from 1 to 10 on a Visual Analogue Scale. Results  Significantly lower pain scores were recorded for cryoablation versus RF ablation (0.96 ± 0.73 versus 4.2 ± 2.4, p = 0.00004). Cryoablation was associated with significantly longer procedure duration and ablation time (137 ± 35 versus 111 ± 29 min, p = 0.016 and 81 ± 40 versus 48 ± 30 min, p = 0.007) and lower acute success rate (56% versus 100%, p = 0.001) than RF ablation. The recurrence of AFl was 20% (cryo) versus 15% (RF; p = 0.45) after a mean of 15.1 months follow-up. Conclusion  Cryoablation results in significantly less pain and discomfort compared to RF ablation of AFl, which is offset by the significantly lower acute success rate.     

Extracorporeal Membrane Oxygenation Induced Cardiac Dysfunction in Newborn Lambs

Extracorporeal membrane oxygenation (ECMO) is routinely used to support cardiopulmonary failure in infants and children. Suboptimal outcomes for primary cardiac support suggest a need for investigation of the impact of ECMO on the heart. Twenty-four newborn lambs received a brief period of ECMO support to investigate the hypothesis that ECMO produces cardiac dysfunction in newborn lamb. Dorset newborn lambs, 4–7 days of age, were exposed to ECMO for 5 min at a 100 ml/kg flow rate and quickly weaned off. Measurements included echocardiographic mean left ventricular (LV) velocity of circumferential fiber shortening corrected for heart rate (mVCFc), LV shortening fraction, and peak systolic wall stress plus hemodynamic measurement of LV maximum rate of pressure change with time (LV dp/dt max), maximum rate of pressure change divided by developed pressure (LV dp/dtP), right atrial pressure, pulmonary capillary wedge pressure, mean pulmonary artery pressure, LV peak and end-diastolic pressure, and aortic pressure. These measures were also obtained after an exposure to 5 min of ECMO and immediate disconnect for 5 min, followed by ECMO administration for 1 h again, followed by discontinuation of ECMO. LV mVCFc is decreased after exposure to 5 min of ECMO support despite a decrease in LV peak systolic wall stress that provides afterload reduction. LV mVCFc is inversely related to peak systolic wall stress at a significance level of p < 0.0001. The time period after initiation of ECMO is a significant factor in the model (p = 0.0097). Time [baseline] was different from the other time points with p = 0.0010. Average mVCFc at baseline is 1.27 ± 0.35 and decreases to 1.01 ± 0.42 after 5 min of ECMO that is then withdrawn. Peak systolic wall stress decreases from 36.0 ± 13.1 at baseline to 29.8 ± 12.1 after 5 min of ECMO. LV dp/dt max decreases from 1,769 ± 453 mmHg/s at baseline to 1,311 ± 513 mmHg/s after exposure to 5 min of ECMO (p = 0.0005). Baseline LV dp/dt max is different from each point after start of ECMO. Diastolic LVdp/dt min increased from −1,340 ± 477 mmHg/s to −908 ± 393 mmHg/s at 5 min. Echocardiographic mVCFc, when considered in isolation or as a function of LV peak systolic wall stress, shows diminished LV function after ECMO. Hemodynamic measurement of LV dp/dt max and LV dp/dt min confirms the observation. Separation of the humoral from mechanical effect of ECMO with the short exposure to the extracorporeal circuit shows that an immediate decrement of LV function occurs at initiation of ECMO, a finding that has not been stressed with previous studies of extracorporeal support. This implies a potentially outcome-limiting deleterious effect for the patient who requires ECMO support for the heart rather than the lungs. We should continue to strive to understand and ameliorate this deleterious effect of the extracorporeal circulation circuit.     

Atorvastatin in Factorial with Omega-3 EE90 Risk Reduction in Diabetes (AFORRD): a randomised controlled trial

Aims/hypothesis  The aim of the study was to examine the impact of statin or omega-3-acid ethyl esters 90 (omega-3 EE90; omega-3-acid ethyl esters 90 refers to a mixture of ethyl esters of n-3 fatty acids) on estimated cardiovascular disease (CVD) risk in community-based people with type 2 diabetes but without known CVD and not taking lipid-lowering therapy. Methods  A central computer randomised 800 patients in 59 UK general practices to atorvastatin (n = 401, 20 mg/day) or placebo (n = 399) and omega-3 EE90 (n = 397, 2 g/day) or placebo (n = 403) in a concealed factorial manner. Participants with LDL-cholesterol <2.6 mmol/l, triacylglycerol <1.5 mmol/l and estimated 10-year CVD risk <20% were compared at 4 months. Results  Mean (SD) age was 63.5 (11.7) years, HbA_1c 6.9 (1.1) % and known diabetes duration (median [interquartile range]) was 4 (2–8) years. Fifty-seven per cent were men, 90% white and 74% had an estimated 10-year CVD risk ≥20%. Of 732 patients with 4-month data, more allocated atorvastatin (n = 371) compared with placebo (n = 361) achieved LDL-cholesterol <2.6 mmol/l (91% vs 24%, p < 0.001) and had estimated 10-year CVD risks <20% (38% vs 26%, p < 0.001). No differences were seen between those allocated omega-3 EE90 (n = 371) compared with placebo (n = 361) for participants achieving triacylglycerol <1.5 mmol/l (65% vs 60%, p = 0.18) or estimated 10-year CVD risks <20% (34% vs 30%, p = 0.18). There were no side effects of note. Conclusions/interpretation  Many community-based diabetic patients without known CVD remain at high CVD risk despite statin treatment and require additional risk-reduction strategies. The impact of omega-3 EE90 on CVD risk will remain uncertain until clinical endpoint trial results are available. Trial registration: ISRCT no. 76737502 Funding: The study was funded by Pfizer. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Remote postconditioning by humoral factors in effluent from ischemic preconditioned rat hearts is mediated via PI3K/Akt-dependent cell-survival signaling at reperfusion

Short non-lethal ischemic episodes administered to hearts prior to (ischemic preconditioning, IPC) or directly after (ischemic postconditioning, IPost) ischemic events facilitate myocardial protection. Transferring coronary effluent collected during IPC treatment to un-preconditioned recipient hearts protects from lethal ischemic insults. We propose that coronary IPC effluent contains hydrophobic cytoprotective mediators acting via PI3K/Akt-dependent pro-survival signaling at ischemic reperfusion. Ex vivo rat hearts were subjected to 30 min of regional ischemia and 120 min of reperfusion. IPC effluent administered for 10 min prior to index ischemia attenuated infarct size by ≥55% versus control hearts (P < 0.05). Effluent administration for 10 min at immediate reperfusion (reperfusion therapy) or as a mimetic of pharmacological postconditioning (remote postconditioning, RIPost) significantly reduced infarct size compared to control (P < 0.05). The IPC effluent significantly increased Akt phosphorylation in un-preconditioned hearts when administered before ischemia or at reperfusion, while pharmacological inhibition of PI3K/Akt-signaling at reperfusion completely abrogated the cardioprotection offered by effluent administration. Fractionation of coronary IPC effluent revealed that cytoprotective humoral mediator(s) released during the conditioning phase were of hydrophobic nature as all hydrophobic fractions with molecules under 30 kDa significantly reduced infarct size versus the control and hydrophilic fraction-treated hearts (P < 0.05). The total hydrophobic effluent fraction significantly reduced infarct size independently of temporal administration (before ischemia, at reperfusion or as remote postconditioning). In conclusion, the IPC effluent retains strong cardioprotective properties, containing hydrophobic mediator(s) < 30 kDa offering cytoprotection via PI3K/Akt-dependent signaling at ischemic reperfusion.     

Serum levels of natriuretic peptides in patients with Behcet’s disease

The objective of our study was to elucidate serum levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) in Behcet’s disease (BD) patients with active and inactive period. The multicenter study included 53 patients with active (n = 28) and inactive (n = 25) BD (mean age, 34.3 ± 9 years; 15 men and 38 women) satisfying the International Study Group criteria and 26 healthy controls (mean age, 34.4 ± 6.1 years; seven men and 19 women) matched for age and gender from a similar ethnic background. Serum natriuretic peptides levels were determined by enzyme immunoassay kit. Mean serum ANP concentrations in the active patients (4.01 ± 1.21 ng/ml) were significantly lower than in the healthy controls (5.76 ± 1.99 ng/ml, p = 0.004). Mean serum BNP levels were found to be significantly higher in both the active (6.19 ± 2.97 ng/ml) and inactive (6.49 ± 2.88 ng/ml) BD groups compared with the control group (3.82 ± 1.1 ng/ml, p = 0.004 and p = 0.001, respectively). Mean serum CNP concentrations in the active patients (0.49 ± 0.12 ng/ml) were significantly lower than in the inactive patients (0.65 ± 0.2 ng/ml, p = 0.017) and the healthy controls (0.8 ± 0.27 ng/ml, p < 0.001). Our results suggest that changes in natriuretic peptide levels may be associated with vasculitis that play role in the etiopathogenesis of the BD.     

Healing of colonic anastomoses after immediate postoperative intraperitoneal administration of oxaliplatin

Aim  The aim of this experimental study was to investigate the effect of intraperitoneal administration of oxaliplatin on the healing of colonic anastomoses when injected immediately after colon resection. Materials and methods  Thirty male Wistar rats were used. During the operation, the rats were randomized to two groups of 15 rats each. Immediately after colonic anastomoses were performed, the rats were injected intraperitoneally with either 3 ml of 0.9% NaCl solution or oxaliplatin (2.4 mg/kg body weight) depending on their group. All rats were killed on the eighth postoperative day. The anastomoses were examined macroscopically. The anastomotic bursting pressures were recorded, the anastomoses graded histologically, and the hydroxyproline tissue contents determined. Results  Anastomotic leakage was noted in four rats (26.7%) of the oxaliplatin group, whereas no anastomotic dehiscence was detected among rats of the control group (p = 0.016). The adhesion formation at the anastomotic sites and the inflammatory cell infiltration were significantly higher in the oxaliplatin group than in the control group (p = 0.001). The bursting pressures (p = 0.001), the hydroxyproline tissue content (p = 0.001), the neoangiogenesis (p = 0.033), the fibroblast activity (p = 0.001), and the collagen deposition (p = 0.001) were significantly lower in the oxaliplatin group in comparison to the control group. Conclusion  The immediate postoperative intraperitoneal administration of oxaliplatin seems to impair healing of colonic anastomoses in rats.     

Dexrazoxane Prevents Myocardial Ischemia/Reperfusion-Induced Oxidative Stress in the Rat Heart

Introduction Dexrazoxane (Dex), used clinically to protect against anthracycline-induced cardiotoxicity, possesses iron-chelating properties. The present study was designed to examine whether Dex could inhibit the ischemia/reperfusion (I/R) induced damage to the rat heart. Materials and methods Isolated perfused rat hearts were exposed to global ischemia (37°C) and 60 min reperfusion. Dex was perfused for 10 min prior to the ischemia, or administered intraperitoneally (150 mg) 30 min prior to anesthesia of the rats. I/R caused a significant hemodynamic function decline in control hearts during the reperfusion (e.g., the work index LVDP X HR declined to 42.7 ± 10%). Dex (200 μM) applied during the preischemia significantly increased the hemodynamic recovery following reperfusion (LVDP X HR recovered to 55.7 ± 8.8%, p < 0.05 vs. control). Intraperitoneal Dex, too, significantly increased the hemodynamic recovery of the reperfused hearts. I/R caused an increase in oxidation of cytosolic proteins, while Dex decreased this oxidation. Discussion The decrease in proteins carbonylation and correlative hemodynamic improvement suggests that Dex decreases I/R free radical formation and reperfusion injury. Eyal Ramu and Amit Korach contributed equally to this study.     

Impact of a comprehensive safety program on radiation exposure during catheter ablation of atrial fibrillation: a prospective study

Background  Pulmonary vein antral isolation (PVAI) is an effective treatment for atrial fibrillation and involves prolonged procedure and fluoroscopy times. This study assesses the impact of a comprehensive radiation safety program on patient and operator radiation exposure during PVAI. Methods and Results  We evaluated a comprehensive radiation safety program including: (1) verbal reinforcement of previous fluoroscopy times (2) effective collimation (3) minimizing source-intensifier distance and (4) effective lead shield use. Exposure doses in 41 consecutive patients without (group-I, n = 21) and with (group-II, n = 20) the use of radiation safety program were assessed. PVAI was done using intracardiac echo (ICE) guided roving circular mapping catheter. A 3-dimensional mapping system was used in 27% cases for additional guidance. Operator and patient exposure was measured during the PVAI. The age, gender, body mass index and AF duration were similar in both of the groups. The total procedure (166 ± 56 vs 178 ± 38 min, p = 0.54) and fluoroscopy times (74 ± 24 vs 70 ± 20 min, p = 0.72) were comparable. Group-II had significantly lower dose area product (234 ± 120 vs 548 ± 363 Gy cm², p = 0.03) compared to group-I. The mean operator exposure was reduced by half and mean patient peak skin dose by three to ten times with comprehensive radiation safety program. None of the patients were noted to have radiation related skin injuries. Additional lifetime cancer risk was significantly lower in group-II patients (0.08 vs 0.2%, p < 0.001) than group-I. Conclusions  Implementation of a comprehensive radiation safety program described above significantly decreases the radiation exposure to the patient as well as the operator.     

Repeated doses of cardiac mesenchymal cells are therapeutically superior to a single dose in mice with old myocardial infarction

This study aimed to investigate the role of the intrinsic cardiac nervous system in the mechanism of classical myocardial ischaemic preconditioning (IPC). Isolated perfused rat hearts were subjected to 35-min regional ischaemia and 60-min reperfusion. IPC was induced as three cycles of 5-min global ischaemia–reperfusion, and provided significant reduction in infarct size (IS/AAR = 14 ± 2% vs control IS/AAR = 48 ± 3%, p < 0.05). Treatment with the ganglionic antagonist, hexamethonium (50 μM), blocked IPC protection (IS/AAR = 37 ± 7%, p < 0.05 vs IPC). Moreover, the muscarinic antagonist, atropine (100 nM), also abrogated IPC-mediated protection (IS/AAR = 40 ± 3%, p < 0.05 vs IPC). This indicates that intrinsic cardiac ganglia remain intact in the Langendorff preparation and are important in the mechanism of IPC. In a second group of experiments, coronary effluent collected following IPC, from ex vivo perfused rat hearts, provided significant cardioprotection when perfused through a naïve isolated rat heart prior to induction of regional ischaemia–reperfusion injury (IRI) (IS/ARR = 19 ± 2, p < 0.05 vs control effluent). This protection was also abrogated by treating the naïve heart with hexamethonium, indicating the humoral trigger of IPC induces protection via an intrinsic neuronal mechanism (IS/AAR = 46 ± 5%, p < 0.05 vs IPC effluent). In addition, a large release in ACh was observed in coronary effluent was observed following IPC (IPC_eff = 0.36 ± 0.03 μM vs C _eff = 0.04 ± 0.04 μM, n = 4, p < 0.001). Interestingly, however, IPC effluent was not able to significantly protect isolated cardiomyocytes from simulated ischaemia–reperfusion injury (cell death = 45 ± 6%, p = 0.09 vs control effluent). In conclusion, IPC involves activation of the intrinsic cardiac nervous system, leading to release of ACh in the ventricles and induction of protection via activation of muscarinic receptors.

     

Effects of obstructive sleep apnea treatment on left atrial volume and left atrial volume index

Obstructive sleep apnea (OSA) and increased left atrial volume (LAV) both independently increase cardiovascular mortality. We hypothesized that treatment of OSA with continuous positive airway pressure (CPAP) may decrease LAV. We retrospectively identified 47 OSA patients receiving CPAP who had echocardiograms done before and after polysomnography. Compliance was defined as CPAP use at-least five nights weekly and 5 h per night. The compliant group (n = 23) had a significant decrease in diastolic blood pressure (DBP; 4.4 ± 8.9 mmHg, p < 0.05) and mean arterial pressure (MAP; 4.7 ± 10.3 mmHg, p < 0.05), while no significant changes were observed in the noncompliant group (n = 24). LAV data were available in 13 compliant and 20 noncompliant patients. LAV decreased nonsignificantly (3.54 ± 16.6 mL, n = 13, p = 0.65) in CPAP-compliant patients, while it increased (15.47 ± 22.3 mL, n = 20, p < 0.006) in noncompliant patients. Similar changes were seen in the LAV index. Untreated OSA was associated with an increase in LAV and LAV index without significant changes in blood pressure. Treatment of OSA was associated with a decrease in DBP and MAP with a nonsignificant decrease in LAV. Treatment of OSA may prevent adverse left atrial remodeling. There are no conflicts of interest or financial disclosures for any of the authors.     

Relationship between Retrograde Coronary Blood Flow and the Extent of No-Reflow and Infarct Size in a Porcine Ischemia–Reperfusion Model

Recanalization of an infarct-related artery does not predictably reflect tissue reperfusion. We examined the relationship between coronary blood flow (CBF) pattern during reperfusion and infarcted (IA) and no-reflow (NR) area in a porcine ischemia–reperfusion model. The mid-left anterior descending artery of 18 pigs was occluded for 1 h and reperfused for 2 h. CBF during reperfusion was measured with a transit-time ultrasound flowmeter, while systemic arterial and left atrial pressures were monitored. IA and NR were measured with triphenyl tetrazolium chloride and thioflavin staining, respectively. In 13 pigs, early systolic retrograde CBF developed within the first 30 min and persisted throughout reperfusion. No retrograde CBF was observed in five pigs. Mean retrograde CBF at 2 h of reperfusion predicted a larger IA (r = 0.71; p = 0.001). Time-to-development of retrograde CBF was inversely related to IA (r = −0.55; p = 0.019) and NR (r = −0.62; p = 0.006). A larger IA (OR 1.12, 95% CI 1.01–1.24, p = 0.037) and NR (OR 1.09, 95% CI 1.01–1.18, p = 0.037) predicted the presence of retrograde CBF. Retrograde CBF during recanalization of the infarct-related artery predicts IA and NR and might be used as an index of successful reperfusion at the tissue level.     

Abnormal surface markers expression on bone marrow CD34<Superscript>+</Superscript> cells and correlation with disease activity in patients with systemic lupus erythematosus

Defects of hematopoietic stem cells (HSCs) have been suggested to contribute to the development of systemic lupus erythematosus (SLE). The aim of this study was to investigate the phenotypic characteristics of bone marrow (BM) CD34⁺ cells in patients with SLE and its relationship with SLE disease activity. Ten SLE patients and 10 healthy subjects were recruited and their BM CD34⁺ cells were analyzed by flow cytometric analysis with CD45/SSC gating for the expression of CD90, CD95, CD117, CD123, CD164, CD166, FAS-L, and HLA-DR. The percentage of BM CD34⁺ cells was significantly decreased in active SLE patients (1.48 ± 0.41%, n = 7) compared to the healthy controls (2.31 ± 0.75%, n = 10, p < 0.01), but no significant difference was found between the inactive patients (2.04 ± 0.44%, n = 3) and the controls. The expression of CD95, CD123, and CD166 on BM CD34⁺ cells were significantly increased in SLE patients (48.31 ± 10.59%, 44.9 ± 21.5%, 30.9 ± 19.54%, respectively, n = 10) when compared with the control subjects (24.33 ± 11.1%, 19.5 ± 4.4%, 10.7 ± 5.5%, respectively, n = 10, p < 0.05). The increased CD123 expression was negatively correlated with the number of peripheral white blood cells (r = −0.700, p < 0.05, n = 10). The percentage of CD166 expression was found significantly correlated with the index of SLE disease activity (r = 0.472, p < 0.05, n = 10) and 24 h proteinuria (r = 0.558, p < 0.05, n = 10), but negatively correlated with serum C3 level (r = −0.712, p < 0.01, n = 10). Our study found that the surface marker expression of CD95, CD123, and CD166 on BM CD34⁺ cells were significantly increased in patients. This supports the hypothesis that there are abnormalities of the HSC in SLE. Since CD166 and CD123 correlated with the overall lupus activity, their role as a biomarker of inflammatory disease activity also requires further study.     

Comparison of the effect of multiple short-duration with single long-duration exercise sessions on glucose homeostasis in type 2 diabetes mellitus

Aims/hypothesis We evaluated and compared the effects on glycaemic control of two different exercise protocols in elderly men with type 2 diabetes mellitus. Methods Eighteen patients with type 2 diabetes mellitus carried out home-based bicycle training for 5 weeks. Patients were randomly assigned to one of two training programmes at 60% of maximal oxygen uptake: three 10 min sessions per day (3 × 10) or one 30 min session per day (1 × 30). Plasma insulin, C-peptide and glucose concentrations were measured during a 3 h oral glucose tolerance test (OGTT). Insulin sensitivity index (ISI_composite), pre-hepatic insulin secretion rates (ISR) and change in insulin secretion per unit change in glucose concentrations (B_total) were calculated. Results Cardiorespiratory fitness increased in response to training in both groups. In group 3 × 10 (n = 9) fasting plasma glucose (p = 0.01), 120 min glucose OGTT (p = 0.04) and plasma glucose concentration areas under the curve at 120 min (p < 0.04) and 180 min (p = 0.07) decreased. These parameters remained unchanged in group 1 × 30 (n = 9). No significant changes were found in ISI_composite, ISR and B_total in either of the exercise groups. In a matched time-control group (n = 10), glycaemic control did not change. Conclusions/interpretation Moderate to high-intensity training performed at 3 × 10 min/day is preferable to 1 × 30 min/day with regard to effects on glycaemic control. This is in spite of the fact that cardiorespiratory fitness increased similarly in both exercise groups. A possible explanation is that the energy expenditure associated with multiple short daily sessions may be greater than that in a single daily session.     

Does exercise affect the antioxidant system in patients with ankylosing spondylitis?

We aimed to investigate the effect of regular supervised exercise program on functinal status, disease activity, and total antioxidant status (TAS) level in patients with ankylosing spondylitis (AS). Thirty-two patients (mean age: 44 years) with AS were included in the study and divided into two groups. Group 1, the exercise group (n = 16), attended a supervised exercise program that consisted of aerobic, strengthening, and stretching exercises for 1 h a day, five times a week for 3 weeks. Group 2, the control group, received a home exercise program (n:16). Bath AS Activity Index (BASDAI) and Bath AS Functional Index (BASFI) were calculated and serum TAS levels were measured for each patient at 0 and 3 weeks. There was no significant difference in patients' baseline characteristics (age, disease duration, BASFI, and BASDAI scores) between exercise and control groups. In the exercise group, there were significant improvements between pre-exercise and post-exercise assessments in BASFI (2.8 ± 1,8; 1.7 ± 1,40, p = 0.004) and BASDAI scores (2.1 ± 1.7; 1.2 ± 1.3, p = 0.01). Mean TAS levels were significantly decreased after supervised exercise program (1.48 ± 0.16 mmol/L; 1.36 ± 0.20 mmol/L, p = 0.03). In the control group, BASFI score (2.4 ± 1.7; 2.9 ± 2.1, p = 0.19), BASDAI score (2.6 ± 2.2; 3.1 ± 2.6, p = 0.33), and mean TAS levels (1.38 ± 0.23 mmol/L; 1.39 ± 0.20 mmol/L, p = 0.66) did not differ significantly between 0 and 3 weeks. Short-term, supervised exercise program improved functional status and decreased disease activity. However, the mechanism of this beneficial clinical effect does not seem to be through antioxidant activity.     

Relationship between glyco-oxidation, antioxidant status and microalbuminuria in type 2 diabetic patients

Aims/hypothesis  This study examined the relationship, if any, between glucose-induced oxidative stress, antioxidant status and microalbuminuria in patients with type 2 diabetes. Methods  The study involved 99 consecutive type 2 diabetic patients (57 men, 42 women). Patients with persistent microalbuminuria were identified and the following variables evaluated: fasting plasma glucose, HbA_1c, malonyldialdehyde (MDA), pentosidine, AGE, the total radical-trapping antioxidant parameter (TRAP), vitamin E, creatinine, estimated GFR and lipid profile. Results  Patients were divided into two groups, i.e. 37 individuals without microalbuminuria (AER <20 μg/min) and 62 with microalbuminuria (AER ≥20 μg/min). The following variables were significantly higher in patients with microalbuminuria than in those without microalbuminuria (mean ± SD): fasting plasma glucose 9.41 ± 2.88 vs 8.19 ± 1.93 mmol/l, p < 0.05; HbA_1c 7.97 ± 1.51 vs 7.39 ± 1.03%, p < 0.05; MDA 1.18 ± 0.35 vs 1.02 ± 0.29 μmol/l, p < 0.05; pentosidine 98.5 ± 24.6 vs 82.9 ± 20.9 pmol/ml, p < 0.005; and AGE 13.2 ± 4.8 vs 10.6 ± 3.8 μg/mg protein, p < 0.01. However, vitamin E and TRAP did not differ between the two groups. Serum creatinine values and estimated GFR were similar in the two groups. Only in patients with microalbuminuria were significant linear correlations seen between AER and both oxidation (HbA_1c r = 0.33, p < 0.01; MDA r = 0.59, p < 0.001; pentosidine r = 0.48, p < 0.001; and AGE r = 0.44, p < 0.001) and antioxidation variables (vitamin E r = −0.55, p < 0.001; TRAP r = −0.49, p < 0.001). Considering all variables together, multiple regression revealed a correlation between microalbuminuria and vitamin E, TRAP, HbA_1c and MDA, but not pentosidine or AGE. Conclusions/interpretation  Our data suggest that microalbuminuria in type 2 diabetic patients might be promoted by an insufficient counter-regulation of the antioxidant system in the event of increased glyco-oxidation/glycation.     

Ginsenoside Rb1 Preconditioning Protects Against Myocardial Infarction After Regional Ischemia and Reperfusion by Activation of Phosphatidylinositol-3-kinase Signal Transduction

Background  Ginsenoside Rb1, a major bioactive component of Panax ginseng, bears various beneficial effects on the cardiovascular system. This study investigated whether ginsenoside Rb1 preconditioning has protective effects on myocardial ischemia–reperfusion injury and its potential mechanism. Methods  Rats subjected to 45 min of myocardial ischemia followed by 120 min of reperfusion were assigned to the following groups: sham-operated, ischemia–reperfusion (I/R), ginsenoside Rb1+I/R, wortmannin(a specific PI3K inhibitor)+I/R, wortmannin drug vehicle (dimethyl sulfoxide, DMSO), wortmannin+sham, ginsenoside Rb1+ wortmannin +I/R. Infarct size was assessed by triphenyltetrazolium chloride staining. Plasma creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB), lactate dehydrogenase (LDH), and troponin T levels were also measured. Akt phosphorylation expression was assessed by immunoblotting. Results  Ginsenoside Rb1 preconditioning reduced infarct size compared with that in the I/R group: 30 ± 2.6% versus 51 ± 2.7% (p < 0.01). Ginsenoside Rb1 preconditioning also markedly reduced the plasma CK, CK-MB, LDH and troponin T levels in blood. Akt phosphorylation expression increased after ginsenoside Rb1 preconditioning. These effects of ginsenoside Rb1 preconditoning were significantly inhibited by wortmannin. Conclusion  This is the first study to demonstrate that ginsenoside Rb1 preconditioning has protective effects on myocardial ischemia and reperfusion injury, partly by mediating the activation of the PI3K pathway and phosphorylation of Akt. Project supported by the National Basic Research Program of China (a.k.a. 973 Program) (No.2005CB523305).