Cardioprotective Effects In Patients Research Articles

Epigallocatechin-3-gallate, a green tea catechin, protects the heart against regional ischemia–reperfusion injuries through activation of RISK survival pathways in rats

Epigallocatechin-3-gallate (EGCG), the major catechin derived from green tea, has been shown to modulate numerous molecular targets in the setting of inflammation. This study aimed to determine whether EGCG protects against regional myocardial ischemia/reperfusion (I/R) injuries and its underlying mechanisms involving the role of reperfusion injury salvage kinase (RISK) pathways (PI3K-Akt and ERK 1/2) and GSK-3β or apoptotic kinases (p38 and JNK). The rats were subjected to I/R injuries consisting of 30 min ischemia followed by 2 h reperfusion. EGCG (10 mg/kg, intravenously) was administered alone or along with wortmannin (PI3K inhibitor, 0.6 mg/kg, intravenously) 5 min before the onset of reperfusion. Wortmannin was administered 10 min before the reperfusion. Infarct size was measured at the end of the reperfusion. The phosphorylation of Akt, GSK-3β, and MAPK kinases (ERK1/2, P38 and JNK) was determined by Western blotting after 10 min of reperfusion. EGCG reduced the infarct size compared with the control (25.4 ± 9.2 versus 43.2 ± 8.2 %, p < 0.05). Wortmannin alone did not affect the infarct size, but abolished the EGCG-induced infarct size limiting effect, indicating that EGCG may protect the heart by modulating the PI3K-Akt. EGCG significantly enhanced the phosphorylation of Akt and GSK-3β but not ERK1/2, while it reduced that of p38 and JNK. These results suggest that EGCG has a protective effect against regional myocardial I/R injuries through activation of the RISK pathway and attenuation of p38 and JNK. EGCG may have cardioprotective effects in patients undergoing surgeries prone to myocardial I/R injuries.

Ischaemic POSTconditioning—a long harvest for a little corn

In the POST trial, mechanical ischaemic postconditioning did not have a significant cardioprotective effect in patients with ST-segment elevation myocardial infarction. However, the sample size, the principal end point (ST-segment regression), and the postconditioning protocol used are important limitations in this trial. Whether mechanical postconditioning has cardioprotective clinical benefits remains unanswered.

High-Dose Erythropoietin in Acute ST-Segment Elevation Myocardial Infarction: A Meta-Analysis of Randomized Controlled Trials

We sought to perform a meta-analysis to evaluate the potential influence of high-dose erythropoietin (EPO) on cardiac function parameters in patients with acute ST-segment elevation myocardial infarction (STEMI). By searching PubMed, EMBASE, and the Cochrane Library (up to December 2012), seven randomized controlled trials (RCTs) reporting cardiac functional parameters with a total of 1,250 acute STEMI patients were identified. When applied to patients with acute STEMI, high-dose EPO was relatively safe and no increase in all-caused death and severe adverse effects were indicated. Estimates were pooled from fixed or random effects models. Compared with controls, high-dose EPO resulted in a slight but significant improvement in left ventricular ejection fraction of 1.02% [95% confidence interval (CI) 0.17-1.88, P=0.019, I (2)=0%] and an improvement in left ventricular end-systolic volume of -4.61ml (95% CI -7.64 to -1.58, P=0.003, I (2)=27.7%). Available evidence suggested that high-dose EPO has limited cardio-protective effects in patients with STEMI. However, considering the relatively short follow-up durations and small patient populations in the current RCTs, the effects of high-dose EPO on clinical outcomes in patients with STEMI need to be evaluated in larger prospective RCTs of longer duration.

Abstract 299: The Cardioprotective Mechanism of a Recombinant Atrial Natriuretic Peptide Against Catecholamine-Induced Myocardial Injury in Acute Heart Failure

Background: Catecholamine induces intracellular reactive oxygen species (ROS), enhances abnormal Ca 2+ handling and leads to apoptosis in failing cardiomyocytes. We clarified the mechanism by which an exogenous atrial natriuretic peptide (ANP) exerts cardioprotective effect in patients with acute heart failure (HF). Methods and Results: Blood sampling from both coronary sinus and aorta showed that cardiac tissue produced 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, in patients with HF(n=30), but not in control subjects (n=10). Urinary (U) 8-OHdG (ng/mg creatinine) also increased in only patients with HF(Control;8.0±2.0 vs HF; 14.8±2.5, p&lt;0.05). As protocol 1, we examined whether an infusion of ANP (0.025 µg/kg/min) decreased levels of U-8-OHdG during the treatment of HF (n=15, for 3 days), as compared with that of nitroglycerin (NTG) (n=15, for 3 days). Either treatment with ANP or NTG similarly improved hemodynamic parameters and BNP. In ANP-treated group, however, U 8-OHdG significantly decreased as compared with in NTG-treated group (ANP: 9.8±3.5; NTG: 14.5±4.2, p&lt;0.05). As Protocol 2, we investigated the effect of ANP on 1) intracellular ROS production by DCFH-DA, 2) local Ca 2+ release event by confocal microscopy using Fluo 4-AM, 3) myocyte apoptosis (TUNNEL staining) and survival rate after 48h in failing myocytes isolated from LV in canine tachycardia-induced HF(n=6, EF 20 ± 5%). In failing myocytes, isoproterenol (ISO) markedly increased intracellular ROS, concurrently with an increase in the frequency of Ca2+ sparks (SpF:s -1 •100µm -1 :HF: 8.0 ± 2.0 , Normal: 1.6 ± 0.5, p&lt;0.01) . Interestingly, in failing myocytes, ANP(1x10 -8 mol/L) significantly suppressed the ISO-induced ROS production, SpF, and myocyte apoptosis respectively. Eventually, the survival rate (%)in failing myocytes was significantly lower in the presence of ISO than in its absence, while it was significantly improved by co-incubation of ISO plus ANP (ISO(-);59±12, ANP(+); 63±8, ISO(+);33±13, ISO plus ANP; 55±5, p&lt;0.01). Conclusions: ANP has a potent antioxidant action against catecholamine-induced ROS, which may correct abnormal Ca 2+ release and inhibit myocyte apoptosis, eventually contribute to improvement of myocytes survival in HF.

Beyond glucose: cardiovascular effects of incretins and dipeptidyl peptidase-4 substrates

The incretins are naturally occurring peptides that are pro-glucagon derivatives that have been implicated in the control of appetite and satiety. The class includes both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Incretins, particularly GLP-1 (7–36) amide, have been exploited clinically by virtue of their insulinotropic properties that are glucose dependent, thus mitigating the risk of hypoglycaemia that accompanies conventional secretagogues and exogenous insulins. However, the short circulating half-life of the native peptide limits their use as a therapeutic option. Dipeptidyl peptidase-4 (DPP-4) is an enzyme with multiple substrates, including GLP-1 and GIP. Dipeptidyl peptidase-4 inactivates GLP-1 and GIP via cleavage at specific sites within the molecules. This has led to the development of novel GLP-1 receptor (GLP-1R) agonists and analogues that are DPP-4 resistant and have a longer duration of action than GLP-1, and agents that inhibit DPP-4 to increase the circulating half-life of the native GLP-1 peptide. Dipeptidyl peptidase-4 inhibitors reduce fasting and post-prandial glucose concentrations and haemoglobin A1C in patients with type 2 diabetes mellitus (T2DM), similar to the effects of the GLP-1-like peptides. Preliminary evidence suggests that the native GLP-1 peptide, its active metabolites, GLP-1R agonists (exenatide) and analogues (liraglutide, albiglutide), and DPP-4 inhibitors themselves may also have direct cardiovascular (CV) benefits outside of glycaemic control. Whereas the on-target effects of these classes of anti-diabetic agents are similar in their ability to improve glycaemic control, the off-target effects are agent-specific and mediated through discrete cellular mechanisms. Randomized controlled trials are under way to determine whether GLP-1 analogues and DPP-4 inhibitors confer cardioprotective effects in patients with T2DM. This review discusses the potential CV benefits of native GLP-1, its metabolites, receptor agonists and analogues, and DPP-4 inhibition mediated through distinct DPP-4 substrates.

Concomitant use of beta-1 adrenoreceptor blocker and norepinephrine in patients with septic shock

Betablockade has been shown to have cardioprotective effects in patients under perioperative stress. Besides animal model of septic shock and a small cohort of septic patients, these benefits have not been studied in septic shock patients who require norepinephrine administration. After correction of preload, an esmolol bolus (0.2-0.5mg/kg) followed by continuous 24h infusion was administered in septic patients with sinus or supraventricular tachycardia (HR > 120/min). Exclusion criteria were severe LV systolic dysfunction, atrioventricular blockade and norepinephrine infusion at rates over 0.5mg/kg/min. Monitoring with echocardiography and pulmonary artery catheter before, at 2, 6, 12, 24h following the start and 6h after ceasing of the esmolol drip. Patients were maintained normovolemic throughout the study and adjustments of concomitant norepinephrine infusion rates were made as required. Ten septic patients (mean age 54.4 ± 18.7), APACHE II 21.5 ± 6.2, CRP 275 ± 78mg/l, procalcitonin 14.5 ± 10.1mg/l, were given esmolol drip of 212.5 ± 63.5mg/h at start to 272.5 ± 89.5mg/h at 24h. Heart rate decreased from mean 142 ± 11/min to 112 ± 9/min (p < 0.001) with parallel insignificant reduction of cardiac index (4.94 ± 0.76 to 4.35 ± 0.72l/min/m(2)). Stroke volume insignificantly increased from 67.1 ± 16.3ml to 72.9 ± 15.3ml. No parallel change of pulmonary artery wedge pressure was observed (15.9 ± 3.2 to 15.0 ± 2.4mmHg) as well as no significant changes of norepinephrine infusion (0.13 ± 0.17 to 0.17 ± 0.19mg/kg/min), DO(2), VO(2), OER or arterial lactate. Saving the heart 30beats/min did not demonstrate adverse impact on global haemodynamics in rates above 110/min. Using well titratable betablocker seems to be safe and cardioprotective in septic shock patients with high cardiac output.

Exenatide Reduces Final Infarct Size in Patients With ST-Segment–Elevation Myocardial Infarction and Short-Duration of Ischemia

Exenatide has been demonstrated to be cardioprotective as an adjunct to primary percutaneous coronary intervention in patients with ST-segment-elevation myocardial infarction (STEMI). The aim of the post hoc analysis study was to evaluate the effect of exenatide in relation to system delay, defined as time from first medical contact to first balloon. Patients with STEMI and Thrombolysis In Myocardial Infarction flow 0/1 were randomly assigned to intravenous exenatide or placebo continuous infusion. Study treatment was commenced 15 minutes before intervention and maintained for 6 hours after the procedure. The patients were stratified according to median system delay (132 minutes). Final infarct size and myocardial area at risk were measured by cardiovascular magnetic resonance. Among patients with a system delay ≤132 minutes (n=74), treatment with exenatide resulted in a smaller infarct size (9 grams [interquartile range (IQR), 4-13] versus 13 grams [IQR, 8-24], P=0.008, corresponding to 8% [IQR, 4-12] versus 11% [IQR, 7-17] of the left ventricle, P=0.015). In a regression analysis adjusting for myocardial area at risk the data points of the exenatide group lay significantly lower than for the placebo group (P=0.006). In the patients with system delay >132 minutes (n=74) no difference was observed in infarct size expressed as grams (P=0.49) or percentage (P=0.46). There was significant interaction between system delay (less than or equal to median versus greater than median) and treatment allocation in terms of infarct size (P=0.018). In this post hoc analysis, exenatide treatment was associated with a 30% decrease in final infarct size in patients with short system delay, whereas no cardioprotective effect in patients with long system delay was seen. However, this finding must be confirmed in larger studies. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00835848.

Are drug treatments for psoriasis a cardiovascular risk?

Multiple studies have shown psoriasis to be an independent risk factor for cardiovascular disease, particularly in patients with moderate-to-severe disease. Chronic, systemic inflammation is the proposed etiology for the increase in cardiovascular morbidity. Previous studies had suggested that the control of systemic inflammation with the use of methotrexate and antitumor necrosis factor agents had a cardioprotective effect in patients with psoriasis. While our recent meta-anlaysis of 22 randomized controlled trials (RCTs) did not show a statistically significant association between anti-IL-12/23 therapies and anti-TNF agents and major adverse cardiovascular events (MACE), the study had limited power to detect changes in rare events over a short period of time. Collection of comprehensive postmarketing safety data, and the use of observational pharmacoepidemiological studies plus drug registries will play an important role in addressing this limitation in addition to providing more conclusive data regarding the impact of established and future psoriasis therapies on cardiovascular events. Psoriasis is a common autoimmune disease of cutaneous inflammation and keratinocyte hyperproliferation, manifesting clinically as scaly, raised, erythematous plaques. While the pathogenesis remains to be fully elucidated, a complex interplay between genetic and environmental influences is paramount in the development of the disease [1]. Recent studies have shown that patients with moderate-to-severe psoriasis have a clinically significant increased risk of cardiovascular disease together with cardiovascular risk factors such as Type 2 diabetes mellitus, obesity, smoking and the metabolic syndrome compared to the general population, with an overall increase in all-cause mortality [2]. The mechanistic link between psoriasis and this observed increase in cardiovascular comorbidities has not been fully defined. It is clear, however, that common inflammatory pathways are at play in the pathophysiology of psoriasis, obesity and coronary artery disease.

Cardioprotection by resveratrol: A human clinical trial in patients with stable coronary artery disease

Several beneficial effects of resveratrol (RES), a natural antioxidant present in red wine have already been described. The aim of our study was to investigate if RES had a clinically measurable cardioprotective effect in patients after myocardial infarction. In this double-blind, placebo controlled trial 40 post-infarction Caucasian patients were randomized into two groups. One group received 10 mg RES capsule daily for 3 months. Systolic and diastolic left ventricular function, flow-mediated vasodilation (FMD), several laboratory and hemorheological parameters were measured before and after the treatment. Left ventricular ejection fraction showed an increasing tendency (ns) by RES treatment. However, left ventricular diastolic function was improved significantly (p < 0.01) by RES. A significant improvement in endothelial function measured by FMD was also observed (p < 0.05). Low-density lipoprotein (LDL) level significantly decreased (p < 0.05) in the RES treated group. Red blood cell deformability decreased and platelet aggregation increased significantly in the placebo group (p < 0.05), while resveratrol treatment has prevented these unfavourable changes. Concerning other measured parameters no significant changes were observed neither in placebo nor in RES group. Our results show that resveratrol improved left ventricle diastolic function, endothelial function, lowered LDL-cholesterol level and protected against unfavourable hemorheological changes measured in patients with coronary artery disease (CAD).

Dexrazoxane Use in Pediatric Patients with Acute Lymphoblastic or Myeloid Leukemia: Analysis of a National Cohort of Patients in the Pediatric Health Information Systems Database From 1999 to 2009

Abstract 4242 Background:Acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) account for approximately 26% of all pediatric cancers. Anthracyclines are critical in the treatment of ALL and AML; however, their use is limited by cardiotoxicity. Dexrazoxane (DZX) is an FDA-approved cardioprotective agent that chelates intracellular free iron and iron bound to anthracyclines. Evidence for the efficacy of DZX as a cardioprotectant in children is limited, but available data support a short term cardioprotective effect in patients with ALL. The frequency of DZX use in pediatric cancer patients at high risk of developing cardiac toxicity is unknown. Objective:We sought to describe patterns of DZX use between 1999 and 2009 in a retrospective cohort study of pediatric patients diagnosed with ALL or AML in 43 pediatric hospitals across the United States in the Pediatric Health Information Systems (PHIS) database. Methods:Patients previously identified and validated as having de novo ALL and AML at these PHIS hospitals were included. Demographic data, as well as chemotherapy and DZX use were obtained from PHIS. Results:Of 8733 patients with de novo ALL and 2556 with de novo AML, 207 and 52 received DZX, respectively. The proportion of patients receiving DZX was higher in older children with ALL or AML and in African-Americans and males with ALL (Table 1). There was no trend in the proportion of patients receiving DZX per year in either group (Figure 1). DZX use varied by region in ALL, with 55% of the patients receiving DZX being treated in the northeast, but was not significantly different in AML. There was substantial variability in prescribing practices across institutions (Figure 2). Most patients with ALL and AML received the first dose of DZX in the first 30 days (67% and 31%, respectively) or >360 days from their first leukemia admission (23.5% and 31%, respectively).Table 1Demographic characteristics of the patients in the PHIS ALL and AML cohortsALLPAMLPALL patients w/o DZX exp (n=8526)ALL patients w/DZX exp (n=207)AML patients w/o DZX exp (n=2504)AML patients w/DZX exp (n=52)Age, n (%)<.001.042<1 year252 (3)0 (0)254 (10)1 (2)1 to <5 years3777 (44)47 (23)623 (25)14 (27)5 to <10 years2211 (26)45 (22)426 (17)4 (7)10 to <15 years1409 (17)70 (34)567 (23)12 (30)15 to <20 years826 (10)41 (20)574 (23)18 (27)≥ 20 years51 (0.6)4 (2)60 (2)3 (4)Sex, n (%).038.600Male4777 (56)131 (63)1353 (54)30 (58)Female3749 (44)76 (37)1151 (46)22 (42)Race, n (%).024.595White6395 (75)155 (75)1707 (68)40 (77)Black616 (7)27 (13)309 (12)4 (9)Asian252 (3)6 (3)85 (3)1 (2)Native American42 (0.5)2 (1)14 (0.5)0 (0)Other586 (7)13 (6)182 (7)5 (9)Missing631 (7)8 (4)207 (8)2 (4)Ethnicity, n (%).042.029Hispanic1952 (23)47 (23)472 (19)17 (34)Non-Hispanic87 (1)7 (3)51 (2)0 (0)Unknown6485 (76)155 (74)1981 (79)35 (66)Missing0 (0)0 (0)0 (0)Region, n (%)<.001.002Midwest2328 (27)19 (0.5)724 (29)10 (19)Northeast715 (8)113 (55)250 (10)13 (25)South2876 (34)38 (18)870 (35)13 (25)West2607 (31)37 (18)660 (26)16 (31)AnthracyclineDoxorubicin171 (82)1 (2)Daunorubicin15 (7)16 (31)Mitoxantrone2 (1)28 (54)Idarubicin3 (1)3 (6)Unknown17 (8)4 (8) [Display omitted] [Display omitted] Conclusions:To our knowledge, this is the only description of DZX use in patients with ALL and AML using national, population-based data. Older children and those treated in the Northeastern U.S. were more likely to have received DZX, with the first dose being given either early or late in the study period. In general, DZX administration was relatively rare and was driven by only a few institutions, especially in ALL patients. This lack of universal acceptance of DZX is likely multi-factorial, including concerns about acute and long-term side effects, impact on the antitumor effect of anthracyclines, and risk for secondary malignant neoplasm. Work is ongoing to substantiate or refute these concerns using PHIS data. Disclosures:No relevant conflicts of interest to declare.

An Increase in Endogenous Erythropoietin Concentrations Has No Cardioprotective Effects in Patients Undergoing Coronary Artery Bypass Graft Surgery

Preliminary data showed an increase in endogenous erythropoietin (EPO) concentrations after acute normovolemic hemodilution (ANH) in patients undergoing coronary artery bypass graft (CABG) surgery. Numerous studies have shown the organ protective properties of EPO. The aim of this study was to investigate the cardioprotective effects of these increased EPO concentrations that resulted from ANH during cardiac surgery. A prospective, randomized, blind study. A university hospital. A total of 93 patients undergoing isolated CABG surgery with or without cardiopulmonary bypass (CPB). Subjects with CPB were randomized into the control (C) or ANH group. Those in the off-pump coronary artery bypass group underwent no treatment. In the ANH group, a precalculated amount of blood was withdrawn and replaced by colloids after the induction of anesthesia. Hemodynamic parameters were recorded intra- and postoperatively. Troponin concentrations were measured as a routine parameter postoperatively. Upon intensive care unit arrival, the EPO levels were higher in the ANH group than in the C group. There was no significant difference between the troponin values of the C and the ANH groups at 4 hours postoperatively. In patients undergoing CABG surgery on CPB, an increase in endogenous EPO concentrations in the physiologic range has no cardioprotective effects.

Effect of fixed-dose losartan/hydrochlorothiazide on brain natriuretic peptide in patients with hypertension

Losartan/hydrochlorothiazide (HCTZ) (Preminent®) is a fixed-dose combination of angiotensin II receptor blocker (ARB) and the thiazide diuretic HCTZ that has consistently been shown to be more effective than either losartan or HCTZ. Little is known about the relationship between losartan/HCTZ and blood levels of brain natriuretic peptide (BNP). In this study, 44 patients with hypertension who were being treated with ARB were enrolled. The ARB was changed to losartan/HCTZ because of uncontrolled hypertension. Blood pressure (BP), pulse rate (PR), plasma levels of BNP and other biochemical parameters were analyzed at baseline and 6 and 12 months after the change from ARB. Of the total 44 patients, 33 (75%) achieved the target BP at 12 months. While there was no significant change in PR, systolic and diastolic BP were significantly reduced (-23 ± 3 mmHg and -10 ± 2 mmHg, respectively) during this period. Although there were no significant changes in biochemical parameters, plasma levels of BNP were significantly decreased, especially in patients who had higher levels of BNP at baseline, during this period. Losartan/HCTZ therapy significantly reduced not only BP but also plasma levels of BNP in patients with hypertension. These findings suggest that losartan/HCTZ might have cardioprotective effects in patients with higher levels of BNP.

P-06 The effect of desflurane preconditioning in off-pump coronary artery bypass grafting surgery

Volatile anaesthetics can induce preconditioning and have been shown to have cardio-protective properties. OPCAB is a safe model for the study of cardiac damage in humans. Desflurane and other volatile anaesthetics could be administered for 5 to 30 minutes for preconditioning effect [1-3].This study investigated whether a 15 min desflurane administration before revascularization has a cardio-protective effect in patients undergoing OPCAB.

Cardioprotective effect of sevoflurane in patients undergoing heart surgery under cardiopulmonary bypass:a meta-analysis

Objective:To systematically review the cardioprotective of sevoflurane in patients undergoing heart surgery under cardiopulmonary bypass,so as to provide evidence for anesthesia decision of cardiac surgery.Methods:Trials about the cardioprotective effect of sevoflurane under CPB were collected through electronic search of Medline,CNKI,and CMBdisk (from the date of database establishment to October 2008); manual search was also conducted.Based on the inclusion and exclusion criteria,fourteen randomized-controlled trials were finally included in the present analysis.The details of the trial design,the characters of the subjects,and the results of the studies were reviewed and analyzed using RevMan 4.2 software.Results:The 14 trials involved 1 226 patients,including 616 receiving sevoflurane and 610 receiving total intravenous anesthesia (TIVA).Compared with TIVA,our analysis showed the following results.(1) Cardiac function:sevoflurane significantly increased the postoperative cardio index (CI,P0.01) and cardiac output(CO,P0.01).(2) Serum cTnI concentration at 24 h postoperation:sevoflurane group was significantly lower than that of TIVA group (P0.01).(3)Sevoflurane significantly decreased the period of mechanical ventilation (P0.01) and the length of intensive care unit stay (P0.01),but the postoperative hospital stay was similar between the two groups.(4)The postoperative usage of inotropic agent was lower in sevoflurane group ( P0.01).There were no significant differences in the mortality (P=0.59),the incidence of atrial fibrillation (P=0.11),and the myocardial infarction rate (P=0.11) between the two groups.Conclusion:Sevoflurane has cardioprotective effect in patients undergoing heart surgery under CPB.

Nicorandil Treatment in Patients With Acute Myocardial Infarction A Meta-Analysis

It is controversial as to whether nicorandil would have cardioprotective effects in patients with acute myocardial infarction (AMI) who are undergoing reperfusion therapy. A meta-analysis was performed to study the impacts of nicorandil on functional outcomes after AMI. Randomized prospective cohort or retrospective cohort publications were identified up to October 2007 by means of a computer search of MEDLINE and Google Scholar databases. Two reviewers checked the quality of the studies and extracted data regarding patient and disease characteristics, study design, functional parameters such as Thrombolysis In Myocardial Infarction (TIMI) flow grade after reperfusion, left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume index (LVEDVI). Seventeen studies were included for the meta-analysis in this study. Nicorandil treatment reduced the incidence of TIMI flow grade < or =2 in 1,337 patients of 10 studies (risk ratio 0.63; 95% confidence interval (CI) 0.44 to 0.91). While no beneficial effect was observed on the peak creatine kinase value, nicorandil treatment was associated with greater LVEF (by 3.7%, 95%CI 1.8 to 5.7%), and lower LVEDVI (by 8.8 ml/kg, -14.4 to -3.3 ml/kg) in 905 patients of 11 studies. The meta-analysis demonstrated that nicorandil treatment adjunctive to reperfusion therapy has beneficial effects on microvascular function and on functional recovery after AMI.

Aliskiren and Its Rapidly, Evolving Role in the Management of Cardio-Thoracic Diseases

I read with great interest the recent article by Campbell et al about aliskiren [ [1] Campbell D. Zhang Y. Kelly D. Gilbert R. Aliskiren increases tissue kallikrein expression and bradykinin levels in the heart. Heart, Lung and Circulation. 2008; 17: S1 Abstract Full Text Full Text PDF PubMed Google Scholar ]. The authors have clearly shown that aliskiren increases tissue kallikrein expression and bradykinin levels in the heart. Interestingly, other aliskiren has significant direct cardio-protective effects in patients with significant cardio-thoracic pathologies.

Effects of Long-term Nicorandil Administration on Endothelial Function, Inflammation, and Oxidative Stress in Patients Without Coronary Artery Disease

Long-term administration of nicorandil has been shown to improve outcomes through cardioprotective effects in patients with coronary artery disease. To identify the mechanisms responsible for these effects, this study examined the impact of long-term nicorandil administration on endothelial function, systemic inflammatory markers, and oxidative stress in patients with cardiovascular risk factors. Fifty-three patients were assigned to receive either nicorandil therapy (15 mg/day; n = 26) (nicorandil group) or usual care (n = 27) (nonnicorandil group). All study participants underwent flow-mediated vasodilatation (FMD) of the brachial artery 1 month before treatment, just before treatment, and at 3, 6, and 12 months following treatment. At identical time points, serum levels of malondialdehyde-modified low-density lipoprotein (MDA-LDL) and high-sensitivity C-reactive protein (hs-CRP) were collected. Compared with the nonnicorandil group, the nicorandil group demonstrated significantly increased FMD at 12 months, a finding not replicated for endothelium-independent vasodilatation with nitroglycerine. Analysis of biochemical markers revealed significantly reduced MAD-LDL levels in the nicorandil group at 12 months, as compared to slightly increased MAD-LDL levels in the nonnicorandil group. Significant reductions in hs-CRP levels were also noted at 6 and 12 months in the nicorandil group, while no change was found in the nonnicorandil group. Results demonstrated that long-term nicorandil therapy is associated with gradual improvements in endothelial function. Our findings also suggest that nicorandil treatment may result in cardiovascular protection through pleiotropic effects including reductions in oxidative injury and systemic inflammation.

Sevoflurane preconditioning at 1 MAC only provides limited protection in patients undergoing coronary artery bypass surgery: a randomized bi-centre trial

Volatile agents can mimic ischaemic preconditioning leading to a decrease in myocardial infarct size. The present study investigated if a 15 min sevoflurane administration before cardiopulmonary bypass (CPB) has a cardioprotective effect in patients undergoing coronary surgery. Seventy-two patients were randomized in two centres. The intervention group (S) received 1 MAC sevoflurane administrated via the ventilator for 15 min followed by a 15 min washout before CPB, the control group did not. The primary outcome was the postoperative troponin Ic peak. A biopsy of the atrium was taken during canulation for enzyme dosages. Results are expressed as mean (SD). Neither troponin Ic nor tissular enzyme measurement exhibited any difference between the groups: peak of troponin Ic was 4.4 (5.6) in S group vs 5.2 (6.6) ng ml(-1) in control group (ns). Intratissular ecto-5'-nucleotidase activity was 7.1 (4.3) vs 8.5 (11.9), protein kinase C activity was 27.1 (15.7) vs 29.2 (28.7), tyrosine kinase activity was 101 (54.1) vs 98.5 (63.3), and P38 MAPKinase activity was 131.1 (76.1) vs 127.1 (86.8) nmol mg protein(-1) min(-1) in S group and control group, respectively (ns). However there were fewer patients with low postoperative cardiac index in S group (11% in S vs 35% in control group, P < 0.05) when considering the per protocol population. In S group, 25% of patients required an inotropic support during the postoperative period, vs 36% of patients in control group (ns). This study did not show a significant preconditioning signal after 15 min of sevoflurane administration. The 15 min duration might be too short or the concentration of sevoflurane too low to induce cardioprotection detected by troponin I levels.

Cardiopulmonary and Systemic Effects of Methylprednisolone in Patients Undergoing Cardiac Surgery

Cardiopulmonary bypass (CPB)-related inflammatory response can be attenuated by glucocorticoid treatment, but its impact on postoperative cardiopulmonary function remains controversial. It was investigated whether the systemic and myocardial antiinflammatory effects of glucocorticoids are associated with improved cardiopulmonary function in cardiac surgery patients. Eighty patients undergoing elective coronary artery bypass grafting were randomly assigned to receive a single shot of methylprednisolone (15 mg/kg) or placebo before CPB. Variables of myocardial and pulmonary function and systemic hemodynamics were measured before and 1, 4, 10, and 24 hours after CPB. Blood was sampled for measurement of proinflammatory (tumor necrosis factor-alpha, interleukin 6, interleukin 8) and antiinflammatory (interleukin 10) cytokines (by enzyme-linked immunoassay), troponin T, and C-reactive protein. Phosphorylation of inhibitory kappa-B alpha and p38 mitogen-activated protein kinase was determined in right atrial biopsies before and after CPB (phosphoprotein assay). Preoperative and intraoperative characteristics of patients were not different between groups. Methylprednisolone attenuated postoperative tumor necrosis factor-alpha, interleukin 6, interleukin 8, and C-reactive protein levels while increasing interleukin 10 release. Myocardial inhibitory kappa-B alpha was preserved with methylprednisolone (p < 0.05 versus placebo), but p38 mitogen-activated protein kinase activation occurred in both groups after CPB (p < 0.05 versus before CPB). Methylprednisolone improved postoperative cardiac index and was associated with decreased troponin T when compared with placebo (p < 0.05). Postoperative blood glucose, oxygen delivery index, and pulmonary shunt flow were increased in the methylprednisolone group (p < 0.05). There was no difference in postoperative oxygenation index, ventilation time, and clinical outcome between treatment groups. Glucocorticoid treatment before CPB attenuates perioperative release of systemic and myocardial inflammatory mediators and improves myocardial function, suggesting potential cardioprotective effects in patients undergoing cardiac surgery.

Levosimendan, a calcium-sensitizer with cardioprotective effects in patients with acute ischaemia undergoing cardiac surgery

1Department of Anaesthesiology, 2Department of Cardiac Surgery, Klinikum der Stadt Ludwigshafen, Ludwigshafen, Germany