Cardioprotective effect of boswellic acids against doxorubicin induced myocardial infarction in rats.

The aim of the present study was to evaluate the cardioprotective activity of boswellic acids in doxorubicin (DOX) induced cardiotoxicity. DOX (2.5mg/kg) was used intraperitoneally in rats to induce cardiotoxicity in six divided doses every alternate day over a period of two weeks. Dexrazoxane (10:1) was used as a standard drug. Boswellic acids (250, 500 and 750 mg/kg) were orally administered to rats for 14 days. After 14 days, rats were sacrificed, and blood was withdrawn through cardiac puncture. The blood lipid profile and cardiac biomarkers including LDH, CK-MB, CPK, SGOT and troponin T were measured. The heart of rats was isolated for histopathological studies. Graphpad Prism was used for statistical analysis. There was a significant increase in the level of cardiac enzymes and complete lipid profile parameters in diseased group as compared to control group. Pre-treatment with boswellic acids decreased level of all the measured parameters and decreased the severity of myocardial damage as supported by histopathological studies. It was concluded that boswellic acids possess cardioprotective potential by lowering cardiac biomarkers and blood lipid profile. Thus, boswellic acids might act as cardioprotective agent against doxorubicin induced cardiotoxicity.

Cerebral Perfusion Pressure Directed-Therapy Modulates Cardiac Dysfunction After Traumatic Brain Injury to Influence Cerebral Autoregulation in Pigs.

BACKGROUND: Traumatic brain injury (TBI) is an important contributor to morbidity and mortality. Low cerebral perfusion pressure (CPP, mean arterial pressure [MAP] minus intracranial pressure) after TBI is associated with cerebral ischemia, impaired cerebral autoregulation, and poor outcomes. Normalization of CPP and limitation of cerebral autoregulation impairment is a key therapeutic goal. However, some vasoactive agents used to elevate MAP such as phenylephrine (Phe) improve outcome in females but not male piglets after TBI while dopamine (DA) does so in both sexes. Clinical evidence has implicated neurological injuries as a cause of cardiac dysfunction, and we recently described cardiac dysfunction after TBI. Cardiac dysfunction may, in turn, influence brain health. One mechanism of myocyte injury may involve catecholamine excess. We therefore tested the hypothesis that TBI caused cardiac dysfunction and catecholamine excess which may reciprocally be modulated by vasoactive agent choice to normalize CPP and prevent impairment of cerebral autoregulation after injury. METHODS: TBI was produced in anesthetized pigs equipped with a closed cranial window, and Phe or DA administered to normalize CPP. RESULTS: Plasma cardiac enzymes troponin and creatine kinase and catecholamines epinephrine and norepinephrine were elevated by TBI, such release potentiated by Phe in males but blocked in female piglets and blocked in both sexes after DA. Cerebral autoregulation was impaired after TBI, worsened by Phe in males but protected in females and males treated with DA. Papaverine-induced dilation was unchanged by fluid percussion brain injury, DA, and Phe. CONCLUSIONS: These data indicate that pressor choice in elevation of CPP is important in limiting cardiac dysfunction and suggest that DA protects cerebral autoregulation in both sexes via reduction of cardiac biomarkers of injury and catecholamines released after TBI.

Everolimus Attenuates Myocardial Hypertrophy and Improves Diastolic Function in Heart Transplant Recipients.

Everolimus (EVL), one of the mammalian targets of rapamycin, is a next generation immunosuppressant that may have accessory anti-proliferative effects in heart transplant (HTx) recipients. However, little is known about the clinical relationship between EVL and regression of cardiac hypertrophy. A total of 42 HTx recipients received EVL therapy at post-HTx 150 days on median and had been followed at our institute for > 1 year between 2008 and 2014 [EVL (+) group]. We also observed 18 patients without EVL from post-HTx 150 days for 1 year [EVL (-) group]. There were no significant differences in baseline variables between the two groups. Left ventricular mass index (LVMI) and the ratio of early transmitral filling velocity to the peak early diastolic mitral annular motion velocity (E/e') decreased significantly during 1-year EVL treatment compared with the EVL (-) group. There were no differences in blood pressure and medications between the 2 groups. Improvement of LVMI and the E/e' ratio was not associated with trough levels of calcineurin inhibitors or EVL, but correlated with each baseline value. In conclusion, this EVL-incorporated immunosuppressant regimen attenuated cardiac hypertrophy as well as diastolic dysfunction in HTx recipients.

Effects of isoxsuprine hydrochloride on electrocardiographic and trace element status in sheeps.

OBJECTIVE: To study the effect of isoxsuprine hydrochloride on the ischaemic electrocardiographic change and trace element status in sheep. METHODS: This study was conducted from March 16 to 23, 2012, at Istanbul University, Turkey, and comprised sheep aged 6 months. The animals were divided into two equal groups. The control group was fed a standard diet and had free access to water. In the experimental group, isoxsuprine hydrochloride was injected at a dose of 0.6 mg/kg through the intramuscular route. Electrocardiographic changes, including creatine kinase and cardiac troponin-I, and serum levels of selenium, copper, calcium, magnesium, iron and zinc were investigated in healthy sheep. SPSS 15 was used for statistical analysis. RESULTS: The 14 sheep were divided into two groups of 7(50%) each. The overall mean weight of the study population was 35±10kg. Selenium, calcium, iron and zinc concentrations did not show any difference in serum samples (p>0.05). However, copper and magnesium concentrations decreased in serum after the administration of the drug (p<0.05). In the experimental group, ST segment depression and abnormal T-wave was found in 6(86%) animals within 60min. CONCLUSIONS: Isoxsuprine hydrochloride increased cardiotoxicity risk in sheep.

Allopurinol prevents cardiac and skeletal muscle damage in professional soccer players.

Xanthine oxidase (XO), a free radical-generating enzyme, is involved in tissue damage produced during exhaustive exercise. Our aim was to test whether allopurinol, a powerful inhibitor of XO, may be effective in preventing exercise-induced tissue damage in soccer players. Twelve soccer players were randomized into two experimental groups. One received allopurinol, before a match of the premier Spanish Football League, and the other placebo. Allopurinol prevented the exercise-induced increase in all the markers of skeletal muscle damage analyzed: creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and myoglobin. Creatine kinase-MB isoenzyme and highly sensitive troponin T, specific biomarkers of myocardial injury, increased significantly in the placebo but not in the allopurinol-treated group after the football match. We also found that the exercise-induced lipid peroxidation, as reflected by malondialdehyde measurements, was prevented after allopurinol administration. However, inhibition of XO did not prevent the increment in the activity of alanine aminotransferase found after the match. No changes in the serum gamma glutamyltransferase activity was found after the match on either the placebo and the allopurinol groups. These two enzymes were determined as biomarkers of liver injury. Allopurinol represents an effective and inexpensive pharmacological agent to prevent tissue damage in soccer players.

Beneficial role of spironolactone, telmisartan and their combination on isoproterenol-induced cardiac hypertrophy.

INTRODUCTION: Although spironolactone and telmisartan are reported to reduce the risk of morbidity and death, direct studies on their effects on isoproterenol-induced cardiac hypertrophy are scanty. Hence the present investigation was carried out to study the effect of spironolactone, telmisartan and their combination on isoproterenol-induced cardiac hypertrophy. METHODS: Isoproterenol was administered intra-peritoneally in a dose of 5 mg/kg once daily for 10 days to Wistar rats. Spironolactone (20 mg/kg/ day) (SL), telmisartan (5 mg/kg/day) (TM) or their combination (SLTM) was administered for 10 days after which various biochemical and cardiac parameters were measured. RESULTS: Isoproterenol produced dyslipidaemia, hypertension, elevated cardiac enzyme and C-reactive protein levels (CRP), worsened haemodynamic parameters and produced cardiac hypertrophy, left ventricular (LV) hypertrophy and oxidative stress. Chronic treatment with SL,TM or SLTM significantly controlled dyslipidaemia and produced a significant reduction in the elevated creatine-kinase (CK) and CRP levels. TM or SLTM produced a decrease in elevated lactate de-hydrogenase levels; however, SL failed to produce this effect. Hypotension, tachycardia, and decreased rate of pressure development and decay were prevented by SL, TM and SLTM treatment. Chronic treatment with SL, TM or SLTM also produced significant reduction in LV collagen levels, cardiac and LV hypertrophy index and prevented oxidative stress. CONCLUSIONS: Our data suggests that SL, TM and SLTM produced a beneficial effect on cardiac hypertrophy.

Effect of Inula racemosa root extract on cardiac function and oxidative stress against isoproterenol-induced myocardial infarction.

The cardioprotective potential of Inula racemosa root hydroalcoholic extract against isoproterenol-induced myocardial infarction was investigated in rats. The rats treated with isoproterenol (85 mg/kg, s.c.) exhibited myocardial infarction, as evidenced by significant (P < 0.05) decrease in mean arterial pressure, heart rate, contractility, relaxation along with increased left ventricular end diastolic pressure, as well as decreased endogenous myocardial enzymatic and non-enzymatic antioxidants. Isoproterenol also significantly (P < 0.05) induced lipid peroxidation and increased leakage of myocyte injury marker enzymes. Pretreatment with I. racemosa extract (50, 100 or 200 mg/kg per day, p.o.) for 21 consecutive days, followed by isoproterenol injections on days 19th and 20th significantly (P < 0.05) improved cardiac function by increasing the heart rate, mean arterial pressure, contractility and relaxation along with decreasing left ventricular end diastolic pressure. Pretreatment with I. racemosa also significantly (P < 0.05) restored the reduced form of glutathione and endogenous antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase from the heart, which were depleted after isoproterenol administration. In addition to restoration of antioxidants, I. racemosa significantly (P < 0.05) inhibited lipid peroxidation and prevented the leakage of myocytes specific marker enzymes creatine phosphokinase-MB and lactate dehydrogenase from the heart. Thus, it is concluded that I. racemosa protects heart from isoproterenol-induced myocardial injury by reducing oxidative stress and modulating hemodynamic and ventricular functions of the heart. Present study findings demonstrate the cardioprotective effect of I. racemosa and support the pharmacological relevance of its use and cardioprotection mechanism in ischemic heart disease as well as substantiate its traditional claim.

Myocarditis in hair dye poisoning.

A 16-year-old male presented to us after consuming hair dye with features of facial puffiness but normal respiratory parameters. His recorded ECGs revealed RBBB, supraventricular, ventricularextrasystoleandventricular tachycardia. Elevated CPK-MB and positive C-trophonin-Tconfirmed the myocardial damage. The patient died following cardiac arrest. This is a uncommon manifestation of para-phenylenediamine (PPD) poisoning. The aim of this report is to highlight the cardiac manifestation of PPD poisoning as this substance is used extensively and available freely.

Effects of rotigotine and rotigotine extended-release microsphere therapy on myocardial ischemic injury in mice.

Rotigotine is a dopamine receptor agonist that can improve motor function in Parkinson's disease (PD) patients. Rotigotine extended-release microsphere (RoMS) is an extended-release intramuscular formulation that exhibits a sustained release of rotigotine over a 14-day period. The clinical trials of RoMS has been carried out in USA and China. The purpose of this study is to observe the effects of RoMS therapy on myocardial ischemic injury in mice, to know whether RoMS alleviate or deteriorate the myocardial ischemic injury while PD patient has onset of myocardial ischemia concurrent after administered with RoMS. A mouse model of myocardial ischemia was established using isoproterenol, and mice were pretreated with rotigotine or RoMS before inducing myocardial ischemic injury. The effects of rotigotine or RoMS therapy on the degree of myocardial ischemic injury were studied by evaluating troponin I level, creatine kinase-MB (CK-MB) activity, and histopathological changes in cardiomyocytes. The dopamine receptor blocker chlorpromazine was used to further investigate the effects of rotigotine or RoMS on myocardial ischemic injury. Furthermore, serum rotigotine concentrations were also assayed. When myocardial ischemia occurred during rotigotine or RoMS administration, troponin I level and CK-MB activity were decreased, and ischemia-induced histopathological changes in cardiomyocytes were alleviated. The effects of rotigotine were maintained only 12 h and after that no protective effect was observed. RoMS releases continuously into the circulation after intramuscular injection. The cardioprotective effects of RoMS were maintained 14 days after a single RoMS administration. When combined with chlorpromazine, the protective effects of rotigotine on myocardial ischemic injury were eliminated, and the protective effects of RoMS were also partially abolished. In the animal model of myocardial ischemia, pretreatment with rotigotine or RoMS does not deteriorate, but can alleviate cardiomyocyte injury. Furthermore, RoMS pretreatment show long-term and continuous protective effects on cardiomyocyte injury. RoMS therapy in PD patients at high risk for cardiovascular diseases may attenuate the degree of cardiomyocyte injury caused by ischemia.

Total flavones of Rhododendron simsii Planch flower protect isolated rat heart from ischaemia-reperfusion injury and its mechanism of UTR-RhoA-ROCK pathway inhibition.

OBJECTIVES: Total flavones of Rhododendron simsii Planch flower (TFR) are an effective part extracted from the flower. The present study was designed to investigate the protective effect of TFR in isolated rat heart following global ischaemia-reperfusion and the possible underlying mechanisms. METHODS: Langendorff perfusion apparatus was used to perfuse isolated rat heart which was subjected to global ischaemia-reperfusion. The hemodynamic parameters were continuously monitored. Coronary flow as well as lactate dehydrogenase (LDH), creatine phosphokinase-MB (CK-MB) and cardiac troponin I (cTnI) in coronary effluents was measured. RhoA activity and urotensin receptor (UTR) and Rho-related coiled-coil-forming protein kinase (ROCK) protein expressions in rat myocardium were examined, respectively. Cardiac dysfunction was indicated by the alterations of hemodynamic parameters and the reduced coronary flow. KEY FINDINGS: Total flavones of Rhododendron simsii Planch flower significantly improved ischaemia-reperfusion-induced cardiac dysfunction and leakages of LDH, CK-MB and cTnI, and inhibited myocardial ischaemia-reperfusion-increased RhoA activity and UTR, ROCK1 and ROCK2 protein expressions. The improvement of TFR in the cardiac dysfunction and the leakage of LDH, CK-MB and cTnI were markedly attenuated under the UTR blockade and ROCK inhibition. TFR-inhibited RhoA activity was decreased under the UTR blockade. CONCLUSIONS: Total flavones of Rhododendron simsii Planch flower had a protective effect on ischaemia-reperfusion injury in isolated rat heart, which may be attributed to the blocking of UTR and subsequent inhibition of the RhoA-ROCK pathway.

Alprostadil attenuates myocardial ischemia/reperfusion injury by promoting antioxidant activity and eNOS activation in rats.

PURPOSE: To investigate the effect of alprostadil on myocardial ischemia/reperfusion (I/R) in rats. METHODS: Rats were subjected to myocardial ischemia for 30 min followed by 24h reperfusion. Alprostadil (4 or 8 µg/kg) was intravenously administered at the time of reperfusion and myocardial infarct size, levels of troponin T, and the activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in the serum were measured. Antioxidative parameters, nitric oxide (NO) content and phosphorylated endothelial nitric oxide synthase 3 (p-eNOS) expression in the left ventricles were also measured. Histopathological examinations of the left ventricles were also performed. RESULTS: Alprostadil treatment significantly reduced myocardial infarct size, serum troponin T levels, and CK-MB and LDH activity (P<0.05). Furthermore, treatment with alprostadil significantly decreased malondialdehyde (MDA) content (P<0.05) and markedly reduced myonecrosis, edema and infiltration of inflammatory cells. Superoxide dismutase and catalase activities (P<0.05), NO level (P<0.01) and p-eNOS (P<0.05) were significantly increased in rats treated with alprostadil compared with control rats. CONCLUSION: These results indicate that alprostadil protects against myocardial I/R injury and that these protective effects are achieved, at least in part, via the promotion of antioxidant activity and activation of eNOS.

Measuring aspirin resistance, clopidogrel responsiveness, and postprocedural markers of myonecrosis in patients undergoing percutaneous coronary intervention.

Aspirin and clopidogrel are proven to prevent thromboembolic events during percutaneous coronary intervention (PCI). Enzyme release of creatine kinase-MB (CK-MB) enzyme during PCI has been associated with an increased risk of future adverse cardiac events. This study examined the correlation between measurements of aspirin resistance and the level of inhibition of the thienopyridine-specific P2Y12 platelet receptor and CK-MB release after PCI. We prospectively studied 330 patients with elective PCI treated with drug-eluting stents. Patients were pretreated with aspirin and clopidogrel. Patients with positive CK-MB or acute coronary syndrome and those on glycoprotein IIb/IIIa inhibitors were excluded. Serum assays of aspirin resistance (Ultegra Rapid Platelet Function Assay-ASA, Accumetrics) and clopidogrel resistance (Rapid Platelet Function Assay P2Y12, Accumetrics) were performed before PCI. Serum troponinI and CK-MB levels were measured at 8, 16, and 24 hours after PCI. Aspirin resistance unit (ARU) measurement > or =550 was detected in 12 patients (3.7%). Mean platelet reactivity unit (PRU; measurement of inhibition of P2Y12 activity) was 192.2 +/- 95.4 (lower PRU, more inhibition of P2Y12 receptor). There was no correlation between level of ARU or PRU and troponin I or CK-MB release after PCI at any time point. Only multivessel coronary disease was found to be a predictor of any increase in CK-MB in a multivariate analysis (odds ratio 2.2, 95% confidence interval 1.4 to 3.3, p = 0.0003). A positive correlation was found between levels of ARU and PRU. Target vessel revascularization/major adverse cardiac event rate at 6 months was 8.2% with no correlation between ARU or PRU and release of cardiac enzymes or occurrence of adverse cardiac events. In conclusion, this study does not support routine measurements of aspirin and clopidogrel resistance in stable patients undergoing PCI.

Does pravastatin therapy affect cardiac enzyme levels after percutaneous coronary intervention?

Serum cardiac enzyme elevation after percutaneous coronary intervention (PCI), a relatively common complication, is a prognostic determinant of long-term outcome in patients who undergo these procedures. Statins are postulated to reduce such complications. This study investigated the short-term effects of pravastatin on serum creatine kinase myocardial isoform (CK-MB) and serum cardiac troponin I (cTpI) levels after elective PCI. Of 93 patients studied, 72 (77.4%) were men, and 21 (22.6%) were women (mean age, 58.9+/-11.0 y). Patients were randomly divided into 3 groups before they underwent elective PCI. Preoperatively, group 1 patients (n=30) received pravastatin 10 mg/d, and group 2 patients (n=29) received pravastatin 40 mg/d. Control group patients (n=34) received no lipid-lowering medication. Serum CK-MB and serum cTpI levels were measured preoperatively and then again at 6, 24, and 36 h postoperatively. Demographic features of patients and characteristics of the PCI procedure, including number of vessels/lesions and duration and number of inflations, did not differ among groups (P>.05). Mean serum CK-MB and serum cTpI levels were significantly increased after PCI in all patients (P<.001). When compared with control group patients, those given pravastatin did not experience significantly lowered postprocedural serum CK-MB or serum cTpI levels (P>.05). Preprocedural pravastatin therapy at dosages of 10 mg/d and 40 mg/d seems inadequate for preventing serum cardiac enzyme elevations during short-term follow-up after PCI. Additional research on this topic is recommended.

Punicalagin Pretreatment Attenuates Myocardial Ischemia-Reperfusion Injury via Activation of AMPK.

Punicalagin (PUN), a major bioactive component in pomegranate juice, has been proven to exert neuroprotective effects against cerebral ischemia/reperfusion (I/R) insult via anti-oxidant properties. This study aims to investigate whether PUN provides cardioprotection against myocardial I/R (MI/R) injury and the underlying mechanisms. PUN (30[Formula: see text]mg/kg/d) or vehicle was intragastrically administered to Sprague-Dawley rats for one week before the operation. MI/R was induced by ligating the left anterior descending coronary artery for 30[Formula: see text]min and subsequent reperfusion for 3[Formula: see text]h. PUN pretreatment conferred cardioprotective effects against MI/R injury by improving cardiac function, limiting infarct size, reducing serum creatine kinase-MB and lactate dehydrogenase activities, and suppressing cardiomyocyte apoptosis. Moreover, PUN pretreatment inhibited I/R-induced myocardial oxidative stress as evidenced by decreased generation of superoxide content and malonaldialdehyde formation and increased antioxidant capability. Furthermore, PUN pretreatment increased adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation in I/R hearts. AMPK inhibitor compound c inhibited PUN-enhanced AMPK phosphorylation, and blunted PUN-mediated anti-oxidative effects and cardioprotection. These results indicate for the first time that PUN pretreatment protect against I/R-induced oxidative stress and myocardial injury via activation of AMPK.

Nicorandil reduces the incidence of minor cardiac marker elevation after coronary stenting.

BACKGROUND: Minor cardiac marker elevation after percutaneous coronary intervention has long-term prognostic significance. We examined whether nicorandil, a nicotinamide-nitrate ester, reduces the incidence of minor cardiac marker elevation after coronary stenting. METHODS: Patients (n=192) undergoing coronary stenting were randomly assigned to receive nicorandil (nicorandil group, n=91) or vehicle (control group, n=101). Nicorandil (2 mug/kg/min, intravenously) was administered immediately after the patients were transferred into the catheterization laboratory and continued for 6 h. We measured the serum concentrations of creatine kinase isoenzyme MB (CK-MB) before, immediately after, and 6, 12, and 24 h after the procedure, and those of cardiac troponin T (cTnT) 24 h after the procedure. RESULTS: There was no significant difference in clinical background between the 2 groups. The nicorandil group showed a significantly lower incidence of CK-MB elevation (>1x upper limit of control range, 20 IU/l) than the control group (8.8% vs 21.8%, p<0.05). The levels of serum CK-MB in the nicorandil group were significantly lower than those in the control group (13.4+/-5.7 vs 16.5+/-9.7 IU/l, p<0.01). Similarly, the nicorandil group showed a significantly lower incidence of cTnT elevation [>1x (0.1 ng/ml) or >2x (0.2 ng/ml)] upper limit of control range than the control group (14.3% vs 26.7%, p<0.05, or 7.7% vs 17.8%, p<0.05). Serum cTnT levels were also significantly lower in the nicorandil group than in the control group (0.05+/-0.10 vs 0.15+/-0.36 ng/ml, p<0.05). CONCLUSIONS: The results demonstrated that nicorandil reduces minor cardiac marker elevation after coronary stenting.

Puerarin attenuates severe burn-induced acute myocardial injury in rats.

BACKGROUND: Puerarin, the main isoflavone glycoside extracted from the root of Pueraria lobata, is widely prescribed for patients with cardiovascular disorders in China. This study investigates the effect of puerarin on severe burn-induced acute myocardial injury in rats and its underlying mechanisms. MATERIALS AND METHODS: Healthy adult Wistar rats were divided into three groups: (1) sham group, sham burn treatment; (2) burn group, third-degree burns over 30% of the total body surface area (TBSA) with lactated Ringer's solution for resuscitation; and (3) burn plus puerarin group, third-degree burns over 30% of TBSA with lactated Ringer's solution containing puerarin for resuscitation. The burned animals were sacrificed at 1, 3, 6, 12, and 24 h after burn injury. Myocardial injury was evaluated by analyzing serum creatine kinase MB fraction (CK-MB) activity and cardiac troponin T (cTNT) level. Changes in cardiomyocyte ultrastructure were also determined using a transmission electron microscope. Tumor necrosis factor (TNF)-α concentration in serum was measured by radioimmunoassay. Cardiac myeloperoxidase (MPO) activity and malondialdehyde (MDA) concentration were measured to determine neutrophil infiltration and oxidative stress in the heart, respectively. The expression of p38 mitogen-activated protein (MAP) kinase in the heart was determined by Western blot analysis. RESULTS: After the 30% TBSA full-thickness burn injury, serum CK-MB activities and cTnT levels increased markedly, both of which were significantly decreased by the puerarin treatment. The level of serum TNF-α concentration in burn group at each time-point was obviously higher than those in sham group (1.09±0.09 ng/ml), and it reached the peak value at 12 h post burn. Burn trauma also resulted in worsen ultrastructural condition, elevated MPO activity and MDA content in heart tissue, and a significant activation of cardiac p38 MAP kinase. Administration of puerarin improved the ultrastructural changes in cardiomyocytes, decreased TNF-α concentration in serum as well as suppressed cardiac MPO activity and reduced MDA content, and abolished the activation of p38 MAP kinase in heart tissue after severe burn. CONCLUSIONS: These results suggest that puerarin attenuates inflammatory responses, reduces neutrophil infiltration and oxidative stress in the heart, and protects against acute myocardial injury induced by severe burn.

Quantification of the effect of clopidogrel on enzymatic infarct size related to a percutaneous coronary intervention in patients with acute coronary syndromes: insights from the CHAMPION percutaneous coronary intervention trial.

OBJECTIVES: Using data from the CHAMPION percutaneous coronary intervention (PCI), we determined the relationship between clopidogrel started at least 5 days before PCI (maintenance of clopidogrel) and PCI-related enzymatic infarct size. BACKGROUND: Clopidogrel is recommended in patients with acute coronary syndrome (ACS) managed with PCI, but its effect on PCI-related myonecrosis in contemporary patients has not been quantified. PATIENTS AND METHODS: Patients with ACS (with or without ST-segment elevation) who underwent PCI and had at least three creatine kinase-MB (CK-MB) samples after PCI were included. Enzymatic infarct size was defined as the peak CK-MB concentration indexed by its upper limit of normal. Associations between maintenance clopidogrel and enzymatic infarct size were explored using multivariable linear regression (with and without missing data imputation) and propensity score analysis using inverse probability weighting. RESULTS: Of 8877 patients randomized, 6327 (71.3%) were included (median age 61 years, 73% male, 13% ACS with ST-segment elevation). Of these 6327 patients, 2015 (31.8%) were on maintenance clopidogrel. After multivariable adjustment, maintenance clopidogrel was associated with a reduction in enzymatic infarct size {ß=-0.63; 47% decrease in peak CK-MB [95% confidence interval (CI) 35, 56%]}. Multivariable linear regression with multiple imputations and inverse probability weighting propensity score analysis yielded similar results, with maintenance clopidogrel associated with 44% (95% CI 33, 53%) and 29% (95% CI 24, 33%) infarct size reductions. CONCLUSION: In this subgroup analysis of modern ACS patients, clopidogrel maintenance was independently associated with smaller enzymatic infarct size after PCI. These results are consistent with previous observations suggesting a benefit of clopidogrel on the procedural outcome and quantify this benefit.

Alprostadil attenuates myocardial ischemia/reperfusion injury by promoting antioxidant activity and eNOS activation in rats

Abstract Purpose: To investigate the effect of alprostadil on myocardial ischemia/reperfusion (I/R) in rats. Methods: Rats were subjected to myocardial ischemia for 30 min followed by 24h reperfusion. Alprostadil (4 or 8 μg/kg) was intravenously administered at the time of reperfusion and myocardial infarct size, levels of troponin T, and the activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in the serum were measured. Antioxidative parameters, nitric oxide (NO) content and phosphorylated endothelial nitric oxide synthase 3 (p-eNOS) expression in the left ventricles were also measured. Histopathological examinations of the left ventricles were also performed. Results: Alprostadil treatment significantly reduced myocardial infarct size, serum troponin T levels, and CK-MB and LDH activity (P<0.05). Furthermore, treatment with alprostadil significantly decreased malondialdehyde (MDA) content (P<0.05) and markedly reduced myonecrosis, edema and infiltration of inflammatory cells. Superoxide dismutase and catalase activities (P<0.05), NO level (P<0.01) and p-eNOS (P<0.05) were significantly increased in rats treated with alprostadil compared with control rats. Conclusion: These results indicate that alprostadil protects against myocardial I/R injury and that these protective effects are achieved, at least in part, via the promotion of antioxidant activity and activation of eNOS.

Effect of high bolus dose tirofiban on the inflammatory response following percutaneous coronary intervention.

BACKGROUND: Tirofiban at the bolus dose of 10 microg/kg does not suppress the inflammatory response following percutaneous coronary intervention (PCI). This may be due to less than optimal inhibition of platelet aggregation. High bolus dose tirofiban (25 microg/kg) allows better inhibition of platelet aggregation but its anti-inflammatory effect remains unknown. HYPOTHESIS: High bolus dose tirofiban exhibits anti-inflammatory activity. METHODS: A total of 100 patients referred for PCI were randomized to receive high bolus dose tirofiban followed by a 24-h infusion or a bolus and an infusion of saline. Patients with elevated troponin or with thrombus in the culprit lesion were excluded. Inflammatory markers were measured at baseline and at 24 h. RESULTS: Levels of soluble CD40 ligand (sCD40L) were not affected by PCI while those of interleukin-6 (IL-6) and of high sensitivity C-reactive protein (hs-CRP) significantly increased. Despite inhibiting platelet's aggregation by > 90%, tirofiban did not suppress the rise of IL-6 and hs-CRP. Median (interquartile range) elevation of IL-6 was 0.6 pg/mL (-1.5-3.6) versus 0.4 pg/mL (-0.7-1.8) and that of hs-CRP was 2.1 mg/L (0.7-5.2) versus 2.4 mg/L (1-4.7) in the tirofiban and the control groups, respectively (p = ns). However, in patients with diabetes mellitus, tirofiban significantly suppressed the rise of hs-CRP by 65% (p = 0.01), but did not significantly affect the rise of IL-6. CONCLUSION: In low-risk patients undergoing PCI, tirofiban did not attenuate the rise of inflammatory markers. However, the significant effect in diabetics suggests that tirofiban may have anti-inflammatory activity in higher risk patients.

The effects of low dose N-acetylcysteine (NAC) as an adjunct to cardioplegia in coronary artery bypass surgery.

OBJECTIVE: We aimed to evaluate the efficacy of low dose N-acetylcysteine (NAC) against myocardial ischemia-reperfusion damage in coronary artery bypass surgery accompanied by cardiopulmonary bypass (CPB). METHODS: Thirty patients operated due to triple coronary artery disease were enrolled into this prospective randomized study (control group -n=15 and NAC group - n=15). N-acetylcysteine was added to induction cardioplegia solution in dose of 4 mmol/l and in dose of 2 mmol/l to maintenance cardioplegia solution in the NAC group. Hemodynamic measurements were performed before and after anesthesia with different intervals. Creatine kinase-MB (CK-MB) levels were analyzed during 24 hours postoperatively. Blood samples were obtained from coronary sinus before CPB (T1), just before the cross-clamp removed (T2) and 30 minutes later (T3). Malondialdehyde (MDA), glutathione peroxidase (GSH-Px), nitric oxide (NO) levels and neutrophil percentage were determined. Statistical analysis was performed using student's t test, Chi-square and two-way ANOVA tests. RESULTS: There were no significant differences between the two groups with regard to the hemodynamic parameters, and CK-MB levels. The MDA levels were significantly lower in NAC group than in control group during reperfusion period (0.75 nmol/l vs 0.88 nmol/l, p<0.05). Neutrophil percentage in coronary sinus blood was significantly lower in NAC group than in control group during the reperfusion period (77.6% vs 82.7%, p<0.05). The GSH-Px and NO levels were also not statistically different between groups. CONCLUSION: Low dose NAC as an adjunct to cardioplegic solutions effectively reduces myocardial oxidative stress in coronary bypass surgery with cardiopulmonary bypass, but may not restore the myocardial injury.