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Ginsenosides, major active ingredients of Panax ginseng, that exhibit various pharmacological and physiological actions are transformed into compound K (CK) or M4 by intestinal microorganisms. CK is a metabolite derived from protopanaxadiol (PD) ginsenosides, whereas M4 is a metabolite derived from protopanaxatriol (PT) ginsenosides. Recent reports shows that ginsenosides might play a role as pro-drugs for these metabolites. In present study, we investigated the effect of bovine serum albumin (BSA), which is one of major binding proteins on various neurotransmitters, hormones, and other pharmacological agents, on ginsenoside Rg2-, CK-, or M4-induced regulation of α3β4 nicotinic acetylcholine (ACh) receptor channel activity expressed in Xenopus oocytes. In the absence of BSA, treatment of ACh elicited inward peak current ( l ACh) in oocytes expressing α3β4 nicotinic ACh receptor. Co-treatment of ginsenoside Rg2, CK, or M4 with ACh inhibited l ACh in oocytes expressing α3β4 nicotinic ACh receptor with reversible and dose-dependent manner. In the presence of 1% BSA, treatment of ACh still elicited l ACh in oocytes expressing α3β4 nicotinic ACh receptor and co-treatment of ginsenoside Rg2 or M4 but not CK with ACh inhibited l ACh in oocytes expressing α3β4 nicotinic ACh receptor with reversible and dose-dependent manner. These results show that BSA interferes the action of CK rather than M4 on the inhibitory effect of l ACh in oocytes expressing α3β4 nicotinic ACh receptor and further suggest that BSA exhibits a differential interaction on ginsenoside metabolites. [ABSTRACT FROM AUTHOR]

: ObjectivesThis study evaluated myocardial function in relation to high-energy phosphate (HEP) metabolism in asymptomatic patients with uncomplicated type 2 diabetes mellitus using magnetic resonance (MR) techniques.: BackgroundMyocardial dysfunction may occur in patients with type 2 diabetes mellitus in the absence of coronary artery disease or left ventricular (LV) hypertrophy. The mechanisms underlying this diabetic cardiomyopathy are largely unknown, but may involve altered myocardial energy metabolism.: MethodsWe assessed myocardial systolic and diastolic function and HEP metabolism in 12 asymptomatic normotensive male patients with recently diagnosed, well-controlled type 2 diabetes and 12 controls, using MR imaging and phosphorus-31-nuclear MR spectroscopy (31P-MRS) on a 1.5 T clinical scanner; 31P-MR spectra were quantified, and myocardial HEP metabolism was expressed as phosphocreatine to adenosine-triphosphate (PCr/ATP) ratio.: ResultsNo differences were found in LV mass and systolic function between patients and controls. However, early (E) acceleration peak, deceleration peak, peak filling rate, and transmitral early-to-late diastolic peak flow (E/A) ratio, all indexes of diastolic function, were significantly decreased in patients compared with controls (p < 0.02). In addition, myocardial PCr/ATP in patients was significantly lower than in controls (1.47 vs. 1.88, p < 0.01). Inverse associations were found between myocardial PCr/ATP and E acceleration peak, E deceleration peak, and E peak filling rate (all, p < 0.05).: ConclusionsThese results indicate that altered myocardial energy metabolism may contribute to LV diastolic functional changes in patients with recently diagnosed, well-controlled and uncomplicated type 2 diabetes. [Copyright &y& Elsevier]

: ObjectivesThe purpose of this paper is to examine the incidence and determinants of permanent complete heart block (CHB) after nonsurgical septal reduction therapy (NSRT), and to evaluate the clinical impact of permanent pacemaker (PPM) placement.: BackgroundNonsurgical septal reduction therapy with ethanol improves the clinical and hemodynamic parameters in patients with symptomatic hypertrophic obstructive cardiomyopathy. Complete heart block is a common complication after NSRT.: MethodsThe database of 261 consecutive patients who underwent NSRT at Baylor College of Medicine was reviewed. Clinical variables that were considered as possible determinants for CHB after NSRT were: age, gender, New York Heart Association (NYHA) functional class, left ventricular outflow tract (LVOT) gradient at rest or with provocation, septal thickness, and baseline exercise duration. For electrocardiographic (ECG) variables, the presence of first-degree atrioventricular (AV) block, bifascicular block, left bundle branch block, atrial fibrillation, and left ventricular hypertrophy were analyzed. In addition, the volume of ethanol injected, the method of administration of ethanol (i.e., bolus vs. slow injection [over 30 to 60 s]), number of septal arteries occluded, use of myocardial echocardiography, and infarct size as determined by peak creatine kinase level.: ResultsOf 261 consecutive patients, 37 had PPM or automatic implantable cardiac defibrillator placed before NSRT. Of the remaining 224 patients, 31 (14%) developed CHB after the procedure. Multivariate logistic regression analysis showed that female gender (odds ratio [OR] 4.3; p = 0.02), bolus injection of ethanol (OR 51; p = 0.004), injecting more than one septal artery (OR 4.6; p = 0.016), the presence of left bundle branch block (OR 39; p = 0.002), and first-degree AV block (OR 14; p = 0.001) on the baseline ECG are independent predictors of CHB after NSRT. Patients requiring PPM placement had a similar improvement in their NYHA functional class, septal thickness reduction, LVOT gradient reduction, and improvement of exercise capacity when compared with patients who did not require pacing.: ConclusionsMultiple demographic, electrocardiographic, and technical factors seem to increase the risk of CHB after NSRT. Patients with CHB after NSRT derive similar clinical and hemodynamic benefit to patients who did not require permanent pacing. [Copyright &y& Elsevier]

: ObjectivesWe sought to determine whether intrinsic mitochondrial function and regulation were altered in heart transplant recipients (HTRs) and to investigate the response of mitochondrial function to six-week endurance training in these patients.: BackgroundDespite the normalization of central oxygen transport during exercise, HTRs are still characterized by limited exercise capacity, which is thought to result from skeletal muscle metabolic abnormalities.: MethodsTwenty HTRs agreed to have vastus lateralis biopsies and exercise testing: before and after training for 12 of them and before and after the same control period for eight subjects unwilling to train. Mitochondrial respiration was evaluated on saponin-permeabilized muscle fibers in the absence or presence (maximum respiration rate [Vmax]) of saturating adenosine diphosphate.: ResultsMitochondrial function was preserved at the level of sedentary subjects in untrained HTRs, although they showed 28 ± 5% functional aerobic impairment (FAI). After training, Vmax, citrate synthase, cytochrome c oxidase, and mitochondrial creatine kinase (CK) activities were significantly increased by 48%, 40%, 67%, and 53%, respectively (p < 0.05), whereas FAI decreased to 12 ± 5% (p < 0.01). The control of mitochondrial respiration by creatine and mitochondrial CK was also improved (p < 0.01), suggesting that phosphocreatine synthesis and transfer by the mitochondrial CK become coupled to oxidative phosphorylation, as shown in trained, healthy subjects.: ConclusionsIn HTRs, the mitochondrial properties of skeletal muscle were preserved and responded well to training, reaching values of physically active, healthy subjects. This suggests that, in HTRs, immunosuppressive drugs do not alter the intrinsic muscle oxidative capacities and that the patients’ physical handicap results from nonmitochondrial mechanisms. [Copyright &y& Elsevier]

: ObjectivesWe sought to identify patient and hospital features associated with early glycoprotein (GP) IIb/IIIa inhibitor therapy for non–ST-elevation (NSTE) myocardial infarction (MI) and to relate this treatment to in-hospital outcomes.: BackgroundGlycoprotein IIb/IIIa inhibitors have improved outcomes in randomized trials of NSTE MI, leading national treatment guidelines to recommend their use. Their actual use, safety, and effectiveness have not been well characterized beyond trial populations.: MethodsWe studied 60,770 patients with NSTE MI treated between July 2000 and July 2001 at 1,189 hospitals in a U.S. registry. Using logistic regression, we identified patient and hospital features associated with GP IIb/IIIa inhibition within 24 h after presentation. We also compared outcomes by early treatment versus no treatment after adjusting for patient and hospital characteristics and treatment propensity.: ResultsOnly 25% of eligible patients received early GP IIb/IIIa therapy. Elderly patients, women, minority patients, and those without private insurance received such therapy less often than their counterparts. Treated patients had lower unadjusted in-hospital mortality (3.3% vs. 9.6%, p < 0.0001) remaining significantly lower after adjustment for patient risk, treatment propensity, and hospital characteristics (adjusted odds ratio, 0.88; 95% confidence interval, 0.79 to 0.97). Hospitals that adopted early GP IIb/IIIa inhibition more rapidly also had lower adjusted mortality rates than those slower to adopt such therapy.: ConclusionsGlycoprotein IIb/IIIa inhibitor therapy appears to be underused in early management of NSTE MI patients. Because this therapy is associated with better outcomes, it represents a target for quality improvement. [Copyright &y& Elsevier]

: ObjectivesWe hypothesized that early recurrent myocardial infarction (MI) following fibrinolytic administration would be assessed with higher mortality at both 30 days and 2 years.: BackgroundAlthough early recurrent MI after fibrinolytic therapy has been associated with increased early mortality in the acute MI setting, its relation to long-term mortality has not been fully explored.: MethodsMortality data were ascertained in 20,101 patients enrolled in the Thrombolysis In Myocardial Infarction (TIMI) 4, 9, and 10B and Intravenous NPA for the Treatment of Infarcting Myocardium Early (InTIME-II) acute MI trials.: ResultsThe frequency of symptomatic recurrent MI during the index hospitalization was 4.2% (836/20,101). Recurrent MI during the index hospital period was associated with increased 30-day mortality (16.4% [137/836] vs. 6.2% [1,188/19,260], p < 0.001). Likewise, recurrent MI was associated with a sustained increase in mortality up to two years, even after adjustments were made for covariates known to be associated with mortality and recurrent MI (hazard ratio 2.11, p < 0.001). However, this higher mortality at 2 years was due to an early divergence in mortality by 30 days and was not due to a significant increase in late mortality between 30 days and 2 years (4.38% [31/707] vs. 3.76% [685/18,206], p = NS). Percutaneous coronary intervention during the index hospitalization was associated with a lower rate of in-hospital recurrent MI (1.6% vs. 4.5%, p < 0.001) and lower two-year mortality (5.6% vs. 11.6%, p < 0.001). Performance of coronary artery bypass graft surgery was also associated with a lower recurrent rate of MI (0.7% vs. 4.3%, p < 0.001) and lower two-year mortality rate (7.95% vs. 10.6%, p = 0.0008).: ConclusionsEarly recurrent MI is associated with increased mortality up to two years. However, most deaths occur early, and the risk of additional deaths between the index hospital period and two years was not significantly increased among patients with recurrent MI. Percutaneous coronary intervention during the index hospitalization was associated with a lower risk of recurrent MI and a lower risk of two-year mortality. [Copyright &y& Elsevier]

: ObjectivesWe conducted a pilot study to evaluate the feasibility of transendocardial delivery of autologous bone marrow (ABM) strategy in patients with severe symptomatic chronic myocardial ischemia not amenable to conventional revascularization.: BackgroundTransendocardial injection of ABM cells appears to enhance perfusion of ischemic porcine myocardium.: MethodsTen patients underwent transendocardial injection of freshly aspirated and filtered unfractionated ABM using left ventricular electromechanical guidance. Twelve injections of 0.2 ml each were successfully delivered into ischemic noninfarcted myocardium pre-identified by single-photon emission computed tomography perfusion imaging.: ResultsAutologous bone marrow injection was successful in all patients and was associated with no serious adverse effects; in particular, there was no arrhythmia, evidence of infection, myocardial inflammation, or increased scar formation. Two patients were readmitted for recurrent chest pain. At three months, Canadian Cardiovascular Society angina score significantly improved (3.1 ± 0.3 vs. 2.0 ± 0.94, p = 0.001), as well as stress-induced ischemia occurring within the injected territories (2.1 ± 0.8 vs. 1.6 ± 0.8, p < 0.001). Treadmill exercise duration, available in nine patients, increased, but the change was not significant (391 ± 155 vs. 485 ± 198, p = 0.11).: ConclusionsThis study provides preliminary clinical data indicating feasibility of catheter-based transendocardial delivery of ABM to ischemic myocardium. [Copyright &y& Elsevier]

: ObjectivesThe purpose of this study was to determine the characteristics and outcomes of patients with acute myocardial infarction (MI) complicated by cardiogenic shock due to predominant right ventricular (RV) infarction.: BackgroundAlthough RV infarction has been shown to have favorable long-term outcomes, the influence of RV infarction on mortality in cardiogenic shock is unknown.: MethodsWe evaluated 933 patients in cardiogenic shock due to predominant RV (n = 49) or left ventricular (LV) failure (n = 884) in the SHould we emergently revascularize Occluded coronaries for Cardiogenic shocK? (SHOCK) trial registry.: ResultsPatients with predominant RV shock were younger, with a lower prevalence of previous MI (25.5 vs. 40.1%, p = 0.047), anterior MI, and multivessel disease (34.8 vs. 77.8%, p < 0.001) and a shorter median time between the index MI and the diagnosis of shock (2.9 vs. 6.2 h, p = 0.003) in comparison to patients with LV shock. In-hospital mortality was 53.1% versus 60.8% (p = 0.296) for patients with predominant RV and LV shock, respectively, and the influence of revascularization on mortality was not different between groups. Multivariate analysis revealed that RV shock was not an independent predictor of lower in-hospital mortality (odds ratio 1.07, 95% confidence interval 0.54 to 2.13).: ConclusionsDespite the younger age, lower rate of anterior MI, and higher prevalence of single-vessel coronary disease of RV compared with LV shock patients, and their similar benefit from revascularization, mortality is unexpectedly high in patients with predominant RV shock and similar to patients with LV shock. [Copyright &y& Elsevier]

: ObjectivesWe tested the hypothesis that thinner-strut stents are associated with a reduced rate of restenosis when comparing two stents with different design.: BackgroundWe have previously shown that, for two stents with similar design, the risk for restenosis is dependent on the strut thickness. It is unknown whether strut thickness preserves its relevance as a determinant of restenosis even in the presence of different stent designs.: MethodsA total of 611 patients with symptomatic coronary artery disease were randomly assigned to receive either the thin-strut ACS RX Multilink stent (Guidant, Advanced Cardiovascular Systems, Santa Clara, California) (strut thickness 50 μm, interconnected ring design; n = 309) or the thick-strut BX Velocity stent (Cordis Corp., Miami, Florida) (strut thickness 140 μm, closed cell design; n = 302). The primary end point was angiographic restenosis (≥50% diameter stenosis at follow-up angiography). Secondary end points were the incidence of target-vessel revascularization (TVR) and the combined rate of death and myocardial infarction (MI) at one year.: ResultsThe incidence of angiographic restenosis was 17.9% in the thin-strut group and 31.4% in the thick-strut group, relative risk, 0.57 (95% confidence interval, 0.39 to 0.84), p < 0.001. A TVR due to restenosis was required in 12.3% of the thin-strut group and 21.9% of the thick-strut group, relative risk, 0.56 (95% confidence interval, 0.38 to 0.84), p = 0.002. No significant difference was observed in the combined incidence of death and MI at one year.: ConclusionsWhen two stents with different design are compared, the stent with thinner struts elicits less angiographic and clinical restenosis than the thicker-strut stent. [Copyright &y& Elsevier]

: ObjectivesThe aim of the present study was to compare clopidogrel and ticlopidine after coronary stenting with regard to cardiovascular death during long-term follow-up.: BackgroundRandomized trials comparing clopidogrel and ticlopidine with a restricted use of intravenous glycoprotein IIb/IIIa inhibition have reported a trend toward a higher incidence of thrombotic stent occlusion with clopidogrel at 30 days.: MethodsAfter successful coronary stent implantation, 700 patients with 899 lesions were randomly assigned to receive a four-week course of either 500 mg ticlopidine (n = 345) or 75 mg clopidogrel (n = 355) in addition to 100 mg aspirin. Cardiovascular death was the primary end point and was recorded during a median follow-up period of 28 months.: ResultsCardiovascular death occurred in eight patients with ticlopidine versus 26 patients with clopidogrel (hazard ratio with ticlopidine compared with clopidogrel, 0.30; 95% confidence interval [CI], 0.14 to 0.66; p = 0.003). After adjustment for co-variables, ticlopidine reduced the risk of cardiovascular death by 63% compared with clopidogrel. The combined end point of cardiovascular death or nonfatal myocardial infarction was present in 19 patients assigned ticlopidine, compared with 40 patients assigned clopidogrel (hazard ratio, 0.45; p = 0.005). The hazard ratio for all-cause mortality with ticlopidine as compared with clopidogrel was 0.30 (95% CI, 0.14 to 0.64; p = 0.002).: ConclusionsAfter the placement of coronary artery stents in unselected patients, ticlopidine was associated with a significantly lower mortality than clopidogrel. This raises concern about the current practice of substituting clopidogrel for ticlopidine after stenting and highlights the need for further long-term studies. [Copyright &y& Elsevier]

: ObjectivesThis study was designed to investigate the impact of percutaneous coronary interventions (PCIs) in degenerated saphenous vein grafts (SVGs) without distal embolic protection.: BackgroundDistal embolic protection devices have been shown to reduce the incidence of no reflow/slow flow during PCI of de novo lesions in degenerated SVGs. It is unclear whether PCI of in-stent restenosis (ISR) lesions in degenerated SVGs is associated with no reflow/slow flow and whether distal embolic protection is beneficial in these cases as well.: MethodsWe studied 54 consecutive patients with treated ISR lesions in degenerated SVGs who underwent PCI without distal embolic protection in a single center. Procedural and in-hospital outcomes were examined.: ResultsThe average age was 71 ± 8 years; 32% of the patients had diabetes. The mean lesion length was 13 ± 6 mm and the procedural success rate was 98% (53/54). Cutting balloon angioplasty was used in 46% (25/54) of cases, and a new stent was inserted in 46% (25/54) of patients. Gamma brachytherapy was performed in 19% (10/54) of patients. During the procedure there were no episodes of no reflow/slow flow, and there were no patients with in-hospital Q-wave or non–Q-wave myocardial infarction. There was one in-hospital noncardiac death.: ConclusionsIn this consecutive series of patients with ISR of degenerated SVGs undergoing PCI without distal protection, there were no episodes of slow flow/no reflow and no procedure-related myocardial infarctions. It appears that distal embolic protection may not be necessary during PCI of ISR lesions in degenerated SVGs. [Copyright &y& Elsevier]

The activities of NAD- and NADP-dependent dehydrogenases and creatine kinase were compared in extracts of spermatozoa from herring (Clupea harengus), carp (Cyprinus carpio) and catfish (Clarias gariepinus). The activity of malic enzyme in herring spermatozoa was approximately 5 and 36 times higher than in carp and catfish spermatozoa. In contrast, lactate dehydrogenase activity in herring spermatozoa was very low. Herring spermatozoa possess two isoenzymes of lactate dehydrogenase: LDH-A2B2 and LDH-B4. Both herring spermatozoa isozymes were separated, partly purified and characterized by kinetic and physico-chemical properties. The pH optima and Km values for pyruvate reduction were 7.1, 7.25, 7.6 and 0.22, 0.07, 0.09 mM for LDH-A4, LDH-A2B2 and LDH-B4, respectively. The isoenzymes also have different thermostabilities. High activity of malic enzyme in herring spermatozoa suggests adaptation to metabolism at high oxygen tension. [Copyright &y& Elsevier]

: ObjectivesThis study was designed to determine how long nuclear myocardial perfusion imaging (MPI) remains abnormal following transient myocardial ischemia.: BackgroundAcute rest MPI identifies myocardial ischemia with a high sensitivity when the radionuclide is injected during chest pain. However, the sensitivity of this technique is uncertain when the radionuclide is injected following the resolution of symptoms.: MethodsForty patients undergoing successful coronary angioplasty were randomized into four equal groups. Tc-99m sestamibi was injected intravenously during the last balloon inflation (acute MPI) in 30 patients and then reinjected 1, 2, or 3 h later (delayed MPI). In a fourth group, the radiopharmaceutical was injected at 15 min following balloon deflation (delayed MPI). A final injection was performed at 24 to 48 h (late MPI) in 37 patients (93%).: ResultsA perfusion defect was detected in all 30 acute MPI studies; in 7/10 patients (70%) injected at 15 min; in 11/30 patients (37%) injected at 1, 2, or 3 h; and in 7/37 patients (19%) injected at 24 to 48 h. Perfusion scores were 13.0 ± 9.2 on acute MPI, 5.1 ± 2.8 at 15 min (p < 0.001 vs. acute MPI); 2.6 ± 3.0 at 1, 2, and 3 h (p < 0.001 vs. acute MPI); and 1.3 ± 2.4 at 24 to 48 h (p < 0.001 vs. acute MPI; p < 0.03 vs. delayed MPI).: ConclusionsMyocardial perfusion imaging may remain abnormal for several hours following transient myocardial ischemia even when normal flow is restored in the epicardial coronary artery. [Copyright &y& Elsevier]

: ObjectivesThis study investigated whether temperature measurements are influenced by blood flow.: BackgroundPrevious ex vivo studies showed marked thermal heterogeneity in atheromatic plaques. In stable lesions, however, trivial in vivo temperature variations are recorded, perhaps due to the “cooling effect” of blood flow.: MethodsEighteen patients with effort angina were studied. Coronary flow velocity was continuously recorded; over another guidewire, temperature measurements were performed at the proximal vessel wall and at the lesion before, during, and after complete interruption of blood flow by inflation of a balloon. The ΔTp was assigned as the difference between the proximal vessel wall temperature and the maximal temperature during and after balloon inflation. The ΔTl was assigned as the difference between the atherosclerotic plaque and the proximal vessel wall.: ResultsThe procedure was not complicated. During and after complete interruption of flow, ΔTp was 0.012 ± 0.01°C and −0.006 ± −0.01°C (p < 0.001), respectively. The ΔTl was 0.08 ± 0.04°C at baseline and went to 0.18 ± 0.05°C (60.5 ± 14.1% increase) during and 0.08 ± 0.04°C after flow interruption (p < 0.001). The ΔTl was greater than ΔTp during and after impairment of flow (p < 0.001). A correlation between the baseline average peak velocity and ΔTl during flow interruption was found (R = 0.57, p = 0.01). In seven patients thermal heterogeneity was not detected at baseline, and during balloon inflation ΔTl increased by 76.0 ± 8.4%.: ConclusionsThermal heterogeneity is underestimated in atherosclerotic plaques in patients with effort angina. Potential in vivo underestimation of heat production locally in human atherosclerotic is due to the “cooling effect” of coronary blood flow. [Copyright &y& Elsevier]

: ObjectivesThis study was designed to assess whether use of enoxaparin during percutaneous coronary intervention (PCI) increased bleeding compared with unfractionated heparin, in addition to background therapy with eptifibatide.: BackgroundData supporting the benefits of enoxaparin and the glycoprotein IIb/IIIa inhibitor eptifibatide evolved in parallel. Information on combining these two classes of medications is limited.: MethodsA total of 261 patients undergoing elective or urgent PCI were randomized to either eptifibatide plus enoxaparin or eptifibatide plus unfractionated heparin.: ResultsThe primary end point of the study, the bleeding index (change in hemoglobin corrected for blood transfusions), was 0.8 in the patients randomized to enoxaparin and 1.1 in patients randomized to unfractionated heparin (p = 0.15). The rate of vascular access site complications was 9.3% in the enoxaparin arm versus 9.8% in the unfractionated heparin arm (p = NS). The rate of bleeding complications was not significantly different between the two arms of the study, including in those patients who received vascular closure devices. The rate of angiographic complications was 6.3% in the enoxaparin group and 6.2% in the unfractionated heparin group (p = NS). Similarly, there were no significant differences in the composite of death, myocardial infarction, or urgent target vessel revascularization at 48 h or 30 days.: ConclusionsCompared with unfractionated heparin plus eptifibatide, the combination of enoxaparin plus eptifibatide is not associated with an excess of bleeding or vascular complications, including in those receiving closure devices. Despite no monitoring of anticoagulation activity with enoxaparin, there was no apparent increase in angiographic or clinical complications. [Copyright &y& Elsevier]

: ObjectivesWe investigated the association between hyperglycemia and the no-reflow phenomenon in patients with acute myocardial infarction (AMI).: BackgroundHyperglycemia is associated with increased risks of heart failure, cardiogenic shock, and death after AMI, but its underlying mechanism remains unknown.: MethodsA total of 146 consecutive patients with a first AMI were studied by intracoronary myocardial contrast echocardiography (MCE) after successful reperfusion within 24 h after symptom onset. Two-dimensional echocardiography was recorded on day 1 and three months later to determine the change in the wall motion score (ΔWMS; sum of 16 segmental scores; dyskinesia = 4 to normokinesia = 0).: ResultsThe no-reflow phenomenon was found on MCE in 49 (33.6%) of 146 patients; their glucose level on hospital admission was significantly higher than that of patients who did not exhibit this phenomenon (209 ± 79 vs. 159 ± 56 mg/dl; p < 0.0001). There was no difference in glycosylated hemoglobin or in the incidence of diabetes mellitus between the two subsets. The no-reflow phenomenon was more often observed in the 75 patients with hyperglycemia (≥160 mg/dl) than in those without hyperglycemia (52.0% vs. 14.1%; p < 0.0001). Patients with hyperglycemia had a higher peak creatine kinase level (2,497 ± 1,603 vs. 1,804 ± 1,300 IU/l; p = 0.005) and a lower ΔWMS (3.7 ± 4.8 vs. 5.7 ± 4.3; p = 0.01) than did those without hyperglycemia. The blood glucose level was an independent prognostic factor for no reflow, along with age, gender, absence of pre-infarction angina, complete occlusion of the culprit lesion, and anterior AMI.: ConclusionsHyperglycemia might be associated with impaired microvascular function after AMI, resulting in a larger infarct size and worse functional recovery. [Copyright &y& Elsevier]

: ObjectivesThis study examined plasma levels of certain matrix metalloproteinase (MMP) and tissue inhibitor of matrix metalloproteinase (TIMP) species before and after alcohol-induced myocardial infarction (MI) in patients with hypertrophic obstructive cardiomyopathy (HOCM).: BackgroundMatrix metalloproteinases contribute to tissue remodeling, and endogenous control of MMP activity is achieved by the concordant release and binding of TIMPs. Animal models of MI have demonstrated a role for MMP activation in myocardial remodeling. However, the temporal relationship of MMP and TIMP release following a controlled myocardial injury in humans remains unknown.: MethodsPlasma levels for the gelatinases MMP-2 and MMP-9, and for the collagenases MMP-8 and MMP-13, as well as TIMP-1 profiles were examined (by enzyme-linked immunosorbent assay) at baseline and serially up to 60 h following alcohol injection into the septal perforator artery in order to induce an MI in 51 patients with HOCM (age 55 ± 2 years).: ResultsPlasma creatine kinase (MB isoform), indicating myocardial injury, increased 2,150% 18 h post-MI (p < 0.05). Plasma MMP-9 increased by over 400% and MMP-8 by over 100% from baseline values by 12 h post-MI (p < 0.05 vs. baseline). A similar temporal profile was not observed for MMP-2 and MMP-13. In addition, a concomitant increase in plasma TIMP-1 levels did not occur post-MI. As a result, MMP/TIMP stoichiometry (MMP-9/TIMP-1 ratio) increased significantly post-MI, suggestive of reduced TIMP-1 mediated MMP-9 inhibition, which would potentially enhance extracellular myocardial remodeling.: ConclusionsThese unique results demonstrated that induction of a controlled myocardial injury in humans, specifically through alcohol-induced MI, caused species- and time-dependent perturbations of MMP/TIMP stoichiometry that would facilitate myocardial remodeling in the early post-MI setting. [Copyright &y& Elsevier]

: ObjectivesThis study was designed to determine whether simvastatin improves endothelial function in children with familial hypercholesterolemia (FH).: BackgroundEndothelial function measured by flow-mediated dilation of the brachial artery (FMD) is used as a surrogate marker of cardiovascular disease (CVD). Adult studies have shown that statins reverse endothelial dysfunction and therefore reduce the risk for future CVD.: MethodsThe study included 50 children with FH (9 to 18 years) and 19 healthy, non-FH controls. Children with FH were randomized to receive simvastatin or placebo for 28 weeks. The FMD was performed at baseline and at 28 weeks of treatment.: ResultsAt baseline, FMD was impaired in children with FH versus non-FH controls (p < 0.024). In the simvastatin FH group, FMD improved significantly, whereas the FMD remained unaltered in the placebo FH group throughout the study period (absolute increase 3.9% ± 4.3% vs. 1.2% ± 3.9%, p < 0.05). In the simvastatin FH group, FMD increased to a level similar to the non-FH controls (15.6% ± 6.8% vs. 15.5% ± 5.4%, p = 0.958). Upon treatment, the simvastatin FH group showed significant absolute reductions of total cholesterol (TC) (−2.16 ± 1.04 mmol/l, 30.1%) and low-density lipoprotein cholesterol (LDL-C) (−2.13 ± 0.99 mmol/l, 39.8%). The absolute change of FMD after 28 weeks of therapy was inversely correlated to changes of TC (r = −0.31, p < 0.05) and LDL-C (r = −0.31, p < 0.05).: ConclusionsOur data show significant improvement of endothelial dysfunction towards normal levels after short-term simvastatin therapy in children with FH. These results emphasize the relevance of statin therapy in patients with FH at an early stage, when the atherosclerotic process is still reversible. [Copyright &y& Elsevier]

: ObjectivesThis study was designed to examine a unique and low dose of intravenous enoxaparin in elective percutaneous coronary intervention (PCI) that would be applicable to an unselected population regardless of age, weight, renal function, or use of glycoprotein IIb/IIIa inhibitors.: BackgroundThere is limited experience of anticoagulation using intravenous (IV) low-molecular-weight heparin in PCI, which has been obtained with high doses causing elevated anticoagulation levels and delayed sheath withdrawal.: MethodsA total of 242 consecutive patients undergoing elective PCI were treated with a single IV bolus of enoxaparin (0.5 mg/kg), and 26% of patients (n = 64) also received eptifibatide. Sheaths were removed immediately after the procedure in patients treated with enoxaparin only, and 4 h after the procedure in those also treated with eptifibatide.: ResultsA peak anti-Xa >0.5 IU/ml was obtained in 97.5% of the population, and 94.6% of patients had their peak anti-Xa level in the predefined target range of 0.5 to 1.5 IU/ml. Advanced age, renal failure, being overweight, and eptifibatide use did not alter the anticoagulation profile. At one-month follow-up, six patients (2.5%) had died, had a myocardial infarction, or undergone an urgent revascularization; all the patients had an anti-Xa level >0.5 IU/ml during PCI. Patients without an ischemic event and without a creatine kinase rise, but with a detectable troponin release in the next 24 h of PCI (>2 μg/ml, n = 21), had similar anti-Xa levels as those without troponin elevation. There were one major and three minor bleeding events that were not associated with anti-Xa overshoot.: ConclusionsLow-dose (0.5 mg/kg) IV enoxaparin allows a prespecified target level of anticoagulation (anti-Xa >0.5 IU/ml) in the vast majority of patients undergoing PCI, appears to be safe and effective, allows immediate sheath removal when used alone, and does not require dose adjustment when used with eptifibatide. [Copyright &y& Elsevier]

: ObjectivesThis study tested the effect of oral prednisone on clinical and angiographic restenosis rate after successful stent implantation in patients with persistent elevation of systemic markers of inflammation after the procedure.: BackgroundExperimental studies have shown that corticosteroids have the potential to reduce the inflammatory response associated with stent implantation.: MethodsEighty-three patients undergoing successful stenting with C-reactive protein (CRP) levels >0.5 mg/dl 72 h after the procedure were randomized to receive oral prednisone or placebo for 45 days. The primary clinical end point was 12-month event-free survival rate (defined as freedom from death, from myocardial infarction, and from recurrence of symptoms requiring additional revascularization). The angiographic end points were restenosis rate and late loss at six months.: ResultsTwelve-month event-free survival rates were 93% and 65% in patients treated with prednisone and placebo, respectively (relative risk [RR] 0.18, 95% confidence intervals [CI], 0.05 to 0.61, p = 0.0063). Six-month restenosis rate and late loss were lower in prednisone-treated than in placebo-treated patients (7% vs. 33%, p = 0.001, and 0.39 ± 0.6 mm vs. 0.85 ± 0.6 mm, p = 0.001, respectively).: ConclusionsIn patients with persistently high CRP levels after successful coronary artery stent implantation, oral immunosuppressive therapy with prednisone results in a striking reduction of clinical events and angiographic restenosis rate. [Copyright &y& Elsevier]

This study was carried out to determine a possible correlation between disease activity and creatine kinase (CK), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in patients with rheumatoid arthritis. The clinical activity was evaluated by clinical and laboratory findings. Laboratory parameters included ESR and CRP.No statistically significant correlation between ALTand AST was found. CK was instead significantly lower in the active group than in non-active and control groups. No difference was found between non-active and control groups. There was also a statistically significant negative correlation between CK levels, and ESR and CRP. [ABSTRACT FROM AUTHOR]

: ObjectivesPatent perforators, noninvasively imaged by transthoracic color-Doppler echocardiography, may reflect adequate reperfusion in anterior myocardial infarction (MI).: BackgroundThe Thrombolysis In Myocardial Infarction (TIMI) classification may not fully reflect adequate myocardial reperfusion in MI.: MethodsWe studied 61 patients with anterior MI undergoing thrombolysis (n = 28), primary stenting (n = 20), or neither one (n = 13). High-resolution color-Doppler ultrasound was used to image the left anterior descending coronary artery (LAD) and perforators in four segments of the anterior-apical wall and to build a new recanalization score (RS). The TIMI flow was assessed by angiography. Wall motion score index (WMSI), ejection fraction (EF), end-diastolic volume index, and end-systolic volume index (ESVI) were measured by echocardiography at baseline and at three-month follow-up. Linear regression equations, considering RS or TIMI flow as independent variables, were compared among these functional recovery parameters. A multivariate linear model, predicting percent changes of WMSI, EF, or ESVI, was used to investigate the contribution of several clinical covariates along with RS and TIMI flow.: ResultsSensitivity, specificity, and diagnostic accuracy of color-Doppler ultrasound in detecting LAD patency were 86%, 98%, and 97%, respectively. Mean and peak flow velocities discriminated (0.004 < p < 0.008) TIMI flow but not RS. Regression equations showed that RS discriminated better than TIMI flow recovery of ventricular function (p < 0.012). The RS was the best single multivariate predictor (p < 0.0001) of percent changes in WMSI, EF, and ESVI.: ConclusionsTransthoracic color-Doppler ultrasound detects an open LAD after MI. Perforators reflect adequate myocardial reperfusion and are early noninvasive markers of myocardial viability. [Copyright &y& Elsevier]

: ObjectivesWe sought to determine whether elevation of plasma creatine kinase muscle-brain fraction (CK-MB) would be useful to triage patients with acute coronary syndromes (ACS) to early angiography/revascularization.: BackgroundIt is unknown whether the measurement of CK-MB is effective for triage to an aggressive management strategy.: MethodsPatients in the Treat Angina With Aggrastat and Determine Cost of Therapy With an Invasive or Conservative Strategy (TACTICS-TIMI) 18 study received aspirin, heparin, and tirofiban for treatment of ACS, were randomized to an invasive or a conservative strategy (angiography/revascularization between 4 and 48 h), and were followed up for a composite end point of death, myocardial infarction, or rehospitalization for ACS.: ResultsOf 2,220 patients, CK-MB was elevated in 826 (37%). Of the patients with negative CK-MB, troponin T was elevated in 361 (31.2%). Event rates at 30 and 180 days were twice as high in patients with elevated CK-MB than in patients without elevated CK-MB. Both groups had similar benefit from an invasive strategy; there was no evidence of interaction between CK-MB elevation and strategy on the composite end point at 30 or 180 days. When patients were stratified according to both CK-MB and troponin status, there was evidence of a benefit in the invasive strategy among patients who were CK-negative but troponin-positive (odds ratios [95% confidence interval]: 0.13 [0.04 to 0.39] at 30 days and 0.29 [0.16 to 0.52] at 180 days).: ConclusionsPatients with minimal amounts of recent onset myonecrosis but elevated risk as indicated by CK-MB and troponin, respectively, benefit most from invasive management. Determination of troponin levels yielded significant information regarding triage to an invasive strategy, particularly in CK-MB-negative patients. [Copyright &y& Elsevier]

: ObjectivesThe Troponin in Planned PTCA/Stent Implantation With or Without Administration of the Glycoprotein IIb/IIIa Receptor Antagonist Tirofiban (TOPSTAR) trial investigated: 1) the amount of troponin T (TnT) release after nonacute, elective percutaneous coronary intervention (PCI) in patients pretreated with aspirin and clopidogrel; and 2) the effect of additional glycoprotein (GP) IIb/IIIa receptor inhibiton on postinterventional TnT release.: BackgroundNo data are available yet as to whether additional administration of a GP IIb/IIIa receptor antagonist might be beneficial in patients undergoing elective PCI already pretreated with aspirin and clopidogrel.: MethodsAfter bolus application of the study medication (tirofiban [T] or placebo [P]), PCI was performed followed by an 18-h continuous infusion of T/P. Primary end point of the study was incidence and amount of TnT release after elective PCI after 24 h.: ResultsA total of 12 h after PCI troponin release was detected in 63% of the patients receiving P and in 40% of the patients receiving T (p < 0.05), after 24 h in 69% (P) and 48% (T) (p < 0.05) and after 48 h in 74% (P) versus 58% (T) (p < 0.08) of the patients. No differences were observed regarding major bleeding, intracranial bleeding or nonhemorrhagic strokes. After nine months a reduction of combined death/myocardial infarction/target vessel revascularization could be observed in the tirofiban group ([T] 2.3% vs. [P] 13.04%, p < 0.05).: ConclusionsTroponin T release occurs after successful intervention in 74% of the patients undergoing elective PCI after 48 h even after pretreatment with aspirin and clopidogrel. The GP IIb/IIIa receptor antagonist tirofiban is able to decrease the incidence of troponin release significantly in this patient population. [Copyright &y& Elsevier]

: ObjectivesThe goal of this study was to evaluate the mortality benefit of beta-blockers after successful percutaneous coronary intervention (PCI).: BackgroundBeta-blockers reduce mortality after myocardial infarction (MI), though limited data are available regarding their role after successful PCI.: MethodsEach year from 1993 through 1999, the first 1,000 consecutive patients undergoing PCI were systematically followed up. Patients presenting with acute or recent MI, shock, or unsuccessful revascularization procedures were excluded from the analysis. Clinical, procedural, and follow-up data of beta-blocker-treated and non-beta-blocker-treated patients were compared. A multivariate survival analysis model using propensity analysis was used to adjust for heterogeneity between the two groups.: ResultsOf the 4,553 patients, 2,056 (45%) were treated with beta-blockers at the time of the procedure. Beta-blocker therapy was associated with a mortality reduction from 1.3% to 0.8% at 30 days (p = 0.13) and a reduction from 6.0% to 3.9% at one year (p = 0.0014). This survival benefit of beta-blockers was independent of left ventricular function, diabetic status, history of hypertension, or history of MI. Using propensity analysis, beta-blocker therapy remained an independent predictor for one-year survival after PCI (hazard ratio, 0.63; 95% confidence interval, 0.46 to 0.87; p = 0.0054).: ConclusionsWithin this large prospective registry, beta-blocker use was associated with a marked long-term survival benefit among patients undergoing successful elective percutaneous coronary revascularization. [Copyright &y& Elsevier]

: ObjectivesThe aim of this study was to determine the impact of diabetes mellitus (DM) on short-term mortality and morbidity in patients undergoing coronary artery bypass surgery (CABG).: BackgroundDiabetes mellitus is present in approximately 20% to 30% of patients undergoing CABG, and the impact of diabetes on short-term outcome is unclear.: MethodsWe performed a retrospective cohort study in 434 hospitals from North America. The study population included 146,786 patients undergoing CABG during 1997: 41,663 patients with DM and 105,123 without DM. The primary outcome was 30-day mortality. Secondary outcomes were in-hospital morbidity, infections and composite outcomes of mortality or morbidity and mortality or infection.: ResultsThe 30-day mortality was 3.7% in patients with DM and 2.7% in those without DM; the unadjusted odds ratio was 1.40 (95% confidence interval [CI], 1.31 to 1.49). After adjusting for other baseline risk factors, the overall adjusted odds ratio for diabetics was 1.23 (95% CI, 1.15 to 1.32). Patients treated with oral hypoglycemic medications had adjusted odds ratio 1.13; 95% CI, 1.04 to 1.23, whereas those on insulin had an adjusted odds ratio 1.39; 95% CI, 1.27 to 1.52. Morbidity, infections and the composite outcomes occurred more commonly in diabetic patients and were associated with an adjusted risk about 35% higher in diabetics than nondiabetics, particularly among insulin-treated diabetics (adjusted risk between 1.5 to 1.61).: ConclusionsDiabetes mellitus is an important risk factor for mortality and morbidity among those undergoing CABG. Research is needed to determine if good control of glucose levels during the perioperative time period improves outcome. [Copyright &y& Elsevier]

: ObjectivesThis study sought to assess gender-based differences in long-term outcome after very early aggressive revascularization for non–ST-elevation acute coronary syndromes (NSTACS).: BackgroundThe Fragmin and fast Revascularization during InStability in Coronary artery disease (FRISC) II study suggested that women have less to gain from an early invasive strategy.: MethodsWe conducted a prospective cohort study in 1,450 consecutive patients with NSTACS undergoing coronary angiography and subsequent coronary stenting of the culprit lesion as the primary revascularization strategy within 24 h of admission. The combined primary end point was defined as death or nonfatal myocardial infarction (MI) and recorded for a mean of 20 months.: ResultsPercutaneous coronary intervention was performed in more than 50% of patients in women and men and accompanied with stenting in 80%. The percutaneous coronary intervention:coronary artery bypass grafting ratio was 4:1 in men and 5:1 in women. The primary end point occurred in 29 (7.0%) women as compared with 108 (10.5%) men (hazard ratio for women, 0.65; 95% confidence interval [CI] 0.42 to 0.99; p = 0.045). Backward-stepwise multivariate Cox regression analysis identified female gender as an independent predictor of death or MI (hazard ratio for female gender, 0.51; 95% CI, 0.28 to 0.92; p = 0.024). Kaplan-Meier analysis showed that women had consistently lower event rates during the entire follow-up period (p = 0.037 by log-rank for death or MI).: ConclusionsWomen treated with very early aggressive revascularization with coronary stenting of the culprit lesion as the primary revascularization strategy have a better long-term outcome as compared with men. [Copyright &y& Elsevier]

: ObjectivesThis study investigated whether ST-segment elevation and T-wave normalization (TWN) in Q-wave leads on pre-discharge exercise electrocardiogram (ECG) can contribute to patient management after a recent myocardial infarction (MI).: BackgroundThe clinical relevance of these exercise ECG changes remains controversial despite accumulating evidence of their association with myocardial viability. Because discrepancies of previous studies may depend on patient selection, the value of these ST/T abnormalities in the thrombolytic era should be better defined.: MethodsOne-hundred one patients, age 58 ± 11 years, with a recent, first Q-wave MI (57% thrombolyzed, ejection fraction 43 ± 7%) underwent pre-discharge, submaximal treadmill testing followed, in the absence of severe ischemia, by dobutamine stress echocardiography, thallium-201 single photon emission computed tomography, and coronary angiography.: ResultsST elevation at peak exercise, but not TWN, was associated with more severe infarctions as indicated by higher peak creatine kinase (p < 0.05) and with a greater number of scarred segments both on echocardiography (p < 0.05) and scintigraphy (p < 0.01). However, the incidence of myocardial viability and ischemia did not differ between groups with or without these ST/T changes. Anterior infarction location and ≥3 echocardiographically scarred segments were among the independent predictors of ST elevation at peak ergometric exercise. During follow-up (31 ± 13 months), the rate of hard events was low (8%) and similar between the study groups.: ConclusionsIn patients after acute Q-wave MI without severe ischemia according to clinical and standard ECG criteria, exercise-induced ST elevation, but not TWN, is associated with larger infarctions. The contribution of these ST/T abnormalities toward identifying patients with myocardial viability or ischemia and determining risk stratification is poor. In-hospital management of such patients based on routine clinical practice is sufficient for selection of a population with a relatively low long-term risk. [Copyright &y& Elsevier]

: ObjectivesWe examined whether unloading of the left ventricle with a ventricular assist device (LVAD) can result in normalization of the creatine kinase (CK) abnormalities in the failing human heart.: BackgroundLeft ventricular failure is associated with a decrease of myocardial total CK activity and a fetal shift in CK isoform expression that results in an increase in the cytosolic brain type homodimeric-creatine kinase (CK-B) subunit and decreases of the cytosolic muscle-creatine kinase (CK-M) and CK-mitochondrial (CK-Mt) isoforms. The mechanisms of this abnormality are not known.: MethodsTotal CK activity and CK protein isoform expression (Western blotting) were examined in 11 patients with end-stage cardiomyopathy. In 7 patients, myocardial tissue was also obtained after 4.1 ± 1.1 months of left ventricular assist device (LVAD) support.: ResultsLeft ventricular unloading produced by LVAD implantation resulted in a 270% ± 114% increase in total CK activity (p < 0.01) that was associated with a 69% ± 18% increase in CK-M protein expression (p < 0.01) and a 121% ± 69% increase in CK-Mt protein expression (p < 0.01), but no significant change in CK-B expression.: ConclusionsSystolic and diastolic unloading provided by the LVAD resulted in increases of total CK activity as well as CK-Mt and CK-M protein expression. The failure of CK-B expression to decrease suggests that abnormalities other than increased loading are responsible for the increase in CK-B expression in the failing heart. [Copyright &y& Elsevier]

: ObjectivesWe sought to assess the relationship of antecedent hypertension to neurohormones, ventricular remodeling and clinical heart failure (HF) after myocardial infarction (MI).: BackgroundHeart failure is a probable contributor to the increased mortality observed after MI in those with antecedent hypertension. Hence, neurohormonal activation, adverse ventricular remodeling and a higher incidence of clinical HF may be expected in this group. However, no previous report has documented serial postinfarction neurohumoral status, serial left ventricular imaging and clinical outcomes over prolonged follow-up in a broad spectrum of patients with and without antecedent hypertension.: MethodsInpatient events were documented in 1,093 consecutive patients (436 hypertensive and 657 normotensive) with acute MI. In 68% (282 hypertensive, 465 normotensive) serial neurohormonal sampling and radionuclide ventriculography were performed one to four days and three to five months after infarction. Clinical outcomes were recorded over a mean follow-up of two years.: ResultsPlasma neurohormones were significantly higher in hypertensives than in normotensives one to four days and three to five months after infarction. From similar initial values, left ventricular volumes increased significantly in hypertensives, compared with normotensives. Left ventricular ejection fraction rose significantly in normotensive but not hypertensive patients. Together with higher inpatient (8.1% vs. 4.4%, p < 0.002) and post-discharge mortality (9.5% vs. 5.5%, p = 0.043), hypertensive patients incurred more inpatient HF (33% vs. 24%, p < 0.001) and more late HF requiring readmission to hospital (12.4% vs. 5.5%, p < 0.001). Antecedent hypertension predicted late HF in patients >64 years of age with neurohormonal activation and early left ventricular dilation.: ConclusionsAntecedent hypertension interacts with age, neurohumoral activation and early ventricular remodeling to confer greater risk of HF after MI. [Copyright &y& Elsevier]

: ObjectivesThis study was designed to compare the in-hospital outcome of patients presenting with >12 h from onset of chest pain and acute ST elevation myocardial infarction (AMI) who received either immediate invasive or conservative therapy.: BackgroundThe benefits of fibrinolytic therapy diminish in patients presenting with AMI and onset of chest pain >12 h. Primary angioplasty has been suggested as a possible treatment for such patients, but they have been excluded from most trials of primary angioplasty. It remains unclear if an invasive treatment strategy is beneficial to these patients.: MethodsPatients presenting with >12 h of chest pain and AMI were identified from the National Registry of Myocardial Infarction 2 database. Patients receiving invasive therapy <6 h after hospital admission were compared with those receiving conservative therapy. Short-term outcomes were compared on the basis of the initial therapy received. To help control for baseline differences in the groups, patients were matched with controls by propensity score methodology.: ResultsOn preliminary analysis, in-hospital outcome was improved in terms of recurrent ischemia, angina, myocardial infarction and mortality in patients receiving initial invasive therapy (odds ratio [OR] = 0.67; 95% confidence interval [CI] 0.49 to 0.92 for mortality). After matching by propensity score, the mortality benefit persisted on bivariate analysis (3.5% vs. 5.0%, p = 0.036), though on multivariate analysis, only a non-significant but strong trend toward decreased mortality remained (OR = 0.73; 95% CI 0.53 to 1.01).: ConclusionsPatients receiving early invasive therapy had lower risk features on presentation. Selection bias may play an important role in choosing these patients’ course of treatment and their subsequent outcomes. Certain patients presenting with AMI and duration of chest pain >12 h may benefit from early invasive therapy. These patients could be characterized in a randomized trial. [Copyright &y& Elsevier]

: ObjectivesWe sought to investigate the clinical benefit of additional stent implantation after achieving an optimal result of balloon angioplasty (BA) in long coronary lesions (>20 mm).: BackgroundLong coronary lesions are associated with increased early complications and late restenosis after BA. Stenting improves the early outcome, but stent restenosis is also related to both lesion length and stent length.: MethodsA total of 437 patients with a single native lesion 20 to 50 mm in length were included and underwent BA, using long balloons matched to lesion length and vessel diameter (balloon/artery ratio 1.1) to achieve a diameter stenosis (DS) <30% by on-line quantitative coronary angiography (QCA). “Bail-out stenting” was performed for flow-limiting dissections or >50% DS. Patients in whom an optimal BA result was achieved were randomized to additional stenting (using NIR stents) or no stenting. The primary end point was freedom from major adverse cardiac events (MACE) at nine months, and core laboratory QCA was performed on serial angiograms.: ResultsBailout stenting was necessary in 149 patients (34%) and was associated with a significantly increased risk of peri-procedural infarction (p < 0.02). Among the 288 randomized patients, the mean lesion length was 27 ± 9 mm, and the vessel diameter was 2.78 ± 0.52 mm. The procedural success rate was 90% for the 143 patients assigned to BA alone (control group), as compared with 93% in the 145 patients assigned to additional stenting (stent group), which resulted in a superior early minimal lumen diameter (0.54 mm, p < 0.001) and led to reduced angiographic restenosis (27% vs. 42%, p = 0.022). Freedom from MACE at nine months was 77% in both groups.: ConclusionsA strategy of provisional stenting for long coronary lesions led to bailout stenting in one-third of patients, with a threefold increase in peri-procedural infarction. Additional stenting yielded a lower angiographic restenosis rate, but no reduction in MACE at nine months. [Copyright &y& Elsevier]

: ObjectivesThe aim of this study was to determine the significance of peripheral monocytosis in clinical outcome after reperfused acute myocardial infarction (AMI), especially relating to post-infarct left ventricular (LV) remodeling.: BackgroundPeripheral monocytosis occurs two to three days after AMI, reflecting infiltration of monocytes and macrophages into the necrotic myocardium. However, the prognostic significance of peripheral monocytosis after AMI remains to be determined.: MethodsA total of 149 patients with first Q-wave AMI were studied. White blood cell (WBC) count, percentage of monocytes and serum C-reactive protein level were measured every 24 h for four days after the onset of AMI. We assessed association between peripheral monocytosis and prognosis including pump failure, LV aneurysm and long-term outcome after AMI.: ResultsPatients with pump failure (p < 0.0001) or LV aneurysm (p = 0.005) had higher peak monocyte counts than those without these complications. Predischarge left ventriculography revealed that peak monocyte count was positively correlated with LV end-diastolic volume (p = 0.024) and negatively correlated with ejection fraction (p = 0.023). Multivariate analyses showed that peak monocyte count ≥900/mm3 was an independent determinant of pump failure (relative risk [RR] 9.83, p < 0.0001), LV aneurysm (RR 4.78, p = 0.046) and cardiac events (RR 6.30, p < 0.0001), including readmission for heart failure, recurrent myocardial infarction and cardiac deaths, including sudden deaths.: ConclusionsPeripheral monocytosis is associated with LV dysfunction and LV aneurysm, suggesting a possible role of monocytes in the development of LV remodeling after reperfused AMI. [Copyright &y& Elsevier]

: ObjectivesThis study was designed to determine whether antisense oligodeoxynucleotides (ODN) directed against the nuclear proto-oncogene c-myc could inhibit restenosis when given by local delivery immediately after coronary stent implantation.: BackgroundFailure of conventional pharmacologic therapies to reduce the incidence of coronary restenosis after percutaneous revascularization techniques has prompted interest in the use of agents that target intracellular central regulatory mechanisms.: MethodsEighty-five patients were randomly assigned to receive either 10 mg of phosphorothioate-modified 15-mer antisense ODN or saline vehicle by intracoronary local delivery after coronary stent implantation. The primary end point was percent neointimal volume obstruction measured by computerized analysis of electrocardiogram-gated intravascular ultrasound (IVUS) at six-month follow-up. Secondary end points included clinical outcome and quantitative coronary angiography analysis.: ResultsAnalysis of follow-up IVUS data was performed on 77 patients. In-stent volume obstruction was similar between groups (44 ± 16% and 46 ± 14%, placebo vs. ODN; p = 0.57; 95% confidence interval: −1.13 to 0.85). Minimum luminal diameter increased from 0.84 ± 0.36 and 0.90 ± 0.45 (p = 0.55) to 2.70 ± 0.37 and 2.80 ± 0.37 (p = 0.28) after stent implantation, which decreased to 1.50 ± 0.61 and 1.50 ± 0.53 (p = 0.98) by six months, yielding similar loss indexes (placebo vs. ODN, respectively). There were no differences in angiographic restenosis rates (38.5 and 34.2%; p = 0.81; placebo vs. ODN) or clinical outcome.: ConclusionsTreatment with 10 mg of phosphorothioate-modified ODN directed against c-myc does not reduce neointimal volume obstruction or the angiographic restenosis rate in this patient population. [Copyright &y& Elsevier]

: ObjectivesThe study investigated the relationship among creatine kinase (CK) elevations, clinical characteristics and cardiac events across the whole spectrum of acute coronary syndromes (ACS).: BackgroundElevated serum levels of cardiac enzymes have been shown to be a major prognostic determinant in acute myocardial ischemia. Yet prior to this report, the relation between cardiac enzyme levels and other prognostic determinants across the entire spectrum of ACS has not been explored by a large clinical study.: MethodsWe evaluated the relation between the maximum CK ratio (CK level/upper limit of normal) in the early hours following admission and cardiac events at six months in 11,725 patients enrolled in a large trial of ACS.: ResultsPatients with higher risk characteristics, such as older age, female gender, hypertension, diabetes, prior coronary events or heart failure, more frequently presented without ST-segment elevation on the electrocardiogram and tended to develop lesser enzyme elevations. After adjusting for significant baseline predictors of cardiac events, a continuous correlation was observed between the CK ratio and death (chi-square 63.04, p < 0.0001) and (re)infarction or death (chi-square 55.48, p < 0.0001). This correlation was similar for patients with and without ST-segment elevation. The adjusted incidence of cardiac events at follow-up began to rise even for CK levels within the normal range, the steepest part of the curve residing between one and three times the upper limit of normal. In patients with a CK ratio of >1 to 2 compared with those within the normal range, the adjusted odds ratio for death was 1.26 (95% confidence interval [CI] 0.98 to 1.63), and 1.59 (95% CI 1.38 to 1.90) for (re)infarction and death. For all CK levels, the event rate was higher among patients without ST-segment elevation.: ConclusionsAlthough high-risk patients with ACS often develop lesser CK elevations, this study demonstrated that even minor enzyme elevations appear to have important and independent prognostic implications. [Copyright &y& Elsevier]

Fractures have an extraordinarily negative impact on an individual's quality of life and functional status, particularly delayed or non-union fractures. Osteogenesis and angiogenesis are closely related to bone growth and regeneration, and bone modeling and remodeling. Recently Chinese medicine has been extensively studied to promote osteogenic differentiation in MSCs. Studies have found that Ginseng can be used as an alternative for tissue regeneration and engineering. Ginseng is a commonly used herbal medicine in clinical practice, and one of its components, Ginsenoside Compound K (CK), has received much attention. Evidence indicates that CK has health-promoting effects in inflammation, atherosclerosis, diabetics, aging, etc. But relatively little is known about its effect on bone regeneration and the underlying cellular and molecular mechanisms. In this study, CK was found to promote osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) by RT-PCR and Alizarin Red S staining in vitro . Mechanistically, we found CK could promote osteogenesis through activating Wnt/β-catenin signaling pathway by immunofluorescence staining and luciferase reporter assay. And we also showed that the tube formation capacity of human umbilical vein endothelial cells (HUVECs) was increased by CK. Furthermore, using the rat open femoral fracture model, we found that CK could improve fracture repair as demonstrated by Micro-CT, biomechanical and histology staining analysis. The formation of H type vessel in the fracture callus was also increased by CK. These findings provide a scientific basis for treating fractures with CK, which may expand its application in clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ding, Gu, Zhou, Wang, Zhang, Wu, Zou, Zhao, Gao and Xu.)

Background: There is a large amount of evidence that anti-angiogenic drugs are effective safe. However, few studies have evaluated the specific effects of anti-angiogenic drugs on myocardial enzyme injury biomarkers: aspartate aminotransferase (AST), lactic dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). The purpose of our study was to determine whether anti-angiogenic drugs serum AST, LDH, CK, and CK-MB activities of cancer patients treated with anti-angiogenic drugs. Methods: This study retrospectively analyzed 81 cancer patients. Patients who had used anti-angiogenic drugs were selected. Serum AST, LDH, CK, and CK-MB activities were measured before and after treatment with anti-angiogenic drugs for 3 weeks. Results: A total of 16 cancer types were analyzed. The distribution of the cancer types in the patients was mainly concentrated in lung, gastric, and colorectal cancers. The anti-angiogenic treatment markedly increased AST, LDH, CK, and CK-MB activities by 32.51, 7.29, 31.25, and 55.56%, respectively in serum. Conclusions: Our findings suggest that patients, who had used anti-angiogenic drugs were likely to have elevated AST, LDH, and CK, indicators of myocardial muscle injury. Use of anti-angiogenic drugs should not be assumed to be completely safe and without any cardiovascular risks., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zheng, Wang, Hou and Zhang.)

A correlation study was performed on the degree of muscle weakness in 36 patients with dermatomyositis and 69 with polymyositis in relation to muscle biopsy findings, electromyography (EMG) abnormalities, and serum concentrations of creatine kinase (CK), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymes. Statistically significant correlations were found between muscle weakness and EMG results in patients with polymyositis, and between muscle weakness and serum CK and AST levels in dermatomyositis. As expected, correlations were found between the results of the three enzyme determinations in both groups of patients. [ABSTRACT FROM AUTHOR]

We studied the predictive power at admission of troponin T and myoglobin and compared them with that of CK and CK-MB activity and ECG in 290 consecutive patients admitted for evaluation of a suspected AMI. The likelihood ratio for an ischaemic ECG at admission <4 h (between 4 and 12 h) after onset of chest pain was 2·85 (1·92), for a inconclusive ECG 1·53 (1·98) and for a normal ECG 0·27 (0·35). In patients admitted <4 h after onset of chest pain, the likelihood ratio for abnormal and normal nyoglobin concentrations (8·06 and 0·67) was considerably better for detection of AMI as defined by the WHO criteria than for the other markers, including the ECG. In patients admitted 4–12 h after onset of chest pain, the likelihood ratios for abnormal and normal myoglobin concentrations were 4·88 and 0·42; for troponin T 3·11 and 0·31, for CK activity 3·44 and 0·49 and for CK-MB activity 4·08 and 0·54 respectively. The sensitivity for troponin T (64%) was better than that of the other markers but its specificity (74%)was worse, because in patients with unstable angina troponin T was frequently elevated (37%). Stepwise logistic regression analysis showed that the best predictors of AMI within 4 h after onset of chest pain were the ECG and myoglobin and between 4–12 h after onset of chest pain the ECG, CK-MB activity and myoglobin. [ABSTRACT FROM PUBLISHER]

An atypical creatine kinase (CK) isoenzyme migrating cathodically to CK-MM in the electrophoresis was observed as response to the embolization of the right hepatic artery in two patients with liver metastasis. The time course of the atypical CK release was compared to that of tumor secretion products, i.e., insulin and 5-hydroxy-indol-acetic acid. The CK isoenzyme probably reflects a mitochondrial breakdown of the metastasis in question. The influence of the treatment on liver function was characterized by a marginal augmentation of ASAT and ALAT and by a small but significant leakage of mitochondrial glutamate dehydrogenase. In addition to the atypical CK, CK-BB, and CK-MB isoenzymes were found in the serum of the patient with primary carcinoid carcinoma. [ABSTRACT FROM AUTHOR]

McLeod syndrome was originally described on the basis of a specific blood group phenotype with weak expression of Kell antigens. This erythrocyte abnormality also causes acanthocytosis. The haematological findings are associated with abnormalities in other organ systems, including neuromuscular manifestations. A 51-year-old patient was followed up for 11 years. He presented with persistent muscle creatine kinase elevation and progressive heart disease and later developed a slowly progressive neuropathy and choreic movements. His younger brother presented with grand mal seizures, involuntary movements and high muscle creatine kinase when aged 43 years. Clinical myopathy was absent in both, yet muscle biopsy showed mild myopathic changes. The presence of a motor axonopathy was supported by electrophysiological findings. One brother also showed sensory axonopathy. The movement disorder suggested accompanying basal ganglia dysfunction. Earlier reports of McLeod syndrome are reviewed with respect to neuromuscular involvement. Absence of the Kx membrane protein seems to be the cause of this multi-system disorder. [ABSTRACT FROM AUTHOR]

This study was designed to investigate the alterations in thiobarbituric acid reactants (TBA-reactants) and enzymatic and nonenzymatic antioxidant levels induced by dexamethasone (Dex) in heart and kidney and to find out whether these alterations induced by Dex and its hypertensive effect had any role in the maintenance of hypertension in this model. Administration of dexamethasone induced severe loss of body weight, significant increase in heart and kidney weights and also marked electrocardiographic changes. The protein content in heart and kidney increased significantly during Dex administration and returned to near normalcy after withdrawal. Total activity of lactate dehydrogenase showed a significant increase in heart till day 8 of treatment, whereas in serum, it exhibited a significant decrease. The activity of CK in heart showed an increase till day 8 of treatment and approached normalcy thereafter. In serum, CK exhibited a decrease till day 8, remaining insignificant thereafter. CKMB in heart showed an insignificant increase initially, reaching normal levels on Dex withdrawal, whereas in serum, it showed a significant decrease throughout the experimental period. Mean arterial pressure (MAP) and heart rate increased significantly, while a significant elevation in the ST segment was noticed during administration as well as after withdrawal of dex. The TBA-reactants levels were found to increase in heart and kidney during days 12 and 16 of administration with Dex and even after withdrawal of Dex, the levels were insignificantly elevated. The level of glutathione in heart and kidney increased from day 4 onwards and reached normalcy during the later stages of treatment and after withdrawal of Dex. The total sulfhydryl groups exhibited a significant increase in both heart and kidney throughout the experiment. The antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase and glutathione S-transferase exhibited a significant decrease in heart during Dex administration whereas, in kidney, they exhibited a significant increase during treatment and after withdrawal of Dex. Thus, Dex induced rise in mean arterial pressure, significant alterations in electrocardiographic parameters and also marked alterations in enzymatic and nonenzymatic antioxidant levels and in the TBA-reactants level in heart and kidney. [ABSTRACT FROM AUTHOR]