Severity Of Ischemic Heart Disease Research Articles

Evaluation of the relationship between concentration of endothelin-1 and magnesium in the blood and the severity of ischemic heart disease

Aim. To study the relationship between concentrations of endothelin-1 and magnesium in blood depending on functional class and old myocardial infarction in patients with stable angina.Methods. The study included 58 patients with ischemic heart disease, II and III functional class stable angina. 19 of these patients suffered a myocardial infarction in the past. The control group consisted of 25 healthy volunteers. Endothelin-1 level in blood serum was determined by enzyme immunoassay, the concentration of magnesium by colorimetric method.Results.Endothelin-1 level in the general group of patients with stable angina was 1.28±0.23 fmol/ml and was significantly higher than that of control group (0.52±0.13 fmol/ml, pConclusion. In patients with II-III functional class stable angina statistically significant increase in level of endothelin-1 and a decrease in the concentration of magnesium in blood serum compared with the control group was revealed; a negative correlation between endothelin-1 and magnesium levels in the blood, which is characterized by increasing the degree of correlation depending on the severity of the ischemic heart disease clinical form was established.

Bone Marrow-Derived Progenitor Cells Are Functionally Impaired in Ischemic Heart Disease.

To determine whether the presence of ischemic heart disease (IHD) per se, or rather the co-presence of heart failure (HF), is the primum movens for less effective stem cell products in autologous stem cell therapy, we assessed numbers and function of bone marrow (BM)-derived progenitor cells in patients with coronary artery disease (n = 17), HF due to ischemic cardiomyopathy (n = 8), non-ischemic HF (n = 7), and control subjects (n = 11). Myeloid and erythroid differentiation capacity of BM-derived mononuclear cells was impaired in patients with underlying IHD but not with non-ischemic HF. Migration capacity decreased with increasing IHD severity. Hence, IHD, with or without associated cardiomyopathy, is an important determinant of progenitor cell function. No depletion of hematopoietic and endothelial progenitor cells (EPC) within the BM was observed, while circulating EPC numbers were increased in the presence of IHD, suggesting active recruitment. The observed myelosuppression was not driven by inflammation and thus other mechanisms are at play.Electronic supplementary materialThe online version of this article (doi:10.1007/s12265-016-9707-z) contains supplementary material, which is available to authorized users.

C-terminal variable AGES domain of Thymosin β4: the molecule's primary contribution in support of post-ischemic cardiac function and repair

Repairing defective cardiac cells is important towards improving heart function. Due to the frequency and severity of ischemic heart disease, management of patients featuring this type of cardiac failure receives significant interest. Previously we discovered that Thymosin β4 (TB4), a 43 amino-acid secreted actin sequestering peptide, is beneficial for myocardial cell survival and coronary re-growth after infarction in adult mammals. Considering the regenerative potential of full-length TB4 in the heart, and that minimal structural variations alter TB4's influence on actin assembly and cell movement, we investigated how various TB4 domains affect cardiac cell behavior and post-ischemic mammalian heart function.We synthesized 17 domain combinations of full-length TB4 and analyzed their impact on embryonic cardiac cells in vitro, and after cardiac infarction in vivo. We discovered the domains of TB4 affect cardiac cell behavior distinctly. We revealed TB4 specific C-terminal tetrapeptide, AGES, increases embryonic cardiac cell migration and myocyte beating in culture, and improves adult mammalian heart function following ischemia. Investigating the molecular background and mechanism we discovered systemic injection of AGES enhances early myocyte survival by activating Akt-mediated signaling mechanisms, increases coronary vessel growth and inhibits inflammation in mice and pigs. Biodistribution analyses revealed cardiomyocytes uptake AGES efficiently in vitro and in vivo projecting a potential independent clinical utilization for the tetrapeptide. Our comprehensive domain investigations also suggest, preservation and/or restoration of cardiomyocyte communication is a target of TB4 and AGES, and critical to improve post-ischemic heart function in pigs.In summary, we identified the C-terminal four amino-acid variable end of TB4 as the essential and responsible domain for the molecule's full benefits in the hypoxic heart. Additionally, we introduced AGES as a novel, systemically applicable drug candidate to aid cardiac infarction in adult mammals.

Тревожность и полиморфизм Val66Met гена BDNF — предикторы выраженности депрессии при ишемической болезни сердца

In a framework of search for early predictors of depression in patients with ischemic heart disease (IHD) we studied effect of molecular-genetic factors (polymorphism of brain-derived neirotrophic factor--BDNF), personality traits (anxiety, neuroticism), IHD severity, and psychosocial stressors on manifestations of depression in men with verified diagnosis of IHD. Severity of depression was assessed by Hamilton Depression Rating Scale 21-item (HAMD 21), anxiety and neuroticism were evaluated by the Spielberger State-Trait Anxiety Inventory and "Big Five" questionnaire, respectively. It wa shown that personal anxiety and ValVal genotype of BDNF gene appeared to be predictors of moderate and severe depression.

South Asians and Anglo Australians with heart disease in Australia.

The aim of the present study was to determine cardiovascular disease (CVD) risk tactors and compare presentation and severity of ischaemic heart disease (IHD) among South Asians (SAs) and Anglo Australians (AAs). A retrospective clinical case audit was conducted at a public tertiary hospital. The study population included SA and AA patients hospitalised for IHD. Baseline characteristics, evidence of diabetes and other CVD risk factors were recorded. Angiography data were also included to determine severity, and these were assessed using a modified Gensini score. SAs had lower mean (± s.d.) age of IHD presentation that AAs (52 ± 9 vs 55 ± 9 years, respectively; P = 0.02), as well as a lower average body mass index (BMI; 26 ± 4 vs 29 ± 6 kg/m2, respectively; P = 0.005), but a higher prevalence of type 2 diabetes (57% vs 31%, respectively; P = 0.00 1). No significant differences were found in coronary angiography parameters. There were no significant differences in the median (interquartile range) Gensini score between SAs and AAs (43.5 (27-75) vs 44 (26.5-68.5), respectively), median vessel score (1 (1-2) vs 2 (1-3), respectively) or multivessel score (37% (33/89) vs 54% (22/41), respectively). The findings show that in those with established IHD, cardiovascular risk factors, such as age at onset and BMI, differ between SAs and AAs and these differences should be considered in the prevention and management of IHD.

TCT-51 Prognostic impact of chronic total occlusion in patients with different severity of coronary artery disease - A report from the Swedish Coronary Angiography and Angioplasty Registry

Chronic total coronary occlusion (CTO) is a frequent finding in patients with ischemic heart disease. Our aim was to evaluate the prognostic impact of CTO on long-term survival in patients with different severity of ischemic heart disease at the level of one whole nation. The study population

Relationship of serum uric acid level and angiographicseverity of coronary artery disease in male patients with acute coronary syndrome

The association between serum uric acid and ischemic heart disease remains controversial and it has not yet been established as cardiovascular risk factor. Our objective was to study the association of serum uric acid level with angiographic severity of coronary artery disease in men with acute coronary syndrome (ACS). Methods : This cross-sectional study was conducted on 100 consecutive male patients presenting with ACS at Punjab Institute of Cardiology. Hyperuricemia was defined as serum uric acid level > 6.5 mg/dl. Severity of ischemic heart disease was assessed on the basis of Gensini score, number of diseased vessels, critical lesions and total occlusions on coronary angiogram. Mean age of normouricemic group (n=59) was 52.62 ± 9.46 years and mean age of hyperuricemic group (n=41) was 50.52 ± 9.40 years (p=0.273). Mean uric acid level; normouricemic group (4.75 ± 1.05), hyperuricemic group (7.61 ± 1.24), p<0.001. Mean Gensini score; normouricemic group (22.15 ± 21.52), hyperuricemic group (35.69 ± 26.80). Mann Whitney U test was applied to compare the Gensini score of two groups and it showed statistically significant difference (p value <0.006). Critical lesions, total occlusions and multi-vessel disease were more frequent in hyperuricemic group but statistically significant difference was found only for total occlusions (p=0.013) and critical lesions (p=0.046). Conclusions : Hyeruricemia is associated with higher Gensini score and more frequent total occlusions and critical lesions in men presenting with acute coronary syndrome.

Correlation between plasma proBNP, echocardiographic and clinical parameters in patientswith type 2 diabetes mellitus

Aims. To assess plasma level of N-terminal precursor for brain natriuretic peptide (proBNP) in patients with type 2 diabetes mellitus (T2DM) and arterial hypertension without overt heart failure ? and further estimation of its correlation with data from echocardiog- raphy and clinical parameters (severity of ischemic heart disease (IHD), age, sex, duration of T2DM and hypertension experience, characteristics of glucose and lipid metabolism, renal function. Materials and methods. We examined 94 patients with T2DM and arterial hypertension (aged 40?65 years), determining character- istics of glucose and lipid metabolism and renal function. We also performed six minute walk test, ECG, echocardiography and blood tests for N-terminal proBNP (NT-proBNP) in all study subjects. Acquired data was compared to the group of 30 healthy controls. Results. We observed an increase in plasma NT-proBNP in patients with IHD, history of left venctricular (LV) myocardial infarction or clinical signs of heart failure (II NYHA class and higher). Results from patients with T2DM and arterial hypertension but without IHD did not significantly differ from control group. Plasma NT-proBNP levels correlated with left ventricular ejection fraction, left ventricular EDD and ESD, but not with LV diastolic function parameters. Duration of T2DM and arterial hypertension, HbA1c levels,27Сахар ный диабет КардиологияСахарный диабет. 2013;(1):27?32BMI, lipid and uric acid metabolism parameters had no influence on plasma NT-proBNP in diabetic patients. Conclusion. According to our study, NT-proBNP was elevated in T2DM patients with IHD (and a history of LV myocardial infarc- tion in particular) or clinical evidence for heart failure beyond II NYHA class, thus indicating unfavorable prognosis for this group of patients and need for correction of therapy with subsequent re-evaluation of plasma NT-proBNP.

Tendencias de la mortalidad por infarto de miocardio en España y Estados Unidos: ¿una carrera cuesta abajo o cuesta arriba en el siglo xxi?

Tendencias de la mortalidad por infarto de miocardio en España y Estados Unidos: ¿una carrera cuesta abajo o cuesta arriba en el siglo xxi?

Clinical role of the Duke Activity Status Index in the selection of the optimal type of stress myocardial perfusion imaging study in patients with known or suspected ischemic heart disease

BackgroundExercise treadmill stress myocardial perfusion imaging (MPI) with single photon emission computed tomography is commonly used to evaluate the extent and severity of inducible ischemia as well as to risk stratify patients with suspected and known coronary artery disease (CAD). Failure to reach adequate stress, defined as not attaining age-appropriate metabolic equivalents (METs), can underestimate the extent and severity of ischemic heart disease, resulting in false negative results. This study evaluates the efficacy of the Duke Activity Status Index (DASI), a simple self-administered 12-item questionnaire, as a predictor of METs achieved by treadmill stress testing. MethodsThe DASI was prospectively administered to 200 randomly selected men and women referred to the nuclear cardiology laboratory at New York University Langone Medical Center for stress MPI. Each patient was asked to complete the 12-item DASI questionnaire independently. 136 patients underwent treadmill exercise with MPI and 64 had pharmacologic stress with MPI. The association between exercise capacity in METs as estimated by the DASI questionnaire and performance on the Bruce treadmill protocol in METS was compared using chi-square statistics. ResultsOver 70% of those patients whose DASI score predicted the ability to perform <10 METs were unable to exercise beyond stage 2 of the Bruce protocol (7 METs). For those whose DASI score predicted ability to perform >12.5 METs, over 80% of patients reached >stage 2 of the Bruce protocol with 40% reaching beyond stage 3 (10 METs). When patient age was incorporated into the calculation, a more linear relationship was observed between predicted and obtained METs. ConclusionThe DASI is a simple self-administered questionnaire which is a useful pretest tool to determine a patient’s ability to achieve appropriate METs. In the nuclear cardiology laboratory, the DASI has the potential to guide selection of exercise treadmill vs pharmacologic stress and ultimately improve laboratory efficiency.

Serum oxidizability potential is associated with age and exercise test results

Abstract The purpose of this paper is to find out whether serum oxidizability potential measured before an exercise test (EXT) correlates with age and ischemic heart disease severity. Oxidizability potential was determined in 3 age groups, in gr. I patients &lt; 45 years, in gr. II age $$ {\hbox{range}} = {45} - {7}0{\hbox{years}} $$ , and in gr. III patients &gt; 70 years. Included subjects had chronic ischemic heart disease (IHD) and underwent a symptom-limited EXT upon initiation of a cardiac rehabilitation program. The thermo-chemiluminescence (TCL) assay was used to assess serum oxidizability potential. This assay is based on heat-induced oxidation of serum, leading to the formation of electronically excited species in the form of unstable carbonyls, which further decompose into stable carbonyls and light energy (low chemiluminescence). Measured photons emission is represented by a kinetic curve which is described by its amplitude and slope (=ratio). We assessed the correlations of TCL ratio with age, exercise duration, metabolic equivalents (METS), maximal heart rate (mHR), maximal systolic BP, &gt;1 mm S-T depression, diabetes, hypertension, smoking, left ventricular ejection fraction (LVEF)&gt; or &lt;40%, previous myocardial infarction, and aorto-coronary bypass surgery. A high TCL ratio (%) correlated well with METS (r = 0.82), mHR (r = 0.77) and with exercise-induced S-T segment shift (r = 0.86, p &lt; 0.05). A lower serum oxidizability potential, expressed as a low TCL ratio, thus suggestive of a previous high oxidative stress, was found in the two older age groups compared to gr. I (&lt;45 years), p = 0.041, and in particular, in gr. III patients with low LVEF%. The TCL ratio (%) in gr. III was 188.7 ± 14.5, 192 ± 17 in gr. II, and 214 ± 13 in gr. I (p &lt; 0.05), and was 166 ± 13.1 in gr. III with LVEF &lt; 45% as compared to 271 ± 15.7 in gr. I patients with LVEF &gt; 45% (p &lt; 0.01). A trend for lower TCL ratio (%) was found in diabetic, hypertensive, and post-coronary bypass surgery patients. A paradoxically low TCL ratio (low oxidizability potential) was observed in patients without S-T depression compared to patients with S-T depression (189 ± 22 vs. 201 ± 15, p = NS), due to the fact these patients had a much lower LVEF% and a lower exercise capacity. Serum oxidizability potential is associated with age, EXT parameters, results, and IHD severity. TCL ratio is an “easy-to-measure marker” that might be incorporated into risk assessment and prediction in aged IHD patients.

Elective coronary stent patients: preinterventional functional status and clinical-instrumental assessment

The functional status of ischemic heart disease (IHD) is currently assessed using the Seattle Angina Questionnaire (SAQ), a tool for monitoring and predicting the patient's prognosis. Illness perceptions (IP) are associated with IHD behavioral risk factors. The aim of the study was to find whether different IP, as evaluated by the IP Questionnaire (IPQr), can predict any of the features of the SAQ, i.e., to determine whether the SAQ is influenced and/or biased by illness perceptions. Moreover, whether New York Heart Association class and Ejection Fraction (EF%) are predictors of IHD severity measured as need of subsequent stenting procedures was also assessed. Eighty IHD patients eligible for percutaneous coronary intervention (PCI) and drug-eluting stent implant were asked to complete the IPQr and the SAQ. Laboratory analyses, echocardiography, and coronary diagnostic and interventional procedures were performed concurrently. Physical limitations of the SAQ are predicted by IPQr emotional representation. Ischemic heart disease functional status is regulated by illness perceptions and beliefs. Thus, some of the inferences drawn from the SAQ regarding IHD prognosis and even interventional indications may be biased and compromise the prognostic reliability of the SAQ information on physical function. This can also have consequences for therapeutic indications.

Serum oxidizability potential of ischemic heart disease patients predicts exercise test results and disease severity.

Background: Little is known about the relationship between exercise test indices and serum oxidizability potential in chronic ischemic heart disease (IHD) patients. Aim: to find out whether serum oxidizability potential correlates with exercise test parameters and predicts its result in chronic IHD patients. Methods: 54 chronic IHD patients and 11 normal controls underwent a symptom limited exercise test (EXT) upon initiation of a cardiac rehabilitation program; prior to the test a thermo-chemiluminiscence (TCL) assay of serum oxidizability potential was performed. This assay is based on heat-induced oxidation of the serum which leads to the formation electronically excited species in the form of unstable carbonyls, which further decompose into stable carbonyls and light energy (low chemiluminiscence). Measured photons emission is represented by a kinetic curve which is described by its amplitude and slope (= ratio). Correlations of TCL ratio with exercise duration (ED), metabolic equivalents (METS), maximal heart rate (mHR), maximal systolic BP (mSBP), >1mm S-T depression, Diabetes, Hypertension, Smoking, LV ejection fraction (LVEF) > or 40%, p<.01. A trend for lower TCL ratio (%) was found in diabetic, hypertensive, and postCABG patients. A paradoxically low TCL ratio (low oxidizablity potential) was observed in patients without S-T depression compared to patients with S-T depression (189+/-22 vs 201+/-15, p= ns) which is due to the fact these patients had a much lower LVEF% as well as a lower exercise capacity. Conclusion: Serum oxidizability potential is associated with exercise test parameters, results, and IHD severity. TCL ratio is an easy to measure marker that might be incorporated into risk assessment and prediction in chronic ischemic heart disease patients.

The mannose-binding lectin pathway is a significant contributor to reperfusion injury in the type 2 diabetic heart

The severity of ischaemic heart disease is markedly enhanced in type 2 diabetes. We recently reported that complement activation exacerbates I/R injury in the type 2 diabetic heart. The purpose of this study was to isolate and examine MBL pathway activation following I/R injury in the diabetic heart. ZLC and ZDF rats underwent 30 minutes of left coronary artery occlusion followed by 120 minutes of reperfusion. Two different groups of ZDF rats were treated with either FUT-175, a broad complement inhibitor, or P2D5, a monoclonal antibody raised against rat MBL-A. ZDF rats treated with FUT175 and P2D5 had significantly decreased myocardial infarct size, C3 deposition and neutrophil accumulation compared with untreated ZDF controls. Taken together, these findings indicate that the MBL pathway plays a key role in the severity of complement-mediated I/R injury in the type 2 diabetic heart.

Serum oxidizability potential of ischemic heart disease patients is associated with exercise test results and disease severity

To find out whether serum oxidizability potential correlates with exercise test (EXT) parameters and predicts their results in chronic ischemic heart disease (IHD) patients. Oxidizability potential was determined in a group of chronic IHD patients who underwent a symptom limited EXT upon initiation of a cardiac rehabilitation program. The thermo-chemiluminescence (TCL) assay was used to assess serum oxidizability potential. This assay is based on heat-induced oxidation of serum, leading to the formation of electronically excited species in the form of unstable carbonyls, which further decompose into stable carbonyls and light energy (low chemiluminescence). Measured photons emission is represented by a kinetic curve which is described by its amplitude and slope (= ratio). We assessed the correlations of TCL ratio with exercise duration, metabolic equivalents (METS), maximal heart rate (mHR), maximal systolic BP, > 1 mm S-T depression, diabetes, hypertension, smoking, left ventricular ejection fraction (LVEF) > or < 40%, previous myocardial infarction, and aorto-coronary by-pass surgery and compared to the TCL ratio measured in a group of healthy controls. A high TCL ratio (%) correlated well with METS (r = 0.84), with mHR (r = 0.79) and with exercise induced S-T segment shift (r = 0.87, P < 0.05). A lower serum oxidizability potential, expressed as a low TCL ratio, thus suggestive of a previous high oxidative stress, was found in IHD patients compared to healthy controls, and, in particular, in patients with low LVEF%. The TCL ratio (%) in IHD patients was 193 ± 21, compared to 215 ± 13 in controls (P < 0.05), and was 188 ± 14.7 in patients with LVEF < 40% as compared to 200 ± 11.9 in those with LVEF > 40% (P < 0.01). A trend for lower TCL ratio (%) was found in diabetic, hypertensive, and post-coronary bypass surgery patients. A paradoxically low TCL ratio (low oxidizability potential) was observed in patients without S-T depression compared to patients with S-T depression (189 ± 22 vs 201 ± 15, P = NS), due to the fact these patients had a much lower LVEF% and a lower exercise capacity. Serum oxidizability potential is associated with EXT parameters, results, and IHD severity. TCL ratio is an "easy-to-measure marker" that might be incorporated into risk assessment and prediction in chronic IHD patients.

Effect of Statins on Serum Apolipoprotein J and Paraoxonase-1 Levels in Patients With Ischemic Heart Disease Undergoing Coronary Angiography

It has been proposed that apolipoprotein J (apo J) and paraoxonase-1 (PON1) correlate with the extent and severity of ischemic heart disease (IHD). This article compares apo J and PON1 serum concentrations, PON1 activity, and the apo J/PON1 ratio in 138 IHD patients (64 statins users and 74 statin nonusers) referred for angiography and possible percutaneous coronary intervention. The effect of statin treatment on apo J and PON1 concentrations, PON1 activity, and the degree of coronary artery stenosis were evaluated. In both groups, apo J levels were increased, whereas PON1 concentration and activity decreased. IHD patients on statins had significantly lower apo J concentration and higher PON1 concentration and activity. Patients on statins had less coronary artery stenosis. High apo J levels, low PON1 levels, low PON1 activity, and a high apo J/PON1 ratio were associated with IHD. Statin treatment reverses these changes, probably by multiple beneficial actions.

Instillation of Coarse Ash Particulate Matter and Lipopolysaccharide Produces a Systemic Inflammatory Response in Mice

Coronary ischemic events increase significantly following a “bad air” day. Ambient particulate matter (PM10) is the pollutant most strongly associated with these events. PM10 produces inflammatory injury to the lower airways. It is not clear, however, whether pulmonary inflammation translates to a systemic response. Lipopolysaccharide (LPS) is a proinflammatory molecule often associated with the coarse fraction of PM. It was hypothesized that PM>2.5 from coal plus LPS induce pulmonary inflammation leading to a systemic inflammatory response. Mice were intratracheally instilled with saline, PM (200 μg), PM + LPS10 (PM + 10 μg LPS), or PM + LPS100 (PM + 100 μg LPS). Eighteen hours later, histologic analysis was performed on lungs from each group. Pulmonary and systemic inflammation were assessed by measuring the proinflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the pulmonary supernatant and plasma. In a follow-up study, the effects of LPS alone were assessed. Histologic analysis revealed a dose-dependent elevation in pulmonary inflammation with all treatments. Pulmonary TNF-α and IL-6 both increased significantly with PM + LPS100 treatment. Regarding plasma, TNF-α significantly increased in both PM + LPS10 and PM + LPS100 treatments. For plasma IL-6, all groups tended to rise with a significant increase in the PM + LPS100 group. The results of the follow-up study indicate that the responses to PM + LPS were not due to LPS alone. These results suggest that coarse coal fly ash PM>2.5 combined with LPS produced pulmonary and systemic inflammatory responses. The resulting low-level systemic inflammation may contribute to the increased severity of ischemic heart disease observed immediately following a bad air day.

Complement Gene Expression is Upregulated in the Type 2 Diabetic Heart Following Myocardial Ischemia and Reperfusion

There are several complications that contribute to the increased severity of ischemic heart disease in type 2 diabetes. Recent evidence suggests that activation of the complement component of innate immunity may contribute to the increased severity and mortality observed in the diabetic heart after ischemia/reperfusion (I/R). To further understand the role of complement gene expression in I/R injury, qRTPCR was performed on cardiac tissue samples taken from the at-risk region of Zucker Diabetic Fatty (ZDF) rats following 30 minutes of left anterior descending coronary artery occlusion and 120 minutes of reperfusion. Comparison of gene expression in myocardial I/R tissues from ischemic ZDF rats to non-ischemic ZDF demonstrates that complement component C3 gene expression was increased 1.6 fold. This finding parallels work from our laboratory demonstrating that there is significant complement component C3 deposition in the at-risk region of the ZDF heart compared to the Zucker Lean Control (ZLC) (ZLC: 44.3 ± 8.5%; ZDF: 82.4 ± 12.5%; p < 0.05). These results suggest that generation of complement within the myocardium may contribute to total complement content within the type 2 diabetic heart following I/R. The increased expression of C3 may play a role in the exacerbated inflammatory response to ischemia and reperfusion observed in the type 2 diabetic heart. Supported by NIH HLB 58859, AHA 0610018Z, and HHMI 52003749

Increased mRNA Expression of Endothelial Adhesion Molecules and Proinflammatory Cytokines in the Type 2 Diabetic Heart Following Ischemia/Reperfusion Injury

Restoration of blood flow is essential to preserve cardiac tissue viability and function, however it is now evident that cardiac reperfusion may lead to additional injury mediated largely by polymorphonuclear cells (PMNs). Recent work from our laboratory demonstrated that leukocyte accumulation in the coronary microcirculation may contribute to the severity of ischemic heart disease observed in the diabetic heart. PMN sequestration may be enhanced in the diabetic heart under situations of chronic endothelial cell activation, increased adhesion molecule, and/or other proinflammatory molecule expression. This observation of increased neutrophil sequestration in the myocardium following I/R led us to investigate the role of proinflammatory and endothelial adhesion molecule gene expression following I/R injury in the diabetic heart. Tumor necrosis factor (TNF)-α, interleukin (IL)-6, P-selectin, inducible nitric oxide synthase (iNOS), vascular cellular adhesion molecule (VCAM), and intercellular adhesion molecule (ICAM) were assessed by quantitative real time polymerase chain reaction (qRTPCR) in the at-risk region of the left ventricle following 30min of ischemia and 120min of reperfusion. Zucker Diabetic Fatty (ZDF) rats demonstrated an upregulation of VCAM (10.9 fold change), ICAM (1.7 fold change), and TNF-α (1.7 fold change) compared to Zucker Lean controls (ZLC). These results indicate a hyper-responsiveness of the ZDF heart to I/R, which may contribute to enhanced PMN-mediated I/R injury. Supported by AHA 0610018Z and NIH HLB 58859

Vitamin E reduces myocardial infarct size in type 2 diabetes

The interrelationship of type 2 diabetes (T2D), inflammation and ischemic heart disease (IHD) is not clear. We suspect that a low-level, chronic inflammatory response aggravates leukocyte-mediated ischemia-reperfusion (I/R) injury in the T2D heart. The purposes of this study were to: 1.) determine if myocardial injury due to I/R was increased in the Zucker Diabetic Fatty (ZDF) model of T2D, 2.) determine if treatment with vitamin E would attenuate ischemic injury. Zucker Lean Controls (ZLC) and ZDF rats were subjected to a left anterior descending coronary artery occlusion-reperfusion protocol. The recovery of left ventricular function and myocardial infarct size were determined. Neutrophil reactive oxygen species (PMN ROS) was measured in whole blood prior to ischemia. Four groups were studied. Group 1: ZLC-Placebo, Group 2: ZLC-Vit E, Group 3: ZDF-P and Group 4: ZDF-E. We found that the recovery of ventricular function (+dP/dt) was somewhat depressed in the diabetic group (ZLC-P = 87.4% ± 11.7 SEM, ZDF-P = 68.1% ± 5.5, P=NS), however, the recovery of the ZDF-E group was improved significantly (ZDF-E = 97.4% ± 10.3). The myocardial infarct size was significantly increased in the ZDF-P group but was reduced with vitamin E treatment (ZLC-P = 43.0% ± 1.9, ZDF-P = 57.0% ± 3.9, ZDF-E = 33.9% ± 5.1, P≤0.05). In addition, vitamin E treatment significantly reduced the chronic increase in PMN ROS observed in the ZDF-P group (P≤0.05). These findings indicate that ischemic injury is significantly increased in the ZDF heart and is associated with increased PMN ROS. Treatment with vitamin E reduced both PMN ROS and the severity of IHD in T2D. Supported by NIH HLB 58859.