Effects In Ischemic Heart Disease Research Articles

Tactics for Treating Thoracic Aortic Aneurysms using Hybrid and Endovascular Techniques in Patients with Concomitant Coronary Heart Disease

The presence of ischemic heart disease (IHD) in patients with aortic dissection increases the risk of intraoperative and postoperative complications during aortic repair. Researches on the effect of IHD on the treatment outcomes of patients with type B aortic dissection have not been carried out often. Only single publications based on relatively small statistical material are devoted to this problem in the literature. The cohort of patients with aortic dissection and IHD is extremely complex, and surgical correction of this comorbid condition is still a controversial topic. The aim. To analyze the impact of IHD with prior correction of coronary artery lesions on the results of hybrid and endovascular treatment of patients with thoracic aortic aneurysms. Materials and methods. From 2017 to 2023, on the basis of the National Amosov Institute of Cardiovascular Surgery of the National Academy of Medical Sciences of Ukraine, 245 patients with thoracic aortic aneurysm were treated using hybrid and endovascular techniques. Of these, 14 (5.7%) patients with coronary malperfusion underwent previous cor-rection of IHD either alone or in combination with prosthetics of the aortic valve, ascending aorta and arch of the aorta, initial section of the descending aorta (elephant trunk) with a good outcome. The comparison group included 30 (12.2%) patients who underwent endovascular or hybrid correction of the descending thoracic aorta without coronary pathology. Results. In the experimental group, 5 complications (42.9%) were detected (3 in the intraoperative period and 2 in the postoperative period). The frequency of complications of a similar nature in patients without concomitant IHD (com-parison group) was 13.3%. Endoleak type 1 was also dominant in this group. In most cases, it was eliminated by balloon dilatation of the stent graft. Only in 1 case, Endoleak type 1b was the reason for re-intervention with placement of an additional stent after 6 months. Conclusions. Studies show that the presence of even corrected IHD complicates the course of endovascular and hy-brid surgical treatment of thoracic aortic aneurysms, as evidenced by significantly higher rates of postoperative compli-cations, longer length of stay in the intensive care unit, as well as time on mechanical ventilation. Preliminary myocardial revascularization in patients with IHD should be one of the main conditions for the endovas-cular treatment of aortic aneurysms, taking into account the specifics of performing such operations and the possibility of fatal complications with hemodynamically significant narrowing of the coronary arteries.

Association of ischemic heart disease with long-term risk of cognitive decline and dementia: A cohort study.

The independent and joint effect of ischemic heart disease (IHD) and coexisting atrial fibrillation (AF) and heart failure (HF) on dementia risk is largely unknown. This population-based cohort study included 2568 dementia-free participants (age ≥60 years) in SNAC-K, who were regularly examined from 2001-2004 through 2013-2016. Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria. Global cognitive function was assessed using a global cognitive composite z-score derived from five cognitive domains. Data were analyzed using Cox, Fine-Gray, and linear mixed-effects models. Overall, IHD at baseline was associated with multivariable-adjusted hazard ratio (HR) of 1.39 (95% confidence interval=1.06-1.82) for dementia and multivariable-adjusted β-coefficient of -0.02 (-0.03 to -0.01) for annual changes in global cognitive z-score, independent of AF, HF, and cerebrovascular disease. Coexisting AF or HF did not add further risk to dementia and cognitive decline. IHD is independently associated with dementia and cognitive decline in older adults, whereas coexisting AF/HF is not associated with an increased risk. Is a history of ischemic heart disease (IHD) associated with a risk for dementia? How do coexisting heart diseases affect this association? IHD was an independent risk factor for dementia in older adults. This association was independent of coexisting heart and cerebrovascular diseases. The coexistence of heart diseases did not confer additional risk for dementia.

Evaluation of the Physical Parameters on Ischemic Heart Disease Patients Using Echocardiography

Background: Left ventricular function and volumes have major diagnostic and prognostic importance in patients with various cardiac diseases, such as ischemic heart disease which is a life-threatening heart disease condition characterized by systolic dysfunction and a decrease in cardiac output. According to left ventricular ejection fraction, the degree of ischemic heart disease was classified as mild, moderate, and severe. To determine cardiac function and hemodynamics, the echocardiography technique is used, which is a noninvasive diagnostic method. Patients and Methods: The study included 216 patients between 25 and 75 years old; 121 males and 95 females; 265 normal individuals (age range: 25 to 75 years old); 84 males and 181 females. Doppler echocardiography was used to assess left ventricular function. The measurements included left ventricular end-diastole diameter (LVIDd), left ventricular end-systole diameter (LVIDs), and left ventricular ejection fraction (LVEF%). Results show a significant correlation in the values of EDV, ESV and LVEF (all: p < 0.05). The change difference in left ventricular ejection fraction (LVEF) was (61.88%), (47.57%), and (36.76%), respectively, for all degrees of ischemia. While the change difference in left ventricular end diastolic volume (LVEDV)between patients and control groups was (173.38%), (248.83%), and (289.82%), respectively. On the other hand, the change in left ventricular end systolic volume (LVESV) was (258.73%), (495.13%), and (569.72%), respectively, for all degree of ischemia. Conclusion: The findings suggest that diastolic dysfunction is more common in patients than in healthy people. This could be due to the adverse effects of ischemic heart disease on the cardiac muscle. These changes in left ventricular structure may include left ventricular hypertrophy, increase in stiffness, and reduction in compliance.

Macrophage Polarization, Metabolic Reprogramming, and Inflammatory Effects in Ischemic Heart Disease.

Macrophages are highly plastic cells, and the polarization-activating actions that represent their functional focus are closely related to metabolic reprogramming. The metabolic reprogramming of macrophages manifests itself as a bias toward energy utilization, transforming their inflammatory phenotype by changing how they use energy. Metabolic reprogramming effects crosstalk with the biological processes of inflammatory action and are key to the inflammatory function of macrophages. In ischemic heart disease, phenotypic polarization and metabolic shifts in circulating recruitment and tissue-resident macrophages can influence the balance of inflammatory effects in the heart and determine disease regression and prognosis. In this review, we present the intrinsic link between macrophage polarization and metabolic reprogramming, discussing the factors that regulate macrophages in the inflammatory effects of ischemic heart disease. Our aim is to estabilsh reliable regulatory pathways that will allow us to better target the macrophage metabolic reprogramming process and improve the symptoms of ischemic heart disease.

Conditional depletion of the acetyltransferase Tip60 protects against the damaging effects of myocardial infarction

Injury from myocardial infarction (MI) and consequent post-MI remodeling is accompanied by massive loss of cardiomyocytes (CM), a cell type critical for contractile function that is for all practical purposes non-regenerable due to its profound state of proliferative senescence. Identification of factors that limit CM survival and/or constrain CM renewal provides potential therapeutic targets. Tip60, a pan-acetyltransferase encoded by the Kat5 gene, has been reported to activate apoptosis as well as multiple anti-proliferative pathways in non-cardiac cells; however, its role in CMs, wherein it is abundantly expressed, remains unknown. Here, using mice containing floxed Kat5 alleles and a tamoxifen-activated Myh6-MerCreMer recombinase transgene, we report that conditional depletion of Tip60 in CMs three days after MI induced by permanent coronary artery ligation greatly improves functional recovery for up to 28 days. This is accompanied by diminished scarring, activation of cell-cycle transit markers in CMs within the infarct border and remote zones, reduced expression of cell-cycle inhibitors pAtm and p27, and reduced apoptosis in the remote regions. These findings implicate Tip60 as a novel, multifactorial target for limiting the damaging effects of ischemic heart disease.

Ranolazine may exert its beneficial effects by increasing myocardial adenosine levels.

We hypothesized that ranolazine-induced adenosine release is responsible for its beneficial effects in ischemic heart disease. Sixteen open-chest anesthetized dogs with noncritical coronary stenosis were studied at rest, during dobutamine stress, and during dobutamine stress with ranolazine. Six additional dogs without stenosis were studied only at rest. Regional myocardial function and perfusion were assessed. Coronary venous blood was drawn. Murine endothelial cells and cardiomyocytes were incubated with ranolazine and adenosine metabolic enzyme inhibitors, and adenosine levels were measured. Cardiomyocytes were also exposed to dobutamine and dobutamine with ranolazine. Modeling was employed to determine whether ranolazine can bind to an enzyme that alters adenosine stores. Ranolazine was associated with increased adenosine levels in the absence (21.7 ± 3.0 vs. 9.4 ± 2.1 ng/mL, P < 0.05) and presence of ischemia (43.1 ± 13.2 vs. 23.4 ± 5.3 ng/mL, P < 0.05). Left ventricular end-systolic wall stress decreased (49.85 ± 4.68 vs. 57.42 ± 3.73 dyn/cm2, P < 0.05) and endocardial-to-epicardial myocardial blood flow ratio tended to normalize (0.89 ± 0.08 vs. 0.76 ± 0.10, P = nonsignificant). Adenosine levels increased in cardiac endothelial cells and cardiomyocytes when incubated with ranolazine that was reversed when cytosolic-5'-nucleotidase (cN-II) was inhibited. Point mutation of cN-II aborted an increase in its specific activity by ranolazine. Similarly, adenosine levels did not increase when cardiomyocytes were incubated with dobutamine. Modeling demonstrated plausible binding of ranolazine to cN-II with a docking energy of -11.7 kcal/mol. We conclude that the anti-adrenergic and cardioprotective effects of ranolazine-induced increase in tissue adenosine levels, likely mediated by increasing cN-II activity, may contribute to its beneficial effects in ischemic heart disease.NEW & NOTEWORTHY Ranolazine is a drug used for treatment of angina pectoris in patients with ischemic heart disease. We discovered a novel mechanism by which this drug may exhibit its beneficial effects. It increases coronary venous levels of adenosine both at rest and during dobutamine-induced myocardial ischemia. Ranolazine also increases adenosine levels in endothelial cells and cardiomyocytes in vitro, by principally increasing activity of the enzyme cytosolic-5'-nucleotidase. Adenosine has well-known myocardial protective and anti-adrenergic properties that may explain, in part, ranolazine's beneficial effect in ischemic heart disease.

Do blood eosinophils strictly reflect airway inflammation in COPD? Comparison with asthmatic patients

IntroductionAirway eosinophilic inflammation is a characteristic of asthmatic patients and of a sub group of COPD subjects. Blood eosinophils are deemed as a good surrogate marker of sputum eosinophilic inflammation; however, controversial data have been published particularly in COPD. The aim of our study was to compare blood and sputum eosinophils in COPD and asthmatic patients in “real life”.MethodsSputum was induced in stable patients with COPD or asthma with hypertonic saline solution and blood eosinophils were evaluated. Frequency of comorbidities was recorded. Correlations were performed stratifying patients by disease and comorbidities.Results146 patients, 57 with COPD and 89 with asthma were evaluated. Blood and sputum eosinophils expressed as percentages were correlated in COPD (rho = 0.40; p = 0.004), but the entity of correlation was lower compared with asthmatic subjects (rho = 0.71; p < 0.0001). When blood eosinophils were expressed as counts the correlation was slightly lower than when expressed as percentages in COPD (rho = 0.35; p = 0.01) and in asthmatic patients (rho = 0.68; p < 0.0001). In COPD patients older than 73 years or with blood eosinophils higher than the median value (210.6 eos/μl), or co-diagnosed with hypertension, ischemic heart disease or atrial fibrillation no correlation between blood and sputum eosinophils was found.However, the effect of ischemic heart disease and atrial fibrillation could be driven by hypertension since most of these patients have this comorbidity.ConclusionBlood eosinophils correlated with sputum eosinophils to a lesser degree in COPD than in asthmatic patients. Older age, high blood eosinophils and hypertension affected the correlation between blood and sputum eosinophils, more studies are needed to evaluate the role of other cardiac comobidities.

Cardiovascular events associated with nicorandil administration prior to primary percutaneous coronary intervention in patients with acute ST-segment elevated myocardial infarction: a systematic review and meta-analysis

ABSTRACTIntroduction: Nicorandil may exert cardioprotective effects in ischemic heart disease. However, its efficacy in combination with early reperfusion is uncertain. The authors performed a meta-analysis of the short- and long-term clinical outcomes of nicorandil administration at the time of primary percutaneous coronary intervention (PCI) in patients with ST-elevated myocardial infarction (STEMI).Methods: PubMed, MEDLINE, Embase, and the Cochrane Library databases were systematically searched for eligible randomized controlled studies. The primary endpoint was major adverse cardiovascular events (MACE), both in-hospital and post-discharge. The secondary endpoint was the incidence of no-reflow phenomenon.Results: Ten studies were included (n = 1105). Mean patient age was 63.0 ± 10.0 years; 76.6% of patients were male. Compared with controls who received primary PCI, combined nicorandil/primary PCI significantly reduced in-hospital MACE (pooled odds ratio [OR] 0.16; 95% confidence interval [CI] 0.09–0.27), follow-up MACE (pooled OR 0.53; 95% CI 0.37–0.75), and total MACE (pooled OR 0.27; 95% CI 0.15–0.49). The combined treatment also reduced the incidence of no-reflow phenomenon (pooled OR 0.34; 95% CI 0.23–0.50).Conclusion: Nicorandil administration at the time of primary PCI is associated with reduced MACE (both short- and long-term) and no-reflow phenomenon in patients with STEMI.

Cerebrovascular Control After Cardiac Rehabilitation in Ischemic Heart Disease Patients

In this study we evaluate the impact of ischemic heart disease (IHD) and cardiac rehabilitation (CR) on cerebrovascular control and peripheral vascular health. Patients with IHD are at greater risk for stroke, a risk determined in part by cerebrovasoreactivity tests (i.e., dilation or constriction to a known stimulus). Exercise provides cerebrovascular health benefits in the aging population; yet, effects of IHD and CR (exercise) on cerebrovascular health indicators and cerebral blood flow control are not understood. We explored cerebrovascular control (i.e., vasoreactivity and autoregulation), peripheral vascular health, brain volume, and white matter hyperintensities (WMH) in a group of healthy adults (CTL), and patients with IHD after cardiac event (pre‐CR) and following 6 months CR (post‐CR) comprised of 2–3 sessions/week of 30 minutes moderate intensity aerobic exercise and 30 minutes of resistance training. In 23 participants (CTL: 11, IHD: 12; age range: 40–75 years), we measured changes in cross‐sectional area (ΔCSA) divided by changes in end‐tidal CO2 (ΔPetCO2: CTL: 2.3±1.2, pre‐CR: 4.1±3.2, post‐CR: 5.2±2.2 mmHg)] during hypercapnic (5% CO2, 95% oxygen; ADInstruments) conditions using a 3 Tesla (Siemens) scanner and T1‐weighted pulse sequence (0.7 mm isotropic). Vasoreactivity was calculated for the basilar (BA), left (L) and right (R) internal carotid (ICA), anterior (ACA), middle (MCA), and posterior cerebral arteries (PCA) using OsiriX software. Autoregulation of the MCA was assessed by measuring relative changes in MCA flow velocity with respect to changes in mean arterial pressure during a sit‐to‐stand task, quantified by rate of regulation (ROR). Peripheral vascular health metrics included brachial artery flow‐mediated dilation (FMD; %) and common carotid artery (CCA) intima media thickness (mm) using duplex ultrasound. Compared to CTL, those with IHD had lower CSA reactivity (mm/mmHg; mean±SD; p&lt;0.05) in the BA (CTL: 0.74±0.73, pre‐CR: 0.29±0.29, post‐CR: 0.14±0.24), LICA (CTL: 1.1±0.86, pre‐CR: 0.93±1.03, post‐CR: 0.42±0.51), RICA (CTL: 0.93±0.71, pre‐CR: 0.48±0.35, post‐CR: 0.27±0.34), LMCA (CTL: 0.67±0.53, pre‐CR: 0.37±0.48, post‐CR: 0.14±0.12), and RMCA (CTL: 0.93±0.95, pre‐CR: 0.33±0.37, post‐CR: 0.29±0.33), which were not improved with CR. Compared to CTL, those with IHD had greater CCA IMT (CTL: 0.43±0.05, pre‐CR: 0.58±0.09, post‐CR: 0.59±0.07) which was not improved with CR, as well as lower ROR (CTL: 0.18±0.02, pre‐CR: 0.14±0.03, post‐CR: 0.16±0.03) and lower FMD (CTL: 9.1±4.3, pre‐CR: 4.7±2.3, post‐CR: 6.1±1.3; p&lt;0.05) which were improved with CR. Finally, brain volume and white matter lesions were similar across groups. Therefore, compared to healthy individuals, the IHD patients exhibited impaired cerebrovascular control and peripheral endothelial function. Peripheral vascular health, and cerebrovascular autoregulation, were improved with 6 months of CR in these IHD patients.Support or Funding InformationCanadian Institute of Health Research (201503MOP‐342412‐MOV‐CEEA).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The Role of Cardiac MRI In Coronary Heart Disease Management

Coronary artery disease is still the major cause of mortality in the western countries . Many studies have been conducted to find what are the best investigation to be included in the diagnosis, risk assessment and to assess the effect of ischemic heart disease ( including ACS) on the cardiac function as well as predict the response to treatment and future possibility of recurrent disease. CMR is now a crucial part of the diagnosis of heart disease especially the coronary artery disease (CAD) for many reasons: It makes early diagnosis which in turn means early intervention and less incidence of some of the complications of CAD. As the CMR examination do not expose patients to radiation, it can be used repetitively without harming the Since CAD is considered to be a chronic disease, the role of CMR in monitoring CAD patients regularly over many decades is highly valuable. In this litriture review, the specific role of CMR in the management of ischemic heart disease is studied in details by looking at many published articles . These articles focused on the performance of CMR in comparison to others methods of diagnosis. Some of these studies demonstrate the capability of CMR to diagnose CAD with both high sensitivity and specificity which could be comparable to other modalities like x-ray angiography ,CT scan and SPECT and others. Although the current role of CMR in the diagnosis of CDA is limited ,in comparison to other tests like CT and SPECT , this review has proved that CMR is an accurate diagnostic tool and has a comparable sensitivity and specificity to all other tests with exclusion of CT scan which has better performance

A high risk of hyperlipidemia in epilepsy patients: a nationwide population-based cohort study

PurposeThis study evaluated the effect of epilepsy on the development of hyperlipidemia (HL) in Taiwan. MethodsWe conducted a nationwide population-based cohort study based on data obtained from the National Health Insurance Research Database of Taiwan. We identified 990 cases involving patients whose epilepsy was newly diagnosed between 2000 and 2005, and we also selected a comparison cohort comprising 3960 patients without epilepsy. Cox proportional hazards regression models were used to examine the association between epilepsy and HL. ResultsThe mean follow-up period was 6.63 years for the epilepsy cohort and 7.49 years for the comparison cohort. The incidence rate of HL was 1.28-fold higher in the epilepsy cohort than it was in the comparison cohort (34.14 vs. 26.96 per 1000 person-years), with an adjusted hazard ratio of 1.17 (95% confidence interval, 1.01–1.36) after adjusting the model to account for the effects of sex and comorbidities. The most at-risk patients were those aged 50 to 59 years (hazard ratio, 1.35; 95% confidence interval, 1.04–1.79). For the epilepsy patients, the combined effect of ischemic heart disease, hypertension, and diabetes was associated with a significantly higher risk of developing HL compared with the patients with neither epilepsy nor any comorbidity. ConclusionsMiddle-aged epilepsy patients are at a significantly higher risk of developing HL. The results could assist in explaining the high risk of cerebral and cardiac vascular disease in epilepsy patients.

Novel Approaches and Opportunities for Cardioprotective Signaling Through 3′,5′-Cyclic Guanosine Monophosphate Manipulation

Limiting the injurious effects of myocardial ischemia-reperfusion is a desirable therapeutic target, which has been investigated extensively over the last three decades. Here we provide an up to date review of the literature documenting the experimental and clinical research demonstrating the effects of manipulating cGMP for the therapeutic targeting of the injurious effects of ischemic heart disease. Augmentation of the cyclic nucleotide cGMP plays a crucial role in many cardioprotective signaling pathways. There is an extensive body of literature which supports pharmacological targeting of cGMP or upstream activators in models of ischemia-reperfusion to limit injury. NO donors have long been utilised to manipulate cGMP, and more recently non-NO synthase derived NOx species have been investigated, resulting in their evaluation in clinical trials for the treatment of ischemic heart disease. Encouraging results demonstrate that natriuretic peptides are worthy candidates in manipulating cGMP and its downstream effectors to afford cytoprotection. Synthetic ligands have been designed which co-activate natriuretic peptide receptors to improve targeting this pathway. Advances have been made in targeting the soluble guanylyl cyclase which catalyzes the production of cGMP independently of the endogenous ligand NO using NO-independent stimulators and activators of sGC. These novel compounds show promise as a new class of drugs that target this signaling cascade specifically under pathological conditions when endogenous NO production may be compromised. Regulating the degradation of cGMP via phosphodiesterase inhibition also shows therapeutic potential. It is clear that production and regulation of cGMP is complex, indeed its spatial production and cellular distribution are only just emerging.

Mechanisms of the beneficial effects of vitamin B6 and pyridoxal 5-phosphate on cardiac performance in ischemic heart disease

Although vitamin B6 and its metabolite, pyridoxal 5'-phosphate (PLP), have been shown to exert beneficial effects in ischemic heart disease, the mechanisms of their action are not fully understood. Some studies have shown that ventricular arrhythmias and mortality upon the occlusion of coronary artery were attenuated by pretreatment of animals with PLP. Furthermore, ischemia-reperfusion-induced abnormalities in cardiac performance and defects in sarcoplasmic reticular Ca2+-transport activities were decreased by PLP. The increase in cardiac contractile activity of isolated heart by ATP was reduced by PLP, unlike propranolol, whereas that by isoproterenol was not depressed by PLP. ATP-induced increase in [Ca2+]i, unlike KCl-induced increase in [Ca2+]i in cardiomyocytes was depressed by PLP. Both high- and low-affinity sites for ATP binding in sarcolemmal membranes were also decreased by PLP. These observations support the view that PLP may produce cardioprotective effects in ischemic heart disease by attenuating the occurrence of intracellular Ca2+ overload due to the blockade of purinergic receptors.

Trends in Ischemic Heart Disease Mortality in Korea, 1985-2009: An Age-period-cohort Analysis

ObjectivesEconomic growth and development of medical technology help to improve the average life expectancy, but the western diet and rapid conversions to poor lifestyles lead an increasing risk of major chronic diseases. Coronary heart disease mortality in Korea has been on the increase, while showing a steady decline in the other industrialized countries. An age-period-cohort analysis can help understand the trends in mortality and predict the near future.MethodsWe analyzed the time trends of ischemic heart disease mortality, which is on the increase, from 1985 to 2009 using an age-period-cohort model to characterize the effects of ischemic heart disease on changes in the mortality rate over time.ResultsAll three effects on total ischemic heart disease mortality were statistically significant. Regarding the period effect, the mortality rate was decreased slightly in 2000 to 2004, after it had continuously increased since the late 1980s that trend was similar in both sexes. The expected age effect was noticeable, starting from the mid-60's. In addition, the age effect in women was more remarkable than that in men. Women born from the early 1900s to 1925 observed an increase in ischemic heart mortality. That cohort effect showed significance only in women.ConclusionsThe future cohort effect might have a lasting impact on the risk of ischemic heart disease in women with the increasing elderly population, and a national prevention policy is need to establish management of high risk by considering the age-period-cohort effect.

Clinical Diagnoses Before Age 75 and Men's Survival to Their 85th Birthday: The Manitoba Follow-up Study

Of all Canadian and American men who live to age 75 years, about half can expect to live to age 85. Our objective is to examine how clinical diagnoses made before age 75 relate to a man's survival to age 85 years. Since 1948, a cohort of 3,983 young men (mean age of 31 years at entry) has been followed with routine contact and medical examinations to prospectively document incident disease. Over 62 years of follow-up, 2,414 of the cohort lived to celebrate their 75th birthday. Of these survivors, 1,060 (44%) died before their 85th birthday. Cox proportional hazard models were used to examine the effects of ischemic heart disease, cancer, cerebrovascular disease, diabetes mellitus, peripheral arterial disease, and chronic obstructive pulmonary disease on all-cause mortality between age 75 and 85 years. Modeled as six binary risk factors at age 75 years, all were significantly (p < .01) and independently related to 10-year mortality. Multivariate risk ratios ranged from 1.36 to 1.46 except for chronic obstructive pulmonary disease with a risk ratio of 1.85 (95% CI: 1.38, 2.49). The cumulative 10-year probability of survival from age 75 to 85 among men with none of these diagnoses was 63%, 52% for any one diagnosis, 39% for two diagnoses, and 22% for three or more diagnoses. Joint independence of these six common clinical diagnoses implies that each is important and their effects on mortality are cumulative.

Assessment of heart rate variability in patients with chronic stable angina

Background and objectives: A prospective study performed in Ibn-Albitar hospital a tertiary center to assess the effect of ischemic heart disease on heart rate variability. Methods: Thirty nine consecutive patients all with history of chronic stable angina &amp;with positive treadmill test underwent 24 hours holter test to assess heart rate variability. Compared it with 25 age &amp; sex matched control volunteer group. Results: Thirty one (79.48%) male of patients group&amp; 20 (80%) male of control group . heart rate variability expressed as (SDNN) standard deviation of normal to normal interval, (RMSSD) square root of the mean squared differences of successive normal to normal intervals&amp; (pNN50) the proportion derived by dividing (NN50) the number of interval differences of successive normal to normal intervals greater than 50 milliseconds (ms.) by the total number of normal to normal intervals all were significantly lower in patients group. Conclusion: This study showed that heart rate variability significantly lower in patients with chronic stable angina.

Vagal Stimulation, Through its Nicotinic Action, Limits Infarct Size and the Inflammatory Response to Myocardial Ischemia and Reperfusion

Vagal activity has protective effects in ischemic heart disease. We tested whether vagal stimulation (VS) could modulate the inflammatory reaction, a major determinant of cardiac injury after ischemia/reperfusion. Four groups of male rats underwent myocardial ischemia (30 minutes) and reperfusion (24 hours). One group underwent VS (40 minutes), 1 VS plus atrial pacing (VS + Pacing), and 1 VS plus nicotinic inhibition by mecamylamine (VS + MEC). After 24 hours, the area at risk, infarct size, inflammation parameters, and apoptosis were quantified. Infarct size was reduced in all VS-treated rats (controls, 53 ± 18%; VS, 6.5 ± 3%; VS + Pacing, 23 ± 6%; VS + MEC, 33 ± 9%; P < 0.005 vs. controls). The infarct size in the VS + MEC group was larger than that in VS-treated animals, despite similar heart rate, suggesting partial loss of protection. The number of macrophages, neutrophils, and apoptotic cells in the area at risk and the plasma cytokines levels were significantly reduced in all VS-treated animals. In conclusion, VS decreases infarct size and inflammatory markers during ischemia/reperfusion independent of the heart rate. The anti-inflammatory and antiapoptotic properties of the nicotinic pathway are the primary underlying mechanism. The vagally mediated modulation of inflammatory responses may prove valuable in the clinical management of acute coronary syndromes and of heart failure.

Apelin protects heart against ischemia/reperfusion injury in rat

Apelin, the endogenous ligand of the G protein-coupled APJ receptor, is a peptide mediator with emerging regulatory actions in the heart. We aimed to determine whether the endogenous apelin/APJ system is an intrinsic protective pathway in ischemic/reperfusion injury. A Langendorff model of perfused isolated rat hearts and primary cultured myocardial cells from neonatal rats were used. Cardiac function was monitored and apelin/APJ expression was determined by real-time PCR and Western blot analysis. In rats under I/R, cardiac function was significantly decreased as compared with controls, and APJ was over-expressed at both the mRNA and protein levels (by 7-fold and 35%, respectively, both p < 0.01). However, pre-administration of apelin (30 pmol/L) greatly ameliorated the reduced heart function. To gain mechanistic insight into the cardio-protective effects of apelin/APJ, cultured cardiomyocytes were treated with apelin (30 pmol/L), and those under hypoxia/re-oxygenation showed H/R-induced apoptosis and up-regulated apelin/APJ mRNA expression by 6-fold and 7-fold, respectively (both p < 0.01). And lactate dehydrogenase leakage was greatly increased as well. Meanwhile, apoptosis, the generation of reactive oxygen species and malonaldehyde content as well as lactate dehydrogenase leakage were inhibited by apelin. Furthermore, apelin enhanced superoxide dismutase activity and phosphorylation of extracellular signal-regulated kinase 1/2 and Akt after hypoxia/re-oxygenation. In conclusion, apelin/APJ has protective effects in ischemic heart disease and might constitute an important therapy target.

Effects of ischemic heart disease and exercise training on mechanisms of nitric oxide production

Control and collateral‐dependent coronary arteries of exercise trained swine display enhanced nitric oxide‐dependent bradykinin‐mediated relaxation. For this study, we hypothesized that exercise training elicits cellular adaptations to enhance nitric oxide production in coronary arteries of ischemic hearts. Ameroid constrictors were placed around the proximal left circumflex coronary artery (LCX) of adult female Yucatan miniswine. Collateral‐dependent (LCX) and control (nonoccluded left anterior descending) arteries (∼1–2 mm diam) were isolated from sedentary and exercise trained (treadmill; 14 wks) pigs. Endothelial cells were dissociated and intracellular Ca2+ (fura‐2) responses to bradykinin were studied. Caveolin‐1 and eNOS protein levels were evaluated by immunoblot. Exercise training significantly enhanced bradykinin‐stimulated Ca2+ levels in cells of both control and collateral‐dependent arteries. Caveolin‐1 protein was significantly elevated in collateral‐dependent arteries of sedentary pigs; an increase that was reversed with exercise training. eNOS protein was not altered by occlusion or exercise training. Our studies suggest that increased bradykinin‐stimulated endothelial Ca2+ levels and reduced caveolin‐1 protein contribute to improved bradykinin‐mediated relaxation in both control and collateral‐dependent arteries of exercise trained swine. NIH HL64931

A Comparative Analysis of Short- and Long-Term Outcomes After Ventricular Fibrillation Out-of-Hospital Cardiac Arrest in Patients With Ischemic and Nonischemic Heart Disease

Although ventricular fibrillation (VF) out-of-hospital cardiac arrest (OHCA) occurs primarily in the setting of severe ischemic heart disease (IHD), a significant proportion of events occurs in patients who do not have severe IHD. The relative effect of IHD on survival after VF OHCA is unknown. All residents of Rochester, Minnesota, who presented with a VF OHCA from November 1990 to December 2004, treated by emergency medical services, were included in the study. During the study, emergency medical services treated 208 patients (64.1 +/- 13.6 years of age) for VF OHCA, with an average call-to-shock time of 6.3 +/- 1.8 minutes. Of these patients, 156 had IHD and 39 had non-IHD. In 13, the underlying heart disease was unknown. Eighty-seven patients (41.8%) survived to hospital discharge with neurologic recovery (66 with IDH [42%] vs 21 with non-IHD [54%], p = 0.211)]. Five-year survival was 79 +/- 6% for patients with IHD versus 100% for those with non-IHD (p = 0.047). After adjustment for other patient characteristics, IHD was not predictive of 5-year survival (hazard ratio [HR] 2.2, 95% confidence interval [CI] 0.7 to 9.8, p = 0.177). Variables associated with poor outcomes included age >65 years (HR 4.9, 95% CI 2.0 to 13.4, p = 0.0003), ejection fraction <0.35% (HR 3.0, 95% CI 1.3 to 7.3, p = 0.012), and hypertension (HR 4.9, 95% CI 1.4 to 16.3, p = 0.001). In patients with IHD, use of an implantable cardioverter-defibrillator (HR 0.32, 95% CI 0.16 to 0.88, p = 0.024) and statin therapy (HR 0.68, 95% CI 0.17 to 0.73, p = 0.001) were associated with decreased mortality. In conclusion, compared with patients with non-IHD, those with IHD had similar short- and long-term survival rates. Long-term survival in patients with IHD was primarily influenced by other co-morbid conditions. Nonetheless, in patients with IHD, use of an implantable cardioverter-defibrillator and statin therapy were associated with higher long-term survival rates.