Stem cell therapy for ischemic heart disease

Recent experimental and clinical observations have suggested that cell transplantation could be of therapeutic value for the treatment of heart disease. This approach was based on the idea that transplanted donor cardiomyocytes would integrate with the host myocardium and thereby directly contribute to cardiac function. Surprisingly, the observation that non-cardiomyogenic cells could also improve cardiac function indicates that functional integration of donor cells might not be required to achieve a beneficial effect. More recently, several observations have suggested the presence of a greater than anticipated developmental repertoire in adult-derived stem cells, which, if further validated, would offer unprecedented opportunities for the restoration of cardiac function in diseased hearts. Here, we discuss current issues regarding the potential use of stem cell transplantation for the treatment of ischemic heart disease.     

Blood filterability in ischemic heart disease

The aim of this paper is to test whether an alteration of blood flow in microcirculation and in particular of red cell deformability is present in myocardial ischaemia. To this end we determined by the method proposed by Reid and Dormandy (J. Clin. Pharmacol. 1976, 29, 855) whole-blood filterability in 23 patients with myocardial ischaemia, in 15 clinically healthy subjects and in 99 subjects without clinical evidence of ischemic pathology displaying one or more vascular risk factors. Blood filterability turned out to be significantly lower in cases of coronary diseases than in controls (p less than 0,001), while it was lower but not significantly so, than in subjects displaying risk factors. We conclude therefore that the presence of risk factors is enough important to be considered one of the fundamental elements (though non the only one) in causing the reduction of blood-filterability encountered in ischemic cardiopathology.     

Changing patterns in drug therapy for ischemic heart disease

To determine the possible influence of studies on β-blocker therapy following myocardial infarction and the introduction of calcium-channel blockers on the prescribing habits of physicians in a large urban centre, the drug therapy received by 100 patients with ischemic heart disease (IHD) (50 with myocardial infarction and 50 with unstable angina) admitted to a university teaching hospital in 1980 was compared with that received by another such group of 100 patients admitted in 1983-84. The proportion of patients with myocardial infarction receiving drug therapy was significantly higher in 1983-84, at the time of both admission (p < 0.01) and discharge (p < 0.001). Much of the increase was due to greater use of β-blockers. Of the 50 patients with unstable angina in 1983-84, 20 were taking calcium-channel blockers when admitted, and 29 were taking them when discharged. In both 1980 and 1983-84 unstable angina was treated more vigorously than myocardial infarction. The results suggest that physicians have developed a more aggressive approach to drug therapy for IHD since the publication of the β-blocker studies and the introduction of calcium-channel blockers.     

Copper and ischemic heart disease

Absolute or relative deficiency of copper is hypothesized to be of prime importance in the etiology of ischemic heart disease. According to recent estimates, only 25% of the diets in the United States contain the 2 mg of copper thought to be required daily by adults. Some of these diets have ratios of zinc to copper greater than those that have produced hypercholesteremia in animals. There are many epidemiologic associations between the ratio of zinc to copper and dietary characteristics, organ analyses, clinical status, and environmental features that relate the metabolism of these elements to the anatomy, chemistry, pathology, pharmacology, and physiology of ischemic heart disease. Animals deficient in copper or exposed to a high dietary ratio of zinc to copper, which can produce a relative copper deficiency, are hypercholesteremic and hyperuricemic, and have glucose intolerance and abnormalities of the electrocardiogram. Their hearts and arteries have abnormal connective tissue, lipid deposits, and inflammatory changes; they die suddenly, often with ruptured hearts. Hypercholesteremia and glucose intolerance have been found in men depleted of copper and in children with Menkes’ disease, an inability to absorb copper.     

Sex differences in ischemic heart disease and heart failure biomarkers

Since 1984, each year, more women than men die of ischemic heart disease (IHD) and heart failure (HF), yet more men are diagnosed. Because biomarker assessment is often the first diagnostic employed in such patients, understanding biomarker differences in men vs. women may improve female morbidity and mortality rates.Some key examples of cardiac biomarker utility based on sex include contemporary use of “unisex” troponin reference intervals under-diagnosing myocardial necrosis in women; greater use of hsCRP in the setting of acute coronary syndrome (ACS) could lead to better stratification in women; and greater use of BNP with sex-specific thresholds in ACS could also lead to more timely risk stratification in women.Accurate diagnosis, appropriate risk management, and monitoring are key in the prevention and treatment of cardiovascular diseases; however, the assessment tools used must also be useful or at least assessed for utility in both sexes. In other words, going forward, we need to evaluate sex-specific reference intervals or cutoffs for laboratory tests used to assess cardiovascular disease to help close the diagnostic gap between men and women.     

The changing pattern of ischemic heart disease

Male and female death rates from all the major forms of cardiovascular disease were approximately equal until about 1920. Since that time the male:female ratio in fatal ischemic heart disease (IHD) has risen dramatically, but some closely related diseases such as cerebrovascular disease and uncomplicated angina pectoris have maintained sex ratios close to unity. It is difficult to reconcile this divergent trend in the sex ratio of IHD with a simple stenotic-thrombotic view of myocardial infarction (MI) and it is suggested that the modern epidemic of MI in men may be the result of a disorder of muscle metabolism (“vulnerable myocardium”) superimposed on a relatively stable background of stenotic-thrombotic arterial disease. The proposed mechanism would also help to explain the selective action of some modern “coronary risk factors” (such as cigarette smoking and physical inactivity) which increase the risk of MI but have little or no effect on the risk of developing cerebrovascular disease or uncomplicated angina pectoris.     

血液稀释在缺血性心脏疾患中的应用

近年来,血液稀释(hemodilution,HD)作为一种治疗方法受到普遍重视,尤其是用于心脏外科和脑卒中等取得显著疗效之际,现正在扩大其应用范围。HD指的是输注不含血液成份的液体、抽取或不抽取血液而造成血液成份浓度的降低。血液被稀释的程度,均以血细胞压积(Hct)表示,临床上常作如下分级:轻度HD:Hct>30%,中度HD:Hct 20～30%,重度HD:Hct 10～20％,极度HD:Hct<10％。根据HD的血容量又可分为等容的HD和超容的HD两种。等容HD所补给的液体量等于抽出的血量;超容的HD补给液体量超过抽出的血量,甚至不抽取血液只输注液体,亦使循环血容量超过正常血循环量。     

Behavioural prevention of ischemic heart disease.

Heart disease continues to be a major cause of disablement and death in Canada. Elevated serum cholesterol concentrations, hypertension and cigarette smoking are among the standard risk factors associated with ischemic heart disease. Research attention has also been directed at the role of behavioural factors in the development of atherosclerosis and myocardial infarction. Experimental findings support a conceptual approach to the interplay of psychologic stress, the type A "coronary"-prone behaviour pattern and pathophysiologic mechanisms that have been implicated in the development of coronary artery disease. It is concluded that type A behaviour and stress contribute substantially to the pathogenesis of cardiovascular disease. However, assessment of the manner in which these two variables influence the pathophysiology of ischemic heart disease requires further research, with systematic examination of physiologic and biochemical processes. Potential strategies for modifying type A behaviour are reviewed. However, unequivocal support for the preventive efficacy of behavioural approaches must await future research.     

Hemorheologic findings in patients with ischemic heart disease

The paper deals with the rheological properties of the blood of 38 male patients affected by ischaemic heart diseases (age: 40-75 years) and 19 healthy test persons of comparable age. The following haemorheological properties were measured. 1. Relative plasma viscosity 2. Erythrocyte aggregation 3. Erythrocyte deformability 4. Thrombocyte aggregation and 5. Whole blood viscosity. For the purpose of representing and assessing the results of measurement obtained a division was made into different groups according to the appearances of ischaemic heart disease (chronic ischaemic heart disease, unstable angina pectoris, acute heart infarct) and risk factors (smoking, diabetes mellitus, blood high pressure and hyperlipidaemia). The methods 1-3 proved to be especially suitable for representing gradual differences in the examined rheological parameters. The results obtained are discussed and evaluated.     

Magnetic resonance stress tagging in ischemic heart disease

High-dose dobutamine magnetic resonance stress testing has been shown to be superior to dobutamine stress echocardiography for diagnosis of coronary artery disease (CAD). We determined the feasibility of quantitative myocardial tagging during low- and high-dose dobutamine stress and tested the ability of global systolic and diastolic quantitative parameters to identify patients with significant CAD. Twenty-five patients suspected of having significant CAD were examined with a standard high-dose dobutamine/atropine stress magnetic resonance protocol (1.5-T scanner, Philips). All patients underwent invasive coronary angiography as the standard of reference for the presence (n = 13) or absence (n = 12) of significant CAD. During low-dose dobutamine stress, systolic (circumferential shortening, systolic rotation, and systolic rotation velocity) and diastolic (velocity of circumferential lengthening and diastolic rotation velocity) parameters changed significantly in patients without CAD (all P < 0.05 vs. rest) but not in patients with CAD. Identification of patients without and with CAD during low-dose stress was possible using the diastolic parameter of "time to peak untwist." At high-dose stress, none of the global systolic or diastolic parameters showed the potential to identify the presence of significant CAD. With myocardial tagging, a quantitative analysis of systolic and diastolic function was feasible during low- and high-dose dobutamine stress. In our study, the diastolic parameter of time to peak untwist as assessed during low-dose dobutamine stress was the most promising global parameter for identification of patients with significant CAD. Thus quantitative myocardial tagging may become a tool that reduces the need for high-dose dobutamine stress.     

Erythrocyte membrane fatty acids in ischemic heart disease

The erythrocyte ghosts fatty acid composition of 27 patients with coronary artery disease (CAD) and 6 healthy people were investigated. Patients suffering from CAD were divided in two groups. The first group was matched by 18 patients with CAD and essential hypertension (EH) and 9 patients with CAD without EH. Significant decrease of the levels of some saturated fatty acids such as palmitic, stearic and begenic acids in the erythrocyte ghosts of the patients with CAD without EH was established among the major changes of the erythrocyte ghosts fatty acid composition. At the same time the amount, of arachidonic acid increased by 74% and docosahexaenoic acid--by 5.7 times. The content of miristic, palmitic and stearic acids was also diminished in patients with CAD and EH. The percent of arachidonic acid was elevated by 51% and docosatrienic acid--by 94%. It is notable that the quantity of docosahexaenoic acid did not change markedly if copmare to healthy people but was fallen for 5 times if compare to patients with CAD without EH. It was suggested that the lack of adaptive changes in erythrocyte ghosts omega-3 fatty acids of patients with CAD and EH was an important factor which could rise the risk of heart attack development.     

Innate immunity and cardiomyocytes in ischemic heart disease

Myocardial ischemia/reperfusion (I/R) is the most common cause of myocardial inflammation, which is primarily a manifestation of the innate immune responses. Innate immunity is activated when pattern recognition receptors (PRRs) respond to molecular patterns common to microbes and to danger signals expressed by injured or infected cells, so called pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). The expression of various PRRs in cardiomyocytes and the release of DAMPs from cardiomyocytes subjected to I/R injury, through active mechanisms as well as passive processes, enable cardiomyocytes to generate innate immune responses. Studies in isolated heart and cardiomyocytes have confirmed the inflammatory and functional effects of cardiac PRRs especially Toll-like receptors in response to I/R-derived DAMPs, such as heat shock proteins. This review addresses the active role of cardiomyocytes in mediating innate inflammatory responses to myocardial I/R. We propose that cardiomyocytes act as innate immune cells in myocardial I/R injury.     

Early results of endovascular treatment of chronic coronary occlusion in patients with ischemic heart disease

The early results of endovascular treatment of chronic coronary occlusion were studied. Immediate success rates were 67%. The factors that promote successful endovascular treatment in patients with this condition were as follows: less than 2-month disease duration, well-developed intersystemic collaterals, no "bridge" collaterals. Successful recanalization for chronic coronary occlusion improves the quality of life and bicycle ergometer test finding in patients, which reduces their needs of nitrates and beta-blockers. Coronary occlusion stenting yields better immediate angiographic results than does balloon angioplasty: residual stenosis and the minimum diameter of stenosis after stenting were 13.61 +/- 6.3% and 2.69 +/- 0.4 mm, respectively; those after balloon angioplasty were 23.1 +/- 8.1% and 2.31 +/- 0.37 mm, respectively.     

Properties of human serum albumin in ischemic heart disease

Conformational changes in blood serum albumin under heart ischemia are found from the dispersion parameters of optical rotation and circular dichroism. It is also found that patients with myocardium infarction have a considerable amount of carbohydrate components in the modified albumin form.     

Cellular cardiomyoplasty with autologous skeletal myoblasts for ischemic heart disease and heart failure

Cell transplantation to repair or regenerate injured myocardium is a new frontier in the treatment of cardiovascular disease. Even though it is based on many years of pre-clinical studies, much remains to be understood about this methodology, even as it progresses to the clinic. For example, controversies exist over the specific cells to be used, the dosages needed for tissue repair, how cells will affect the electrical activity of the myocardium, and even whether the cells can improve myocardial function after transplantation — all of which are briefly reviewed here. Autologous skeletal myoblasts appear to be the most well studied and best first generation cells for cardiac repair. Yet cardiocytes and, more recently, stem cells have been proposed as cell sources for this technology. Their advantages and limitations are also discussed. Although cellular cardiomyoplasty (cell transplantation for cardiac repair) shows great pre-clinical promise, its future will heavily depend on conducting carefully controlled, randomized clinical trials with appropriate endpoints. Utilizing biologically active cells provides both an opportunity for tissue repair and the potential for not yet understood outcomes. As with any frontier, many pioneers will attempt to conquer it. But also as with any frontier, there are pitfalls and consequences to be considered that may surpass those of previous endeavors. The future thus requires careful consideration and well-designed trials rather than haste. The promise for cell transplantation is too great to be spoiled by ill-designed attempts that forget to account for the biology of both the cells and the myocardium.     

Angiogenic strategy for human ischemic heart disease: Brief overview

Diabetes mellitus is one of the most common endocrine diseases. In UAE many traditional plants such as the Citrullus colocynthis (Handal) are used as antidiabetic remedies. The aim of this study was to examine the effect of the aqueous extract of the seed of C. colocynthis on the biochemical parameters of normal and streptozotocin (STZ)-induced diabetic rats. Diabetes mellitus was induced by a single intraperitoneal (60 mg/kg body wt1) injection of STZ. Normal and diabetic rats were fed with the plant extract daily by oral intubation for 2 weeks. Blood sample were collected at the beginning and end of the experiment for the measurement of biochemical parameters. The plasma level of alanine aminotranferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), lactic dehydrogenase (LDH) increased significantly after the onset of diabetes. Oral administration of the plant extract reduced the plasma level of AST and LDH significantly. However, the plant extract failed to reduce the increased blood level of GGT and ALP in diabetic rats. Blood urea nitrogen (BUN) increased significantly after the onset of diabetes. No significant difference was observed in the blood creatinine, K+, Na+, Ca2+ and P levels of normal and diabetic rats. The plant extract did not have any effect on BUN level, however, it caused an increase in the level of K+, Na+ in diabetic rats. In conclusion, oral administration of the aqueous extract of the C. colocynthis can ameliorate some of the toxic effects of streptozotocin.