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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bicaval anastomoses in orthotopic cardiac transplantation offer the advantage of preserving the right atrial geometry. To elucidate the impact of this anastomotic technique on atrial natriuretic peptide plasma levels at rest and with exercise, nine patients were submitted to a symptom-limited supine exercise test. Atrial natriuretic peptide plasma levels in samples obtained from the right atrium were elevated at rest (274.4 +/- 60.4 pg/ml), at peak exercise (438.1 +/- 71.7 pg/ml), and thereafter (328.1 +/- 71.2 pg/ml) with respect to normal reference values of 21 +/- 1 pg/ml at rest and 92 +/- 14 at peak exercise. Renin, angiotensin, and aldosterone plasma levels were almost normal and did not indicate any pathologic processes in volume homeoostasis. Right-sided hemodynamic parameters were not correlated with atrial natriuretic peptide secretion. An adverse relationship between cold ischemic time of the donor organ and atrial natriuretic peptide release was found (r = 0.88, p < 0.0008), indicating that endocrine cardiocytes are sensitive to prolonged ischemia. Atrial natriuretic peptide release may thus be independent of the surgical approach, and other unique characteristics of the transplanted heart, such as denervation, are more likely to be responsible for elevated atrial natriuretic peptide plasma concentrations after orthotopic heart transplantation.
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PMID:Atrial natriuretic peptide release at rest and with exercise after cardiac transplantation with bicaval anastomoses. 852 69

Left ventricular hypertrophy is considered to be an independent risk factor giving rise to ischemia, arrhythmias, and left ventricular dysfunction. Slow movement of intracellular calcium contributes to the impaired contraction and relaxation function of hypertrophied myocardium. Myofibril content may also be shifted to fetal-type isoforms with decreased contraction and relaxation properties in left ventricular hypertrophy. Myocyte hypertrophy and interstitial fibrosis are regulated independently by mechanical and neurohumoral mechanisms. In severely hypertrophied myocardium, capillary density is reduced, the diffusion distance for oxygen, nutrients, and metabolites is increased, and the ratio of energy-production sites to energy-consumption sites is decreased. The metabolic state of severely hypertrophied myocardium is anaerobic, as indicated by the shift of lactate dehydrogenase marker enzymes. Therefore, the hypertrophied myocardium is more vulnerable to ischemic events. As a compensatory response to severe cardiac hypertrophy and congestive heart failure, the ADP/ATP carrier is activated and atrial natriuretic peptide is released to increase high-energy phosphate production and reduce cardiac energy consumption by vasodilation and sodium and fluid elimination. However, in severely hypertrophied and failing myocardium, vasoconstrictor and sodium- and fluid-retaining factors, such as the renin-angiotensin system, aldosterone, and sympathetic nerve activity, play an overwhelming role. Angiotensin-converting enzyme inhibitors (ACEIs) are able to prevent cardiac hypertrophy and improve cardiac function and metabolism. Under experimental conditions, these beneficial effects can be ascribed mainly to bradykinin potentiation, although a contribution of the ACEI-induced angiotensin II reduction cannot be excluded.
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PMID:Substrate metabolism, hormone interaction, and angiotensin-converting enzyme inhibitors in left ventricular hypertrophy. 852 2

In chronic heart failure, angiotensin-converting enzyme inhibitors produce an acute decrease in aldosterone levels. Long-term angiotensin-converting enzyme inhibition is, however, associated with aldosterone suppression that is weak, variable, and unsustained (ie, aldosterone escapes). The possible harmful effects of this residual aldosterone are multiple Magnesium loss caused by aldosterone and by diuretics could contribute to coronary artery spasm and arrhythmias. Aldosterone blocks norepinephrine uptake by the myocardium; extracellular catecholamines may, therefore, lead to arrhythmias and ischemia. Aldosterone has been shown to have an acute arrhythmogenic effect as well as a detrimental effect on parasympathetic and baroreflex function. Both angiotensin II and aldosterone stimulate myocardial fibrosis, which may lead to a higher incidence of malignant ventricular arrhythmias. Spironolactone therapy added to the regimen of an angiotensin-converting enzyme inhibitor and diuretic has been shown to cause natriuresis, magnesium retention, increased myocardial norepinephrine uptake, and reduced incidence of ventricular arrhythmias. It may well be that residual aldosterone mediates many harmful effects in chronic heart failure and that to optimize the benefit of blocking the renin-angiotensin-aldosterone system may require specific blockade of residual aldosterone as well as traditional angiotensin-converting enzyme inhibition.
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PMID:Aldosterone escape during angiotensin-converting enzyme inhibitor therapy in chronic heart failure. 879 5

While it is well known that unilateral tissue ischemia may result in contralateral damage in some paired organs, there is no universally accepted mechanism to explain why these contralateral changes occur. The aim of the present study was to investigate the ultrastructural and hormonal changes that occur in the contralateral nonischemic adrenal gland after unilateral ischemia of an adrenal gland in a rat model. The animals were divided into four groups of four rats each; namely, a control group which received a sham operation without any ischemic insult, a 2-h ischemic group, a 4-h ischemic group, and an 8-h ischemic group. The left adrenal blood vessels were ligated in all ischemia groups and blood samples were taken for hormonal study 2, 4, and 8 h later, after which bilateral adrenalectomy was performed to determine the ultrastructural changes. The plasma concentrations of aldosterone and cortisol were determined by radioimmunoassays. There was an increase in both aldosterone and cortisol levels related to the duration of the ischemia, but the differences among the groups were not statistically significant. Contralateral ultrastructural damage such as heterochromatin in nuclei, mitochondrial degeneration, endoplasmic reticulum cisternal widening, increased lipid droplets, and lysosomes, were demonstrated electron-microscopically after unilateral adrenal ischemia.
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PMID:Ultrastructural and hormonal changes in the contralateral adrenal gland in unilateral adrenal gland ischemia: an experimental study in rats. 974 99

The usefulness in cirrhotic patients of hemodynamic measurements by Doppler ultrasonography (US) is still not defined. We investigated the relationships between Doppler measurements and the severity of ascites. Portal blood flow velocity and volume, and hepatic and renal arterial resistance indexes (RI) were measured in 57 cirrhotic patients (19 without ascites, 28 with responsive ascites, and 10 with refractory ascites) and 15 healthy controls. The renal arterial RI were obtained for the main renal artery, interlobar vessels, and cortical vessels. Cirrhotic patients had decreased portal blood flow and an increased congestion index (CI). Only the CI was correlated to the severity of ascites, showing that it is also a reliable measure of the severity of portal hypertension in patients with ascites. The hepatic and renal artery RI were increased in cirrhotic patients, and the two values were correlated (r = .68; P = .00001). The RI of renal interlobar and cortical vessels were higher in patients with refractory ascites than in patients without ascites (P < .02 and P < .009), and correlated with sodium excretion rate (r = -.45; P < .003), the renin-aldosterone system, and creatinine clearance (r = -.62; P < .0002). The RI decreased from the hilum of the kidney to the outer parenchyma in healthy subjects and patients with responsive ascites, but this difference disappeared in patients with refractory ascites. This indicates that the degree of renal vasoconstriction varies in different areas according to the severity of the ascites. Cortical vessels are involved mainly in patients with refractory ascites, suggesting that the intrarenal blood flow distribution in cirrhosis tends to preserve the cortical area and that severe cortical ischemia is a feature of refractory ascites.
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PMID:Reduction of renal cortical blood flow assessed by Doppler in cirrhotic patients with refractory ascites. 979 6

Hospital mortality from acute myocardial infarction has decreased in the last two decades. Left ventricular dysfunction therefore have been mainly due to ischemia. After extensive myocardial infarction, there are processes of adaptation (remodeling) which result in altered geometry of the left ventricle. The effects of this on neurohormonal systems (organ regulation), on the changed ratio of myocyte mass and collagen content owing to reactive and reparative fibrosis (organ texture) and on the molecular and cellular mechanisms (organ structure) are of crucial importance. Depending on the structural changes, the myocardial contractility decreases. This is associated with an activation of the circulating renin-angiotensin-aldosterone system (RAAS). The fundamental knowledge available has led to the therapeutic use of ACE inhibitors in the post-infarct period. This treatment enabled a sustained reduction of mortality in several large-scale randomized studies. The effect of early administration in patients with clinical signs of heart failure and/or left ventricular dysfunction was very much greater compared to unselected controls. Only 17 and 13 patients had to be treated after selection in order to save one life in the AIRE and TREACE Study respectively (NNT: number needed to treat), whereas e.g. in the ISIS-4 study 200 unselected patients had to be treated. In clinical practice, however, this life-saving therapy is only used in every second patient requiring treatment. With consideration of an individual form of treatment (anterior infarction, large infarct area, reinfarction, clinical signs of heart failure as well as arterial hypertension and diabetes mellitus), a greater acceptance of evidence-based guidelines is thus desirable. Treatment with a high dose may be expected to be of additional benefit.
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PMID:[Left ventricular remodeling: pathophysiological mechanisms and therapeutic recommendations]. 1065 89

Ischemic heart disease is the principal etiology of heart failure in the Western world. Myocardial ischemia is important in cardiac remodeling, a process that leads to a progressive change in the shape and size of the heart and significantly worsens the prognosis of patients with heart failure. Preventing ischemic events, therefore, is an important goal in the management of patients with coronary artery disease. Statins have been shown to reduce the number of ischemic events in these patients, whereas the benefit of beta-blocker and aldosterone antagonist therapy on ischemic causes of heart failure remains unclear. Several large trials involving patients with asymptomatic left ventricular dysfunction after myocardial infarction or heart failure have shown that angiotensin-converting enzyme (ACE) inhibitors reduce the incidence of progressive heart failure, death, and ischemic events, thus establishing ACE inhibitors as first-line therapy for these patients. Other lines of evidence have suggested that ACE inhibitor therapy may also benefit patients with preserved left ventricular function, a hypothesis that is being evaluated in three large, controlled, randomized trials. One of these trials, the Heart Outcomes Prevention Evaluation (HOPE) study, was terminated prematurely because it demonstrated the significant positive effects of the ACE inhibitor ramipril on cardiovascular outcomes in patients with coronary artery disease and preserved left ventricular function. A growing body of data confirms the relationship between ischemia and heart failure and the benefits of ACE inhibitor treatment in a broad range of high-risk patients.
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PMID:Overview of the relationship between ischemia and congestive heart failure. 1089 49

Recent data show that blockade of aldosterone receptors by spironoloctone reduces the risk of morbidity and death among patients with severe heart failure. Heart failure secondary to ischemia is characterized by an imbalance of the autonomic nervous system, which can be assessed by analysis of the heart rate variability (HRV). Spironolactone's effects on HRV are not well defined. If spironolactone has beneficial effects on HRV, this would contribute to favorable results. We therefore measured Holter-derived HRV indexes in a group of 126 patients with heart failure, aged 36 to 83 years, with angiographically proved coronary artery disease, on 3 separate occasions. Patients' sodium intake was restricted; therapy with enalapril, furosemide, and digoxin was begun, and 2 weeks after this standard therapy, spironolactone 50 mg/day was added. Evaluations were done at baseline, and the first and 12th months. After spironolactone, the triangular interpolation of the NN histogram (from 233.0 +/- 98 to 291.7 +/- 74 ms and 340.5 +/- 130 ms, p <0.001) and the percentage of differences between successive normal RR intervals differing >50 ms over a 24-hour electrocardiography (from 2.9 +/- 2.4% to 4.3 +/- 5.2% and 3.9 +/- 2.6%, p <0.002) increased significantly. Ejection fraction and functional classes were also improved. These data imply that in patients with heart failure who are taking conventional drugs, the addition of spironolactone induces a favorable sympathovagal balance. These changes, as assessed by the triangular interpolation of the NN histogram and the percentage of differences between successive normal RR intervals differing >50 ms over a 24-hour electrocardiography, and observed at 1 month after therapy, persisted in the long term.
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PMID:Effects of spironolactone on heart rate variability and left ventricular systolic function in severe ischemic heart failure. 1098 Feb 17

The paraventricular nucleus (PVN) of the hypothalamus has critical homeostatic functions, including the regulation of fluid balance and sympathetic drive. It has been suggested that altered activity of this nucleus contributes to the progression of congestive heart failure (HF). We hypothesized that forebrain influences of the renin-angiotensin-aldosterone system augment the activity of PVN neurons in HF. The rate of PVN neurons (n = 68) from rats with ischemia-induced HF was higher than that of PVN neurons (n = 42) from sham-operated controls (8.7 +/- 0.8 vs. 2.7 +/- 0.3 spikes/s, P < 0.001, HF vs. SHAM). Forebrain-directed intracarotid artery injections of the angiotensin type 1 receptor antagonist losartan, the angiotensin-converting enzyme inhibitor captopril, and the mineralocorticoid receptor antagonist spironolactone all significantly (P < 0.05) reduced PVN neuronal activity in HF rats. These findings demonstrate that the renin-angiotensin-aldosterone system drives PVN neuronal activity in HF, likely resulting in increased sympathetic drive and volume accumulation. This mechanism of neurohumoral excitation in HF is accessible to manipulation by blood-borne therapeutic agents.
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PMID:The renin-angiotensin-aldosterone system excites hypothalamic paraventricular nucleus neurons in heart failure. 1206 17

Cardiac remodeling, CR, is a complex and rather controversial issue and results from the, sometimes opposite, trophic effects of pure mechanical overload, and susceptibility factors, as senescence, aetiologies, as ischemia, and the neurohormonal reaction. The molecular mechanisms of CR are heritable and had, in the past, increased fitness, as such CR belongs to evolutionary medicine. Aldosterone production plays an important role in the remodeling of the heart. (i) There are numerous evidences that aldosterone induces fibrosis in all the cardiovascular system in the presence of high sodium diet. The aldosterone receptor is a transcriptional factor and the pathways that lead to aldosterone-induced fibrosis are multiple. Aldosterone induces the expression of the angiotensin II receptors subtype I and that of the glucocorticoid receptors. The RALES trial have recently evidenced a significant beneficial effect of spironolactone on both mortality and morbidity in heart failure, and a substudy has shown that these effects are linked to a reduction is fibrosis. (ii) An intracardiac production of aldosterone and corticosterone have been evidenced in the rat. Aldosterone production is regulated by low sodium/high potassium diets and by angiotensin II and is predominant in atria, cardiac production is low as compared to the adrenal production, nevertheless it results in high local concentrations, just like angiotensin II. In rats, myocardial infarction activates aldosterone production and this activation is prevented by losartan. Heart failure, in human, activates aldosterone production and is accompanied by a significant increase of the arteriovenous difference in aldosterone by the myocardium. To conclude (i) after a myocardial infarction local production of aldosterone and angiotensin II are likely to play a major role in regulating collagen turnover and fibrous tissue formation; (ii) during heart failure, the activation of adrenal and cardiovascular production of aldosterone belongs to the neurohormonal reaction and would play a detrimental role in producing reactive fibrosis.
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PMID:Molecular mechanisms of myocardial remodeling. The role of aldosterone. 1250 56


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