Heart failure

Heart failure (HP) is a clinical syndrome caused by the inability of the heart to pump sufficient blood to meet the metabolic needs of the body. HP can result from any disorder that reduces ventricular filling (diastolic dysfunction) and/or myocardial contractility (systolic dysfunction). 

Causes of systolic dysfunction (decreased contractility) are reduction in muscle mass (e.g., myocardial infarction [MI]), dilated cardiomyopathies, and ventricular hypertrophy. Ventricular hypertrophy can be caused by pressure overload (e.g., systemic or pulmonary hypertension, aortic or pulmonic valve stenosis) or volume overload (e.g., valvular regurgitation, shunts, high-output states). 

Causes of diastolic dysfunction (restriction in ventricular filling) are increased ventricular stiffness, ventricular hypertrophy, infiltrative myocardial diseases, myocardial ischemia and infarction, mitral or tricuspid valve stenosis, and pericardial disease (e.g., pericarditis, pericardial tamponade). The leading causes of HP are coronary artery disease and hypertension. 

Common precipitating factors that may cause a previously compensated patient to decompensate include noncompliance with diet or drug therapy, coronary ischemia, inappropriate medication use, cardiac events (e.g., MI, atrial fibrillation), pulmonary infections, and anemia. 

Drugs may precipitate or exacerbate HF because of their negative inotropic, cardiotoxic, or sodium- and water-retaining properties. 

Compensation in heart failure is offset by specific drugs that can  

ACEIs block formation of All and inhibit bradykinin metabolism —aldosterone —fluid retention —vasodilation — 4- preload and afterload. 

In addition to improving symptoms and exercise tolerance, they slow progression of heart failure and prolong survival. In addition, ACEIs have prophylactic value post-MI because they oppose remodeling that can lead to heart failure. 

ACEIs are now the primary drugs used for management of heart failure. AT-1 antagonists appear to have similar efficacy. For characteristics, see the section on antihypertensive drugs. 

Cardiac glycosides exert positive inotropic actions on the heart Their initial action is to inhibit cardiac membrane Na+/K+-ATPase -aX Na+/Caz+ exchange — T Ca2+ in sarcoplasmic reticulum - T Ca2+ release and binding to troponin — tropomyosin moves — T actin and myosin interac- ion — T contractile force. 

The degree of severity of myocardial failure is categorized according to the New York Heart Association (NYHA) Functional Classification System Stages I—IV reflect an increasing level of disability. 

ACE inhibitors are the appropriate agents for inhibiting the renin-angiotensin II system they prevent the production of angiotensin II. The effect of angiotensin II receptor antagonists is equivalent to that of ACE inhibitors. Both interventions for attenuating compensatory mechanisms improve the clinical state of patients (less hospitalization) and increase life expectancy. 

In edemas, dyspnea, and advanced myocardial insuf ciency, diuretics are indispensable. 

Digitalis glycosides augment contractile force and are likewise used in severe forms of insuf ciency, specifically in the presence of concomitant atrial fibrillation. Because of the narrow margin of safety, the digoxin dose must be adjusted individually in each patient. 

Drugs with an acute positive inotropic action (e.g., catecholamines or phosphodiesterase inhibitors) may be of transient help in sudden decompensation but must not be given in chronic congestive failure. 

The response of the failing heart to ischemic stress appears to be variable. Increased incidence of ischemia and reperfusion arrhythmias is observed in hearts from rabbits with heart failure induced by pressure or volume overload.202 Furthermore, hearts from rats with heart failure are shown to be more vulnerable to ischemic injury and acute blockade of RAS with ACE inhibitors improved postischemic recovery of function.203 However, increased susceptibility to ischemia was not evident in specimens of right atrium from patients with impaired ventricular function.204 A number of changes occur in heart failure that potentially could influence the response of the heart to ischemia. Oxidative stress is increased, sustained overexpression of pro-inflammatory mediators is observed, and the activity of the renin-angiotensin system is enhanced. 

Much controversy seems to exist as to whether the diabetic heart is more or less sensitive to ischemic injury. A large number of studies using animal models of experimental diabetes (induced by streptozotocin or alloxan) report no change, increased or decreased sensitivity to ischemia and reperfusion. Differences in the experimental design in relation to metabolic and ion changes that occur in diabetic heart might be the basis of such discrepancies. Short-term diabetes is associated with decreased sensitivity to zero-flow ischemia and reperfusion injury. This beneficial effect disappears with increased duration or severity of diabetes. The diabetic heart appears to be more vulnerable in low-flow ischemia and in the presence of elevated fatty acids in the perfusate. Furthermore, hearts from Zucker diabetic fatty and lean Goto-Kakizaki Type-2 diabetic rats are resistant to reperfusion injury.205 

Abdomen, RUQ - pain Abdomen - distention Abdomen - fullness Abdomen - fluid (ascites) 

Arterial pulse - amplitude, alternating (pulsus alternans) Behavior - changed [ 1 ] 

Bowel movements - diarrhea Breathing - diff, acute (acute dyspnea) 

Breathing - diff, nocturnal (nocturnal dyspnea) Breathing - diff, reclining flat (orthopnea) 

438 SECTION THREE CLINICAL GUIDE—ACUTE COMPLICATIONS 

Whereas digoxin does not improve survival, ACEIs, ARBs, carvedilol, and spironolactone have been proven beneficial in CHF. ACEIs and ARBs are currently drugs of choice for the chronic management of CHF. Inotropes are more beneficial in management of acute CHF. 

Drugs used to treat heart failure include those that deaease preload (e.g., diuretics, ACEls, ARBs, and venodilators), those tfiat decrease afterload (e.g., ACEls, ARBs, and arteriodilators), and those that increase cardiac contractibility (e.g., digoxin and beta agonists). 

Although digoxin ameliorates symptoms, it does not increase survival. That is why the ACEls are the primary choice for treating heart failure. 

Digoxin has potential toxic effects that are in part dependent upon the electrolyte balance. 

Bipyridines, sympathomimetia, diuretic, beta blockers, and nesiritide also have uses in treating heart failure. Rationales for their use are indicated. A newer drug, nesiritide, is a recombinant form of natriuretic peptide. 

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Congestive heart failure Conglomerone [480-25-1] b-Conglycimn Conglycinin Congo Congo red... 

Friedel-Crafts acylation of 3,3-dimethyl-2-indolinone by succinic anhydride gives 3,3-dimethyl-5-(3-catboxyptopionyl)-2-indoline, which is used as an intermediate in the preparation of inotropic agents for treatment of heart failure (94). Antibacterial phlotophenone derivatives have been prepared by Friedel-Crafts acylation with ptopanoyl chlotide (95). 

From a therapeutic point of view, selective agonists may become useful in the treatment of heart failure and catecholamine-insensitive cardiomyopathy, but only if compounds become available that do not stimulate gastric acid secretion or cause other unforeseen problems. 

Phenol. Phenol monomer is highly toxic and absorption by the skin can cause severe blistering. Large quantities can cause paralysis of the central nervous system and death. Ingestion of minor amounts may damage kidneys, Hver, and pancreas. Inhalation can cause headaches, dizziness, vomiting, and heart failure. The threshold limit value (TLV) for phenol is 5 ppm. The health and environmental risks of phenol and alkylated phenols, such as cresols and butylphenols, have been reviewed (66). 

Cardiomyopathy. Cardiomyopathy, or diseased heart muscle, may reach a point at which the heart can no longer function. It arises from a combination of factors, including hypertension, arrhythmias, and valve disease. Other problems, such as congestive heart failure, cause the interrelated heart—lung system to break down. Because the heart can no longer adequately pump, duid builds up in the lungs and other areas. 

Artificial Hearts. Congestive heart failure (CHF) is a common cause of disabiHty and death. It is estimated that three to four million Americans suffer from this condition. Medical therapy in the form of inotropic agents, diuretics (qv), and vasofilators is commonly used to treat this disorder (see Cardiovascularagents). Cardiac transplantation has become the treatment of choice for medically intractable CHF. Although the results of heart transplantation are impressive, the number of patients who might benefit far exceeds the number of potential donors. Long-term circulatory support systems may become an alternative to transplantation (5). 

Agents used in the treatment of congestive heart failure, Antiatherosclerotic agents. 

The Class I agents have many similar side effects and toxicities. The anticholinergic side effects include dry mouth, constipation, and urinary hesitancy and retention. Common gastrointestinal (GI) side effects include nausea, vomiting, diarrhea, and anorexia. Cardiovascular adverse effects are hypotension, tachycardia, arrhythmias, and myocardial depression, especially in patients with congestive heart failure. Common central nervous system (CNS) side effects are headache, dizziness, mental confusion, hallucinations, CNS stimulation, paraesthesias, and convulsions. 

The side effects and toxic reactions to verapamil iaclude upper GI upset, constipation, di22iaess, headaches, flushing and burning, edema, hypotension, bradycardia, and various conduction disturbances. Verapamil has negative iaotropic activity and may precipitate heart failure ia patients having ventricular dysfunction (1,2). 

Nitroglycerin remains the dmg of choice for treatment of angina pectoris. It has also been found useful for the treatment of congestive heart failure, myocardial infarction, peripheral vascular disease, such as Raynaud s disease, and mitral insufficiency, although the benefits of nitroglycerin in mitral insufficiency have been questioned. 

The cardiac effects of the calcium antagonists, ie, slowed rate (negative chronotropy) and decreased contractile force (negative inotropy), are prominent in isolated cardiac preparations. However, in the intact circulation, these effects may be masked by reflex compensatory adjustments to the hypotension that these agents produce. The negative inotropic activity of the calcium antagonists may be a problem in patients having heart failure, where contractility is already depressed, or in patients on concomitant -adrenoceptor blockers where reflex compensatory mechanisms are reduced. 

AGENTS USED IN THE TREATMENT OF CONGESTIVE HEART FAILURE... 

Moreover, digitahs has indirect effects on the circulation, which in normal hearts results in a small increase in arterial pressure, peripheral resistance, and cardiac output (114). The effects of digitahs on the circulation of an individual experiencing congestive heart failure are much more dramatic, however. The increased cardiac output, for example, increases renal blood flow which can reheve in part the edema of CHF associated with salt and water retention (114). 

ACE inhibitors can be administered with diuretics (qv), cardiac glycosides, -adrenoceptor blockers, and calcium channel blockers. Clinical trials indicate they are generally free from serious side effects. The effectiveness of enalapril, another ACE inhibitor, in preventing patient mortaUty in severe (Class IV) heart failure was investigated. In combination with conventional dmgs such as vasodilators and diuretics, a 40% reduction in mortaUty was observed after six months of treatment using 2.5—40 mg/d of enalapril (141). However, patients complain of cough, and occasionally rash and taste disturbances can occur. 

It is well accepted that hypertension is a multifactorial disease. Only about 10% of the hypertensive patients have secondary hypertension for which causes, ie, partial coarctation of the renal artery, pheochromacytoma, aldosteronism, hormonal imbalances, etc, are known. The hallmark of hypertension is an abnormally elevated total peripheral resistance. In most patients hypertension produces no serious symptoms particularly in the early phase of the disease. This is why hypertension is called a silent killer. However, prolonged suffering of high arterial blood pressure leads to end organ damage, causing stroke, myocardial infarction, and heart failure, etc. Adequate treatment of hypertension has been proven to decrease the incidence of cardiovascular morbidity and mortaUty and therefore prolong life (176—183). 

Diuretics are one of the dmg categories most frequendy prescribed. The principal uses of diuretics are for the treatment of hypertension, congestive heart failure, and mobilization of edema fluid in renal failure, fiver cirrhosis, and ascites. Other applications include the treatment of glaucoma and hypercalcemia, as well as the alkafinization of urine to prevent cystine and uric acid kidney stones. 

Nowadays the one of the leading cause of death in industrial country is Heart Failure (HF). Under the pathological conditions (e.g., Ischemic Heart Disease (IHD)) the changes in the enzymes activity and ultrastructure of tissue were obtained. The behavior of trace elements may reflect the activity of different types of enzymes. Pathological changes affects only small area of tissue, hence the amount of samples is strictly limited. Thereby, nondestructive multielemental method SRXRF allow to perfonu the analysis of mass samples in a few milligrams, to save the samples, to investigate the elemental distribution on the sample area. 

Zone-3 - Usually no danger of heart failure (ventricular fibrillation)... 

Zone-5 - Probability of heart failure more than 50%. 

Pyridyl-4-bromo-6-oxo-5,6,7,8-tetrahydrothiazolo[5,4-g]quinolones and analogues were prepared and tested as potential inotropic agents for treatment of heart failure. For example, the 2-(4-pyridyl) substituted thiazoloquinolone 38 gave a 122% increase in contractility of guinea pig papillary muscle (89EUP1). 

Congestive heart failure Throm bocy topenia Renal dysfunction... 

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