Heart failure dilated

Prostacyclin (epoprostanol) is one of the few drugs effective for the treatment of Primary Pulmonary Hypertension (PPH) a rare but frequently fatal illness of young adults. Increased blood pressure in the pulmonary circulation leads to right-heart failure. Continuous infusion of epoprostanol leads to a decrease in blood pressure however, it is unclear whether this is due to direct dilator activity of the IP receptor acting on smooth muscle, or a more indirect mechanism. 

O The most common causes of heart failure are coronary artery disease (CAD), hypertension, and dilated cardiomyopathy. 

Symptoms of intoxication in humans caused by accidental ingestion of Kou-Wen plants have been described as follows. The effect on the digestive system starts with loss of appetite and turn of the stomach, and continues to severe abdominal pain and intestinal bleeding. The effect on the respiratory system presents as breathing difficulties which finally lead to death by respiratory failure. The effect on muscle innervation usually results in generalized muscular weakness and paralysis of the limbs. The effect on the circulatory system starts with heartbeat disorders and a drop in blood pressure, but heart failure is not a common cause of death. In addition to dilation of pupils, a drop in body temperature and proliferation of white blood cells have also been obseryed (70). 

Polymorphisms of the beta adrenergic receptors have also been studied in patients with heart failure and cardiomyopathy, or other complex and rather ill-defined phenotypes. In patients with heart failure due to ischemic or idiopathic dilated cardiomyopathy, the Thrl64Ile polymorphism in the />2-adrerioreceplor was significantly associated with survival rate at one year [62]. Similarly, the Ser49Gly polymorphism of the /Vadrenoreceptor gene has been linked to the improved survival of patients with idiopathic cardiomyopathy [63]. However, sample size was limited in those studies and results need to be confirmed in adequately powered studies. 

Ellis et al. [72] recently studied the effects of short- and long-term vitamin C therapy in the patients with chronic heart failure (CHF). It was found that oxygen radical production and TBAR product formation were higher in patients with CHF than in control subjects. Both short-term (intravenous) and long-term (oral) vitamin C therapy exhibited favorable effects on the parameters of oxidative stress in patients the treatments decreased oxygen radical formation and the level of lipid peroxidation and improved flow-mediated dilation in brachial artery. However, there was no correlation between changes in endothelial function and oxidative stress. 

Angiotensin converting enzymes- inhibitors (ACE-inhibitors) are a group of drugs that are very potent in dilating the blood vessels and through this mechanism lower the blood pressure. Therefore they can also improve heart function in patients with heart failure. In some cases they are also used for preventing renal failure in persons with hypertension and/or diabetes. Paradoxically, this later use of ACE-inhibitors... 

On the other hand, clinical evidence suggests that p-blockers produce favorable effects in certain forms of congestive heart failure (idiopathic dilated cardiomyopathy). 

Gerson MC, Craft LL, McGuire N, Suresh DP, Abraham WT, Wagoner LE. Carvedilol improves left ventricular function in heart failure patients with idiopathic dilated cardiomyopathy and a wide range of sympathetic nervous system function as measured by iodine 123 metaiodoben-zylguanidine. J Nucl Cardiol 2002 9 608-615... 

Conduction system abnormalities are common in chronic heart failure, occurring in 15-30% of the population with low left ventricular ejection fraction (LVEF) [1-3]. The prevalence in ischemic heart disease is roughly similar to that seen in other forms of dilated cardiomyopathy. Conduction system disease can occur both at the time of an acute myocardial infarction as well as slowly progressing in chronic ischemic heart disease. Intraventricular conduction delays are associated with a poor prognosis in heart failure, with up to a 70% increase in the risk of death, and are also more prevalent in patients with advanced symptoms [2,4]. In ischemic heart disease, all components of the conduction system are at risk of ischemic injury, from the sinoatrial node to the His-Pukinje system. These conduction system abnormalities have the potential to impair cardiac function by a number of mechanisms. Since conduction abnormalities impair cardiac function, it is logical that pacing therapies to correct or improve these conduction abnormalities may improve cardiac function. 

Atrial fibrillation is commonly associated with heart failure, and the prevalence of atrial fibrillation is related to the severity of heart failure, with less than 5% affected with very mild heart failure to nearly 50% affected with advanced heart failure [66]. Heart failure and atrial fibrillation are both common cardiovascular disorders and share the same demographic risk factors, including age, history of hypertension, prior myocardial infarction, and valvular heart disease [67, 68]. Further, the incidence of heart failure increases dramatically after the diagnosis of atrial fibrillation [69]. Progression of LV dysfunction can clearly be associated with rapid ventricular rates [70-76]. Conversely, conversion to normal sinus rhythm or control of ventricular response in atrial fibrillation can improve LV function [71-74, 77]. Accordingly, rate control becomes very important in patients with heart failure and dilated cardiomyopathy, and likely even more so when ischemia from rapid rates complicate the patient s course. 

A series of pilot studies began with multisite pacing for patients with heart failure and dilated cardiomyopathy in the early 1990s [52, 105-111]. An improvement in LV function and symptoms of heart failure were demonstrated. This provided the interest in biventricular pacing for heart failure. The term cardiac resynchronization therapy was coined to refer to pacing therapies that attempt to enhance cardiac performance by using pacing to correct electrical conduction abnormalities in the heart. The most common form of this therapy is atrial-synchronous... 

Agarwal AK, Venugopalan P. Beneficial effect of carvedilol on heart rate response to exercise in digitalised patients with heart failure in atrial fibrillation due to idiopathic dilated cardiomyopathy. Eur. J. Heart Fail. 2001 3 437-40. 

Gold MR, Shorofsky SR, Metcalf MD, Feliciano Z, Fisher ML, Gottlieb SS. The acute hemodynamic effects of right ventricular septal pacing in patients with congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am. J. Cardiol. 1997 79 679-81. 

Pachon JC, Pachon El, Albornoz RN, et al. Ventricular endocardial right bifocal stimulation in the treatment of severe dilated cardiomyopathy heart failure with wide QRS. Pacing Clin. Electrophysiol. 2001 24 1369-76. 

Dopamine is used in the treatment of shock owing to inadequate cardiac output (cardiogenic shock), which may be due to myocardial infarction or congestive heart failure. It is also used in the treatment of septic shock, since renal circulation is frequently compromised in this condition. An advantage of using dopamine in the treatment of shock is that its inotropic action increases cardiac output while dilating renal blood vessels and thereby increasing renal blood flow. 

Sodium nitroprusside is used in the management of hypertensive crisis. Although it is effective in every form of hypertension because of its relatively favorable effect on cardiac performance, sodium nitroprusside has special importance in the treatment of severe hypertension with acute myocardial infarction or left ventricular failure. Because the drug reduces preload (by venodila-tion) and after load (by arteriolar dilation), it improves ventricular performance and in fact is sometimes used in patients with refractory heart failure, even in the absence of hypertension. 

In heart diseases like hypertension, heart failure, ischemia, and hypertrophic cardiomyopathy (HCM) as well as dilated cardiomyopathies (DCM), total myocardial jS-AR density is reduced [90-94], A selective reduction of p -ARs without change of P2-AR density is often observed in the failing human heart [89], Therefore, there is a clinical need for the noninvasive assessment of p-AR density in vivo. PET is capable of assessing receptor concentrations in vivo, provided that a radioligand radiolabeled with a positron emitter specifically and selectively binds to the target receptor, and metabolism of the radiotracer does not occur in target tissue. 

S. Yamada, T. Ohkura, S. Uchida, K. Inabe, Y. Iwatani, R. Kimura, T. Hoshino, T. Kaburagi, A sustained increase in /l-adrenoceptors during long-term therapy with metoprolol and bisoprolol in patients with heart failure from idiopathic dilated cardiomyopathy, Life Sci. 58 (1996) 1737-1744. 

Pathophysiology can influence muscarinic activity in other ways as well. Circulating autoantibodies against the second extracellular loop of cardiac M2 muscarinic receptors have been detected in some patients with idiopathic dilated cardiomyopathy and those afflicted with Chagas1 disease caused by the protozoan Trypanosoma cruzi. These antibodies exert parasympathomimetic actions on the heart that are prevented by atropine. In animals immunized with a peptide from the second extracellular loop of the M2 receptor, the antibody is an allosteric modulator of the receptor. Although their role in the pathology of heart failure is unknown, these antibodies should provide clues to the molecular basis of receptor activation because their site of action differs from the orthosteric site where acetylcholine binds (see Chapter 2). 

Hydralazine, a hydrazine derivative, dilates arterioles but not veins. It has been available for many years, although it was initially thought not to be particularly effective because tachyphylaxis to its antihypertensive effects developed rapidly. The benefits of combination therapy are now recognized, and hydralazine may be used more effectively, particularly in severe hypertension. The combination of hydralazine with nitrates is effective in heart failure and should be considered in patients with both hypertension and heart failure, especially in African-American patients. 

Sodium nitroprusside is a powerful parenterally administered vasodilator that is used in treating hypertensive emergencies as well as severe heart failure. Nitroprusside dilates both arterial and venous vessels, resulting in reduced peripheral vascular resistance and venous return. The action occurs as a result of activation of guanylyl cyclase, either via release of nitric oxide or by direct stimulation of the enzyme. The result is increased intracellular cGMP, which relaxes vascular smooth muscle (Figure 12-2). 

Vasodilators are effective in acute heart failure because they provide a reduction in preload (through venodilation), or reduction in afterload (through arteriolar dilation), or both. Some evidence suggests that long-term use of hydralazine and isosorbide dinitrate can also reduce damaging remodeling of the heart. 

By reducing preload and afterload in asymptomatic patients, ACE inhibitors (eg, enalapril) slow the progress of ventricular dilation and thus slow the downward spiral of heart failure. Thus, ACE inhibitors are beneficial in all subsets of patients—from those who are asymptomatic to those in severe chronic failure. This benefit appears to be a class effect that is, all ACE inhibitors appear to be effective. 

Digoxin is indicated in patients with heart failure and atrial fibrillation. It is also most helpful in patients with a dilated heart and third heart sound. It is usually given only when diuretics and ACE inhibitors have failed to control symptoms. Only about 50% of patients with normal sinus rhythm (usually those with documented systolic dysfunction) will have relief of heart failure from digitalis. Better results are obtained in patients with atrial fibrillation. If the decision is made to use a cardiac glycoside, digoxin is the one chosen in most cases (and the only one available in the USA). When symptoms are mild, slow loading (digitalization) with 0.125-0.25 mg per day is safer and just as effective as the rapid method (0.5-0.75 mg every 8 hours for three doses, followed by 0.125-0.25 mg per day). 

Enalapril Inhibits conversion of angiotensin I Arteriolar dilation decreased aldosterone Hypertension heart failure... 

Another cardiac disease often associated with cardiac arrhythmias is heart failure. Many factors including high catecholamine levels, dilated tissue geometry, changes in the [3-adrenoceptor population, impairment of the regulation of the intracellular (diastolic) calcium concentration, possibly enhanced endo-thelin levels and many more contribute to altered cardiac function and make the heart more prone to arrhythmia. However, the question was whether, in addition to the well-known structural changes, gap junction alterations may also partially form the arrhythmogenic substrate. Thus, researchers were interested in whether in the course of heart failure gap junctional alterations may occur. 

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