CVS Pathophysiology Heart Failure br br Cardiac dysfunction precipitates changes in vascular function, blood volume, and neurohumoral status. These changes serve as compensatory mechanisms to help maintain cardiac output (primarily by the Frank-Starling mechanism) and arterial blood pressure (by systemic vasoconstriction). However, these compensatory changes over months and years can worsen cardiac function. Therefore, some of the most effective treatments for chronic heart failure involve modulating non-cardiac factors such as arterial and venous pressures by administering vasodilator and diuretic drugs. br br Cardiac Function br Cardiac and Vascular Changes br Accompanying Heart Failure br Cardiac br Decreased stroke volume & cardiac output br Increased end-diastolic pressure br Ventricular dilation or hypertrophy br Impaired filling (diastolic dysfunction) br Reduced ejection fraction (systolic dysfunction) br Vascular br Increased systemic vascular resistance br Decresed aterial pressure br Impaired arterial pressure br Impaired organ perfusion br Decreased venous compliance br Increased venous pressure br Increased blood volume br Overall, the changes in cardiac function associated with heart failure result in a decrease in cardiac output. This results from a decline in stroke volume that is due to systolic dysfunction, diastolic dysfunction, or a combination of the two. Briefly, systolic dysfunction results from a loss of intrinsic inotropy (contractility), which can be caused by alterations in signal transduction mechanisms responsible for regulating inotropy. Systolic dysfunction can also result from the loss of viable, contracting muscle as occurs following acute myocardial infarction. Diastolic dysfunction refers to the diastolic properties of the ventricle and occurs when the ventricle becomes less compliant (i.e., "stiffer"), which impairs ventricular filling. Reduced filling of the ventricle results in less ejection of blood. Both systolic and diastolic dysfunction result in a higher ventricular end-diastolic pressure, which serves as a compensatory mechanism by utilizing the Frank-Starling mechanism to augment stroke volume. In some types of heart failure (e.g., dilated cardiomyopathy), the ventricle dilates anatomically, which helps to normalize the preload pressures by accomodating the increase in filled volume. br br Therapeutic interventions to improve cardiac function in heart failure include the use of cardiostimulatory drugs (e.g., beta-agonists and digitalis) that stimulate heart rate and contractility, and vasodilator drugs that reduce ventricular afterload and thereby enhance stroke volume. br br Neurohumoral Status br Compensatory Mechanisms During br Heart Failure br Cardiac br Frank-Starling mechanism br Chronic ventricular dilation or hypertrophy br Tachycardia br Autonomic Nerves br Increased sympathetic adrenergic activity br Reduced vagal activity to heart br Hormones br Renin-angiotensin-aldosterone system br Vasopressin (antidiuretic hormone) br Circulating catecholamines br Natriuretic peptides br Neurohumoral responses occur during heart failure. These include activation of sympathetic nerves and the renin-angiotensin system, and increased release of antidiuretic hormone (vasopressin) and atrial natriuretic peptide. The net effect of these neurohumoral responses is to produce arterial vasoconstriction (to help maintain arterial pressure), venous constriction (to increase venous pressure), and increased blood volume to increase ventricular filling. In general, these neurohumoral responses can be viewed as compensatory mechanisms, but they can also aggravate heart failure by increasing ventricular afterload (which depresses stroke volume) and increasing preload to the point where pulmonary or systemic congestion and edema occur. Therefore, it is important to understand the pathophysiology of heart failure because it serves as the rationale for therapeutic intervention. br br There is also evidence that other factors such as nitric oxide and endothelin (both of which are increased in heart failure) may play a role in the pathogenesis of heart failure. br br Some drug treatments for heart failure involve attenuating the neurohumoral changes. For example, certain beta-blockers have been shown to provide significant long-term benefit, quite likely because they block the effects of excessive sympathetic activation on the heart. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone receptor antagonists are commonly used to treat heart failure by inhibiting the actions of the renin-angiotensin-aldosterone system. br br br br Systemic Vascular Function br In order to compensate for reduced cardiac output during heart failure, feedback mechanisms within the body try to maintain normal arterial pressure by constricting arterial resistance vessels through activation of the sympathetic adrenergic nervous system, thereby increasing systemic vascular resistance. Veins are also constricted to elevate venous pressure.