Congestive heart failure afterload decrease

Therapy of congestive heart failure. By lowering peripheral resistance, diuretics aid the heart in ejecting blood (reduction in afterload, pp. 132, 306) cardiac output and exercise tolerance are increased. Due to the increased excretion of fluid, EEV and venous return decrease (reduction in preload, p. 306). Symptoms of venous congestion, such as ankle edema and hepatic enlargement, subside. The drugs principally used are thiazides (possibly combined with K+-sparing diuretics) and loop diuretics. 

Captopril enhances cardiac output in patients with congestive heart failure by inducing a reduction in ventricular afterload and preload. Converting enzyme inhibitors have been shown to decrease the mass and wall... 

Captopril, as well as other ACE inhibitors, is indicated in the treatment of hypertension, congestive heart failure, left ventricular dysfunction after a myocardial infarction, and diabetic nephropathy. In the treatment of essential hypertension, captopril is considered first-choice therapy, either alone or in combination with a thiazide diuretic. Decreases in blood pressure are primarily attributed to decreased total peripheral resistance or afterload. An advantage of combining captopril therapy with a conventional thiazide diuretic is that the thiazide-induced hypokalemia is minimized in the presence of ACE inhibition, since there is a marked decrease in angiotensin Il-induced aldosterone release. 

Dilation of venous blood vessels leads to a decrease in cardiac preload by increasing venous capacitance arterial dilators reduce systemic arteriolar resistance and decrease afterload. Nitrates (see p. 175) are commonly employed venous dilators for patients with congestive heart failure. If the patient is intolerant of ACE inhibitors, the combination of hydralazine and isosorbide dinitrate is most commonly used. Amlodipine and felodipine (see p. 188) have less negative inotropic effect than other calcium channel blockers, and seem to decrease sympathetic nervous activity. 

Acute decreases in renal function and hyperkalemia usually resolve over several days after ACEl or ARB therapy is discontinued. Occasional patients will require management of severe hyperkalemia, usually with sodium polystyrene sulfate (see Chap. 50). ACEl or ARB therapy may frequently be reinitiated, particularly for patients with congestive heart failure, after intravascular volume depletion has been corrected or the diuretic doses reduced. The development of mild renal insufficiency (serum creatinine concentration of 2 to 3 mg/dL) may be an acceptable trade-off for hemodynamic improvement in certain patients with severe congestive heart failure or renovascular disease not amenable to invasive management. Congestive heart failure patients with greater renal insufficiency may be best treated by substitution of hydralazine and nitrates for afterload reduction. 

In heart failure, cardiac output rises again because ventricular afterload diminishes due to a fall in peripheral resistance. Venous congestion abates as a result of (1) increased cardiac output and (2) reduction in venous return (decreased aldosterone secretion, decreased tonus of venous capacitance vessels). 

Heart failure is due to defects in cardiac contractility (the vigor of heart muscle), leading to inadequate cardiac output. Signs and symptoms include decreased exercise tolerance and muscle fatigue, coupled with the results of compensatory responses (neural and humoral) evoked by decreases in mean BP. Increased SANS activity leads to tachycardia, increased arteriolar tone T afterload, 4- output, 4 renal perfusion), and increased venous tone (T preload, T fiber stretch). Activation of the renin-angiotensin system results in edema, dyspnea, and pulmonary congestion. Intrinsic compensation results in myocardial hypertrophy. These effects are summarized in Figure IH-4-1. 

Sulmazole (AR-L 115) (37), an imidazopyridine derivative, increased dp/dt max. by 58% and heart rate by 12 beats/min in anesthetized cats after 1 mg/kg i.v. Systolic blood pressure was decreased by 13 mm Hg.l42 Oral administration augmented dp/dt max. up to 92% for 5 to 12 hours in conscious dogs.143 Despite similar PDE-inhibitory activity of 37 and theophylline, it seems likely that effects other than PDE-inhibi-tion contribute to the positive inotropic action.144 Measurement of the effect of 21 on relations between free Ca++, bound Ca ", and ATPase activity of dog cardiac myofibrils indicates that the positive inotropic actions may involve direct activation of myofibrils by an increased affinity of thin filament receptors for Ca++.145 Several clinical studies in heart failure showed that in patients with congestive cardiomyopathy and with coronary artery disease, 22 improved hemodynamics and regional wall motion via decrease in pre- and afterload and Increase in contractility, myocardial oxygen consumption and coronary sinus flow, with no myocardial ischemia.14 149... 

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