Stroke volume positive inotropes

The sinoatrial (SA) node is innervated by both the sympathetic (beta and parasympathetic (vagus) nervous systems. Sympathetic activation increases the discharge rate of the SA pacemaker cells, and thereby increases heart rate (a positive chronotropic effect). Sympathetic nerves also innervate adrenergic receptors (betaj) on cardiac ventricular cells leading to an increase in stroke volume (a positive inotropic effect). Vagal activation, on the other hand, has the opposite effect and decreases heart rate and conduction velocity. In normal adults, cardiac vagal innervation is functionally predominant, so abolition of vagal activity results in a pronounced tachycardia (increased heart rate). 

Dofetilide has a small positive inotropic effect in animal hearts (15,33). In a double-blind, placebo-controlled study of oral dofetilide 125, 250, or 500 mg bd for the maintenance of sinus rhythm after cardioversion of sustained atrial fibrillation or flutter in 201 patients, there were small changes in echocardiographic measures of atrial contractility, but no changes in stroke volume or cardiac output (34). 

In patients with elevated systemic vascular resistance and normal-to-elevated systemic blood pressure, afterload reduction with nitroprusside is logical it should be emphasized that nitroprus-side also increases venous capacitance, thereby also decreasing preload. In the context of myocardial dysfunction, afterload reduction will typically lead to improved forward cardiac output. Nitroprusside may also be effective when the systemic vascular resistance is elevated and systemic blood pressure is reduced the caveat in this more complex hemodynamic setting is that the load reduction produced by nitroprusside must be counterbalanced by an increase in stroke volume. This derivative increase in stroke volume may not occur in the patient with advanced heart failure rather, the result will be a further reduction in mean arterial pressure and the potential risk of peripheral organ hypoperfusion. An alternative approach would be the use of an inotropic-dilator drug such as milrinone, which will provide both preload and afterload reduction its concurrent positive inotropic effect may offset the reduction in mean arterial pressure that can occur from vasodilation alone. 

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