title: Mechanisms of nitrate action in patients with severe left ventricular failure: conceptual problems with the theory of venosequestration.
abstract: Nitroglycerin and other organic nitrates exert a number of favorable effects on the circulation of patients with severe congestive heart failure, and these effects mediate the short- and long-term hemodynamic and clinical improvement that follows treatment with these drugs. Although these agents are potent dilators of systemic venous capacitance vessels, present evidence indicates that they do not exert their beneficial hemodynamic and clinical effects by decreasing venous return to the heart. Rather, their ability to dilate pulmonary and systemic resistance vessels offsets any decrease in cardiac output that might be expected to occur from a decrease in venous return. Of equal importance, the increase in output of the left side of the heart that results from drug-induced pulmonary and systemic vasodilation prevents any decrease in venous return to the right side of the heart that might be expected to accompany an increase in systemic venous capacitance. The net effect of these two interacting forces is not only to keep cardiac output and venous return constant but also to translocate blood volume from the pulmonary circulation and left ventricle to the systemic vessels. In addition, nitrates also relieve subendocardial ischemia and favorably alter pressure-volume relationships in the left ventricle. These observations support the conclusion that the complex cardiovascular responses to organic nitrates in patients with congestive heart failure cannot be adequately summarized by the single concept of preload reduction.
mesh_terms: D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D001810:Blood Volume / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D007548:Isosorbide Dinitrate / Q000494:pharmacology* / Q000627:therapeutic use; D005996:Nitroglycerin / Q000494:pharmacology* / Q000627:therapeutic use; D011652:Pulmonary Circulation / Q000187:drug effects; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014690:Venous Pressure / Q000187:drug effects*
chemical_list: D005996:Nitroglycerin; D007548:Isosorbide Dinitrate