The prospective human studies considered above reveal that in some patients protamine is associated with decreases in SBP and SVR, especially when administered rapidly. Cardiac output increases reflexly, except perhaps in patients with less compliant ventricles, which are more dependent on preload to maintain stroke volume. In the latter, decreases in filling volume associated with protamine can lower CO. Regardless of the rate of administration, protamine does not produce predictable, acute increases in PAP, although increases in PAP may occur during idiosyncratic reactions (see the section on idiosyncratic reactions below). Left atrial or aortic administration of protamine may not confer protection from its hemodynamic or idiosyncratic sequelae (see below). Little evidence exists to conclude that protamine directly depresses contractility of the human heart.