Cardiovascular responses to hyperosmotic mannitol in anesthetized and conscious dogs

Intravenous infusions of 25% mannitol solution were given in doses of 1.25 ml/kg and 5 ml/kg to anesthetized and conscious dogs. Serum osmolality rose by 3-8 with the smaller dose and 15-25 mOsm/kg H₂O with the larger dose. After the smaller dose, stroke volume and left ventricular maximal dp/dt rose significantly, while no change occurred in left ventricular end diastolic pressure. At the larger dose, further increases in stroke volume and max dp/dt were accompanied by significant elevations in heart rate, mean aortic pressure, and left ventricular end diastolic pressure. Increases in max d ln p/dt also occurred with each infusion. Changes were similar, but slightly less marked, after pretreatment with propranolol. Thus, doses of hypertonic mannitol that are feasible in the clinical setting cause significant hemodynamic alterations in the intact animal, including a substantial direct inotropic effect on the heart. The increased contractile force of the left ventricle is not dependent on changes in sympathetic nervous activity or the Frank Starling mechanism.