Dissociation between macro- and microvascular parameters in the early phase of hemorrhagic shock

Abstract

Hemorrhagic shock (HS) therapy is based on macrohemodynamic improvement, but it is not clear if this therapy correlates directly with increases in tissue perfusion. Aiming to clarify this point, we compared norepinephrine (NE, a vasoconstrictor), sodium nitroprusside (NP, a vasodilator) and levosimendan (LEV, an inodilator) treatments on macro and microvascular parameters using the hamster dorsal skinfold chamber preparation. One hour after HS, animals received Ringer's lactate (RL) solution within 10 min, then animals received RL, NP, NE and LEV during 90 min via jugular vein. Macrovascular variables: mean arterial pressure (MAP), heart rate (HR), maximal ventricle pressure (MVP), change in ventricular pressure over time (dP/dt) and microvascular variables: arteriolar and venular diameters, functional capillary density (FCD) and red blood cell velocity (RBCV) were evaluated at baseline, 60 min after HS, 60 and 90 min after treatments. Lactate blood concentrations were evaluated at baseline, 60 min after HS and 90 min after treatments. Hematocrit (Hct), cardiac output (CO), stroke volume (SV) and number of rolling and adhered leukocytes were assessed at 90 min after treatments. Data were considered significant when p < 0.05. NE increased significantly all macrohemodynamic variables compared to baseline (except MAP), and it was the only treatment that increased Hct, CO and SV significantly. NE decreased significantly all microvascular variables in comparison to baseline. NP increased HR, FCD and RBCV and reduced MVP and dP/dt significantly. LEV decreased MVP and dP/dt, arteriolar diameter and FCD and augmented RBCV significantly in comparison to baseline. Blood concentration of lactate increased significantly 60 min after HS. Leukocyte rolling and adhesion were not different between groups. We concluded that, early, during hemorrhagic shock, norepinephrine associated to fluid therapy improved macrohemodynamic parameters but failed to improved microvascular flow. Conversely, sodium nitroprusside association had the opposite effect. Despite its inodilator properties, levosimendan did not improve macro or microhemodynamic parameters when combined to fluid therapy.

Keywords: Hamster dorsal skinfold chamber; Hemorrhagic shock; Levosimendan; Macrohemodynamic parameters; Microcirculation; Norepinephrine; Sodium nitroprusside.