Experimental Models of Endotheliopathy: Impact of Shock Severity

Hemorrhagic shock (HS) followed by resuscitation is often associated with sympathoadrenal activation (SAA) and endothelial damage (ED).

We aimed to evaluate the impact of HS alone on the magnitude of SAA and consecutive ED, and to characterize potential targets for a standardized and reproducible model of HS-induced endotheliopathy in rats.

Rats were subjected either to a volume-controlled HS (40% of total blood volume: v-HS group) or to a laboratory-guided HS (l-HS) targeting base deficit (BD) more than 5.5 mmol/L and/or lactate more than 2.2 mmol/L using a pressure-controlled volume loss.

At the end of shock, mean arterial pressure was significantly higher in the v-HS than the l-HS group (36 ± 5.6 vs. 30 ± 3.0 mmHg; P < 0.01). Base deficit and lactate were higher in l-HS than the v-HS group (BD: 9.5 ± 2.5 vs. 3.0 ± 1.0 mmol/L; P < 0.001; lactate: 4.1 ± 1.3 vs. 1.6 ± 0.6 mmol/L; P < 0.001). sVEGFR-1 and syndecan-1 were approximately 50% higher in the l-HS than the v-HS group (% changes vs. baseline: 160 ± 10 vs. 116 ± 36; P < 0.01; 170 ± 37 vs. 113 ± 27; P < 0.001). Adrenaline was 2-fold higher in l-HS than the v-HS group (1964 ± 961% vs. 855 ± 451%; P < 0.02, respectively). Moreover, linear regression analysis revealed an independent association of shock severity BD with syndecan-1 (rho = 0.55, P = 0.0005), sVEGFR1 (rho = 0.25, P < 0.05), and adrenaline (rho = 0.31, P = 0.021).

Our findings indicate that ED has already occurred during HS without reperfusion; intensity is strongly related to the severity of HS and consecutive SAA; and severity may appropriately be targeted and standardized in a HS model controlled by biological endpoints such as BD and/or lactate.