Enalaprilat Improves Systemic and Mesenteric Blood Flow During Resuscitation from Hemorrhagic Shock in Dogs

Abstract

We investigated the systemic and mesenteric cardiovascular effects of administering enalaprilat during resuscitation from hemorrhage. Dogs were hemorrhaged (mean arterial pressure [MAP] 40-45 mmHg for 30 min, then 30-35 mmHg for 30 min) and were then resuscitated with intermittent lactated Ringer's solution (200 mL/kg/h during first 40 min, and 60 mL/kg/h during the following 130 min, MAP 75-80 mmHg). A constant-rate infusion of saline with or without enalaprilat (0.02 mg/kg/h) was initiated after 40 min of resuscitation. Blood flows declined with hemorrhage, increased with resuscitation, and then declined during the initial 40 min of resuscitation. Enalaprilat administration resulted in blood flow increases not seen in the controls (ending values for cardiac index: 2.8 +/- 0.4 L/min/m2 vs. 1.6 +/- 0.3 L/min/m2; celiac arterial flow 314 +/- 66 L/min/m2 vs. 139 +/- 13 mL/min/m2; and portal venous flow 596 +/- 172 L/min/m2 vs. 414 +/- 81 mL/min/m2 for enalaprilat versus controls, respectively). The greater flows with enalaprilat appeared to be due to prevention of the increases in afterload noted in the controls (ending arterial elastance values 3.73 +/- 0.97 mmHg/m2/mL vs. 7.74 +/- 1.80 mmHg/m2/mL for enalaprilat versus controls, respectively). We conclude that administration of a constant-rate infusion of enalaprilat during resuscitation can be used to improve systemic and mesenteric blood flow.

Systemic and regional hemodynamic effects of enalaprilat infusion in experimental normotensive sepsis

“…However, all animals presented gradual cardiovascular deterioration without any significant difference between groups. These data contrast with findings of previous studies (24,29). During hypotensive resuscitation from hemorrhagic shock in dogs, enalaprilat infusion increased cardiac index, stroke volume index, superior mesenteric artery flow, stroke work, and left ventricular power output without causing a hypotensive crisis (29).…”

“…During hypotensive resuscitation from hemorrhagic shock in dogs, enalaprilat infusion increased cardiac index, stroke volume index, superior mesenteric artery flow, stroke work, and left ventricular power output without causing a hypotensive crisis (29). In other hemorrhage protocols applied to dogs, Wall et al (24) also showed that enalaprilat infusion during resuscitation was associated with an increase in systemic, celiac and portal blood flow.…”

“…Additionally, animal and human data suggest a primary role of angiotensin II in the etiology of selective gut hypoperfusion after resuscitation from shock states (19,20). In animals, angiotensin-converting enzyme (ACE) inhibitors have been shown to improve splanchnic perfusion (21)(22)(23)(24), to decrease bacterial translocation (25) and to improve survival (26) in various types of shock. Moreover, enalaprilat enhanced gut perfusion measured by gastric tonometry in critically injured trauma patients (27) and improved endothelial function in septic patients (28).…”

Non‐equivalence of canine tissue and intraluminal PCO2 responses at different sites during hemorrhage and during resuscitation

“… Further details regarding the studies are available in Wall et al 20–22 The enalaprilat in each study was administered at 0.02 mg/kg/hr in a 0.9% saline vehicle. The 0.9% saline vehicle was administered at 2 mL/kg/hr whether or not it contained enalaprilat.…”

“…In the hopes of identifying such a site, investigators have evaluated the PCO 2 responses of many sites in both trauma and surgical patients [3][4][5][6][7][8][9][10] and hemorrhage and resuscitation laboratory studies. [11][12][13][14][15][16][17][18][19][20][21][22] In fact, the 'Endpoints of Resuscitation' clinical practice guidelines 23 provided on the Eastern Association for the Surgery of Trauma website (www.east.org/tpg.html) mention gastric intraluminal and other site PCO 2 in their 'Recommendations' sections regarding stratifying physiologic derangement and regarding improved patient outcomes and in their 'Scientific Foundation' section.…”