Microcirculatory Effects of Selective Receptor Blockade During Hemorrhagic Shock Treatment With Vasopressin

Abstract

Hemorrhagic shock is a major cause of death in modern societies. Some patients, when treated, fail to sustain normal cardiovascular parameters, requiring fluid therapy and vasoactive drugs. Among drugs with cardiovascular profile other than catecholamine, vasopressin (VP) is emerging as an option. To better understand its effects during hemorrhagic shock, we compared the effects of VP and noradrenaline (NA), associated to fluid therapy. In this work, hamsters were subjected to shock by withdrawal of 40% of their blood volume and were then divided into five groups. One group was treated with saline solution, and the remaining ones with VP (three groups) and NA (one group) combined to fluid resuscitation. To assess receptor role, two more VP groups were pretreated with specific receptor blockers (anti-V1 or anti-V2, respectively) before its infusion. Microcirculatory parameters such as vessel diameter, red blood cell velocity, and functional capillary density were evaluated. In addition, blood gas analysis and lactate levels were also determined. Measurements were performed at baseline, after shock, and after treatment. At the end, leukocyte-endothelium interaction was evaluated, and animals were followed up to determine survival time. Neither saline solution nor NA recovered microcirculatory parameters, but VP treatment returned to near baseline values, except when V2 receptors were blocked. Functional capillary density was higher in the VP group after treatment, without statistical difference from baseline values. When V2 receptors were blocked, recovery was not achieved after treatment. The VP group also had a smaller number of adhering leukocytes and improved 72-h survival time compared with the NA one. This study suggests that, in hemorrhagic shock, treatment with low-dose VP, in combination with fluid therapy, improves tissue perfusion. This outcome is mediated mostly by V2 receptors, eliciting vasodilatation and consequently blood flow redistribution through the microcirculation.

Therapeutic interventions to restore microcirculatory perfusion following experimental hemorrhagic shock and fluid resuscitation: A systematic review

“…Other non-fluid-based agents with vasoactive properties showed conflicting results. Neither vasopressors 20,57,60,61 nor vasodilators 42,55,59,60 were effective in the preclinical setting. One of the studies investigating the effect of vasopressin reported a decrease in blood flow and an increase in capillary leak as a result of the given treatment, 61 while another study reported no effect of vasopressin on blood flow.…”

“…19,42,[52][53][54][55] Eleven vasoactive agents (58%) did not affect blood flow. 19,22,[56][57][58][59][60] The remaining two studies (10%) reported a decrease in blood flow, 61 or results varied markedly between organs. 20 Vasopressin showed contrasting results with a decrease in intestinal blood flow, 61 but no effect on dorsal blood flow.…”

“…20 Vasopressin showed contrasting results with a decrease in intestinal blood flow, 61 but no effect on dorsal blood flow. 57 This may be because measurements were performed in different organs and different concentrations were given, and high concentrations of vasopressin are known to have adverse effects on microcirculatory perfusion. One study reported the effect of vasoactive agent metaraminol on blood flow under conscious and unconscious conditions in nine different organs.…”

Searching For the Optimal Fluid to Restore Microcirculatory Flow Dynamics After Haemorrhagic Shock

“…There were multiple studies that used drug delivery as interventions (rather than purely comparing different fluids), including additives (108)(109)(110)(111), noradrenaline (112), polydatin (113), nitric oxide (114) and naloxone (115).…”

Effets des vasoconstricteurs sur la microcirculation

“…Lors du choc hémorragique, chez le hamster, après remplissage vasculaire, la vasopressine améliore les paramètres de microcirculation et d'interaction leucocytes-endothé-lium, via son récepteur V2 (vasodilatation avec redistribution du flux sanguin dans la microcirculation) [58]. Chez le chien, l'administration de vasopressine, sans remplissage vasculaire ou transfusion sanguine associés, induit une dété-rioration des paramètres de l'hémodynamique systémique (absence d'amélioration du débit cardiaque) et de la microcirculation conjonctivale (diminution du diamètre des veinules et de la vélocité des globules rouges) [48].…”