Adenosine for Reversal of Hemorrhagic Shock in Rabbits

Abstract

ABSTRACT-The potential use of adenosine in the treatment of hemorrhagic shock was evaluated in rabbits. Hemorrhagic shock was induced by bleeding the animals to a mean arterial blood pressure of 30-35 mmHg that was maintained for 2 hr. The intravenous infusion of 300 pg/kg/min adenosine for 1 hr, after reinfusion of the shed blood, was found to be capable of increasing the survival rate of rabbits subjected to hemorrhagic shock. In shocked rabbits, adenosine profoundly improved the postreinfusion depressed contractility of the heart, but it produced a decrease in the mean arterial blood pressure and heart rate. In the same animals, the plasma concentrations of glucose, lactate and inorganic phosphate, which were markedly elevated during shock, were returned back toward normal levels by the intravenous infusion of adenosine. Similarly the alteration that occurred in the plasma sodium, potassium and calcium levels during shock was corrected by adenosine. It is consequently concluded that the use of adenosine after shock improves tissue perfusion and enhances the functional recovery of cells by restoring their metabolic machinery and thereby improves the survival rate.

The influence of hemorrhagic shock on ocular microcirculation by obtained by laser speckle flowgraphy in a white rabbit model

“…34 We did not compare the LSFG measurements with data obtained by these methods. Finally, we used heparinized blood for the blood-return phase, whereas some experimental animal models used a balanced hydroxyethyl starch solution, 5 Ringer's lactate solution, 35 or normal saline 36 for the resuscitation state. In the present study, we did not compare the effects on ocular and systemic hemodynamics based on the resuscitation fluid.…”

Adenosine A2A receptor activation reduces lung injury in trauma/hemorrhagic shock*

“…Experimental results with systematically injected adenosine are difficult to interpret, because the half-life of injected adenosine in the plasma is very short (1-2 secs) owing to several mechanisms limiting its availability in the extracellular space (45)(46)(47). Nevertheless, intravenous infusion of adenosine for 1 hr after resuscitation increased the survival rate of rabbits subjected to hemorrhagic shock, which occurred despite the fact that adenosine depressed both MAP and heart rate in these animals (48). Intraperitoneal administration of adenosine protected organs and improved survival after volumecontrolled hemorrhagic shock in rats (49).…”

A2A Adenosine Receptors Regulate Multiple Organ Failure After Hemorrhagic Shock in Mice

“…Previous studies have demonstrated that both endogenous adenosine and exogenous adenosine protect organs against from HS (42)(43)(44)(45). However, it is not well understood which receptor (s) mediate this protection.…”

“…Treatment with the ENT1/ENT2 blocker dipyridamole, which increases endogenous adenosine levels, was protective in both rat (43) and canine (44) models of HS. Like endogenous adenosine, exogenously injected adenosine is protective, as it increased cardiac contractility and the survival rate of rabbits when administered after resuscitation from shock (45). The receptor(s) mediating the protective effects of adenosine are not well characterized.…”