ATP-MgCl₂ restores renal microcirculation following trauma and severe hemorrhage

Abstract

Although ATP-MgCl2 enhances the recovery of renal function after ischemia and reperfusion, it is not known whether this agent has any beneficial effects on renal microcirculation and function in a nonheparinized model of trauma and severe hemorrhage. To study this, a midline laparotomy was performed (i.e., trauma induced) and the rats were bled to and maintained at a mean arterial pressure of 40 mmHg (1 mmHg = 133.32 Pa) until 40% of the maximum shed blood volume was returned in the form of Ringer's lactate (RL) solution. Animals were then resuscitated with 4 times the volume of the shed blood in the form of RL. ATP-MgCl2, 50 mumol/kg body weight, or an equivalent volume of saline, was infused intravenously during and following resuscitation. Renal microcirculation was examined by using colloidal carbon infusion and laser Doppler flow-metry. Glomerular filtration rate (GFR) was assessed with [3H]inulin clearance and cardiac output (CO) was determined by dye dilution technique. The results indicate that the depressed renal microcirculation following hemorrhage and resuscitation was restored by ATP-MgCl2 treatment. GFR was significantly higher in ATP-MgCl2-treated than saline-treated rats. ATP-MgCl2 also increased urine output, restored the decreased CO, and prevented the occurrence of renal edema after hemorrhage and resuscitation. Thus, ATP-MgCl2 appears to be a useful adjunct to crystalloid resuscitation following trauma and severe hemorrhagic shock even in the absence of blood resuscitation.

Purinergic Signaling and Blood Vessels in Health and Disease

“…Adenosine uptake mediates recovery of ATP content in postischemic cultured renal tubular cells (Cadnapaphornchai et al, 1991). Enhanced recovery from acute renal failure in rats by postischemic infusion of ATP-MgCl 2 was described earlier (Osias et al, 1977;Glazier et al, 1978;Siegel et al, 1980;Gaudio et al, 1982;Hirasawa et al, 1983;Sumpio et al, 1984;Wang et al, 1992bWang et al, , 1992dMartin et al, 1992). Renal injury can arise as a consequence of ischemia and reperfusion during renal transplant surgery.…”

Attenuation of Vascular Endothelial Dysfunction by Testosterone Receptor Blockade After Trauma and Hemorrhagic Shock

“…5,[8][9][10] Similarly, our previous studies have shown that administration of pentoxifylline or adenosine triphosphate-magnesium chloride after trauma-hemorrhage and resuscitation significantly improves endothelial function and has many other beneficial effects on experimental animals. 1,3,[28][29][30][31][32][33][34][35][36][37][38][39] The precise mechanism responsible for the beneficial effects of flutamide on endothelial function remains unknown. Previous studies have shown that plasma testosterone levels are not significantly altered after traumahemorrhage and resuscitation.…”

Progesterone administration after trauma and hemorrhagic shock improves cardiovascular responses

“…Our previously described nonheparinized model of trauma-hemorrhage in the rat was used with minor modifications (28). Briefly, rats were fasted overnight before the experiment but allowed water ad libitum.…”