Poly (ADP-ribose) polymerase activity during hemorrhagic shock and normotensive versus hypotensive resuscitation

Background

Poly (ADP-ribose) polymerase (PARP-1) over-activation may lead to depletion of NAD+ and ATP within the cell and proceed to necrotic cell death. Recently, published reports demonstrate high levels of PARP-1 activity in a model of porcine hemorrhagic shock. There is also increased interest in hypotensive resuscitation used for battlefield-wounded soldiers and trauma patients. We wished to evaluate PARP-1 activity during a model of porcine hemorrhagic shock with the hypothesis that PARP-1 activity will be increased using a hypotensive resuscitation strategy.

Methods

Hemorrhagic shock was induced in splenectomized pigs with a 35% controlled hemorrhage via IVC cannula. Pigs were resuscitated to either normotensive (towards baseline) or hypotensive (80 mmHg) pressures using hextend and LR. Muscle and liver biopsies were taken prior to hemorrhage, after 90 min of shock, and after resuscitation. PARP-1 activity in biopsies was measured using chemical quantization of NAD⁺. Physiologic and laboratory data collected during the experiment included blood pressure, heart rate, mean arterial pressure, cardiac output, oxygen delivery, oxygen consumption, and serum lactate.

Results

Physiologic and laboratory parameters measured during the experiment were consistent with hemorrhagic shock, normotensive resuscitation and hypotensive resuscitation. PARP-1 activity increased from baseline with hemorrhage and returned towards baseline with resuscitation (Fig. 1). PARP-1 activity during normotensive resuscitation versus hypotensive resuscitation was not statistically different (Fig. 2).

Figure 1

Poly (ADP-ribose) polymerase (PARP-1) activity increased with hemorrhage. With both normotensive and hypotensive resuscitation PARP activity returned towards baseline.

Figure 2

Muscle poly (ADP-ribose) polymerase (PARP-1) activity during normotensive resuscitation was not statistically different from that during hypotensive resuscitation.

Conclusion

PARP-1 activity in our porcine model of hemorrhagic shock increases with the physiologic changes associated with shock. PARP-1 activity decreases with resuscitation in both normotensive and hypotensive resuscitation strategies. This provides evidence in support of short-term hypotensive resuscitation for hemorrhagic shock.