Hemorrhage remains a primary cause of death in civilian and military trauma. Permissive hypotensive resuscitation is a possible approach to reduce bleeding in patients until they can be stabilized in an appropriate hospital setting. Small-volume resuscitation with hypertonic saline (HS) is of particular interest because it allows one to modulate the inflammatory response to hemorrhage and trauma. Here, we tested the utility of permissive hypotensive resuscitation with hypertonic fluids in a rat model of hemorrhagic shock. Animals were subjected to massive hemorrhage [mean arterial pressure (MAP)=30-35 mmHg for 2 h until decompensation] and partially resuscitated with a bolus dose of 4 mL/kg of 7.5% NaCl (HS), hypertonic hydroxyl ethyl starch (HHES; hydroxyl ethyl starch +7.5% NaCl), or normal saline (NS) followed by additional infusion of Ringer solution to maintain MAP at 40 to 45 mmHg for 40 min (hypotensive state). Finally, animals were fully resuscitated with Ringer solution and the heparinized shed blood. Hypotensive resuscitation with NS caused a significant increase in plasma interleukin (IL)-1 beta, IL-6, IL-2, interferon gamma (IFN gamma), IL-10, and granulocyte-macrophage colony stimulating factor (GM-CSF). This increase was blocked by treatment with HS. HHES treatment significantly reduced the increase of IL-1 beta and IL-2 but not that of the other cytokines studied. Despite the strong effects of HS and HHES on cytokine production, both treatments had little effect on plasma lactate, base excess (BE), white blood cell (WBC) count, myeloperoxidase (MPO) content, and the wet/dry weight ratio of the lungs. Moreover, on day 7 after shock, the survival rate in rats treated with HS was markedly, but not significantly, lower than that of NS-treated animals (47% vs. 63%, respectively). In summary, hypotensive resuscitation with hypertonic fluids reduces the inflammatory response but not lung tissue damage or mortality after severe hemorrhagic shock.

Trauma or the tourniquet used in orthopedic surgery is often associated with ischemia–reperfusion (I/R) injury with a consequent decrease of muscle power. To explore whether components of the neuromuscular junction (NMJ) are involved in this muscle dysfunction, NMJs were ultrastructurally characterized in the extensor digitorum longus muscle of rats at reperfusion times of 1, 24, 72, and 168 h after a 120‐min arterial occlusion. Disorganization of the presynaptic membrane and mitochondrial injury was noted at 1 h, followed by fragmentation and partial engulfment of nerve terminals by Schwann cells at 24 and 72 h. The magnitude of degenerative changes declined at 168 h, suggesting the commencement of regeneration. The postsynaptic membrane remained intact throughout the whole period. In our previous study, deafferentation with pretreatment of the sciatic nerve with capsaicin, which reduces neurogenic inflammation and has a selective effect on nociceptive fibers, improved functional recovery of the muscle after I/R. The present results document a significantly delayed structural regeneration of the motor nerve terminals after combined capsaicin and I/R treatment. Since capsaicin treatment alone had no discernible effect on the structure of NMJs, the findings point to a possibly indirect effect of capsaicin on the motor nerves, which may predispose them to increased susceptibility unmasked only by a subsequent injury. The mismatch between the enhanced functional improvement of the muscle and delayed regeneration of the nerve after capsaicin pretreatment questions the efficient use of such deafferentation to protect the integrity of neuromuscular junctions in I/R injury. Muscle Nerve, 2006

The present study analyzes the effect of selective deafferentation on the reperfusion injury of the skeletal muscle when nociceptive sensory fibers of the left sciatic nerve are selectively damaged by capsaicin pretreatment in a rat model following tourniquet ischemia (ISC) applied for 30 min, 1 h, and 2 h on the left hind limb. The isometric tetanic contractile force of the extensor digitorum longus (EDL) muscle was measured after 1 h, and 1, 3, or 7 days of reperfusion. Contractile force of the damaged muscle was compared to the intact contralateral muscle. In another group, ISC was used without capsaicin pre-treatment. After 30 min of ISC, there was no difference between deafferented and non-pretreated groups. Following 1 h ISC, with the exception of 1 h reperfusion, the non-pretreated group produced stronger contractions than the deafferented group. After 2 h ISC, the contractile force of the deafferented muscle was significantly stronger compared to the non-deafferented muscle force at all reperfusion times. In conclusions, it was found that the absence of peptidergic sensory fibers after long-lasting (2 h) ischemia is beneficial in reperfusion injury, whereas the absence of vasodilator peptides has unfavorable effects if tissue damage is milder (after 1 h ischemia).

Bone injury is often associated with major losses of tissue. The lost bone has to be replaced. The purpose of bone replacement is to stimulate new bone formation by osteoinduction and osteoconduction, and to give mechanical support to the skeleton. There are several methods to build up new bone if there are bone defects. Autologous bone can be used, however, the size of the source is limited. Heterologous or xeno transplants can lead to host versus graft complications. Another possibility is to use demineralized or desantigenized materials [3 ±5]. The biological process of bone formation has several steps, among them the infiltration of the gap by undifferentiated cells, which is followed by vascular and neural ingrowth [8]. We have found that neural and vascular ingrowth goes parallel (unpublished), and the neural fibers contain significant amounts of neuropeptides: CGRP, NPY, and SP. These peptides are all vasoactive substances [1, 6, 7]. Therefore, it was interesting to study whether different bone replacing materials can influence differentially the callus bone formation and the microcirculation of the developing callus.

Ludwig Boltzmann Inst. f Exp & Clin Traumatology, Vienna, Austria *National Institute of Traumatology, Budapest, Hungary

Číž, M.; Lojek, A.; Hamar, J.; Slavíková, H.; Vondráček, J.; Dušková, M. Author Information