The effects of transcranial electrical stimulation on anaesthesia and analgesia in rats.

In this study, we determined the effects of transcranial electrical stimulation (TCES) on the anaesthetic requirements of thiopental and the analgesic requirements of remifentanil, in rats. The experiments were performed on 120 albino male Wistar rats, which were randomly allocated to four groups (n=30). (Thiopental, Thiopental+TCES, Thiopental+Remifentanil, and Thiopental+Remifentanil+TCES). Animals were anaesthetized with thiopental, and 15 min later, remifentanil was injected to rats in the Remifentanil groups. TCES was started in the stimulated groups 20 min after thiopental administration. Rats were stimulated 5 times for this experiment. The times for recovery, herein called Cognition Recovery Time and Motion Recovery Time were measured. Cognition Recovery and Motion Recovery Times were not affected by the stimulation. Analgesia was assessed using the wet tail-flick latency (TFL). In the Thiopental group, the analgesia level returned to control values on the 35th min. In the Thiopental+Remifentanil group, the analgesia level returned to control values on the 50th min. In the Thiopental+ TCES group, the analgesia level reached the peak value on the 65th min. In the Thiopental+Remifentanil+TCES group, the analgesia level reached the peak value on the 35th min and analgesia remained high during the 90 min after cessation of the stimulation. The analgesic potency for the Thiopental+Remifentanil+TCES group was increased by 30-40% when compared with the prior TFL values, 160% when compared with the control group, and 50-75% when compared with Thiopental+TCES group on the 35th min (P<0.001). In conclusion, TCES markedly decreases the anaesthetic and analgesic requirements for thiopental and remifentanil in rats.

The effect of antioxidant therapy on cell-mediated immunity following burn injury in an animal model.

Although antioxidant therapy has been introduced into early post burn protocols to prevent oxidative injury, it is still not known how they effect the cellular immunity which was already depressed due to thermal injury. To investigate the effect of antioxidant therapy on postburn immunosuppression following burn injury in a rat model, well known antioxidants: allopurinol (50 mg/kg/day), desferrioxamine (15 mg/kg/day), PEG-catalase (PEG-CAT) (1200 U/kg/day), N-acetylcysteine (NAS) (1 mg/kg/day) and vitamin-C (Vit-C) (0.5 mg/kg/day) were given for 7 days following thermal injury. The immunologic status of the rat was studied using two in vivo measures at seventh day following (30% TBSA) full-thickness burn injury. The contact hypersensitivity response (CHR) of rats, and their ability to induce a host versus graft reaction (HVGR) in the popliteal node were used to assess immune system as in vivo measures. The use of mentioned antioxidants resulted in significant improvement (between P < 0.05 and P < 0.001) of burn induced immunosuppression as reflected by CHR. The treatment with allopurinol and PEG-CAT (P < 0.01) significantly improved, while desferrioxamine, NAS and Vit-C improved, but not significantly, HVG reaction in burned rats. This study demonstrated that a large burn was profoundly immunosuppressive and early intervention of antioxidant therapy was able to significantly restore cell-mediated immunity as reflected by two in vivo assays.

Modulating the functions of neutrophils and lipid peroxidation by FK506 in a rat model of thermal injury.

Neutrophils diffusely invade lung, liver, kidney, intestine, muscle and burned skin following burn injury. To ameliorate this invasion and minimize its effects, neutrophils can be modulated by giving neutrophil inhibitors and modulators. In this study, FK506 was used to decrease neutrophil infiltration and lipid peroxidation in remote organs (lung, liver, kidney and intestine) in a burned rat model. FK506 is a new major immunosuppressive agent that is known to modulate neutrophils during inflammation. Neutrophil infiltration was assessed indirectly by measuring myeloperoxidase (MPO) activity biochemically in remote organs following 30% full thickness burn injury. Malondialdehyde (MDA), the end product of lipid peroxidation, was measured biochemically in remote organs and plasma to determine if there is a relationship between neutrophil infiltration and lipid peroxidation after burn injury. FK506 was given intramuscularly at the dose of 0.5 and 1.0 mg/kg for three days before burn injury. Thermal trauma to the skin caused a statistically significant increase in MPO activity and MDA content in remote organs. FK506 was effective in reducing lipid peroxidation and neutrophil infiltration especially at 24 h postinjury in lung, liver and kidney. FK506 may have some benefit (prophylactic) in reducing systemic neutrophilic injury and related lipid peroxidation in burns.

Effects of raloxifene on cerebral vasospasm after experimental Subarachnoid Hemorrhage in rabbits.

BACKGROUND: The aim of this study was to investigate the ability of a SERM, RLX, to prevent vasospasm in a rabbit model of SAH. METHODS: Thirty-four New Zealand white rabbits were allocated into 3 groups randomly. Subarachnoid hemorrhage was induced by injecting autologous blood into the cisterna magna. The treatment groups were as follows: (1) sham operated (no SAH [n = 12]), (2) SAH only (n = 12), and (3) SAH plus RLX (n = 10). Basilar artery lumen areas and arterial wall thickness were measured to assess vasospams in all groups. RESULTS: There was a statistically significant difference between the mean basilar artery cross-sectional areas and the mean arterial wall thickness measurements of the control and SAH-only groups (P < .05). The difference between the mean basilar artery cross-sectional areas and the mean arterial wall thickness measurements in the RLX-treated group was statistically significant (P < .05). The difference between the SAH group and the SAH + RLX group was also statistically significant (P < .05). CONCLUSIONS: These findings demonstrate that RLX has marked vasodilatatory effect in an experimental model of SAH in rabbits. This observation may have clinical implications suggesting that this SERM drug could be used as possible anti-vasospastic agent in patients without major adverse effects.

Involvement of neutrophils in ischemic injury. I. Biochemical and histopathological investigation of the effect of FK506 on dorsal skin flaps in rats.

The purpose of this study was to investigate the role of neutrophils in ischemic tissue injury and the possible inhibition by pretreatment with FK506, a neutrophilic modulating agent. A dorsal caudally based skin flap (3 x 9 cm) was used as an ischemic injury model in experimental groups. Prior to flap elevation, FK506 at doses of 0.3 mg per kilogram (group 2), 0.5 mg per kilogram (group 3), and 1.0 mg per kilogram (group 4) was given for 3 days intramuscularly. The relationship among neutrophil accumulation (histopathologically), myeloperoxidase (MPO) activity, malondialdehyde (MDA) content (biochemically) of the flap tissue, and flap survival were studied. Skin flaps showed reduced necrosis in the FK506-treated groups (p < 0.08, p < 0.0001, and p < 0.0001 respectively). The increase in accumulation of neutrophils, and MDA and MPO levels (which were induced by ischemia) observed 1 and 24 hours after flap elevation was diminished by FK506 pretreatment. The increased neutrophilic infiltration, and raised tissue MDA content and MPO activity revealed involvement of both free radical production and neutrophils in ischemia. This injury was decreased by FK506, probably by inhibition of neutrophilic chemotaxis, infiltration, and releasing factors.

Oxygen free radicals impair wound healing in ischemic rat skin.

Oxygen free radicals are produced and play an important role in ischemic injury. We therefore wished to investigate the role of free radicals on ischemic skin wound healing. For this purpose, H-shaped flaps, where the test ischemic wound is the horizontal line in the H, were created on the dorsum of the rat. To inhibit the probable hazards of free radicals, allopurinol and superoxide dismutase (SOD) were given to the animals. Most of the studied wound-healing parameters were impaired in the ischemic group. In the allopurinol-treated group, breaking strength was increased by 52% by day 7 and by 109% by day 14 (p < 0.0002 and p < 0.001), and in the SOD-treated group the increase was 69% both by days 7 and 14 of healing when compared with the ischemic control group (p < 0.003 and p < 0.002). Hydroxyproline content was increased 75% with allopurinol and 113% with SOD in the wound by day 7 (p < 0.03 and p < 0.001 respectively). SOD treatment caused a significant decrease in wound edema by day 7 of healing (p < 0.05). Histopathological evaluation revealed that in the SOD- and allopurinol-treated groups, the amount of collagen and its organization were more prominent when compared with the ischemic controls. These results show that oxygen free radicals play an important role in the failure of ischemic wound healing, and antioxidants partly improve the healing in ischemic skin wounds.

An experimental study of skin flap associated with muscle: is muscle nourishment possible through the musculocutaneous perforators?

An experimental study was planned to examine whether the blood supply of muscle would be maintained by reverse flow from the cutaneous arteriolar microcirculatory system via the musculocutaneous perforators. A flap model containing both muscle and skin based on the inferior superficial epigastric vessels was designed with the blood supplied directly from the cutaneous arteriolar microcirculatory system. A total of 154 male Wistar Albino rats were divided into three groups. Group I included the standard vertical rectus abdominis musculocutaneous flap based on the superior deep epigastric vessels (N = 48). Group II included the acute cutaneous muscle flap (N = 53). Group III contained the delayed cutaneous muscle flap (N = 53). Skin flap survival area, muscle scintigraphy with technetium-99m-methoxy-isobutyl-isonitrile, microangiography, and histopathological examination of the flaps were conducted. The mean percentage of surviving skin paddle area was 96.4 +/- 5.2%, 84.9 +/- 21.6%, and 91.0 +/- 16.8% in groups I, II, and III respectively. There was no significant difference between groups. Microangiography revealed the blood flow from skin to muscle through the musculocutaneous perforators. The radioisotope uptake of the muscle flap was expressed as A percentage of the intact contralateral muscle. Mean uptake in group I was 90.1 +/- 4.9% immediately after flap elevation, 62.5 +/- 13.5% on day 2, and 88.3 +/- 12.0% on day 7. These values were 53.7 +/- 7.1%, 63.6 +/- 14.1%, and 89.2 +/- 18.1% in group II, and 64 +/- 7.8%, 75.5 +/- 9.8%, and 92.8 +/- 40.1% in group III. Radioisotope uptake in group I was significantly higher than groups II and III immediately after flap elevation (p < 0.05, analysis of variance), whereas there was no significant difference on days 2 and 7. Histopathological examination revealed surviving muscle tissue without marked atrophy. There was no marked difference between groups histopathologically. These results indicate that muscle tissue may survive by reverse flow through the musculocutaneous perforators when elevated with an axial skin flap.