Objective: To determine if inhaled Hypertonic Saline (7%) improves the Lung Clearance Index in paediatric Cystic Fibrosis patients with FEV1 ≥80% predicted. Methods: In a blinded crossover trial, twenty CF patients received 4 weeks of hypertonic saline (7%) (HS) and 4 weeks of isotonic saline (0.9%) (IS) separated by a 4 week washout period. The primary endpoint was the change in LCI in the HS versus the IS treatment periods. Results: Four weeks of twice daily inhalation of HS significantly improved the LCI as compared to IS by 1.16, 95% CI [0.26, 2.05]; p=0.016. Baseline LCI before IS, 8.71+/-2.10, was not significantly different from baseline LCI before HS inhalation, 8.84+/-1.95 (p=0.73). Randomization order had no significant impact on the treatment effect (p=0.61). Conclusions: Four weeks of twice daily Hypertonic Saline (7%) inhalations improved the LCI and may be a suitable early intervention therapy for CF patients with mild disease.

Objective: To determine if inhaled Hypertonic Saline (7%) improves the Lung Clearance Index in paediatric Cystic Fibrosis patients with FEV1 ≥80% predicted. Methods: In a blinded crossover trial, twenty CF patients received 4 weeks of hypertonic saline (7%) (HS) and 4 weeks of isotonic saline (0.9%) (IS) separated by a 4 week washout period. The primary endpoint was the change in LCI in the HS versus the IS treatment periods. Results: Four weeks of twice daily inhalation of HS significantly improved the LCI as compared to IS by 1.16, 95% CI [0.26, 2.05]; p=0.016. Baseline LCI before IS, 8.71+/-2.10, was not significantly different from baseline LCI before HS inhalation, 8.84+/-1.95 (p=0.73). Randomization order had no significant impact on the treatment effect (p=0.61). Conclusions: Four weeks of twice daily Hypertonic Saline (7%) inhalations improved the LCI and may be a suitable early intervention therapy for CF patients with mild disease.

Justification: Endotoxemia and sepsis are major causes of mortality in horses, resulting in significant economic losses for the equine industry. Objective: To determine the effects of the combination of Hypertonic Saline Solution and Hetastarch in endotoxemic horses. Animals: Eighteen horses divided into three groups of six. Procedure: All horses received a total dose of intravenous E. coli endotoxin infused at 50 ug/kg; divided into a bolus infusion of 20 ug/kg followed by 30 ug/kg given over 30 minutes. After induction of endotoxic shock; group I (control) received a bolus (15 ml/kg) of isotonic solution, group II (isotonic solution) received a bolus (60 ml/kg) of balanced polyionic crystalloid solution and group III (Hypertonic saline plus Hetastarch) received a bolus of 5 ml/kg of hypertonic saline, followed by a bolus of 10 ml/kg of Hetastarch. Hemodynamic and hematological parameters were measure at different time points. Results: Hemodynamic, biochemical and hematological differences were observed among the three groups. Conclusions and Relevance: the use of large volume crystalloid fluid resuscitation causes volume overload, exerting deleterious effects on the cardiovascular and pulmonary systems. The use of small volume resuscitation (HSS-HES) showed a trend towards better cardiovascular and pulmonary function, without the deleterious effects of volume overload. Abnormalities with regard to coagulation were not seen for the time period of the experimental protocol and the dose regimen used for HSS-HES. Small volume resuscitation in critically ill horses shows promise for its beneficial effects in cardiovascular and pulmonary functions. / Master of Science

A hemodiluição normovolêmica aguda (HNA) é terapia mundialmente reconhecida como vantajosa em cirurgias que possuem grande potencial para sangramento, mas o edema provocado pela maior infusão de fluidos pode ser danoso em alguns pacientes. No intuito de avaliar as repercussões hemodinâmicas e laboratoriais da utilização da solução salina hipertônica a 7,5% como líquido parcial de reposição na HNA foram estudados 20 pacientes submetidos à artrodese para correção de escoliose de coluna. No grupo 1 (SS 0,9%, n=10) o sangue retirado na HNA, realizada momentos antes da cirurgia, foi reposto por solução salina 0,9% em um volume três vezes maior que o retirado. No grupo 2 (SS 7,5%, n=10) a metade do que foi retirado foi reposto com solução a 0,9% (três vezes o volume retirado) e a outra metade por 4 ml.kg-1 de solução salina hipertônica 7,5%. Nenhum dos pacientes apresentou distúrbios do equilíbrio ácido-básico e as alterações metabólicas (aumento da osmolaridade, sódio e cloro plasmáticos) foram passageiras. Os pacientes mantiveram-se hemodinamicamente estáveis e não foi observado sangramento anormal intra-operatório. A incidência de transfusão sangüínea foi semelhante embora os pacientes do grupo solução hipertônica tenham ficado clinicamente menos edemaciados. Mesmo não sendo objeto do estudo, observou-se menor incidência de infecções pós-operatórias nos pacientes submetidos à infusão de solução hipertônica, o que pode significar potencial efeito protetor da solução. Embora mais estudos com números maiores de pacientes sejam necessários para se comprovar esses efeitos, a solução hipertônica mostrou-se barata, simples e segura como maneira de redução do volume infundido na HNA. / The acute normovolemic hemodilution (ANH) is a therapy recognized as benefic in surgeries that have a great potential for bleeding but the swelling caused by solutions infused intra-operative can be harmful in some kind of patients. Twenty patients submitted to arthrodesis for scoliosis correction were studied in order to evaluate the hemodynamic and laboratory effects of 7.5% hypertonic saline solution as a partial fluid replacement in ANH. In group 1 (SS 0.9%, n = 10) the collected blood in ANH was replaced by saline solution 0.9% in a volume three times greater than the withdrawal. In group 2 (SS 7.5%, n = 10), half of the blood removed was restored by 0.9% solution (three times the amount withdrawn) and the other half by 4 ml.kg-1 of 7.5% solution. None of the patients presented acid-base disorders. Metabolic changes - enhanced of plasmatic levels of sodium, chlorine and osmolarity - were all transitory. Patients remain hemodynamic stable and no abnormal bleeding was observed. They had similar incidence of blood transfusion but the ones in hypertonic solution group were clinically less swollen. Lower incidences of post-operative infections were found in this group, which could mean a possible protector potential of hypertonic solution. SS 7.5% was a cheap, simple and safe alternative to reduce volume infused in ANH.

Hypertonic saline (HS) is an accepted treatment for traumatic brain injury (TBI). However, the behavioral and cognitive consequences following HS administration have not thoroughly been examined. Recent preclinical evidence has suggested that nicotinamide (NAM) is beneficial for recovery of function following TBI. The first study compared the behavioral and cognitive consequences of HS and NAM as competitive therapeutic agents for the treatment of TBI. Following controlled cortical impact (CCI), bolus administrations of NAM (500 mg/kg), 7.5% HS, or 0.9% saline vehicle (1.0 mL/kg) were given at 2, 24, and 48 hrs post-CCI. Behavioral results revealed that animals treated with NAM and HS showed significant improvements in beam walk and locomotor placing compared to the Vehicle group. The Morris water maze (MWM) retrograde amnesia test was conducted on day 12 post-CCI and showed that all groups had significant retention of memory compared to injured, Vehicle-treated animals. Working memory was also assessed on days 18-20 using the MWM. The NAM and Vehicle groups quickly acquired the task; however, HS animals showed no acquisition of this task. Histological examinations revealed that the HS-treated animals lost significantly more cortical tissue than either the NAM or Vehicle-treated animals. HS-treated animals showed a greater loss of hippocampal tissue compared to the other groups. In general, NAM showed a faster rate of recovery than HS without this associated tissue loss. Study 1 suggested that future research into HS should include drug injection time course studies. Multiple injections may be responsible for the notable tissue damage. Therefore, it is possible that fewer injections will result in comparable behavioral recovery and less tissue damage that was observed. Due to the detrimental effects of 7.5% HS on cognition and hippocampal tissue following multiple administration in study 1, the proposed second study sought to study the behavioral and cognitive effects of HS using either single or multiple injection regime. The proposed study entailed a lengthier testing schedule than in study 1 and included the same histological examination to compare the different dosages. Additionally, edema formation was measured 24 hours following each drug endpoint in order to delineate the possible underlying mechanism of the observed deficits. In Study 2, HS tended to improve function on motor, sensorimotor and neurological tasks. Although this was a trend on all tests, animals treated with a single administration of HS overall performed better on all tasks compared to those receiving double or multiple injections. In the retrograde amnesia test, although not significant, the Sham, HS-2, and HS-24 animals showed improvement; whereas, the Vehicle and HS-48 animals showed no improvement in performance. This could possibly be linked to the additional hippocampal tissue loss that was noted in the HS-48 animals. In the working memory paradigm, the HS-2 and Vehicle groups had longer latencies to reach the platform than did the Sham group. However, after the first testing day, there were no significant differences between any of the groups. All animals treated with HS performed at the same rate and their performance either stayed the same over the three day testing period or became worse. It appears these animals were unable to learn and improve in the new memory acquisition task which is comparable to the results found in study 1. In study 1, there were again no observed hippocampal volume differences between the Sham and Vehicle-treated animals. However, there was extensive hippocampal tissue damage observed in all of the HS groups. Furthermore, animals treated with a single administration of HS had less hippocampal loss than those with double or multiple doses. Those animals receiving more than one dose of HS lost significantly more hippocampal tissue than the Vehicle group. The results of study 2 are comparable, and support, the results of study 1. Both studies support the strengths and weakness of HS therapy following TBI. Although there are potential benefits of HS therapy, there are also detrimental risks involved. Cognitive and structural damage could possible occur if the dosage amounts are not closely studied and monitored. Although the use of HS may be beneficial to reduce ICP following TBI, it appears that the use of HS may also lead to direct or indirect tissue loss possibly by chronic cellular dehydration. Stronger or more delineated effects may be noticed using higher doses or concentrations of HS in future studies. However, due to the nature of these results, caution should be advised with the use of all therapeutic usage of HS until further detailed studies are conducted.

A hemodiluição normovolêmica aguda (HNA) é terapia mundialmente reconhecida como vantajosa em cirurgias que possuem grande potencial para sangramento, mas o edema provocado pela maior infusão de fluidos pode ser danoso em alguns pacientes. No intuito de avaliar as repercussões hemodinâmicas e laboratoriais da utilização da solução salina hipertônica a 7,5% como líquido parcial de reposição na HNA foram estudados 20 pacientes submetidos à artrodese para correção de escoliose de coluna. No grupo 1 (SS 0,9%, n=10) o sangue retirado na HNA, realizada momentos antes da cirurgia, foi reposto por solução salina 0,9% em um volume três vezes maior que o retirado. No grupo 2 (SS 7,5%, n=10) a metade do que foi retirado foi reposto com solução a 0,9% (três vezes o volume retirado) e a outra metade por 4 ml.kg-1 de solução salina hipertônica 7,5%. Nenhum dos pacientes apresentou distúrbios do equilíbrio ácido-básico e as alterações metabólicas (aumento da osmolaridade, sódio e cloro plasmáticos) foram passageiras. Os pacientes mantiveram-se hemodinamicamente estáveis e não foi observado sangramento anormal intra-operatório. A incidência de transfusão sangüínea foi semelhante embora os pacientes do grupo solução hipertônica tenham ficado clinicamente menos edemaciados. Mesmo não sendo objeto do estudo, observou-se menor incidência de infecções pós-operatórias nos pacientes submetidos à infusão de solução hipertônica, o que pode significar potencial efeito protetor da solução. Embora mais estudos com números maiores de pacientes sejam necessários para se comprovar esses efeitos, a solução hipertônica mostrou-se barata, simples e segura como maneira de redução do volume infundido na HNA. / The acute normovolemic hemodilution (ANH) is a therapy recognized as benefic in surgeries that have a great potential for bleeding but the swelling caused by solutions infused intra-operative can be harmful in some kind of patients. Twenty patients submitted to arthrodesis for scoliosis correction were studied in order to evaluate the hemodynamic and laboratory effects of 7.5% hypertonic saline solution as a partial fluid replacement in ANH. In group 1 (SS 0.9%, n = 10) the collected blood in ANH was replaced by saline solution 0.9% in a volume three times greater than the withdrawal. In group 2 (SS 7.5%, n = 10), half of the blood removed was restored by 0.9% solution (three times the amount withdrawn) and the other half by 4 ml.kg-1 of 7.5% solution. None of the patients presented acid-base disorders. Metabolic changes - enhanced of plasmatic levels of sodium, chlorine and osmolarity - were all transitory. Patients remain hemodynamic stable and no abnormal bleeding was observed. They had similar incidence of blood transfusion but the ones in hypertonic solution group were clinically less swollen. Lower incidences of post-operative infections were found in this group, which could mean a possible protector potential of hypertonic solution. SS 7.5% was a cheap, simple and safe alternative to reduce volume infused in ANH.

O presente estudo visou avaliar a influência da diabetes experimental no perfil nociceptivo orofacial de ratos. Foram utilizados 40 ratos Wistar, no qual 20 receberam injeção de estreptozotocina (STZ) para a indução da diabetes experimental (grupo diabetes), e 20 receberam solução de citrato de sódio (CS - grupo controle). Esses animais foram subdivididos em dois subgrupos de 10 ratos que apenas se diferenciaram com relação à substância que foi injetada no músculo masseter: solução salina isotônica (SI) [n=10: Cont-SI; n=10: Diab-SI] ou hipertônica (SH) [n=10: Cont-SH; n=10: Diab-SH]. Num primeiro momento foi feita a administração intraperitoneal de STZ ou CS e quatorze dias após, com os animais levemente anestesiados, foi realizada a injeção de 100 μL de solução SH-5% ou SI-0,9% na região média do músculo masseter esquerdo, numa profundidade de 5 mm e então foi quantificado, por dois minutos, o comportamento nociceptivo caracterizado pelo ato do rato sacudir/agitar a pata posterior ipsilateral o que é aceito como índice de nocicepção muscular. Uma hora após a avaliação comportamental nociceptiva, os ratos foram eutanasiados por sobredose de anestésico e o músculo masseter esquerdo foi retirado com auxílio de um bisturi circular; parte deste músculo foi utilizada para a análise da expressão de RNA para as citocinas pró inflamatórias [fator de necrose tumoral (TNFα), IL1β, IL6, ciclooxigenase 2 (COX-2)] e anti inflamatórias [IL- 2, IL- 10)] por meio da técnica de Reação em Cadeia da Polimerase quantitativa (qPCR); a parte restante foi corada pela técnica de hematoxilina-eosina e depois realizada a análise histopatológica descritiva em microscópio de luz. Foi observado um aumento significativo do comportamento nociceptivo nos ratos não diabéticos ou normoglicêmicos submetidos à injeção de SH (Cont-SH) em relação aos demais grupos que foram similares entre si. Na análise de citocinas, verificamos que o músculo masseter de ratos não diabéticos submetidos à injeção de SH (Cont-SH) apresentaram um aumento significativo da expressão relativa de TNFα em relação aos demais grupos que foram similares entre si; para a IL-1β também foi verificada um aumento da expressão relativa do grupo (Cont-SH) em relação aos grupos Cont-SI e Diab-SI, mas não em relação ao grupo Diab-SH e a IL-6 foi significativamente mais expressa no músculo masseter de ratos não diabéticos submetidos à injeção de SH em relação ao grupo Cont-SI, mas não foi diferente nos demais grupos. As demais citocinas avaliadas (COX-2, IL-2 e IL-10) não mostraram diferenças significativas entre os grupos. Na análise histopatológica não foram identificadas alterações significativas no tecido muscular, apenas um discreto infiltrado inflamatório no grupo Cont-SH. Diante dos resultados obtidos, podemos concluir que os ratos diabéticos apresentaram um reduzido comportamento nociceptivo, o que indica uma hiponocicepção química. / This study aimed to evaluate the influence of experimental diabetes in rats nociceptive orofacial profile. 40 Wistar rats were used, in which 20 received streptozotocin injection (STZ) to induce experimental diabetes (group), and 20 received sodium citrate solution (CS - control group). These animals were divided into two groups of 10 rats differed only with respect to the substance that has been injected into the masseter: isotonic saline (IS) [n = 10: Cont-IS; n = 10: Diab-IS] or hypertonic (HS) [n = 10: Cont-HS; n = 10: Diab-HS]. Initially was taken intraperitoneal administration of STZ or CS and fourteen days with lightly anesthetized animal, injection of 100 μL of 5% HS solution or 0.9% IS in the middle region of the left masseter muscle was performed at a depth of 5 mm and then was quantified for two minutes, the nociceptive behavior characterized by the rats act shake/agitating the ipsilateral hind paw which is accepted as muscle nociception index. One hour after the nociceptive behavioral evaluation, the rats were euthanized by overdose of anesthetic and the left masseter muscle was removed with the aid of a circular scalpel; part of this muscle was used for analysis of RNA expression for pro - inflammatory cytokines [tumor necrosis factor (TNF), IL1β, IL6, cyclooxygenase 2 (COX-2)], and anti - inflammatory [IL-2, IL - 10] by reaction technique of quantitative polymerase chain (qPCR); the remaining half was stained with hematoxylin-eosin and then conducted a descriptive histopathological analysis by light microscopy. It was observed a significant increase of nociceptive behavior in non-diabetic and normoglycemic rats with injection of HS (Cont-HS) compared to other groups that were similar to each other. In cytokine analysis, we find that the masseter muscle of non-diabetic rats with injection of (Cont-HS) showed a significant increase in TNF relative expression compared to the other groups that were similar to each other; for IL-1β was also found an increase of the group relative expression (Cont-HS) with respect to Cont-IS and Diab-IS groups, but not in relation to Diab-HS group and IL-6 was significantly expressed the masseter muscle of rats without diabetes underwent injection compared to Cont-IS group, but was not different in the other groups. On the evaluated cytokines (COX-2, IL-2 and IL-10) showed no significant differences between groups. Histologically significant changes were not found in muscle tissue, just a mild inflammatory infiltrate in the Cont-SH group. Based on these results, we conclude that the diabetic rats had a reduced nociceptive behavior, which indicates a chemical hyponociception.

Isquemia e reperfusão (I/R) de vasos mesentéricos que acarretam insuficiência vascular aguda são acompanhadas de insuficiência em múltiplos órgãos e estão associados a altas morbidade e mortalidade. Os benefícios da solução hipertônica e da pentoxifilina foram testados isoladamente e em conjunto para melhorar o fluxo sanguíneo e o estado de oxigenação dos tecidos com redução da reação inflamatória e de apoptose, tanto no intestino quanto no pulmão enquanto órgão alvo. Foram utilizados 24 ratos Wistar machos pesando entre 200 e 250g distribuídos em 4 grupos (n=6). Foram submetidos à laparotomia e período de isquemia por clampeamento dos vasos mesentéricos por 40 minutos. O período de reperfusão foi de 80 minutos. A cada 40 minutos foram realizadas coletas de sangue arterial para gasometria. Os animais foram alocados nos grupos: grupo I/R (IR) onde I/R foi realizada e os animais receberam 4ml/kg de solução salina isotônica. O grupo solução salina hipertônica (SH) recebeu 4ml/kg de solução hipertônica a 7,5% e o grupo pentoxifilina (PTX) recebeu 30mg/kg de pentoxifilina diluída em NaCl 0,9% em um volume total de 4ml/kg ao final da isquemia intestinal. O grupo solução salina hipertônica+pentoxifilina (SH+PTX) recebeu ambas as soluções com volume total de 4m/kg no mesmo momento. As biopsias de intestino e pulmão foram colhidas ao final do experimento e foram submetidas à coloração em HE e à imuno-histoquímica para COX 2, caspase-3 clivada e Bcl-2. Os valores de sO2 revelaram diferença estatisticamente significante aos 40 (p=0,0099) e 80 (p=0,0074) minutos de reperfusão na comparação do grupo IR com os grupos SH e SH+PTX. Os valores de lactato foram estatisticamente significantes aos 40 minutos (p=0,0069) e 80 minutos (p=0,0098) de reperfusão, entre os grupos IR e os grupos SH e SH+PTX. A avaliação histológica em HE no tecido intestinal evidenciou diferença estatisticamente significantes na comparação dos grupos SH (p=0,0200), PTX (p=0,0200) e HS+PTX (p=0,0412) com o grupo IR, assim como no tecido pulmonar, que evidenciou diferenças estatisticamente significantes na comparação de IR com SH (p=0,006), PTX (p=0,0433) e SH+PTX (p=0,0040). A marcação citoplasmática de COX 2 revelou diferença estatisticamente significante ao comparar o grupo IR com o grupo SH+PTX (p=0,0015), Na avaliação do tecido pulmonar foi observado o grupo IR estabelecendo diferenças estatisticamente significantes na comparação com os grupos SH (p=0,0455), PTX (0,0143) e SH+PTX (p=0,0455). A avaliação de apoptose por imunohistoquímica para caspase 3 clivada evidenciou diferença com significância estatística ente os grupos IR e SH (p=0,0085) e os grupos PTX e SH (p=0,0120) em tecido intestinal. Em tecido pulmonar, entre IR e PTX (p=0,0090) e SH e PTX (p=0.0412). A marcação citoplasmática de Bcl-2 evidenciou que somente entres os grupos IR e SH+PTX (p=0,0012) se estabeleceu significância estatística em tecido intestinal No pulmão a diferença foi evidenciada em relação ao grupo IR e os grupos SH (p=0,0128), PTX (p=0,0085) e SH+PTX (p=0,0066). Conclui-se que o uso associado de pentoxifilina e solução salina hipertônica oferece os melhores resultados dos pontos de vista metabólico, inflamatório e da inibição da apoptose / Ischemia-reperfusion (I/R) of the mesenteric vessels cause acute vascular insufficiency and is followed by multiple organs failure and high morbidity and mortality. The benefits of hypertonic saline (NaCl 7,5%) and pentoxifylline were tested to improve metabolic and oxygen status of tissues with reduced inflammatory reaction and apoptosis, both in the gut as in the lung as target organ. 24 male Wistar rats weighing 200 to 250g. They underwent laparotomy and ischemia by clamping the mesenteric vessels for 40 minutes. The reperfusion period was 80-minute long. Every 40 minutes, blood was collected for arterial gas analysis. The animals were set into 4 groups (n=6): I/R (IR) received isotonic saline just before reperfusion (4ml/kg). Hypertonic saline group (HS) received 7.5% hypertonic saline solution (4ml/kg) and Pentoxifylline group (PTX) received pentoxifylline (30mg/kg)diluted in NaCl 0.9% at the end of the mesenteric ischemia. Hypertonic saline+pentoxifylline group (SH-PTX) received both solutions at the same doses. Biopsies of intestine and lung were collected at the end of the experiment and were subjected to HE staining and immunohistochemistry staining to COX 2, cleaved caspase-3 and Bcl-2. About the values of sO2, a statistically significant difference was established when groups were compared at 40 (p=0.0099) minutes and 80 (p=0.0074) of reperfusion. The lactate values were statistically significant after 40 (p=0.0069) and 80 (p=0.098) minutes of reperfusion as well. Histological evaluation with HE revealed a statistically significant difference in the comparison of SH (p=0.0200), PTX (p=0.0200) and HS + PTX (p=0.0412) groups compared to IR group in intestine tissue and SH (p=0.0006), PTX (p=0.0433) and HS + PTX (p=0.040) in lung tissue. Cytoplasmic staining of COX 2 revealed a statistically significant difference when comparing IR (p=0.0015) to HS+PTX in intestinal tissue. The evaluation of the lung tissue for COX 2 showed IR group setting statistically significance when compared to HS 9p=0,045), PTX (0.0143) and HS+PTX (p=0.0455) groups. The evaluation of apoptosis by immunohistochemistry for cleaved caspase 3 revealed that there was a significant difference between IR versus SH (p=0.0085) and PTX versus HS (p= 0.0120) in intestinal tissue and IR versus PTX (p=0,0090) and PTX versus SH (p=0.0412) in lung tissue. The cytoplasmic Bcl-2 expression shows that only between groups IR versus HS+PTX (p = 0.0012) statistical significance was established in intestinal tissue. Lung tissue showed the difference was evidenced in relation to IR versus SH (p=0.0128), PTX (p=0.0085) and HS+PTX (p=0.0066). It may be concluded that the combined use of pentoxifylline and hypertonic saline offers best results on metabolic, inflammatory and apoptosis inhibitory aspects

Context: Knee injury is a common problem for runners. Knee pain is a common symptom in knee injury and is associated with alterations in knee and hip muscle activation and hip joint angles. Relieving pain through intervention may help to restore neuromuscular function. Objective: To examine the effects of ice and transcutaneous electrical nerve stimulation (TENS) combination treatment on perceived knee pain, hip frontal plane angle, and muscle activation during running in individuals with experimental knee pain (EKP). Design: Crossover. Setting: Laboratory. Subjects: 19 participants (11 males and 8 females, 23.2 ± 1.9 y, 176 ± 11.6 cm, 71.5 ± 16.9 kg; right leg dominant). Interventions: Hypertonic saline was infused into the infrapatellar fat pad for 74 minutes (total 11.1 mL). Subjects underwent 2 treatment conditions (sham; ice/TENS combination). Measurements were recorded during running at 4 time points (preinfusion, postinfusion, posttreatment, and postinterval). Main Outcome Measures: Perceived knee pain on a 100-mm visual analog scale (VAS), knee and hip muscle peak electromyography (EMG) amplitude, and hip adduction angles. Results: Hypertonic saline infusion increased perceived anterior knee pain in all participants. The average of peak perceived knee pain was 28 mm on a 100-mm VAS in EKP application. While the increased perceived knee pain level stayed consistent across time in the sham session, ice/TENS combination treatment significantly reduced perceived knee pain by 35% at 6 minutes after the treatment start (p = 0.049), and the reduced knee pain lasted for 22 minutes (p > 0.05). Peak EMG amplitude of the gluteus medius was decreased by 13.5% and 14.3% (p = 0.023; p = 0.013) during running after EKP in sham and treatment sessions, respectively. However, the peak EMG amplitude was not restored to pain-free level during running after the treatment (p = 0.026). No other muscles changed their peak EMG amplitude due to EKP or treatment. Hip adduction angles during running were also not altered by EKP or treatment (p > 0.3) in both sham and treatment sessions. Conclusions: EKP increased perceived knee pain and decreased peak muscle activation of the gluteus medius during running. Ice/TENS combination treatment reduced perceived knee pain quickly, but did not restore neuromechanics during running.

Resuscitation from haemorrhagic shock and the subsequent circulatory arrest remains a major clinical challenge in the care of trauma patients. Numerous experimental studies in sexually mature animals have shown a gender dimorphism in response to trauma and haemorrhagic shock. The first study was designed to evaluate sex differences in outcome after resuscitation from hypovolemic circulatory arrest. We intended to examine innate sex differences, and chose to study sexually immature animals. The study showed that cerebral cortical blood flow was greater, blood-brain-barrier was better preserved and neuronal injury was smaller in female as compared to male piglets. The second study demonstrated that female sex was associated with enhanced haemodynamic response, cardioprotection, and better survival. This cardioprotective effect was observed despite comparable estradiol and testosterone levels in male and female animals, indicating an innate gender-related cardioprotection. In both studies (I and II) female sex was associated with a smaller increase in the cerebral expression of inducible and neuronal nitric oxide synthase (iNOS and nNOS). Thus in the study III we tested the hypothesis that exogenously administered 17β-estradiol (E2) could improve neurological outcome by NOS modulation. The results showed that compared with the control group, animals in the E2 group exhibited a significantly smaller increase in nNOS and iNOS expression, a smaller blood-brain-barrier disruption and a mitigated neuronal injury. There was also a significant correlation between nNOS and iNOS levels and neuronal injury. A hypothesis if female-specific cardioprotection may be attributed to a smaller NOS activity was tested in study IV. The animals received methylene blue (MB) during CPR, but were otherwise treated according to the same protocol as studies I-II. The female-specific cardioprotection could be attributed to a smaller NOS activity, but NOS inhibition with MB did not improve survival or myocardial injury, although it abated the difference between the sexes.