A new method of measuring intracellular Na and K using Li substitution was applied to a study of vascular smooth muscle and red cell Na changes in haemorrhagic shock. A rat haemorrhagic shock model was used. Controlled haemorrhage was allowed with a syringe reservoir and the arterial blood pressure was maintained at 30 mm Hg. In a pilot study, using 20 rats, the plasma Na and plasma K were monitored. A fall in plasma Na and a rise in plasma K were observed. Both returned towards normal following retransfusion and recovery for one hour. In vascular smooth muscle, significant changes in both cell Na and K occurred following a 2 hour period of haemorrhagic shock. The vascular smooth muscle cell Na in control animals was 27.0±1.5 mEq/kg dry weight and 42.7±1.4 mEq/kg dry weight in the shocked animals (P<0.001). The cell K was 127.8±6.0 in the control animals and 74.7±4.2 in the shocked animals. In red cell studies, significant increases in red cell Na were found. The red cell Na in controls was 7.09±0.29 mEq/litre cells, whilst in the shocked animals the red cell Na was 8.26±0.33 mEq/litre cells (P<0.025). This was associated with a small but not statistically significant fall in red cell K. In both sets of experiments, the plasma Na and K were monitored and similar changes to those of the pilot study were found. Following retransfusion and recovery for 1 hour in the vascular tissue study and 2 hours in the red cell study, no significant recovery of cellular Na or K occurred. The results of these studies are consistent with a significant impairment of cell membrane function in haemorrhagic shock. The importance of both normal vascular responses and red cell function following severe haemorrhage is obvious. The fact that both may be impaired may have important implications in relation to the treatment and prognosis of haemorrhagic shock. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

Bone circulation in Hemorrhagic Shock was studied in 35 male mongrel dogs. The term hemorrhagic shock is defined in this thesis as persistent profound hypotensive syndrome, due to acute hemorrhage of more than one third of blood volume. The method of induction of shock consisted of removal of one third of estimated blood volume (8% of body weight) at a rate of 25 - 50 ml/min, and subsequently dropping the systemic blood pressure in a stepwise manner until the maintaining level of 30 - 35 mmHg is reached. The central venous pressure, pulse and respiratory rates were also recorded. Bone circulation was studied by (1) recording the blood flow through a cannula inserted into the tibial nutrient vein or artery and (2) recording the intramedullary pressure of tibia. When one third of estimated blood volume was removed, the bone blood flow through the nutrient vessel decreased to 22.5 ± 3.4% of control level. The decreased bone blood flow persisted as long as the hemorrhagic shock was maintained for 4-18 hours. The decreased bone blood flow was also evidenced by a profound and persistent fall of the intramedullary pressure of bone. Reinfusion into the animal of lost blood within fifteen minutes to six hours after hemorrhage resulted in a complete or partial recovery of the control systemic blood pressure as well as the control rate of bone blood flow and the control level of intramedullary pressure of bone. The curve showing relationship between the changes in bone blood flow and the systemic blood pressure is an exponential one with concavity towards the flow axis. This indicates that bone has a vasomotor control mechanism of increasing peripheral resistance during hemorrhagic shock. This was substantiated by the following observations: (1) The severity of decrease in bone blood flow on the side of lumbar sympathectomy was much milder (16% less) compared to the side of the intact sympathetic nerve; (2) Dibenzyline (phenoxybenzamine) a sympatholytic drug or alpha-receptor blocking agent alters the pressure-flow curve of bone circulation in chock to a linear pattern which indicates that the drug blocks the bone vasoconstricting mechanism(s). It is concluded that bone blood flow decreases in hemorrhagic shock and is not merely due to a decrease in circulatory blood volume, but also due to sympathetic and catecholamine hormonal vasoconstrictor mechanisms. / Surgery, Department of / Medicine, Faculty of / Graduate

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

Thesis (Ph. D.)--University of Wisconsin, 1954. / Typescript (carbon copy). eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 78-85).

O choque e ressuscitação predispoe os pacientes a uma maior susceptibilidade a uma lesão pulmonar aguda devido a uma exagerada resposta imune a um segundo estimulo inflamatório, conhecida como lesão das duas agressões, cujos mecanismos tem sido extensivamente pesquisados, mas ainda permanecem sem entendimento. Sendo assim, o principal objetivo deste estudo foi investigar a resposta inflamatória em modelo das duas agressões, no qual a primeira e representada pela I-R e a segunda pela instilação intratraqueal de bactérias vivas. O modelo de choque com animais acordados e hemorragia controlada, seguido de inoculação intratraqueal de bactérias vivas E. coli foi utilizado neste estudo. Todos os animais apresentaram variáveis hemodinâmicas similares, onde a PAM alcançou valores de aproximadamente 40 mmHg depois do sangramento. Solução hipertônica (HS, NaCl - 7,5%) ou isotônica (SS,NaCl - 0,9%) foram usadas como soluções de reperfusão, com resultados hemodinâmicos semelhantes. A inflamação pulmonar foi mais evidente nos animais submetidos a I-R e ressuscitados com solução isotônica (grupo SS) antes da inoculação da bactéria (grupo SEC). Animais que receberam solução hipertônica (grupo HS) apresentaram menos inflamação comparados com os animais do grupo SEC. RNAm para TLR2/4 e CD40/CD40L tiveram sua expressões aumentadas depois da instilação com a bactéria. Quando esses animais foram submetidos somente a lesão de I-R o mesmo não acorreu. Animais do grupo HEC apresentaram maior expressão desses receptors que o grupo SEC. Nos concluímos que a lesão de I-R aumenta a resposta a uma segunda agressão e que a HS pode modular favoravelmente esta resposta / Shock and resuscitation renders patients more susceptible to acute lung injury due to an exaggerated immune response to late inflammatory stimuli, the so-called two-hit model, whose mechanisms have been extensively researched, but are still not completely understood. Therefore, the main objective of this study was to investigate the inflammatory response in a two-hit model, in which the first injury is represented by ischemia and reperfusion (I-R), and the second challenge by live bacteria injection. A shock model, with conscious rats and controlled hemorrhage, followed by intratracheal innoculation of live E.coli bacteria was used in this study. All animals showed similar hemodynamic variables, with the mean arterial pressure decreasing to about 40 mmHg after bleeding. Hypertonic saline (HS, NaCl 7,5%) or isotonic saline (SS, NaCl 0,9%) were used as resuscitation fluids, with equal hemodynamic results. Lung inflammation and damage was more evident in the animals submitted to I-R and resuscitated with SS before bacteria innoculation (SEC group). Animals receiving HS displayed less inflammation compared to SEC. TLR2 and TLR4 mRNA expression increased markedly after E.coli injection. When submitted to I-R, these proteins were not up-regulated (except TLR2) when challenged with bacteria. Animals in the HEC group showed higher expression of these modulators than animals in the SEC group. We conclude that I-R blunts inflammatory response, rendering animals more susceptible to damage by a second challenge. Resuscitation with hypertonic saline may favorably modulate this response

Uma função autonômica adequada é essencial para a manutenção da estabilidade hemodinâmica durante a hemorragia. Diversos estudos tem demonstrado que a análise da variabilidade da frequência cardíaca (VFC) é uma técnica não-invasiva promissora para avaliação da modulação autonômica no trauma, mostrando haver uma associação entre a VFC e desfecho clínico. O objetivo deste estudo foi avaliar a VFC durante o choque hemorrágico e reposição volêmica, comparando a variáveis hemodinâmicas e metabólicas tradicionais. Vinte porcos anestesiados e ventilados mecanicamente foram submetidos ao choque hemorrágico (60% da volemia estimada) e avaliados durante 60 minutos sem reposição volêmica. Os animais sobreviventes foram tratados com solução de Ringer lactato e avaliados por mais 180 minutos. Medidas de VFC (no domínio do tempo e da frequência) e variáveis hemodinâmicas e metabólicas foram comparados entre animais sobreviventes e não sobreviventes. Sete dos 20 animais morreram durante o choque hemorrágico e reposição volêmica inicial. Todos os animais apresentaram diminuição do intervalo RR e aumento das medidas de VFC no domínio do tempo durante a hemorragia, sendo restaurados os valores basais após reposição volêmica. Embora não significante estatisticamente, foram observados diminuição de LF e LF/HF durante os estágios iniciais de sangramento, recuperação dos valores basais durante a manutenção do choque hemorrágico e aumento após reposição volêmica. Os animais não sobreviventes apresentaram valores significativamente menores de pressão arterial média (43 ± 7 vs 57 ± 9) e índice cardíaco (1,7 ± 0,2 vs 2,6 ± 0,5) e valores maiores de lactato (7,2 ± 2,4 vs 3,7 ± 1,4), excesso de base (-6,8 ± 3,3 vs -2,3 ± 2,8) e potássio sérico (5,3 ± 0,6 vs 4,2 ± 0,3), trinta minutos após indução do choque hemorrágico. Concluímos que as medidas de VFC não foram capazes de discriminar sobreviventes e não-sobreviventes durante choque hemorrágico. As variáveis metabólicas e hemodinâmicas foram melhores em refletir a gravidade do choque hemorrágico do que as medidas de VFC / An adequate autonomic function is essential for maintaining the hemodynamic stability during hemorrhage. The analysis of heart rate variability (HRV) has been shown as a promising non-invasive technique for assessing the cardiac autonomic modulation in trauma, and several studies have demonstrated the association between HRV and clinical outcome. The aim of this study was to evaluate HRV during hemorrhagic shock and fluid resuscitation, comparing to traditional hemodynamic and metabolic parameters. Twenty anesthetized and mechanically ventilated pigs were submitted to hemorrhagic shock (60% of estimated blood volume) and evaluated for 60 minutes without fluid replacement. Surviving animals were treated with Ringer solution and evaluated for an additional period of 180 minutes. HRV metrics (time domain and frequency domain) as well as hemodynamic and metabolic parameters were evaluated in survivors and non-survivors animals. Seven of the 20 animals died during hemorrhage and initial fluid resuscitation. All animals presented an increase in time-domain HRV measures during haemorrhage and fluid resuscitation restored baseline values. Although not significantly, normalized low-frequency and LF/HF ratio decreased during early stages of haemorrhage, recovering baseline values later during hemorrhagic shock and increased after fluid resuscitation. Non-surviving animals presented significantly lower mean arterial pressure (43 ± 7 vs 57 ± 9) and cardiac index (1.7 ± 0.2 vs 2.6 ± 0.5) and higher levels of plasma lactate (7.2 ± 2.4 vs 3.7 ± 1.4), base excess (-6.8 ± 3.3 vs -2.3±2.8) and potassium (5.3 ± 0.6 vs 4.2 ± 0.3), 30 minutes after hemorrhagic shock compared to surviving animals. Conclusions: The HRV metrics were not able to discriminate survivors from non-survivors during hemorrhagic shock. Moreover, metabolic and hemodynamic variables were more reliable to reflect hemorrhagic shock severity than HRV metrics

Source: Masters Abstracts International, Volume: 47-06, page: 3510. Adviser: Irwin B. Horwitz. Includes bibliographical references.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

Thesis (Ph. D.)--Uniformed Services University of the Health Sciences, 2006. / Typescript (photocopy).

O choque e ressuscitação predispoe os pacientes a uma maior susceptibilidade a uma lesão pulmonar aguda devido a uma exagerada resposta imune a um segundo estimulo inflamatório, conhecida como lesão das duas agressões, cujos mecanismos tem sido extensivamente pesquisados, mas ainda permanecem sem entendimento. Sendo assim, o principal objetivo deste estudo foi investigar a resposta inflamatória em modelo das duas agressões, no qual a primeira e representada pela I-R e a segunda pela instilação intratraqueal de bactérias vivas. O modelo de choque com animais acordados e hemorragia controlada, seguido de inoculação intratraqueal de bactérias vivas E. coli foi utilizado neste estudo. Todos os animais apresentaram variáveis hemodinâmicas similares, onde a PAM alcançou valores de aproximadamente 40 mmHg depois do sangramento. Solução hipertônica (HS, NaCl - 7,5%) ou isotônica (SS,NaCl - 0,9%) foram usadas como soluções de reperfusão, com resultados hemodinâmicos semelhantes. A inflamação pulmonar foi mais evidente nos animais submetidos a I-R e ressuscitados com solução isotônica (grupo SS) antes da inoculação da bactéria (grupo SEC). Animais que receberam solução hipertônica (grupo HS) apresentaram menos inflamação comparados com os animais do grupo SEC. RNAm para TLR2/4 e CD40/CD40L tiveram sua expressões aumentadas depois da instilação com a bactéria. Quando esses animais foram submetidos somente a lesão de I-R o mesmo não acorreu. Animais do grupo HEC apresentaram maior expressão desses receptors que o grupo SEC. Nos concluímos que a lesão de I-R aumenta a resposta a uma segunda agressão e que a HS pode modular favoravelmente esta resposta / Shock and resuscitation renders patients more susceptible to acute lung injury due to an exaggerated immune response to late inflammatory stimuli, the so-called two-hit model, whose mechanisms have been extensively researched, but are still not completely understood. Therefore, the main objective of this study was to investigate the inflammatory response in a two-hit model, in which the first injury is represented by ischemia and reperfusion (I-R), and the second challenge by live bacteria injection. A shock model, with conscious rats and controlled hemorrhage, followed by intratracheal innoculation of live E.coli bacteria was used in this study. All animals showed similar hemodynamic variables, with the mean arterial pressure decreasing to about 40 mmHg after bleeding. Hypertonic saline (HS, NaCl 7,5%) or isotonic saline (SS, NaCl 0,9%) were used as resuscitation fluids, with equal hemodynamic results. Lung inflammation and damage was more evident in the animals submitted to I-R and resuscitated with SS before bacteria innoculation (SEC group). Animals receiving HS displayed less inflammation compared to SEC. TLR2 and TLR4 mRNA expression increased markedly after E.coli injection. When submitted to I-R, these proteins were not up-regulated (except TLR2) when challenged with bacteria. Animals in the HEC group showed higher expression of these modulators than animals in the SEC group. We conclude that I-R blunts inflammatory response, rendering animals more susceptible to damage by a second challenge. Resuscitation with hypertonic saline may favorably modulate this response