Serotoninergic Modulation of Basal Cardiovascular Responses and Responses Induced by Isotonic Extracellular Volume Expansion in Rats / Modulação Serotoninérgica de Respostas Cardiovasculares Basais e Induzidas pela Expansão Isotônica do Volume Extracelular em Ratos

Abstract Background: Isotonic blood volume expansion (BVE) induced alterations of sympathetic and parasympathetic activity in the heart and blood vessels, which can be modulated by serotonergic pathways. Objective: To evaluate the effect of saline or serotonergic agonist (DOI) administration in the hypothalamic paraventricular nucleus (PVN) on cardiovascular responses after BVE. Methods: We recorded pulsatile blood pressure through the femoral artery to obtain the mean arterial pressure (MAP), systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR) and the sympathetic-vagal ratio (LF/HF) of Wistar rats before and after they received bilateral microinjections of saline or DOI into the PVN, followed by BVE. Results: No significant differences were observed in the values of the studied variables in the different treatments from the control group. However, when animals are treated with DOI followed by BVE there is a significant increase in relation to the BE control group in all the studied variables: MBP (114.42±7.85 vs 101.34±9.17); SBP (147.23±14.31 vs 129.39±10.70); DBP (98.01 ±4.91 vs 87.31±8.61); HR (421.02±43.32 vs 356.35±41.99); and LF/HF ratio (2.32±0.80 vs 0.27±0.32). Discussion: The present study showed that the induction of isotonic BVE did not promote alterations in MAP, HR and LF/HF ratio. On the other hand, the injection of DOI into PVN of the hypothalamus followed by isotonic BVE resulted in a significant increase of all variables. Conclusion: These results suggest that serotonin induced a neuromodulation in the PVN level, which promotes an inhibition of the baroreflex response to BVE. Therefore, the present study suggests the involvement of the serotonergic system in the modulation of vagal reflex response at PVN in the normotensive rats.

Resumo Fundamento: Expansão de volume extracelular (EVEC) promove alterações da atividade simpática e parassimpática no coração e vasos sanguíneos, os quais podem ser moduladas por vias serotoninérgicas. Objetivo: Avaliar o efeito da administração de salina ou agonista serotoninérgico (DOI) nos núcleos paraventriculares hipotalâmico (NPV) sobre respostas cardiovasculares após EVEC. Métodos: Foram obtidos registros da pressão arterial pulsátil, por meio da artéria femoral, para obtenção dos valores da pressão arterial média (PAM), sistólica (PAS), diastólica (PAD), frequência cardíaca (FC) e razão simpático-vagal (LF/HF) de ratos Wistar antes e após receberem microinjeções bilaterais no NPV de salina ou DOI seguida de EVEC. Resultados: Não foram observadas diferenças significativas dos valores das variáveis estudadas nos diferentes tratamentos do grupo controle. Entretanto, quando os animais são tratados com DOI seguida de EVEC ocorre aumento significativo em relação ao grupo controle com EVEC em todas as variáveis estudadas: PAM (114,42±7,85 vs 101,34±9,17), PAS (147,23±14,31 vs 129,39±10,70), PAD (98,01 ±4,91 vs 87,31±8,61), FC (421,02±43,32 vs 356,35±41,99) e LF/HF (2,32±0,80 vs 0,27±0,32). Discussão: O presente estudo mostrou que a indução de EVEC isotônica não promoveu alterações na PAM, PAD, PAS, FC e LF/HF. Por outro lado, os animais que receberam microinjeção de DOI no NPV seguida de EVEC apresentaram aumento significativo de todas as variáveis. Conclusão: Esses resultados sugerem que a serotonina exerce uma neuromodulação em nivel do NPV, e essa promove uma inibição da resposta barorreflexa frente à EVEC. Assim, o presente trabalho sugere o envolvimento serotoninérgico na neuromodulação no nivel do NPV na resposta reflexa vagal em ratos normotensos.

Serotoninergic Modulation of Basal Cardiovascular Responses and Responses Induced by Isotonic Extracellular Volume Expansion in Rats.

BACKGROUND:: Isotonic blood volume expansion (BVE) induced alterations of sympathetic and parasympathetic activity in the heart and blood vessels, which can be modulated by serotonergic pathways. OBJECTIVE:: To evaluate the effect of saline or serotonergic agonist (DOI) administration in the hypothalamic paraventricular nucleus (PVN) on cardiovascular responses after BVE. METHODS:: We recorded pulsatile blood pressure through the femoral artery to obtain the mean arterial pressure (MAP), systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR) and the sympathetic-vagal ratio (LF/HF) of Wistar rats before and after they received bilateral microinjections of saline or DOI into the PVN, followed by BVE. RESULTS:: No significant differences were observed in the values of the studied variables in the different treatments from the control group. However, when animals are treated with DOI followed by BVE there is a significant increase in relation to the BE control group in all the studied variables: MBP (114.42±7.85 vs 101.34±9.17); SBP (147.23±14.31 vs 129.39±10.70); DBP (98.01 ±4.91 vs 87.31±8.61); HR (421.02±43.32 vs 356.35±41.99); and LF/HF ratio (2.32±0.80 vs 0.27±0.32). DISCUSSION:: The present study showed that the induction of isotonic BVE did not promote alterations in MAP, HR and LF/HF ratio. On the other hand, the injection of DOI into PVN of the hypothalamus followed by isotonic BVE resulted in a significant increase of all variables. CONCLUSION:: These results suggest that serotonin induced a neuromodulation in the PVN level, which promotes an inhibition of the baroreflex response to BVE. Therefore, the present study suggests the involvement of the serotonergic system in the modulation of vagal reflex response at PVN in the normotensive rats. FUNDAMENTO:: Expansão de volume extracelular (EVEC) promove alterações da atividade simpática e parassimpática no coração e vasos sanguíneos, os quais podem ser moduladas por vias serotoninérgicas. OBJETIVO:: Avaliar o efeito da administração de salina ou agonista serotoninérgico (DOI) nos núcleos paraventriculares hipotalâmico (NPV) sobre respostas cardiovasculares após EVEC. MÉTODOS:: Foram obtidos registros da pressão arterial pulsátil, por meio da artéria femoral, para obtenção dos valores da pressão arterial média (PAM), sistólica (PAS), diastólica (PAD), frequência cardíaca (FC) e razão simpático-vagal (LF/HF) de ratos Wistar antes e após receberem microinjeções bilaterais no NPV de salina ou DOI seguida de EVEC. RESULTADOS:: Não foram observadas diferenças significativas dos valores das variáveis estudadas nos diferentes tratamentos do grupo controle. Entretanto, quando os animais são tratados com DOI seguida de EVEC ocorre aumento significativo em relação ao grupo controle com EVEC em todas as variáveis estudadas: PAM (114,42±7,85 vs 101,34±9,17), PAS (147,23±14,31 vs 129,39±10,70), PAD (98,01 ±4,91 vs 87,31±8,61), FC (421,02±43,32 vs 356,35±41,99) e LF/HF (2,32±0,80 vs 0,27±0,32). DISCUSSÃO:: O presente estudo mostrou que a indução de EVEC isotônica não promoveu alterações na PAM, PAD, PAS, FC e LF/HF. Por outro lado, os animais que receberam microinjeção de DOI no NPV seguida de EVEC apresentaram aumento significativo de todas as variáveis. CONCLUSÃO:: Esses resultados sugerem que a serotonina exerce uma neuromodulação em nivel do NPV, e essa promove uma inibição da resposta barorreflexa frente à EVEC. Assim, o presente trabalho sugere o envolvimento serotoninérgico na neuromodulação no nivel do NPV na resposta reflexa vagal em ratos normotensos.

Curcumin suppresses inflammatory cytokines and heat shock protein 70 release and improves metabolic parameters during experimental sepsis.

CONTEXT: Curcumin has been reported to have anti-inflammatory, antioxidant and hypoglycaemic properties, besides reducing mortality in sepsis. OBJECTIVE: This study evaluates the biological activities of a curcumin dispersion formulated by spray-drying in experimental sepsis. MATERIALS AND METHODS: Male Wistar rats were subjected to sepsis by caecal ligation and puncture (CLP), controls were sham operated. The animals were treated with curcumin dispersion (100 mg/kg, p.o.) or water for 7 days prior to CLP and at 2 h after surgery. One group was used to analyze curcumin absorption through HPLC; another had the survival rate assessed during 48 h; and from a third group, blood was collected by decapitation to analyze metabolic and inflammatory parameters. RESULTS: The plasma curcumin levels reached 2.5 ng/mL at 4 h, dropped significantly (p < 0.001) at 6 h (1.2 ng/mL), and were undetectable at 24 h in both groups. Curcumin temporarily increased the survival rate of the septic rats by 20%. Moreover, it attenuated glycaemia (p < 0.05) and volemia (p < 0.05) alterations typically observed during sepsis, and decreased the levels of the proinflammatory cytokines IL-1ß and IL-6 in plasma (p < 0.001) and peritoneal lavage fluid (p < 0.05) of septic rats. Serum HSP70 levels were decreased (p < 0.01) at 24 h after CLP. DISCUSSION AND CONCLUSION: Our results show that the curcumin dispersion dose employed was not detrimental to the septic rats. In fact, it temporarily increased their survival rate, improved important metabolic parameters, reduced proinflammatory cytokines and HSP70 production.

Noradrenaline and dobutamine effects on the volume expansion with normal saline in rabbits subjected to hemorrhage.

PURPOSE:: To evaluate the effects of dobutamine (DB), noradrenaline (NA), and their combination (NADB), on volume retention in rabbits submitted to hemorrhage. METHODS:: Thirty six rabbits were randomly divided into 6 groups: SHAM, Control, Saline, DB, NA, DB+NA. All the animals, except for SHAM, were subjected to hemorrhage of 25% of the calculated blood volume. Control animals were replaced with their own blood. The other groups received NSS 3 times the volume withdrawn. The intravascular retention, hematocrit, diuresis, central venous pressure, mean arterial pressure, NGAL, dry-to-wet lung weight ratio (DTWR) and the lung and kidney histology were analyzed. RESULTS:: Replacement with NSS and NA, DB or NA+DB did not produce differences in the intravascular retention. After hemorrhage, the animals presented a significant decrease in the MAP and CVP, which were maintained until volume replacement. Regarding NGAL, dry-to-wet-lung-weight ratio, lung and kidney histology, there were no statistical differences between the groups. CONCLUSION:: The use of noradrenaline, dobutamine or their combination did not increase the intravascular retention of volume after normal saline infusion.

Noradrenaline and dobutamine effects on the volume expansion with normal saline in rabbits subjected to hemorrhage

ABSTRACT PURPOSE: To evaluate the effects of dobutamine (DB), noradrenaline (NA), and their combination (NADB), on volume retention in rabbits submitted to hemorrhage. METHODS: Thirty six rabbits were randomly divided into 6 groups: SHAM, Control, Saline, DB, NA, DB+NA. All the animals, except for SHAM, were subjected to hemorrhage of 25% of the calculated blood volume. Control animals were replaced with their own blood. The other groups received NSS 3 times the volume withdrawn. The intravascular retention, hematocrit, diuresis, central venous pressure, mean arterial pressure, NGAL, dry-to-wet lung weight ratio (DTWR) and the lung and kidney histology were analyzed. RESULTS: Replacement with NSS and NA, DB or NA+DB did not produce differences in the intravascular retention. After hemorrhage, the animals presented a significant decrease in the MAP and CVP, which were maintained until volume replacement. Regarding NGAL, dry-to-wet-lung-weight ratio, lung and kidney histology, there were no statistical differences between the groups. CONCLUSION: The use of noradrenaline, dobutamine or their combination did not increase the intravascular retention of volume after normal saline infusion.

Effects of catecholamines on volemic replacement with saline solution and the impact on heart rate variability in rabbits subjected to hemorrhage. A study by spectral analysis.

PURPOSE: To verify the effects of different catecholamines on volemic expansion and on the autonomic nervous system in rabbits that were subjected to hemorrhage. METHODS: Twenty four rabbits subjected to hemorrhage (with a 25% loss of blood volume) and were randomly divided into four experimental groups: 1) HEMO Group underwent replacement with their own blood in an equal volume; 2) SS Group underwent replacement with saline solution (SS) in a volume that corresponded to three times the removed blood volume; 3) ISP Group underwent replacement with SS and isoprenaline; 4) FNL Group underwent replacement with SS and phenylephrine. Spectral Analysis of the heart rate and heart rate variability were performed from the recorded data. Hematocrit was measured throughout the experiment. RESULTS: Replacement with SS and an α- or ß-agonist did not produce differences in the intravascular retention compared to replacement with SS alone. An analysis of HRV showed that the FNL group maintained the LF/HF ratio better than ISP and SS. CONCLUSIONS: No difference in vascular retention when α- or ß- agonists were added to SS during post-hemorrhagic recovery. The animals in the FNL group maintained the integrity of the autonomic response within normal physiological standards during hemorrhagic stress.

Effects of catecholamines on volemic replacement with saline solution and the impact on heart rate variability in rabbits subjected to hemorrhage. A study by spectral analysis

PURPOSE: To verify the effects of different catecholamines on volemic expansion and on the autonomic nervous system in rabbits that were subjected to hemorrhage. METHODS: Twenty four rabbits subjected to hemorrhage (with a 25% loss of blood volume) and were randomly divided into four experimental groups: 1) HEMO Group underwent replacement with their own blood in an equal volume; 2) SS Group underwent replacement with saline solution (SS) in a volume that corresponded to three times the removed blood volume; 3) ISP Group underwent replacement with SS and isoprenaline; 4) FNL Group underwent replacement with SS and phenylephrine. Spectral Analysis of the heart rate and heart rate variability were performed from the recorded data. Hematocrit was measured throughout the experiment. RESULTS: Replacement with SS and an α- or β-agonist did not produce differences in the intravascular retention compared to replacement with SS alone. An analysis of HRV showed that the FNL group maintained the LF/HF ratio better than ISP and SS. CONCLUSIONS: No difference in vascular retention when α- or β- agonists were added to SS during post-hemorrhagic recovery. The animals in the FNL group maintained the integrity of the autonomic response within normal physiological standards during hemorrhagic stress. .

Fluid distribution kinetics during cardiopulmonary bypass.

OBJECTIVE: The purpose of this study was to examine the isovolumetric distribution kinetics of crystalloid fluid during cardiopulmonary bypass. METHODS: Ten patients undergoing coronary artery bypass grafting participated in this prospective observational study. The blood hemoglobin and the serum albumin and sodium concentrations were measured repeatedly during the distribution of priming solution (Ringer's acetate 1470 ml and mannitol 15% 200 ml) and initial cardioplegia. The rate of crystalloid fluid distribution was calculated based on 3-min Hb changes. The preoperative blood volume was extrapolated from the marked hemodilution occurring during the onset of cardiopulmonary bypass. Clinicaltrials.gov: NCT01115166. RESULTS: The distribution half-time of Ringer's acetate averaged 8 minutes, corresponding to a transcapillary escape rate of 0.38 ml/kg/min. The intravascular albumin mass increased by 5.4% according to mass balance calculations. The preoperative blood volume, as extrapolated from the drop in hemoglobin concentration by 32% (mean) at the beginning of cardiopulmonary bypass, was 0.6-1.2 L less than that estimated by anthropometric methods (p<0.02). The mass balance of sodium indicated a translocation from the intracellular to the extracellular fluid space in 8 of the 10 patients, with a median volume of 236 ml. CONCLUSIONS: The distribution half-time of Ringer's solution during isovolumetric cardiopulmonary bypass was 8 minutes, which is the same as for crystalloid fluid infusions in healthy subjects. The intravascular albumin mass increased. Most patients were hypovolemic prior to the start of anesthesia. Intracellular edema did not occur.

Fluid distribution kinetics during cardiopulmonary bypass

OBJECTIVE: The purpose of this study was to examine the isovolumetric distribution kinetics of crystalloid fluid during cardiopulmonary bypass. METHODS: Ten patients undergoing coronary artery bypass grafting participated in this prospective observational study. The blood hemoglobin and the serum albumin and sodium concentrations were measured repeatedly during the distribution of priming solution (Ringer's acetate 1470 ml and mannitol 15% 200 ml) and initial cardioplegia. The rate of crystalloid fluid distribution was calculated based on 3-min Hb changes. The preoperative blood volume was extrapolated from the marked hemodilution occurring during the onset of cardiopulmonary bypass. Clinicaltrials.gov: NCT01115166. RESULTS: The distribution half-time of Ringer's acetate averaged 8 minutes, corresponding to a transcapillary escape rate of 0.38 ml/kg/min. The intravascular albumin mass increased by 5.4% according to mass balance calculations. The preoperative blood volume, as extrapolated from the drop in hemoglobin concentration by 32% (mean) at the beginning of cardiopulmonary bypass, was 0.6-1.2 L less than that estimated by anthropometric methods (p<0.02). The mass balance of sodium indicated a translocation from the intracellular to the extracellular fluid space in 8 of the 10 patients, with a median volume of 236 ml. CONCLUSIONS: The distribution half-time of Ringer's solution during isovolumetric cardiopulmonary bypass was 8 minutes, which is the same as for crystalloid fluid infusions in healthy subjects. The intravascular albumin mass increased. Most patients were hypovolemic prior to the start of anesthesia. Intracellular edema did not occur. .

Animal model of rapid crystalloid infusion in rats.

PURPOSE: To describe an animal model of rapid intravenous infusion with different volumes of crystalloid and discuss the clinical findings. METHODS: Fifty six male Wistar rats were used, divided randomly in seven groups (n = 8). The rats of groups 1 to 6 received lactated Ringer's solution intravenously, in the rate of 25 ml/min, with different volumes proportional to blood volume (BV). The rats of group 0 were submitted to the same procedure, but did not receive the fluid (control group). The data included respiratory rate, heart rate, saturation of peripheral oxygen (SpO(2)) in two times (before and after the infusion), and upshots (respiratory arrest and death). Dunnett's test and ANOVA were used. RESULTS: The clinical signs significantly changed in the 2, 2.5 and 3 fold BV groups. The respiratory arrest was observed in the 1.5, 2, 2.5 and 3 fold BV groups, but death was present only in 2.5 and 3 fold BV groups. CONCLUSIONS: The infusion of crystalloid in the same volume of blood volume did not cause significant variation in respiratory and heart rate, saturation of peripheral oxygen and did not induce respiratory arrest. The infusion of a volume of 3 fold blood volume was lethal to all animals.

Animal model of rapid crystalloid infusion in rats

PURPOSE: To describe an animal model of rapid intravenous infusion with different volumes of crystalloid and discuss the clinical findings. METHODS: Fifty six male Wistar rats were used, divided randomly in seven groups (n = 8). The rats of groups 1 to 6 received lactated Ringer´s solution intravenously, in the rate of 25 ml/min, with different volumes proportional to blood volume (BV). The rats of group 0 were submitted to the same procedure, but did not receive the fluid (control group). The data included respiratory rate, heart rate, saturation of peripheral oxygen (SpO2) in two times (before and after the infusion), and upshots (respiratory arrest and death). Dunnett´s test and ANOVA were used. RESULTS: The clinical signs significantly changed in the 2, 2.5 and 3 fold BV groups. The respiratory arrest was observed in the 1.5, 2, 2.5 and 3 fold BV groups, but death was present only in 2.5 and 3 fold BV groups. CONCLUSIONS: The infusion of crystalloid in the same volume of blood volume did not cause significant variation in respiratory and heart rate, saturation of peripheral oxygen and did not induce respiratory arrest. The infusion of a volume of 3 fold blood volume was lethal to all animals.

Volume replacement therapy during hip arthroplasty using hydroxyethyl starch (130/0.4) compared to lactated Ringer decreases allogeneic blood transfusion and postoperative infection.

BACKGROUND AND OBJECTIVES: Hydroxyethyl starch (HES) 130/0.4 is considered an effective plasma expander when compared to crystalloids. There is controversy around its superiority regarding hemodynamic optimization and about possible detrimental effects on coagulation. The aim of this study was to compare the effects of HES 130/0.4 to lactated Ringer solution during hip arthroplasty in adult patients under spinal anesthesia regarding intraoperative bleeding, hemodynamic parameters, coagulation profile, transfusion requirements and clinical outcomes. METHODS: In this randomized, controlled trial, 48 patients scheduled for hip arthroplasty with spinal anesthesia were randomized into two groups: 24 patients were allocated to receive a preload of 15 mL.kg(-1) of HES 130/0.4 and 24 patients received a preload of 30 mL.kg(-1) lactated Ringer solution before surgery. Hemodynamic measurements, hemoglobin concentrations, biochemical parameters and coagulation tests were evaluated in three periods during surgical procedure. Patients received medical follow-up during their hospital stay and up to postoperative 30 days. Primary outcome was the requirement of red blood cell transfusion between groups during hospital stay. Secondary outcome were hemodynamic parameters, length of hospital stay, mortality and occurrence of clinical postoperative complications. RESULTS: Red blood cell transfusion was required in 17% of patients in the HES group and in 46% in the Ringer group (p = .029). Postoperative infections were more frequently observed in the Ringer group (17%) compared to the HES group (0), p = .037. There were no significant differences between groups in mortality, hospital length of stay and clinical complications other than infection. CONCLUSIONS: During hip arthroplasty, patients treated with hypervolemic hemodilution with hydroxyethyl starch 130/0.4 required less transfusion and presented lower infection rate compared to patients who received lactated Ringer.

Moxonidine into the lateral parabrachial nucleus reduces renal and hormonal responses to cell dehydration.

The deactivation of the inhibitory mechanisms with injections of moxonidine (α2-adrenoceptor/imidazoline receptor agonist) into the lateral parabrachial nucleus (LPBN) increases hypertonic NaCl intake by intra- or extracellular dehydrated rats. In the present study, we investigated the changes in the urinary sodium and volume, sodium balance, and plasma vasopressin and oxytocin in rats treated with intragastric (i.g.) 2 M NaCl load (2 ml/rat) combined with injections of moxonidine into the LPBN. Male Holtzman rats (n=5-12/group) with stainless steel cannulas implanted bilaterally into LPBN were used. Bilateral injections of moxonidine (0.5 nmol/0.2 µl) into the LPBN decreased i.g. 2 M NaCl-induced diuresis (4.6±0.7 vs. vehicle: 7.4±0.6 ml/120 min) and natriuresis (1.65±0.29 vs. vehicle: 2.53±0.17 mEq/120 min), whereas the previous injection of the α2-adrenoceptor antagonist RX 821002 (10 nmol/0.2 µl) into the LPBN abolished the effects of moxonidine. Moxonidine injected into the LPBN reduced i.g. 2 M NaCl-induced increase in plasma oxytocin and vasopressin (14.6±2.8 and 2.2±0.3 vs. vehicle: 25.7±7 and 4.3±0.7 pg/ml, respectively). Moxonidine injected into the LPBN combined with i.g. 2 M NaCl also increased 0.3 M NaCl intake (7.5±1.7 vs. vehicle: 0.5±0.2 mEq/2 h) and produced positive sodium balance (2.3±1.4 vs. vehicle: -1.2±0.4 mEq/2 h) in rats that had access to water and NaCl. The present results show that LPBN α2-adrenoceptor activation reduces renal and hormonal responses to intracellular dehydration and increases sodium and water intake, which facilitates sodium retention and body fluid volume expansion.

Acute l-arginine supplementation increases muscle blood volume but not strength performance.

l-Arginine (L-arg) is an amino acid precursor to nitric oxide (NO). Dietary supplements containing L-arg have been marketed with the purpose of increasing vasodilation, thereby elevating blood flow to the exercising muscle and enhancing the metabolic response to exercise. Our goal was to identify the acute effect of L-arg supplementation on biceps strength performance, indicators of NO production (nitrite and nitrate - NOx), and muscle blood volume (Mbv) and oxygenation (Mox) during recovery from 3 sets of resistance exercise. Fifteen males participated in a randomized, double-blind, placebo-controlled study. After withdrawing resting blood samples, the subjects were supplemented with 6 g of L-arg (ARG) or placebo (PLA). Monitoring of Mbv and Mox with near-infrared spectroscopy began 30 min after supplementation and lasted for 60 min. The exercise protocol (3 sets of 10 maximal voluntary contractions of isokinetic concentric elbow extension at 60°·s(-1), 2-min rest between sets) was initiated 80 min after supplementation. Blood samples were drawn at 30, 60, 90, and 120 min after supplementation. Repeated measures ANOVA showed that Mbv significantly (p ≤ 0.05) increased in ARG compared with the PLA during the recovery period of each set of resistance exercise. NOx, Mox, peak torque, total work, and set total work were not significantly different between groups. We found that acute L-arg supplementation increases Mbv during recovery from sets of resistance exercise with no increase in strength performance. It is still premature to recommend nutritional supplements containing L-arg as an ergogenic aid to increase muscle strength during resistance training in healthy subjects.

The effects of 6% hydroxyethyl starch-hypertonic saline in resuscitation of dogs with hemorrhagic shock.

BACKGROUND: Hemodynamic and global oxygen transport variables have failed to reflect splanchnic hypoperfusion, resulting in a failure to recognize inadequately treated hemorrhagic shock. Volemic expansion after fluid resuscitation is essential to improve global and regional oxygen in hemorrhagic shock. We hypothesized that, in contrast to conventional plasma expanders, the smaller volemic expansion from 7.5 NaCl/6% hydroxyethyl starch (HHES) solution administration in hemorrhagic shock may provide lesser systemic oxygen delivery and gastric perfusion. We used hemorrhaged dogs to compare intravascular volume expansion and the early systemic oxygenation and gastric perfusion effects of fixed fluid bolus administration, which are usually used in clinical situations with severe hemorrhage, of HHES, lactated Ringer (LR), and 6% hydroxyethyl starch (HES) solutions. METHODS: Thirty dogs were bled (30 mL · kg(-1)) to hold mean arterial blood pressure at 40 to 50 mm Hg over 45 minutes and were resuscitated in 3 groups: LR (n = 10) at 3:1 ratio to shed blood; HES (mean molecular weight 130 kDa, degree of substitution 0.4) (n = 10) at 1:1 to shed blood; and HHES (n = 10), 4 mL · kg(-1). Intravascular volume expansion (Evans blue and hemoglobin dilution), hemodynamic, systemic oxygenation, venous-to-arterial CO(2) gradient (Pv-aCO(2)), and gastric intramucosal-arterial PCO(2) gradient (PCO(2) gap) variables were measured at baseline, after 45 minutes of hemorrhage, and 5, 45, and 90 minutes after fluid resuscitation. RESULTS: HHES increased blood volume because of the high volume expansion efficiency, but intravascular volume expansion with this solution was the smallest of the solutions (P < 0.05). All 3 solutions induced a similar hemodynamic performance but HHES showed lower mixed venous PO(2) and higher systemic oxygenation extraction, Pv-aCO(2), and PCO(2) gap than LR and HES (P < 0.05). CONCLUSIONS: In dogs submitted to pressure-guided hemorrhagic shock and fixed-volume resuscitation, the smaller intravascular volume expansion from HHES solutions provides worse recovery of systemic oxygenation and gastric perfusion compared with LR and HES solutions despite its high volume expansion efficiency, which was limited by low infused volume.

Influência do ácido épsilon aminocapróico no sangramento e na hemotransfusão pós-operatória em cirurgia valvar mitral / Epsilon-aminocaproic acid influence in bleeding and hemotransfusion postoperative in mitral valve surgery

INTRODUÇÃO: O ácido épsilon aminocapróico é um antifibrinolítico usado em cirurgia cardiovascular a fim de inibir a fibrinólise e reduzir o sangramento após circulação extracorpórea (CEC). OBJETIVO: Analisar a influência do uso do ácido aminocapróico no sangramento e na necessidade de hemotransfusão nas primeiras 24 horas em pós-operatório de cirurgias valvares mitrais. MÉTODOS: Estudo prospectivo, 42 pacientes, randomizados e divididos em dois grupos, de igual número: grupo I - controle e grupo II - ácido épsilon aminocapróico. No grupo II, foram infundidos 5 gramas de AEAC na indução anestésica, após heparinização plena, no perfusato da CEC, após reversão da heparina e uma hora após o final da cirurgia, totalizando 25 gramas. No grupo I, foi infundido apenas soro fisiológico nestes mesmos momentos. RESULTADOS: O grupo I apresentou volume de sangramento médio de 633,57 ± 305,7 ml e o grupo II média de 308,81 ± 210,1 ml, com diferença estatisticamente significativa (P=0,0003). O volume médio de hemotransfusão nos grupos I e II foi, respectivamente, de 942,86 ± 345,79 ml e de 214,29 ± 330,58 ml, havendo diferença significativa (P<0,0001). CONCLUSÃO: O ácido épsilon aminocapróico foi capaz de reduzir o volume de sangramento e a necessidade de hemoderivados no pós-operatório imediato de pacientes submetidos a cirurgias valvares mitrais.

INTRODUCTION: The epsilon aminocaproic acid is an antifibrinolytic used in cardiovascular surgery to inhibit the fibrinolysis and to reduce the bleeding after CBP. OBJECTIVE: To analyze the influence of the using of epsilon aminocaproic acid in the bleeding and in red-cell transfusion requirement in the first twenty-four hours postoperative of mitral valve surgery. METHODS: Prospective studying, forty-two patients, randomized and divided in two equal groups: group #1 control and group #2 - epsilon aminocaproic acid. In Group II were infused five grams of EACA in the induction of anesthesia, after full heparinization, CPB perfusate after reversal of heparin and one hour after the surgery, totaling 25 grams. In group I, saline solution was infused only in those moments. RESULTS: Group #1 showed average bleeding volume of 633.57 ± 305,7 ml, and Group #2, an average of 308.81 ± 210.1 ml, with significant statistic difference (P=0.0003). Average volume of red-cell transfusion requirement in Groups 1 and 2 was, respectively, 942.86 ± 345.79 ml and 214.29 ± 330.58 ml, with significant difference (P<0.0001). CONCLUSION: The epsilon aminocaproic acid was able to reduce the bleeding volume and the red-cell transfusion requirement in the immediate postoperative of patients submitted to mitral valve surgery.

Vasodilation increases pulse pressure variation, mimicking hypovolemic status in rabbits.

OBJECTIVE: To test the hypothesis that pulse pressure respiratory variation (PPV) amplification, observed in hypovolemia, can also be observed during sodium nitroprusside (SNP)-induced vasodilation. INTRODUCTION: PPV is largely used for early identification of cardiac responsiveness, especially when hypovolemia is suspected. PPV results from respiratory variation in transpulmonary blood flow and reflects the left ventricular preload variations during respiratory cycles. Any factor that decreases left ventricular preload can be associated with PPV amplification, as seen in hypovolemia. METHODS: Ten anesthetized and mechanically ventilated rabbits underwent progressive hypotension by either controlled hemorrhage (Group 1) or intravenous SNP infusion (Group 2). Animals in Group 1 (n = 5) had graded hemorrhage induced at 10% steps until 50% of the total volume was bled. Mean arterial pressure (MAP) steps were registered and assumed as pressure targets to be reached in Group 2. Group 2 (n = 5) was subjected to a progressive SNP infusion to reach similar pressure targets as those defined in Group 1. Heart rate (HR), systolic pressure variation (SPV) and PPV were measured at each MAP step, and the values were compared between the groups. RESULTS: SPV and PPV were similar between the experimental models in all steps (p > 0.16). SPV increased earlier in Group 2. CONCLUSION: Both pharmacologic vasodilation and graded hemorrhage induced PPV amplification similar to that observed in hypovolemia, reinforcing the idea that amplified arterial pressure variation does not necessarily represent hypovolemic status but rather potential cardiovascular responsiveness to fluid infusion.

Blood loss and transcapillary refill in uncontrolled treated hemorrhage in dogs.

OBJECTIVE: This study evaluated retroperitoneal hematomas produced by bilateral injury of iliac arteries (uncontrolled hemorrhage), blood volume loss, transcapillary refill, the effects of volume replacement on retroperitoneal bleeding and the hemodynamic changes with and without treatment. METHODS: Initial blood volume was determined with Tc(99m)-labelled red cells, and bleeding was evaluated by means of a portable scintillation camera positioned over the abdomen. Previously splenectomized mongrel dogs (16.8 +/- 2.2 kg) were submitted to hemorrhage for 30 minutes and randomized into three groups: I - no treatment (n=7); II - treatment with 32 mL/kg of Lactated Ringer's for three to five minutes (n=7); and III - treatment with 4 mL/kg of 7.5% NaCl plus 6.0% dextran 70 for three to five minutes (n=7). They were studied for an additional 45 minutes. RESULTS: Volume replacement produced transitory recovery in hemodynamic variables, including mean pulmonary artery pressure, pulmonary capillary wedge pressure and cardiac index, with significant increase in dogs treated with 32 mL/kg of Lactated Ringer's and 7.5% NaCl plus 6.0% dextran 70 (p<0.001, against no treatment), along with a decrease (p<0.001) in the systemic vascular resistance index. Groups II and III had significant initial decreases in hematocrit and hemoglobin. The treated dogs (groups II and III) presented rebleeding, which was greater during treatment with 32 mL/kg of Lactated Ringer's (group II). CONCLUSIONS: Despite the rebleeding observed in treated groups, the utilization of hypertonic saline solution with dextran proved to be effective in the initial reanimation, producing evident transcapillary refill, while the Lactated Ringer's solution produced capillary extravasation and was ineffective in the initial volume replacement in this model of uncontrolled hemorrhage.

Epsilon-aminocaproic acid influence in postoperative [corrected] bleeding and hemotransfusion [corrected] in mitral valve surgery.

INTRODUCTION: The epsilon aminocaproic acid is an antifibrinolytic used in cardiovascular surgery to inhibit the fibrinolysis and to reduce the bleeding after CPB. [corrected] OBJECTIVE: To analyze the influence of the using of epsilon aminocaproic acid in the bleeding and in red-cell transfusion requirement in the first twenty-four hours postoperative of mitral valve surgery. METHODS: Prospective studying, forty-two patients, randomized and divided in two equal groups: group #1 control and group #2--epsilon aminocaproic acid. In Group II were infused five grams of EACA in the induction of anesthesia, after full heparinization, CPB perfusate after reversal of heparin and one hour after the surgery, totaling 25 grams. In group I, saline solution was infused only in those moments. RESULTS: Group #1 showed average bleeding volume of 633.57 ± 305,7 ml, and Group #2, an average of 308.81 ± 210.1 ml, with significant statistic difference (P = 0.0003). Average volume of red-cell transfusion requirement in Groups 1 and 2 was, respectively, 942.86 ± 345.79 ml and 214.29 ± 330.58 ml, with significant difference (P < 0.0001). CONCLUSION: The epsilon aminocaproic acid was able to reduce the bleeding volume and the red-cell transfusion requirement in the immediate postoperative of patients submitted to mitral valve surgery.

Blood loss and transcapillary refill in uncontrolled treated hemorrhage in dogs

Objetive: This study evaluated retroperitoneal hematomas produced by bilateral injury of iliac arteries (uncontrolled hemorrhage), blood volume loss, transcapillary refill, the effects of volume replacement on retroperitoneal bleeding and the hemodynamic changes with and without treatment. Methods: Initial blood volume was determined with Tc99m-labelled red cells, and bleeding was evaluated by means of a portable scintillation camera positioned over the abdomen. Previously splenectomized mongrel dogs (16.8 ± 2.2 kg) were submitted to hemorrhage for 30 minutes and randomized into three groups: I - no treatment (n=7); II - treatment with 32 mL/kg of Lactated Ringer's for three to five minutes (n=7); and III - treatment with 4 mL/kg of 7.5 percent NaCl plus 6.0 percent dextran 70 for three to five minutes (n=7). They were studied for an additional 45 minutes. Results: Volume replacement produced transitory recovery in hemodynamic variables, including mean pulmonary artery pressure, pulmonary capillary wedge pressure and cardiac index, with significant increase in dogs treated with 32 mL/kg of Lactated Ringer's and 7.5 percent NaCl plus 6.0 percent dextran 70 (p<0.001, against no treatment), along with a decrease (p<0.001) in the systemic vascular resistance index. Groups II and III had significant initial decreases in hematocrit and hemoglobin. The treated dogs (groups II and III) presented rebleeding, which was greater during treatment with 32 mL/kg of Lactated Ringer's (group II). Conclusions: Despite the rebleeding observed in treated groups, the utilization of hypertonic saline solution with dextran proved to be effective in the initial reanimation, producing evident transcapillary refill, while the Lactated Ringer's solution produced capillary extravasation and was ineffective in the initial volume replacement in this model of uncontrolled hemorrhage.