Rabbit model of uncontrolled hemorrhagic shock and hypotensive resuscitation

Clinically relevant animal models capable of simulating traumatic hemorrhagic shock are needed. We developed a hemorrhagic shock model with male New Zealand rabbits (2200-2800 g, 60-70 days old) that simulates the pre-hospital and acute care of a penetrating trauma victim in an urban scenario using current resuscitation strategies. A laparotomy was performed to reproduce tissue trauma and an aortic injury was created using a standardized single puncture to the left side of the infrarenal aorta to induce hemorrhagic shock similar to a penetrating mechanism. A 15-min interval was used to simulate the arrival of pre-hospital care. Fluid resuscitation was then applied using two regimens: normotensive resuscitation to achieve baseline mean arterial blood pressure (MAP, 10 animals) and hypotensive resuscitation at 60 percent of baseline MAP (10 animals). Another 10 animals were sham operated. The total time of the experiment was 85 min, reproducing scene, transport and emergency room times. Intra-abdominal blood loss was significantly greater in animals that underwent normotensive resuscitation compared to hypotensive resuscitation (17.1 ± 2.0 vs 8.0 ± 1.5 mL/kg). Antithrombin levels decreased significantly in normotensive resuscitated animals compared to baseline (102 ± 2.0 vs 59 ± 4.1 percent), sham (95 ± 2.8 vs 59 ± 4.1 percent), and hypotensive resuscitated animals (98 ± 7.8 vs 59 ± 4.1 percent). Evidence of re-bleeding was also noted in the normotensive resuscitation group. A hypotensive resuscitation regimen resulted in decreased blood loss in a clinically relevant small animal model capable of reproducing hemorrhagic shock caused by a penetrating mechanism.

Total hepatic ischemia and reperfusion after state controlled hemorrhagic shock, with used of different solutions: effects of neutrophils sequestration in kidney of rats

OBJETIVO: Avaliar e comparar o seqüestro de neutrófilos no rim de rato, como efeito da isquemia e reperfusão hepática total após estado de choque hemorrágico controlado, com uso de diferentes soluções eletrolíticas.MÉTODOS: Utilizou-se 18 ratos Wistar, machos, adultos, divididos em três grupos conforme a solução utilizada para reanimação: Grupo SF: solução fisiológica; Grupo SH: solução hipertônica de NaCl a 7,5% seguido pela solução de ringer com lactato; Grupo RL: solução de ringer com lactato. Todos os animais foram submetidos à sangria controlada até pressão arterial média (PAM) atingir 40 mmHg, permanecendo por 20 minutos. Realizou-se reanimação volêmica até PAM=80 mmHg com a solução conforme o grupo estudado. Em seguida realizou-se uma laparotomia e a manobra de Pringle por 15 minutos. Os animais foram acompanhados até duas horas. Para comparações estatísticas entre as contagens de neutrófilos, no interstício do córtex renal, foram efetuados os testes ANOVA e a análise de covariância, ajustando-se para o tempo de sobrevida. Os parâmetros hemodinâmicos avaliados foram: PAM, freqüência cardíaca, índice cardíaco, índice de resistência vascular sistêmica. As variáveis metabólicas analisadas foram: pH, bicarbonato, reserva de base e lactato, além de eletrólitos. RESULTADOS: Os valores médios de tempo de sobrevida, em minutos, por grupo foram: Grupo SF 79,0±12,0; Grupo RL 97,0±11,0; Grupo SH 67,0±10. Os valores médios da contagem de neutrófilos/campo no córtex renal foram: Grupo SF 0,55±0,68; Grupo RL 1,68±0,53; Grupo SH 1,33±0,43. E quando são ajustados para o tempo de sobrevida encontram-se: Grupo SF 0,55; Grupo RL 1,62; Grupo SH 1,39. Houve diferença estatisticamente significativa, na contagem de neutrófilo entre o Grupo SF com os demais, usando-se ou não o ajuste pelo tempo de sobrevida (p=0,016 e p=0,0128). CONCLUSAO: As duas situações críticas, choque hemorrágico controlado e manobra de Pringle, promoveram seqüestro de neutrófilos no interstício renal do rato, sendo a solução fisiológica com a menor média, diferenciando estatisticamente das demais soluções, neste modelo.

Blood glucose and lactate levels during hemorrhagic shock reversion by hypertonic NaCl solution

1. Several studies have shown that in irreversible hemorrhagic shock the liver is one of the first vital organs to present metabolic alterations accompanied by an increase in lacticemia. Intravenous infusion of hypertonic solutions increases mesenteric flow as well as liver perfusion, an effect which can be blocked by vagotomy. 2. In the present study we investigate the possible role of the increase in mesenteric flow in the prevention of hepatic failure evaluated by the arterial-venous difference in the generation of glucose from lactate during the reversal of hemorrhagic shock with hypertonic NaCl solution and the possible blockage of this response by bilateral vagotomy. 3. Twenty-eight male dogs, weighing 14-20 kg, were submitted to severe hemorrhagic shock. The animals were then divided into four groups: a) HYPER, 2400 mosm/l NaCl; b) SALINE, 300 mosm/l NaCl; c) HYPERVg, 2400 mosm/l NaCl immediately after bilateral vagotomy; d) SALINEVg, 300 mosm/l NaCl immediately after bilateral vagotomy. Each group received an intravenous infusion of 10 of the shed blood volume of NaCl infusion. 4. Arterial and venous samples were collected to monitor the levels of lactate, glucose and insulin. During hemorrhage, arterial and venous lactate concentrations increased. After infusion, arterial lactate levels decreased from 332 +/- 23 to 115 +/- 12 in the HYPER group in contrast to the SALINE group where it increased from 327 +/- 20 to 422 +/- 19. 5. The decrease in arterial lactate observed after hypertonic solution infusion (2400 mosm/l), in dogs with intact vagus, suggests an increase of lactate uptake by heart and liver. Thus the beneficial effect of hypertonic solution in the reversal of hemorrhagic shock may be to enhance blood flow and oxygen delivery to the liver which would maintain glucose production and prevent hepatic failure. All the metabolic effects of hypertonic solution were abolished by vagotomy.

Effect of venous hypercarbia and hyperventilation on myocardial contractility in canine haemorrhagic shock.

To study the effect of venous hypercarbia on myocardial contractility, haemorrhagic shock was produced in six healthy mongrel dogs by ex-sanguination of 15 ml of blood/kg body weight every 20 minutes till a loss of 45 ml/kg was achieved. After recording haemodynamic and respiratory parameters, the dogs were hyperventilated by positive pressure ventilation for 30 minutes and haemodynamic and blood gas parameters reassessed. During haemorrhagic shock, mean cardiac output decreased from 4.23 l min to 0.98 l min (p < 0.01), stroke index from 2.25 to 0.35 ml/kg (p < 0.05) and left ventricular stroke work index from 3.72 to 0.19 g. m/kg. The mean mixed venous pCO2 increased from 35 mmHg to 56.7 mmHg (p < 0.05). During hypoventilation, mixed venous pCO2 decreased to 40 mmHg (p < 0.05) and without any volume replacement, mean cardiac output increased 2.5 l min (P < 0.05), stroke index to 1.13 ml/kg (p < 0.05) and left ventricular stroke work index, and index of myocardial contractility, increased to 0.78 g.m/kg (p < 0.05). Thus, although hypovolaemia is the major cause of low cardiac output in haemorrhagic shock, this study shows that venous hypercarbia (which probably indicates tissue respiratory acidosis) further worsens circulatory failure by decreasing myocardial contractility. Hyperventilation improves cardiac functions and increases output by relieving tissue hypercarbia in spite of persistent hypovolaemia.

The behavior of transfused platelets in dengue hemorrhagic fever.

The transfusion of platelet concentrate has been proved as a valuable clinical procedure in the management of bleeding in dengue hemorrhagic fever (DHF). This paper described the behavior of transfused platelets as platelet response and platelet increment in DHF patients with and without shock. Fifteen patients with DHF were studied, aged 2 to 12 years old. All had bleeding manifestation, ie GI, skin, nose or gum. Fresh human platelet concentrate was transfused to 5 non-shock cases and 10 shock cases with different dosages as the low dose (0.15-0.23 U/kg) and high dose (0.28-0.46 U/kg). The cessation of active bleeding was noted by clinical observation or hematocrit determination. The degree of elevation of the circulating platelets tended to vary inversely to the degree of shock and directly to the amounts of platelets infused. The survival of transfused platelets was very short in shock cases, about few hours to one day. This may be due to many factors: platelet plug to injured vessels, immune complex reaction, trapping of platelets to the poor circulation area, rapid utilization and destruction of platelets by injured vessels or virus and slow circulation promoting platelet adhesion.