M. M. Yada-Langui

Hypertonic saline and pentoxifylline prevent lung injury and bacterial translocation after hemorrhagic shock

Previous reports have shown beneficial effects of pentoxifylline (PTX) and hypertonic saline (HS) in the treatment of hemorrhagic shock. We compared the effects of these solutions to those of conventional lactated Ringers (LR) treatment on bacterial translocation (BT), lung injury and total and differential cell count in the bronchoalveolar lavage fluid (BAL) after hemorrhagic shock. Rats (280-330 g) were bled to a MAP of 35 mmHg for 1 h and then randomized into 4 groups: LR (3x shed blood); HS (7,5% NaCl, 4 mL/kg); LR+PTX (25 mg/kg) and SHAM (no shock, no treatment). Additionally, total shed blood was reinfused. At 24 h lung injury was analyzed by a pathologist blinded to the groups, and a score was calculated. BT was determined by microbiological cultures of mesenteric lymph node complex. BAL was performed on a separate set of animals that received the same treatments. Lung score was significantly higher in LR group (11.5+/-1.4) as compared to HS (6.8+/-0.9), and PTX treated animals (7.2+/-0.9). The percentage of neutrophils in the BAL of LR animals (15.8%) was also significantly higher as compared with HS (5.25%) and PTX groups (9.72%). BT was noted in 50% of rats for LR group, 30% for PTX, 10% for HS and 0% for sham group. HS and PTX reduced BT and lung injury after hemorrhage. Attenuation of lung injury could be the result of less neutrophil infiltration into the lungs of HS and PTX treated animals. LR resuscitation caused pronounced lung injury and BT.

Resuscitation Affects Microcirculatory Polymorphonuclear Leukocyte Behavior After Hemorrhagic Shock: Role of Hypertonic Saline and Pentoxifylline

We have previously shown that lung injury following fluid resuscitation either with hypertonic saline (HS) or lactated Ringers (LR) plus pentoxifylline (PTX) attenuated acute lung injury when compared with LR resuscitation. The objective of the present study is to determine whether our previous observations are accompanied by changes in polymorphonuclear leukocyte (PMN) behavior. To study this, PMN-endothelial cell interactions, microcirculatory blood flow, lung histology, lung PMN infiltration (WIPO, Myeloperoxidase), and lung intracellular adhesion molecule-1 (ICAM-1) expression were assessed in a controlled hemorrhagic shock model followed by LR, HS, and LR+PTX resuscitation in rodents. Rats (240-300 g) were bled to a mean arterial pressure (MAP) of 35 mm Hg for 1 hr and then randomized into three groups: HS (7.5% NaCl, 4 ml/kg); LR (3× shed blood); and LR+PTX (25 mg/kg). Additionally, total shed blood was reinfused. A sham group underwent no shock and no treatment. The internal spermatic fascia was exteriorized and the microcirculation was observed by closed-circuit TV coupled to a microscope, 2 and 6 hrs after treatment. The number of leukocytes sticking to the venular endothelium was determined 2 hrs after fluid resuscitation. Microcirculatory blood flow was measured by an optical Doppler velocimeter. Lung histology and lung MPO immunostaining were assessed at 6 hrs, and lung ICAM-1 expression was determined by immunostaining at 2 hrs following fluid resuscitation. Two hours after treatment, HS (1.4 ± 0.4), LR+PTX (1.7 ± 0.3), and sham (0.4 ± 0.2) groups presented significant reductions in leukocyte adherence (cells/100 urn venule length), compared with the LR group (4.0 ± 0.9, P < 0.05). No differences were observed 6 hrs after treatment on leukocyte adherence and microcirculatory blood flow. ICAM-1 expression was significantly higher in LR- treated animals compared with the HS, LR+PTX, and sham groups (P < 0.01). PMN infiltration and overall lung injury were significantly attenuated by HS and LR+PTX. These results support earlier studies that indicated the potential application of HS and PTX in shock therapy and the increase in PMN- endothelial cell interaction and lung injury after LR resuscitation.

The Synergistic Effects of Pentoxifylline on Systemic and Regional Perfusion After Hemorrhage and Hypertonic Resuscitation

Small volumes of hypertonic saline solution ([HS] 7.5% NaCl) produce systemic and microcirculatory benefits in hemorrhaged animals. Pentoxifylline (PTX) has beneficial effects when administrated after hemorrhagic shock. We tested the hypothesis that the combination of HS and PTX in the initial treatment of hemorrhagic shock provides synergistic hemodynamic benefits. Twenty-four dogs were bled to a target arterial blood pressure of 40 mm Hg and randomized into 3 groups: lactated Ringer’s solution (33 mL/kg; n = 6); HS (7.5% NaCl 4 mL/kg; n = 9); and HS+PTX (7.5% NaCl 4 mL/kg + PTX 15 mg/kg; n = 9). Systemic hemodynamics were measured by Swan-Ganz and arterial catheters. Gastric mucosal-arterial Pco2 gradient (Dg-aPco2; gas tonometry), portal vein blood flow (ultrasonic flowprobe), and systemic and regional O2-derived variables were also evaluated. HS induced a partial increase in mean arterial blood pressure, cardiac output, and portal vein blood flow. In the HS+PTX group, we observed a significant, but transitory, increase in systemic oxygen delivery (180 ± 17 versus 141 ± 13 mL/min) in comparison to HS alone. PTX infusion during hypertonic resuscitation promoted a significant reduction in Dg-aPco2 (41.8 ± 4.8 to 25.7 ± 3.9 mm Hg) when compared with isolated HS infusion (48.2 ± 6.4 to 39.4 ± 5.5 mm Hg). We conclude that PTX as an adjunct drug during hypertonic resuscitation improves cardiovascular performance and gastric mucosal oxygenation.

Intraarterial pulmonary pentoxifylline improves cardiac performance and oxygen utilization after hemorrhagic shock: a novel resuscitation strategy.

The role of pentoxifylline (PTX) as a resuscitation adjunct in hemorrhagic shock is unclear. PTX infusion into the pulmonary artery and its effects on cardiac performance and oxygen utilization have not been defined. We hypothesized that pulmonary PTX is superior to systemic PTX or lactated Ringer’s (LR) solution alone. The effects of LR solution, systemic PTX, and pulmonary PTX on cardiac performance and oxygen utilization in a hemorrhagic shock model in dogs were compared. Animals were bled to a mean arterial blood pressure (MAP) of 40 mm Hg maintained for 30 min and randomized into 3 resuscitation groups: LR solution (2×shed blood), systemic PTX (10 mg/kg bolus IV) in addition to LR solution (2×shed blood) + PTX (5 mg/kg for 45 min IV), and pulmonary PTX (10 mg/kg bolus + 5 mg/kg for 45 min via a pulmonary artery catheter) plus LR solution (2× shed blood, IV). Arterial blood gases, hemoglobin levels, MAP, cardiac index, systemic vascular resistance index, pulmonary vascular resistance index, oxygen delivery, oxygen consumption, and oxygen extraction ratio (O2 ER) were measured serially. No differences in blood loss, hemoglobin, and MAP were observed. Pulmonary PTX increased cardiac index to levels more than baseline (P = 0.012) and decreased systemic vascular resistance index and pulmonary vascular resistance index to levels less than baseline (P < 0.0001). Pulmonary PTX increased oxygen delivery and oxygen consumption to baseline levels. Post resuscitation O2 ER levels in LR-treated animals remained more than baseline (P < 0.0001). Systemic and pulmonary PTX significantly decreased O2 ER compared with shock levels. PTX resuscitation is superior compared with LR solution alone. Intraarterial pulmonary PTX administration is safe, and improves cardiac performance as well as O2 utilization.

Efeitos iniciais da reposição volêmica com solução salina hipertônica a 7,5% na perfusão e oxigenação esplâncnica após choque hemorrágico

OBJETIVO: Avaliar os efeitos hemodinâmicos sistemicos e esplâncnico da expansao volemica inicial com SSH em modelo de choque hemorragico controlado. METODOS: Dez caes foram submetidos a sangramento controlado (20 ml/min) ate uma pressao arterial media de 40±5 mmHg (PAM). Apos 30 minutos de choque, receberam 4 ml/Kg de SSH em 5 minutos e posteriormente observados sem intervencoes adicionais durante 60 minutos. As variaveis hemodinâmicas sistemicas foram obtidas de um cateter arterial e de um cateter de Swan-Ganz, enquanto as regionais atraves da cateterizacao da veia porta, fluxometro ultrassonico na veia porta e um tonometro na cavidade. A oferta, taxa de extracao e consumo esplâncnico de oxigenio, pH intramucoso e os gradientes veno-arterial, porta-arterial e mucosa-arterial da pCO2 (Dap-apCO2, Dvp-apCO2 e Dt-apCO2, respectivamente), foram calculados. RESULTADOS: A hemorragia (29,8±2,4 ml/Kg) reduziu a pressao arterial media (125±6 para 42±1 mmHg), o DC (1,9±0,2 para 0,6±0,1 L/min) e o fluxo porta (504±73 para 126±12 ml/min), enquanto elevou o Dap-apCO2 (5,3±0,8 para 19,9±1,6 mmHg), Dvp-apCO2 (5,4±1,4 para 22,6±2,1 mmHg) e o Dt-apCO2 (6,1±1,1 para 43,8±7,5 mmHg). A infusao de SSH resultou em recuperacao parcial dos fluxos sistemico e porta. Atenuou os gradientes de CO2 com menor impacto sobre o Dt-apCO2. CONCLUSAO: A SSH promoveu beneficios parciais na perfusao sistemica e esplâncnica, os quais foram especialmente limitados na microcirculacao regional, como demonstrado pelo Dt-apCO2. Alem disso, as variaveis sistemicas e regionais dependentes de oxigenio, nao refletem a adequacao da perfusao da mucosa gastrica, enfatizando a importância da monitorizacao deste territorio - pela tonometria - durante os estados de choque.

Systemic and regional hemodynamic effects of fluid resuscitation in experimental septic shock

Experimental models may help to understand the pathophysiology of septic shock. The aim of this study is to evaluate effects of different volumes of Lactate Ringers solution (RL) on cardiovascular function and intestinal perfusion in experimental hypodynamic septic shock. Anesthetized, ventilated mongrel dogs (n = 21, 16.3 ± 1.9 kg) received an intravenous injection of 1.2 × 1010/kg cfu live Escherichia coli over 30 min (baseline–T30). Then, the animals were randomized to receive 16 ml/kg RL (n = 7), 32 ml/kg RL infused over a 30-min period or a control group (no fluid resuscitation, n = 7) (T60–T90). The animals were followed for 2 hours thereafter (T90–T210). Systemic hemodynamics were determined by arterial and pulmonary artery catheters. Portal and renal vein blood flows were measured with ultrasonic flowprobes. The PCO2 gap (gas tonometry), arterial and portal vein lactate levels were measured at each timepoint. The data are expressed as mean ± SEM. The different variables were analyzed by analysis of variance. Live E. coli injection in dogs promotes low cardiac output, systemic and regional lactic acidosis and severe splanchnic hypoperfusion. The RL solution promoted only modest and transient improvement in blood flows but not in systemic and regional acidosis. There were no differences between the resuscitated groups. Table 1