Crystalloid and colloid resuscitation of uncontrolled hemorrhagic shock following massive splenic injury.

Using a standardized massive splenic injury (MSI) model of uncontrolled hemorrhagic shock we studied the effect of vigorous crystalloid or colloid fluid resuscitation on the hemodynamic response, and survival in rats. The value of massive fluid infusion in uncontrolled hemorrhagic shock following intra-abdominal solid organ injury is still controversial. The effect of crystalloid and colloid infusion was studied following massive splenic injury. The animals were randomized into six groups: group 1 (n = 8) sham-operated, group 2 (n = 12) MSI untreated, group 3 (n = 10) MSI treated with 41.5 mL/kg Ringer's lactate (large-volume Ringer's lactate, LVRL), group 4 (n = 14) MSI treated with 5 mL/kg 7.5% NaCl (hypertonic saline, HTS), group 5 (n = 10) MSI treated with 7.5 mL/kg hydroxyethyl starch (HES-7.5), and group 6 (n = 11) MSI treated with 15 mL/kg hydroxyethyl starch (HES-15). Following MSI mean arterial pressure (MAP) in untreated group 2 decreased from 109.1 +/- 4.5 to 49.8 +/- 9.6 mmHg (P < 0.001) in 60 min. Mean survival time was 132.1 +/- 18.7 min, and total blood loss was 30.2 +/- 4.1% of blood volume. LVRL infusion resulted in an early rise in MAP from 59.7 +/- 7.3 to 90.0 +/- 11.3 mmHg (P < 0.01), which then rapidly dropped to 11.7 +/- 4.5 mmHg (P < 0.001) after 60 min. The mean survival time was 82.5 +/- 18.2 min (P < 0.01), and total blood loss was 53.7 +/- 2.9% (P < 0.01). Total blood loss following HTS infusion was 32.2 +/- 4.0% and survival time was 127.9 +/- 19.7 min. HES-7.5 infusion only moderately increased bleeding to 44.2 +/- 3.9% (P < 0.05), but mortality remained unchanged. HES-15 infusion resulted in an increase in blood loss to 47.8 +/- 7.1% (0.01), survival time dropped to 100.7 +/- 12.3 min (P < 0.05). Vigorous large volume infusion of Ringer's lactate or HES following MSI resulted in a significant increase in intra-abdominal bleeding and shortened survival time compared to untreated, small volume HTS, or HES-7.5-treated animals. The hemodynamic response to crystalloid or colloid infusion in blunt abdominal trauma is primarily dependent on the severity of injury and the rate of fluid resuscitation.     

Crystalloid or colloid resuscitation of uncontrolled hemorrhagic shock after moderate splenic injury

Using a standardized moderate splenic injury (MSI) model of uncontrolled hemorrhagic shock, we studied the effect of vigorous crystalloid or colloid fluid resuscitation on the hemodynamic response and survival time in rats. The animals were randomized into 6 groups: group 1 (n = 8) sham-operated, group 2 (n = 10) MSI untreated, group 3 (n = 10) MSI treated with 41.5 mL/kg Ringer's lactate (large-volume Ringer's lactate [LVRL]), group 4 (n = 10) MSI treated with 5 mL/kg 7.5% NaCl (hypertonic saline [HTS]), group 5 (n = 10) MSI treated with 7.5 mL/kg hydroxyethyl starch (HES-7.5), group 6 (n = 10) MSI treated with 15 mL/kg hydroxyethyl starch (HES-15). After MSI, mean arterial pressure (MAP) in group 2 decreased from 105.0+/-5.6 to 64.0+/-12.7 mmHg (P < 0.001) after 60 min. Mean survival time was 157.4+/-28.9 min, and total blood loss was 24.0+/-5.4% of blood volume. LVRL infusion resulted in an early rise in MAP from 75.2+/-8.7 to 96.7+/-9.0 mmHg (P < 0.01), which then rapidly dropped to 43.0+/-9.7 mmHg (P < 0.001) after 60 min. The mean survival time was 140.7+/-22.3 min, and total blood loss was 41.4+/-4.8% (P < 0.05). Total blood loss following HTS infusion was 24.7+/-3.7%, and mean survival time was 177.5+/-18.9 min. HES-7.5 infusion was followed by bleeding of 25.6+/-5.1%, and mean survival time was 181+/-16.1. HES-15 infusion resulted in an increase in blood loss to 48.2+/-7.3% (P < 0.05), and mean survival time of 133.0+/-27.7 min. Large-volume Ringer's lactate (LVRL) or hydroxyethyl starch (HES-15) infusion in uncontrolled hemorrhagic shock after moderate splenic injury resulted in a significant increase in intra-abdominal bleeding, but survival time remained unchanged compared with untreated, small-volume HTS-, or HES-7.5-treated animals. The hemodynamic response to large-volume crystalloid or colloid infusion was similar to moderate large-vessel injury.     

Arginine vasopressin,but not epinephrine,improves survival in uncontrolled hemorrhagic shock after liver trauma in pigs

OBJECTIVE: Epinephrine is widely used for treatment of life-threatening hypotension, although new vasopressor drugs may merit evaluation. The purpose of this study was to determine the effects of vasopressin vs. epinephrine vs. saline placebo on hemodynamic variables, regional blood flow, and short-term survival in an animal model of uncontrolled hemorrhagic shock and delayed fluid resuscitation. DESIGN: Prospective, randomized, laboratory investigation that used a porcine model for measurement of hemodynamic variables and regional abdominal organ blood flow. SETTING: University hospital laboratory. SUBJECTS: A total of 21 pigs weighing 32 +/- 3 kg. INTERVENTIONS: The anesthetized pigs were subjected to a penetrating liver injury, which resulted in a mean +/- sem loss of 40% +/- 5% of estimated whole blood volume within 30 mins and mean arterial pressures of <20 mm Hg. When heart rate declined progressively, pigs randomly received a bolus dose and continuous infusion of either vasopressin (0.4 units/kg and 0.04 units.kg-1.min-1, n = 7), or epinephrine (45 microg/kg and 5 microg.kg(-1).min(-1), n = 7), or an equal volume of saline placebo (n = 7), respectively. At 30 mins after drug administration, all surviving animals were fluid resuscitated while bleeding was surgically controlled. MEASUREMENTS AND MAIN RESULTS: Mean +/- sem arterial blood pressure at 2.5 and 10 mins was significantly (p <.001) higher after vasopressin vs. epinephrine vs. saline placebo (82 +/- 14 vs. 23 +/- 4 vs. 11 +/- 3 mm Hg, and 42 +/- 4 vs. 10 +/- 5 vs. 6 +/- 3 mm Hg, respectively). Although portal vein blood flow was temporarily impaired by vasopressin, it was subsequently restored and significantly (p <.01) higher when compared with epinephrine or saline placebo (9 +/- 5 vs. 121 +/- 3 vs. 54 +/- 22 mL/min and 150 +/- 20 vs. 31 +/- 17 vs. 0 +/- 0 mL/min, respectively). Hepatic and renal artery blood flow was significantly higher throughout the study in the vasopressin group; however, no further bleeding was observed. Despite a second bolus dose, all epinephrine- and saline placebo-treated animals died within 15 mins after drug administration. By contrast, seven of seven vasopressin-treated animals survived until fluid replacement, and 60 mins thereafter, without further vasopressor therapy (p <.01). Moreover, blood flow to liver, gut, and kidney returned to normal values in the postshock phase. CONCLUSIONS: Vasopressin, but not epinephrine or saline placebo, improved short-term survival in a porcine model of uncontrolled hemorrhagic shock after liver injury when surgical intervention and fluid replacement was delayed.     

Continuous fluid resuscitation for treatment of uncontrolled hemorrhagic shock following massive splenic injury in rats

We have previously observed that bolus fluid resuscitation in uncontrolled hemorrhagic shock induced by solid organ injury leads to increased blood loss and mortality. In the present investigation, we studied the effect of continuous fluid resuscitation on the hemodynamic response and survival following massive splenic injury (MSI) in rats. The animals were randomized into 11 groups: group 1, sham-operated; group 2, MSI untreated; group 3, MSI treated with 17.5 mL/kg/h of Ringers lactate (RL) solution (RL-17.5); group 4, MSI treated with 35 mL/kg/h RL (RL-35); group 5, MSI treated with 70 mL/kg/h RL (RL-70); group 6, MSI treated with 7.5 mL/kg/h of 7.5% NaCl (HTS-7.5); group 7, MSI treated with 15 mL/kg/h of 7.5% NaCl (HTS-15); group S, MSI treated with 30 mL/kg/h of 7.5% NaCl (HTS-30); group 9, MSI treated with 7.5 mL/kg/h 6% hydroxyethyl starch (HES-7.5); group 10, MSI treated with 15 mL/kg/h 6% hydroxyethyl starch (HES-15); and group 11, MSI treated with 30 mL/kg/h 6% hydroxyethyl starch (HES-30). MSI in untreated group 2 was followed by a fall of mean arterial pressure (MAP) to 50.1 +/- 6.7 mmHg (P < 0.001) in 15 min. Mean survival time (MST) was 99.5 +/- 16.6 min, and total blood loss (TBL) was 37.8% +/- 2.6% of blood volume. Fluid treatment with increasing volumes of RL in groups 3, 4, and 5 was followed by a gradual increase in TBL compared with untreated animals, and MST remained unchanged. Increasing volumes of HTS infusion in groups 6, 7, and 8 was also followed by incease in TBL, but MST remained unchanged except for an increase to 123.0 +/- 20.5 min (P < 0.05) in group 6. Increasing volumes of HES in groups 9, 10, and 11 was also followed by increase in TBL, but MST remained unchanged. In conclusion, continuous infusion of LR, HTS, and HES following massive splenic injury resulted in a significant increase in intra-abdominal bleeding, but survival time in the first hour following injury remained unchanged in contrast to bolus fluid infusion, which increases early mortality.     

Leukocyte-independent plasma extravasation during endotoxemia

OBJECTIVES: To determine the meaning of leukocyte-endothelial interactions for the development of endotoxin-induced vascular leakage. DESIGN: Randomized, blinded, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Twenty-four male Wistar rats. INTERVENTIONS: After application of fucoidin to prevent leukocyte rolling and adherence (25 mg/kg; n = 8; fucoidin/LPS group) or saline 0.9% (n = 8; LPS group), animals were given an intravenous infusion of endotoxin (Escherichia coli lipopolysaccharide 026:B6; 2 mg/kg/hr) over 120 mins. Animals in the control group (n = 8) received an equivalent volume of saline 0.9%. MEASUREMENTS AND MAIN RESULTS: Leukocyte rolling and leukocyte adherence, red cell velocity, vessel diameters, venular wall shear rate, volumetric blood flow, and macromolecular leakage were determined in mesenteric postcapillary venules using in vivo videomicroscopy at baseline, 60 mins, and 120 mins after start of a continuous endotoxin infusion. Fucoidin prevented leukocyte rolling (baseline, 3+/-2 rollers; 120 mins, 3+/-1 rollers; not significant vs. baseline; p < .01 vs. LPS group) and reduced the adherence of leukocytes at baseline and during endotoxemia and showed only a slight increase in adherent leukocytes (baseline, 100+/-38 cells/mm2; 120 mins, 244+/-68 cells/mm2; p < .05 vs. baseline; p < .01 vs. LPS group). In the LPS group, endotoxin exposure induced a marked increase in adherent leukocytes (baseline, 248+/-24 cells/mm2; 120 mins, 560+/-57 cells/mm2; p < .01). Leukocyte adherence in control animals (control group) did not increase significantly. Macromolecular leakage, expressed as the ratio of perivenular to intravenular fluorescence intensity after injection of fluorescence-labeled albumin, increased from 0.16+/-0.03 to 0.49+/-0.04 (p < .01 vs. baseline; p < .05 vs. control) during the infusion of endotoxin in the LPS group. Fucoidin application did not diminish the extravasation of albumin (baseline, 0.09+/-0.03; 120 mins, 0.61+/-0.10; p < .01 vs. baseline; p < .01 vs. control). CONCLUSIONS: These results demonstrate that despite a significant reduction of adherent leukocytes to the endothelium by fucoidin, there is no reduction in macromolecular leakage, indicating that leukocyte-endothelial interactions only play a minor role for the development of macromolecular leakage and microvascular damage in the early phase of endotoxemia.     

Vasopressin decreases endogenous catecholamine plasma concentrations during cardiopulmonary resuscitation in pigs

OBJECTIVE: The purpose of this study was to evaluate the effect of vasopressin vs. saline placebo on catecholamine plasma concentrations during cardiopulmonary resuscitation (CPR). DESIGN: Prospective, randomized laboratory investigation by using an established porcine CPR model with instrumentation for measurement of hemodynamic variables, vital organ blood flow, and return of spontaneous circulation. SETTING: University hospital laboratory. SUBJECTS: Sixteen domestic pigs. INTERVENTIONS: After 15 mins of untreated cardiac arrest and 3 mins of CPR, 16 pigs were randomized to be treated with either 0.8 U/kg vasopressin (n = 8) or placebo (normal saline; n = 8). Arterial epinephrine and norepinephrine plasma concentrations were sampled at prearrest, after 1.5 mins of chest compressions, and at 1.5 mins and 5 mins after drug administration during CPR. MEASUREMENTS AND MAIN RESULTS: In comparison with placebo pigs at 1.5 and 5 mins after drug administration, animals resuscitated with vasopressin had significantly (p < .01) higher mean +/- SEM left ventricular myocardial (131+/-27 vs. 10+/-1 mL x mins(-1) x 100 g(-1) and 62+/-13 vs. 9+/-2 mL x mins(-1) x 100 g(-1)); total cerebral (90+/-8 vs. 14+/-3 mL x mins(-1) x 100 g(-1) and 51+/-4 vs. 12+/-2 mL x mins(-1) x 100 g(-1)); and adrenal gland perfusion (299+/-36 vs. 38+/-7 mL x mins(-1) x 100 g(-1) and 194+/-23 vs. 29+/-5 mL x mins(-1) x 100 g(-1)). Significantly lower mean +/- SEM epinephrine concentrations in the vasopressin pigs compared with the placebo group were measured 1.5 mins and 5 mins after drug administration, (24167+/-7919 vs. 80223+/-19391 pg/mL [p < .01] and 8346+/-1454 vs. 71345+/-10758 pg/mL [p < .01]). Mean +/- SEM norepinephrine plasma concentrations in the vasopressin animals in comparison with placebo were at 1.5 and 5 mins after drug administration significantly lower (41729+/-13918 vs. 82756+/-9904 pg/mL [p = .01] and 10642+/-3193 vs. 62170+/-8797 pg/mL [p < .01]). CONCLUSIONS: Administration of vasopressin during CPR resulted in significantly superior vital organ blood flow, but significantly decreased endogenous catecholamine plasma concentrations when compared with placebo.     

Fluid resuscitation and hyperchloremic acidosis in experimental sepsis: improved short-term survival and acid-base balance with Hextend compared with saline

OBJECTIVE: To compare resuscitation with 0.9% saline with Hextend, a synthetic colloid in a balanced electrolyte solution, in terms of acid-base status and survival time in an experimental model of septic shock in the rat. DESIGN: Randomized, open-label, controlled experiment. SETTING: University research laboratory. SUBJECTS: Sixty adult, male Sprague-Dawley rats. INTERVENTION: Animals were studied for 12 hrs after intravenous infusion of Escherichia coli endotoxin (20 mg/kg). Animals were volume resuscitated to maintain a mean arterial pressure >60 mm Hg using either 0.9% saline (n = 25), Hextend (n = 25), or lactated Ringer's (n = 10). MEASUREMENTS: Arterial blood gases and electrolytes were measured before and after resuscitation (0, 180, 360, and 540 mins after endotoxin infusion). Survival time was measured, up to 12 hrs. RESULTS: Mean survival time among animals treated with saline or Ringer's was 45% less compared with Hextend-treated animals: 391 +/- 151 mins and 362 +/- 94 mins vs. 567 +/- 140 mins, respectively, p <.0001. Overall survival (at 12 hrs) was 0% with saline or Ringer's vs. 20% with Hextend, p =.05. After resuscitation with saline, arterial standard base excess and plasma apparent strong ion difference were both significantly lower (-19.3 +/- 5.2 vs. -12.1 +/- 5.7, p <.001, and 23.0 +/- 6.2 vs. 30.3 +/- 2.9, p <.0001, respectively) and plasma Cl(-) was significantly higher (123 +/- 7 vs. 115 +/- 3 mmol/L, p <.0001) compared with Hextend. Resuscitation with Ringer's solution resulted in a standard base excess, and Cl(-) between that of saline and Hextend (-15.4 +/- 3.1, and 117 +/- 3, respectively). CONCLUSION: Compared with 0.9% saline, volume resuscitation with Hextend was associated with less metabolic acidosis and longer survival in this experimental animal model of septic shock.     

Improved survival in uncontrolled hemorrhagic shock induced by massive splenic injury in the proestrus phase of the reproductive cycle in the female rat

Estrogen has a protective effect in adverse circulatory conditions such as trauma-hemorrhage and ischemia-reperfusion. In the present investigation uncontrolled hemorrhagic shock induced by massive splenic injury (MSI) was studied in male and female rats during the proestrus and metestrus phase of the reproductive cycle. The animals were anesthetized and randomly divided into four groups: group 1 (n = 8) were sham operated female animals; in group 2 (n = 8) MSI was induced in male animals; in group 3 (n = 8) MSI was induced in female animals in proestrus; in group 4 (n = 8) MSI was induced in female animals in metestrus. Plasma 17beta-estradiol was 112.8 +/- 16.7 pg/mL in group 3 and 44.8 +/- 16.7 pg/mL in group 4 (P < 0.04). After MSI the mean arterial pressure dropped in group 2 from 135.6 +/- 3.9 to 47.6 +/- 8.8 mmHg (P < 0.001) in 60 min. Total blood loss in 4 h was 29.6 +/- 3.5% of blood volume and mean survival time 161.3 +/- 30.6 min. In group 3 total blood loss in 4 h was 24.4 +/- 5.7% of blood volume and mean survival time 240 +/- 0 min (P < 0.03 compared with group 2). In group 4, total blood loss in 4 h was 29.6 +/- 3.9% of blood volume and mean survival time was 112.3 +/- 28.7 min (P < 0.001 compared with group 3). These results indicate that female rats in the proestrus phase of the reproductive cycle better maintain hemodynamic stability and survival in uncontrolled hemorrhagic shock than female animals in metestrus or males. This difference is attributed to factors other than blood loss.     

Effects of prophylactic fenoldopam infusion on renal blood flow and renal tubular function during acute hypovolemia in anesthetized dogs

OBJECTIVE: It was hypothesized that fenoldopam mesylate, a selective dopamine agonist, may preserve renal perfusion and decrease tubular oxygen consumption during states of hypoperfusion, such as hypovolemic shock. The objective of this study was to quantify the effects of fenoldopam (0.1 microg x kg(-1) x min(-1)) on renal blood flow, urine output, creatinine clearance, and sodium clearance in pentobarbital anesthetized dogs that had undergone partial exsanguination to acutely decrease cardiac output. DESIGN: Prospective, randomized, controlled experiment. SETTING: University-based animal laboratory and research unit. SUBJECTS: Eight female beagle dogs. INTERVENTIONS: Arterial blood pressure, heart rate, cardiac output, renal blood flow, urine output, creatinine clearance, and fractional excretion of sodium were measured and calculated at four times: a) before infusion of fenoldopam or normal saline; b) during infusion of fenoldopam or normal saline (1 hr); c) during a 90-min period of hypovolemia (induced by acute partial exsanguination), with concurrent infusion of fenoldopam or normal saline; and d) during a 1-hr period after retransfusing the dogs. MEASUREMENTS AND MAIN RESULTS: Administration of fenoldopam (0.1 microg x kg(-1) x min(-1)) was not associated with hemodynamic instability. Renal blood flow and urine output decreased significantly from baseline (p <.01) during the hypovolemic period in the placebo group (72 +/- 20 to 47 +/- 6 mL/min and 0.26 +/- 0.15 to 0.08 +/- 0.05 mL/min, respectively) but not in the fenoldopam group (75 +/- 14 to 73 +/- 17 mL/min and 0.3 +/- 0.19 to 0.14 +/- 0.05 mL/min, respectively). Creatinine clearance and fractional excretion of sodium decreased significantly from baseline (p <.01) in the placebo group during the hypovolemic period (3.0 +/- 0.4 to 1.8 +/- 0.8 mL x kg(-1) x min(-1) and 1.7% +/- 0.9% to 0.4% +/- 0.2%, respectively) but not in the dogs that received fenoldopam (3.0 +/- 1.0 to 2.9 +/- 0.5 mL x kg(-1) x min(-1) and 1.9% +/- 1.1% to 1.7% +/- 2.7%, respectively). CONCLUSIONS: Fenoldopam ablated the tubular prerenal response to profound hypovolemia and maintained renal blood flow, glomerular filtration rate, and natriuresis without causing hypotension. This suggests that fenoldopam may have a renoprotective effect in acute ischemic injury.     

The effect of sympatholytics on uncontrolled hemorrhage.

OBJECTIVE: To assess the possible benefits of sympatholytics on uncontrolled hemorrhage in unanesthetized rats. DESIGN: A randomized laboratory study using rats to test the effects of sympatholytics on uncontrolled hemorrhage. SETTING: Research laboratory. SUBJECTS: Forty female Sprague-Dawley rats, randomly assigned into four groups according to the treatment: untreated (Control); alpha-adrenergic blockade with phenoxybenzamine (Alpha); beta-adrenergic blockade with propranolol (Beta); and a combined alpha- and beta-adrenergic blockade by phenoxybenzamine and propranolol (Alpha/Beta). INTERVENTION: After cannulation under light ether, the rats were allowed to awaken. A baseline blood sample was withdrawn. The uncontrolled hemorrhage was initiated by tail resection and allowed to continue without intervention for the duration of the experiment. After 15 mins, 80 mL/kg isotonic saline fluid was infused at 4.4 mL/min. At 60 mins, another blood sample was drawn; changes in mean arterial pressure, hematocrit, blood loss, and mortality were observed for up to 180 mins. MAIN OUTCOME MEASURE: Survival, mortality, blood loss (amount, prevalence, and rate), and hemodynamic variables (mean arterial pressure, pulse rate, hematocrit). RESULTS: In the Alpha group, there was a reduction in spontaneous blood loss compared with the control group (2.9 vs. 10.6 mL/kg, respectively) and 100% survival. In contrast, the Beta group exhibited an increase in tail blood loss (21.1 mL) and a decreased survival (10%). Despite the enhanced hemorrhage in the Alpha/Beta group (17.0 mL/kg) compared with controls, the survival rate in both of these groups was 60%. In all groups, no significant increase in tail blood loss was observed after 60 mins. CONCLUSIONS: An alpha-adrenergic blockade increased survival in uncontrolled hemorrhage by significantly reducing spontaneous blood loss. Conversely, a beta-adrenergic blockade significantly decreased survival and increased blood loss, whereas a combined blockade significantly increased blood loss without affecting survival.     

Microvascular and systemic effects following top load administration of saturated carbon monoxide-saline solution

OBJECTIVE: To determine how top loads with different doses of carbon monoxide (CO)-saturated saline solutions (CO-saline) affect microvascular and systemic hemodynamics and to delineate the corresponding biochemical mechanisms. DESIGN: Prospective study. SETTING: University research laboratory. SUBJECTS: Male Golden Syrian hamsters. INTERVENTIONS: Hamsters implemented with a dorsal window chamber were given different volumes (characterized as percent of blood volume, BV) by intravenous injection of CO-saturated saline. MEASUREMENTS AND MAIN RESULTS: Hamsters were observed until 90 mins after infusion of CO-saline solution. In the 20% BV CO-saline infusion group, observation was extended until 180 mins. Systemic variables measured included mean arterial pressure, heart rate, systemic arterial blood gases, and cardiac output and index. Microvascular hemodynamic measurements included vessel diameter, red blood cell velocity, and functional capillary density. Cyclic guanosine monophosphate (cGMP) content in the chamber tissue was measured by enzyme immunoassay. 10% BV of CO-saline increased flow maximally in the microcirculation at 30 mins after infusion (207% in arterioles and 238% in venules, p < .05 vs. baseline). Functional capillary density was significantly increased in both 10% and 15% groups (p < .05 vs. baseline), and cardiac index increased 130% (p < .05 vs. baseline) at 10 mins after 10% CO-saline infusion. There were no changes of microhemodynamic variables and functional capillary density with 2.5%, 5%, and 20% CO-saline infusion during the observation period. Microvascular hemodynamic changes by 10% CO-saline infusion were inhibited completely by L-NAME pretreatment and partially by 1H-[1,2,4]oxadiazole[4,3-a]quinoxqalin-1-one pretreatment. cGMP content in skin fold tissues was related to changes of vessel diameter. CONCLUSIONS: Intravenous injection of CO-saturated saline caused vasodilation and improved microvascular hemodynamics in the hamster window chamber model in a dose-dependent manner. These changes were related to increased cardiac output and local cGMP content. These results support the possible use of CO-saturated solutions as a vasodilator in critical conditions.     

Intravenous iloprost increases mesenteric blood flow in experimental acute nonocclusive mesenteric ischemia

OBJECTIVE: To evaluate the effect of an intravenously administered synthetic epoprostenol analog, iloprost, in nonocclusive acute mesenteric ischemia induced by cardiac tamponade. DESIGN: Prospective, randomized, controlled experimental study. SETTING: Animal research laboratory at a university medical center. SUBJECTS: Ten Yorkshire pigs (weight range, 20-25 kg). INTERVENTIONS: Nonocclusive acute mesenteric ischemia was induced by pericardial tamponade. Pigs were randomized to receive either a low-dose, continuous intravenous infusion of iloprost (0.075 microg/kg/min) or an equivalent volume of normal saline to serve as the control. Infusion of iloprost or saline was continued after pericardial tamponade was reversed. METHODS: Ten anesthetized and ventilated pigs underwent laparotomy and thoracotomy. A pulmonary artery catheter was inserted, a magnetic flow probe was positioned around the superior mesenteric artery (SMA), and cannulation of the pericardial space was performed. Pericardial tamponade was induced by injecting 5% dextrose in water into the pericardial space until blood flow in the superior mesenteric artery decreased to half of baseline. After 60 mins, animals received either a continuous intravenous infusion of iloprost at 0.075 microg/kg/min (n = 6) or an equal volume of normal saline (n = 4) for 60 mins. Pericardial fluid was then removed, and iloprost or normal saline infusion was continued for another 60 mins. MEASUREMENTS: Heart rate, blood pressure, cardiac output, oxygen delivery, oxygen consumption, SMA blood flow, ileal Pco2, ileal intramucosal pH, and serum lactate levels of mixed venous blood and mesenteric venous blood were recorded at baseline, after pericardial tamponade was induced, during the iloprost or normal saline infusion with pericardial tamponade, and after removal of pericardial fluid (reperfusion period). RESULTS: Iloprost infusion increased SMA blood flow by 60% in this model of nonocclusive mesenteric ischemia (from 168 +/- 41 to 269 +/- 76 mL/min; p <.05). The effect of iloprost infusion was more prominent after the tamponade (422 +/- 87 mL/min in the iloprost group vs. 232 +/- 111 mL/min in the control group; p <.05). Increased mesenteric perfusion decreased intestinal mucosal hypercarbia, leading to improvement of intramucosal pH.     

Comparison of epinephrine and vasopressin in a pediatric porcine model of asphyxial cardiac arrest

OBJECTIVE: This study was designed to compare the effects of vasopressin vs. epinephrine vs. the combination of epinephrine with vasopressin on vital organ blood flow and return of spontaneous circulation in a pediatric porcine model of asphyxial arrest. DESIGN: Prospective, randomized laboratory investigation using an established porcine model for measurement of hemodynamic variables, organ blood flow, blood gases, and return of spontaneous circulation. SETTING: University hospital laboratory. SUBJECTS: Eighteen piglets weighing 8-11 kg. INTERVENTIONS: Asphyxial cardiac arrest was induced by clamping the endotracheal tube. After 8 mins of cardiac arrest and 8 mins of cardiopulmonary resuscitation, a bolus dose of either 0.8 units/kg vasopressin (n = 6), 200 microg/kg epinephrine (n = 6), or a combination of 45 microg/kg epinephrine with 0.8 units/kg vasopressin (n = 6) was administered in a randomized manner. Defibrillation was attempted 6 mins after drug administration. MEASUREMENTS AND MAIN RESULTS: Mean +/- SEM coronary perfusion pressure, before and 2 mins after drug administration, was 13 +/- 2 and 23 +/- 6 mm Hg in the vasopressin group; 14 +/- 2 and 31 +/- 4 mm Hg in the epinephrine group; and 13 +/- 1 and 33 +/- 6 mm Hg in the epinephrine-vasopressin group, respectively (p = NS). At the same time points, mean +/- SEM left ventricular myocardial blood flow was 44 +/- 31 and 44 +/- 25 mL x min-(1) x 100 g(-1) in the vasopressin group; 30 +/- 18 and 233 +/- 61 mL x min(-1) x 100 g(-1) in the epinephrine group; and 36 +/- 10 and 142 +/- 57 mL x min(-1) x 100 g(-1) in the epinephrine-vasopressin group (p < .01 epinephrine vs. vasopressin; p < .02 epinephrine-vasopressin vs. vasopressin). Total cerebral blood flow trended toward higher values after epinephrine-vasopressin (60 +/- 19 mL x min(-1) x 100 g(-1)) than after vasopressin (36 +/- 17 mL x min(-1) x 100 g(-1)) or epinephrine alone (31 +/- 7 mL x min(-1) x 100 g(-1); p = .07, respectively). One of six vasopressin, six of six epinephrine, and four of six epinephrine-vasopressin-treated animals had return of spontaneous circulation (p < .01, vasopressin vs. epinephrine). CONCLUSIONS: Administration of epinephrine, either alone or in combination with vasopressin, significantly improved left ventricular myocardial blood flow during cardiopulmonary resuscitation. Return of spontaneous circulation was significantly more likely in epinephrine-treated pigs than in animals resuscitated with vasopressin alone.     

Clinical and hemodynamic comparison of 15:2 and 30:2 compression-to-ventilation ratios for cardiopulmonary resuscitation

OBJECTIVE: To compare cardiopulmonary resuscitation (CPR) with a compression to ventilation (C:V) ratio of 15:2 vs. 30:2, with and without use of an impedance threshold device (ITD). DESIGN: Prospective randomized animal and manikin study. SETTING: Animal laboratory and emergency medical technician training facilities. SUBJECTS: Twenty female pigs and 20 Basic Life Support (BLS)-certified rescuers. INTERVENTIONS, MEASUREMENTS, AND MAIN RESULTS: ANIMALS: Acid-base status, cerebral, and cardiovascular hemodynamics were evaluated in 18 pigs in cardiac arrest randomized to a C:V ratio of 15:2 or 30:2. After 6 mins of cardiac arrest and 6 mins of CPR, an ITD was added. Compared to 15:2, 30:2 significantly increased diastolic blood pressure (20 +/- 1 to 26 +/- 1; p < .01); coronary perfusion pressure (18 +/- 1 to 25 +/- 2; p = .04); cerebral perfusion pressure (16 +/- 3 to 18 +/- 3; p = .07); common carotid blood flow (48 +/- 5 to 82 +/- 5 mL/min; p < .001); end-tidal CO2 (7.7 +/- 0.9 to 15.7 +/- 2.4; p < .0001); and mixed venous oxygen saturation (26 +/- 5 to 36 +/- 5, p < .05). Hemodynamics improved further with the ITD. Oxygenation and arterial pH were similar. Only one of nine pigs had return of spontaneous circulation with 15:2, vs. six of nine with 30:2 (p < 0.03). HUMANS: Fatigue and quality of CPR performance were evaluated in 20 BLS-certified rescuers randomized to perform CPR for 5 mins at 15:2 or 30:2 on a recording CPR manikin. There were no significant differences in the quality of CPR performance or measurement of fatigue. Significantly more compressions per minute were delivered with 30:2 in both the animal and human studies. CONCLUSIONS: These data strongly support the contention that a ratio of 30:2 is superior to 15:2 during manual CPR and that the ITD further enhances circulation with both C:V ratios.     

Right ventricular response to high-dose almitrine infusion in patients with severe hypoxemia related to acute respiratory distress syndrome

OBJECTIVE: To evaluate the effects of high-dose almitrine infusion on gas exchange and right ventricular function in patients with severe hypoxemia related to acute respiratory distress syndrome (ARDS). DESIGN: Prospective study. SETTING: Medicosurgical intensive care department (ten beds). PATIENTS: Nine patients with ARDS and severe hypoxemia (PaO2/FIO2 ratio, <150 torr [20 kPa]). INTERVENTION: High-dose almitrine infusion (16 microg/kg/min for 30 mins). MEASUREMENTS AND MAIN RESULTS: Gas exchange and hemodynamic parameters were recorded before and after almitrine infusion. Right ventricular function was evaluated by using a fast response thermistor pulmonary artery catheter that allowed measurement of right ventricular ejection fraction and calculation of right ventricular end-diastolic and end-systolic volumes. Almitrine did not significantly alter arterial oxygenation and intrapulmonary shunt. Almitrine increased mean pulmonary arterial pressure (MPAP) from 31 +/- 4 to 33 +/- 4 mm Hg (p < .05), pulmonary vascular resistance index from 353 +/- 63 to 397 +/- 100 dyne x sec/ cm5 x m2 (p < .05), and right ventricular end-systolic volume index from 71 +/- 22 to 77 +/- 21 mL/m2 (p < .05); almitrine decreased right ventricular ejection fraction from 36% +/- 7% to 34% +/- 8% (p < .05). Stroke volume index and cardiac index did not change. The almitrine-induced changes in right ventricular ejection fraction were closely correlated with the baseline MPAP (r2 = .71, p < .01). CONCLUSION: In patients with severe hypoxemia related to ARDS, high-dose almitrine infusion did not improve arterial oxygenation and impaired the loading conditions of the right ventricle. The decrease in right ventricular ejection fraction induced by almitrine was correlated with the baseline MPAP. Thus, high-dose almitrine infusion may be harmful in ARDS patients with severe hypoxemia and pulmonary hypertension.     

Reduced rate of bacterial translocation and improved variables of natural killer cell and T-cell activity in rats surviving controlled hemorrhagic shock and treated with hypertonic saline

OBJECTIVE: To examine the effect of hypertonic saline on bacterial translocation and the number and function of natural killer and T cells in controlled hemorrhagic shock. DESIGN: Randomized controlled study. Duration of follow-up was 24 hrs. SETTING: University research laboratory. SUBJECTS: Adult male Sprague-Dawley rats, weighing 310-390 g. INTERVENTIONS: Controlled hemorrhagic shock was induced by blood withdrawal (mean arterial pressure, 30-40 mm Hg) and maintained for 30 mins. The animals were randomly divided into three groups: group 1 (n = 10) was sham-operated, group 2 (n = 10) was untreated, and group 3 was treated with 5 mL/kg hypertonic saline (n = 10). The rats were killed after 24 hrs. MEASUREMENTS AND MAIN RESULTS: Infusion of hypertonic saline in group 3 was followed by reduced bacterial translocation rate (5.0 +/- 2.2% vs. 18.3 +/- 5.3%, p <.033). The total mass of bacteria isolated from hypertonic saline-treated animals with bacterial translocation was 7.8- to 10.4-fold less than that from untreated rats. Controlled hemorrhagic shock resulted in a low percentage of CD4+ cells in blood (35.2 +/- 3.9%, p <.05) and lymph nodes (44.4 +/- 4.5%, p <.05) and depressed CD4 expression on blood (82 +/- 13 arbitrary units, p <.005) and lymph node (168 +/- 24 arbitrary units, p <.03) cells. A compensatory mobilization of NKR-P1+ cells from lymph nodes (8.6 +/- 2.3%, p <.05) to blood (21.2 +/- 5.2%, p <.01) with down-regulated NKR-P1 expression on blood cells (59 +/- 10 arbitrary units, p <.005) was observed. Natural killer cell-mediated cytotoxicity was decreased (67.9 +/- 9.7%, p <.05). Hypertonic saline treatment greatly stimulated CD4 expression on blood (419 +/- 113 arbitrary units, p <.005) and lymph node (553 +/- 115 arbitrary units, p <.03) cells. Also, normalization of NKR-P1 expression (160 +/- 19 arbitrary units, p <.005) and restoration of natural killer cell-mediated cytotoxicity to near normal values (88.6 +/- 7.4%, p <.05) were demonstrated. CONCLUSION: Controlled hemorrhagic shock was accompanied by CD4+ cells suppression and excessive recruitment of natural killer cells with abnormally low NKR-P1 expression and suppressed cytolytic activity into circulation. Infusion of hypertonic saline reversed these changes and reduced bacterial translocation.     

Diaspirin-crosslinked hemoglobin reduces mortality of severe hemorrhagic shock in pigs with critical coronary stenosis

OBJECTIVE: To evaluate the effects of resuscitation with a 10% diaspirin-crosslinked hemoglobin (DCLHb) solution on global hemodynamic variables, systemic and myocardial oxygen transport and tissue oxygenation, and contractile function of the left ventricle in an experimental model of severe hemorrhagic shock and critical stenosis of the left anterior descending coronary artery (LAD). DESIGN: Prospective, placebo-controlled, randomized study. SETTING: Experimental animal laboratory. SUBJECTS: A total of 20 anesthetized pigs. INTERVENTIONS: After implementation of a permanent critical LAD stenosis (ie, maintenance of basal blood flow but absence of reactive hyperemia after a 10-sec complete vessel occlusion), hemorrhagic shock (target mean aortic pressure, 45 mm Hg) was induced within 15 mins by programmed withdrawal of blood and maintained for 60 mins. Subsequently, the volume of plasma lost during hemorrhage was replaced by either a balanced electrolyte solution containing 10 g/dL DCLHb (DCLHb group; n = 10) or an 8 g/dL human albumin solution (HSA) oncotically matched to DCLHb (HSA group; n = 10). Data were collected immediately after the infusion of the different solutions and again after 60 mins had elapsed. MEASUREMENTS AND MAIN RESULTS: Although five of ten HSA-treated animals died of acute left ventricular failure within the first 20 mins after complete fluid resuscitation, all of the DCLHb-treated animals survived the 60-min observation period after resuscitation (p < .05). This significant difference in mortality is explained by higher coronary perfusion pressure in DCLHb-treated animals (75 +/- 17 vs. 27 +/- 17 torr DCLHb vs. HSA group; p < .05) and persistence of subendocardial ischemia and hypoxia (radioactive microspheres method) in HSA-treated animals on resuscitation particularly affecting the LAD-supported myocardium (subendocardial oxygen delivery: 20 +/- 11 vs. 3 +/- 1 mL oxygen x g(-1) x min(-1), DCLHb vs. HSA group; p < .05). Except for enhanced myocardial contractility immediately on infusion of DCLHb (maximal left ventricular pressure increase: 2373 +/- 782 vs. 1730 +/- 543 torr x sec(-1) DCLHb vs. HSA group; p < .05), no differences were detected between groups concerning the variables of systemic oxygen transport, tissue oxygenation, and regional contractile function of the myocardium (determined with microsonometry). CONCLUSIONS: Fluid resuscitation with 10% DCLHb solution completely reverses hemorrhagic shock-induced subendocardial ischemia and hypoxia in the presence of compromised coronary circulation and thereby prevents early death after resuscitation.     

Effects of arginine vasopressin during resuscitation from hemorrhagic hypotension after traumatic brain injury

OBJECTIVE: Two series of experiments were designed to evaluate whether early arginine vasopressin improves acute outcome following resuscitation from traumatic brain injury and severe hemorrhagic hypotension. DESIGN: Prospective randomized, blinded animal study. SETTING: University laboratory. SUBJECTS: Thirty-three swine. INTERVENTIONS: In series 1 (n = 19), after traumatic brain injury with hemorrhage and 12 mins of shock (mean arterial pressure approximately 20 mm Hg), survivors (n = 16) were initially resuscitated with 10 mL/kg crystalloid. After 30 mins, crystalloid and blood with either 0.1 unit x kg(-1) x hr(-1) arginine vasopressin or placebo was titrated to a mean arterial pressure target >or=60 mm Hg. After 90 mins, all received mannitol and the target was cerebral perfusion pressure >or=60 mm Hg. To test cerebrovascular function, 7.5% inhaled CO2 was administered periodically. In series 2 (n = 14), the identical protocol was followed except the shock period was 20 mins and survivors (n = 10) received a bolus of either arginine vasopressin (0.2 units/kg) or placebo during the initial fluid resuscitation. MEASUREMENTS AND MAIN RESULTS: In series 1, by 300 mins after traumatic brain injury with arginine vasopressin (n = 8) vs. placebo (n = 8), the fluid and transfusion requirements were reduced (both p < .01), intracranial pressure was improved (11 +/- 1 vs. 23 +/- 2 mmHg; p < .0001), and the CO2-evoked intracranial pressure elevation was reduced (7 +/- 2 vs. 26 +/- 3 mm Hg, p < .001), suggesting improved compliance. In series 2, with arginine vasopressin vs. placebo, cerebral perfusion pressure was more rapidly corrected (p < .05). With arginine vasopressin, five of five animals survived 300 mins, whereas three of five placebo animals died. The survival time with placebo was 54 +/- 4 mins (p < .05 vs. arginine vasopressin). CONCLUSIONS: Early supplemental arginine vasopressin rapidly corrected cerebral perfusion pressure, improved cerebrovascular compliance, and prevented circulatory collapse during fluid resuscitation of hemorrhagic shock after traumatic brain injury.     

Addition of alinidine, a specific bradycardic agent, to dobutamine in a canine model of endotoxic shock.

BACKGROUND AND METHODS: Alinidine is a recently developed antiarrhythmic medication that acts directly on the cardiac pacemaker cells to reduce heart rate (HR). At effective doses, alinidine might have cardiodepressant actions that could be hazardous in the presence of hemodynamic instability. On the other hand, one limitation of the use of catecholamines is tachycardia, and alinidine could be beneficial in situations such as septic shock, where adrenergic agents are commonly required. The present study explored the hemodynamic and gasometric effects of alinidine during dobutamine administration in a canine model of septic shock induced by endotoxin administration. In ten pentobarbital-anesthetized, mechanically ventilated dogs (weight 28 +/- 4 kg), Escherichia coli endotoxin (3 mg/kg) injection was followed 30 mins later by saline infusion to restore and maintain pulmonary artery occlusion pressure at the baseline value. Sixty minutes after the endotoxin administration, a dobutamine infusion was started at a rate of 10 micrograms/kg/min. Thirty minutes later, alinidine was administered as a bolus dosage of 1 mg/kg in five dogs; the other five dogs served as a control group. RESULTS: Alinidine administration resulted in a decrease in HR from 157 +/- 20 to 138 +/- 27 beats/min (p less than .01) and a nonsignificant increase in cardiac output from 5.2 +/- 3.0 to 6.8 +/- 2.8 L/min, as a consequence of increases in stroke volume from 31.9 +/- 15.3 to 49.2 +/- 13.9 mL (p less than .01) and in left ventricular stroke work from 32.1 +/- 20.0 to 57.4 +/- 32.1 g.m (p less than .05). CONCLUSIONS: During experimental septic shock, alinidine administration can reverse dobutamine-induced tachycardia and simultaneously improve ventricular function.     

Effects of different resuscitation fluids on tissue blood flow and oxidant injury in experimental rhabdomyolysis

OBJECTIVE: This study was performed to evaluate the effects of 0.9% saline (SAL), 0.9% saline + sodium bicarbonate + mannitol (SAL/BIC/MAN), and hypertonic saline-dextran (HSD) on hemodynamic variables, tissue blood flow, and oxidant injuries in experimental traumatic rhabdomyolysis (TR) in rats subjected allogeneic muscle extract infusion. DESIGN: Prospective, randomized, experimental. SETTING: Physiology experiment laboratory. SUBJECTS: Male Sprague-Dawley rats, weighing 250-300 g. INTERVENTIONS: All groups (n = 8 each) underwent femoral artery and vein catheterization. The animals in the TR, SAL, SAL/BIC/MAN, and HSD groups received an infusion of 2 mL of autologous muscle extract for 60 mins. After autologous muscle extract infusion, the SAL and HSD groups received 30 mL/kg 0.9% saline for 30 mins or 4 mL/kg HSD for 5 mins, respectively. The SAL/BIC/MAN group received 30 mL/kg 0.9% saline for 30 mins plus a bolus of 1 g/kg mannitol and a bolus of 2 mEq/kg sodium bicarbonate diluted in 1 mL of saline. At 2 hrs of autologous muscle extract infusion, erythrocyte flows in liver and kidney were measured by using a laser Doppler flowmeter. Then, blood samples and kidney and liver biopsies were taken to measure levels of glutathione and malondialdehyde. MEASUREMENTS AND MAIN RESULTS: TR caused decreases in mean arterial pressure, tissue blood flow, and tissue glutathione and an increase in malondialdehyde. Rats in the HSD group had significant metabolic acidosis. SAL resuscitation did not correct tissue blood flow and prevent oxidant injury. HSD increased tissue blood flow, mean arterial pressure, and liver and kidney glutathione and decreased serum, liver, and kidney malondialdehyde. SAL/BIC/MAN resuscitation corrected all oxidant damage variables but did not increase tissue blood flow. SAL/BIC/MAN preserved serum malondialdehyde and liver glutathione better than the HSD did. CONCLUSIONS: HSD prevented oxidant injury and restored tissue blood flow but increased metabolic acidosis that followed autologous muscle extract infusion. SAL/BIC/MAN seems to be more effective than HSD in decreasing oxidant injury. Further research on the effects of the solute overload and metabolic acidosis due to HSD resuscitation on renal function in experimental rhabdomyolysis is warranted.