Lung vascular permeability after reversal of fibronectin deficiency in septic sheep. Correlation with patient studies.

Plasma fibronectin deficiency and opsonic dysfunction exist in critically ill septic surgical, trauma, and burn patients with multiple organ failure. Fibronectin deficiency can be reversed by infusion of fresh plasma cryoprecipitate. The influence of therapy with human cryoprecipitate on lung vascular permeability in septic sheep with plasma fibronectin deficiency following surgery was evaluated. Additionally, selected studies on pulmonary function in septic surgical and trauma patients after infusion of plasma cryoprecipitate were completed. In patients, ventilation-perfusion balance appeared to improve as measured by the multiple inert gas elimination technique. With the lung lymph fistula preparation in fibronectin deficient sheep, infusion of human plasma cryoprecipitate (10 units; 250 ml) delayed the onset and minimized the increase in lung vascular permeability during postoperative Pseudomonas sepsis (5 X 10(9) bacteria, I.V.; 5 X 10(10) bacteria, I.P.). For example, in a first group of sheep, the transvascular protein clearance (TPC) at 2 hrs in septic sheep (n = 4) treated with only saline (volume control) was 20.1 +/- 3.1 ml/hr, compared to 11.23 +/- 0.83 ml/hr in the sheep (n =a 4) treated with fibronectin-rich cryoprecipitate (p less than 0.05). In a second group of sheep, cryoprecipitate depleted of fibronectin by affinity chromatography was used as the control solution. It also did not manifest this protective effect with respect to lung vascular permeability. Thus, at 2 hrs the lymph flow (Qlym) was 30.2 ml/hr and the transvascular protein clearance (TPC) was 18.0 ml/hr in septic sheep given fibronectin-deficient cryoprecipitate. In contrast, in the fibronectin-rich cryoprecipitate treated sheep, the Qlym was 14.8 ml/hr and the TPC was 8.12 ml/hr. It is suggested that fibronectin may influence lung vascular integrity during sepsis following surgery and trauma.     

Reversal of fibronectin and opsonic deficiency in patients. A controlled study

Plasma fibronectin is an opsonic glycoprotein which augments reticuloendothelial phagocytic clearance of nonbacterial particulates. We evaluated the influence of intravenous infusion of plasma cryoprecipitate on circulating immunoreactive fibronectin and associated opsonic activity at 0.5, 2.0, 4.0, 10, and 21 hr postinfusion in septic (n = 8) and nonseptic (n = 6) surgical and/or trauma patients with documented plasma fibronectin deficiency. The study was a randomized, double-blind, crossover clinical protocol in which fibronectin-poor (0.116 +/- 0.025 mg/ml) cryoprecipitate extracted plasma (placebo) was compared to fibronectin-rich (2.139 +/- 0.161 mg/ml) plasma cryoprecipitate. Septic injured patients (149.37 +/- 17.11 micrograms/ml) had lower (p less than 0.05) plasma fibronectin levels than nonseptic injured patients (212.17 +/- 7.14 micrograms/ml) and both were less (p less than 0.05) than normal (330 +/- 30 micrograms/ml). As tested in vitro with a peritoneal macrophage monolayer assay, cryoprecipitate manifested opsonic activity related to its fibronectin concentration. Intravenous infusion of fibronectin rich cryoprecipitate reversed both the immunoreactive fibronectin and opsonic deficiency, while infusion of the placebo at a comparable total protein load did not reverse either deficient parameter. Reversal of fibronectin deficiency was more sustained in nonseptic injured patients as compared to septic injured patients. Thus, reversal of opsonic deficiency in septic and nonseptic injured patients is observed after infusion of plasma cryoprecipitate and not with infusion of fibronectin deficient plasma at comparable protein loads. Also, cryoprecipitate extracted plasma may serve as an appropriate control solution for randomized studies evaluating the therapeutic value of fibronectin-rich plasma cryoprecipitate.     

Large volume crystalloid resuscitation does not increase extravascular lung water

The purpose of this study was to determine whether Ringer's lactate solution increases extravascular lung water (EVLW) during resuscitation after hemorrhagic shock. Ten sheep anesthetized with thiamylal were bled to a mean arterial pressure (MAP) of 50 mm Hg; further bleeding maintained that pressure for 30 min. Resuscitation fluid consisted of Ringer's lactate solution in volumes necessary to restore and maintain for 1 hr MAP, pulmonary capillary wedge pressure (PCWP), and cardiac index at levels equal to those measured before bleeding. After volume replacement, the colloid oncotic pressure (COP) - PCWP gradient (COP - PCWP) decreased from 12 +/- 3 to 2 +/- 5 mm Hg (P less than 0.001). After volume restoration, COP decreased from 19 +/- 8 mm Hg to 12 +/- 2 mm Hg (P less than 0.001). Despite the large volume of fluid administered, EVLW did not increase. Crystalloid resuscitation does not necessarily increase EVLW despite significant decreases in COP and COP - PCWP gradient.     

Optimal fluid management after aortic reconstruction: a prospective study of two crystalloid solutions

To determine optimal fluid management after elective aortic surgery we compared postoperative administration of 5% dextrose Ringer's lactate solution (102 patients) with 5% dextrose half-normal saline solution (80 patients). For 72 hours after operation, intravenous fluids were titrated to maintain urine output between 50 and 100 ml/hr. The group receiving 5% dextrose Ringer's lactate required less intravenous volume per day (2005 +/- 138 ml [mean +/- standard error of the mean] vs. 2701 +/- 145 ml, p less than 0.05), gained less weight (0.8 +/- 0.2 kg vs. 3.2 +/- 0.2 kg, p less than 0.05), and sustained less hyponatremia (serum sodium reduction, 0.1 mEq/L vs. 4.5 mEq/L, p less than 0.05). The group receiving 5% dextrose Ringer's lactate exhibited consistently lower pulmonary capillary wedge pressure (7.3 +/- 1.0 mm Hg vs. 11.4 +/- 1.9 mm Hg) and required treatment for fluid overload in 9 of 102 instances compared with 30 of 80 instances with hypotonic saline solution (p less than 0.05). The patients receiving 5% dextrose Ringer's lactate maintained higher arterial PO2 at 40% forced inspiratory oxygen (PaO2, 83 +/- 3 torr vs. PaO2, 67 +/- 5 torr, p less than 0.05). Optimal fluid management was approached by the use of 5% dextrose Ringer's lactate solution postoperatively. The use of hypotonic saline solution after aortic surgery offered no advantage and predisposed the patient to volume overload.     

Effectiveness of hypertonic saline-dextran 70 for initial fluid resuscitation of major burns.

Small-volume resuscitation (4 ml/kg) with hypertonic saline-dextran (HSD) has been shown effective in hemorrhagic shock. In the present study the effectiveness of an initial 4 ml/kg bolus infusion of HSD on cardiovascular function and fluid resuscitation requirements after a major burn injury was evaluated in anesthetized sheep following a 40% BSA scald burn. One hour after injury resuscitation was initiated by a rapid intravenous bolus infusion (4 ml/kg) of either hypertonic saline-dextran (7.5% NaCl in 6% dextran 70) (HSD) or the same volume of normal (isotonic) saline (NS). Lactated Ringer's was later infused as needed to maintain cardiac output at 90% of baseline. HSD rapidly and effectively restored cardiac output and mean arterial pressure significantly better than the same volume of NS. Hemodynamic improvement by HSD was short lived, and need for further fluid therapy was only marginally delayed (HSD 38 +/- 8 min, NS 20 +/- 3 min; p = 0.06) (mean +/- SEM). The total requirements for fluid therapy during the first 6 hr postburn were not reduced by the initial HSD bolus (HSD 3,145 +/- 605 ml, NS 2,905 +/- 495 ml; n.s.), nor was skin edema formation reduced. We conclude that in anesthetized sheep HSD resuscitation was only transiently effective in treating burn shock. This may be attributed to the sustained increase in vascular permeability and continued plasma leak following thermal injury.     

Pulmonary transvascular fluid filtration response to hypoproteinemia and Hespan infusion.

Management of major blood loss utilizing protein-free fluids for volume replacement frequently results in plasma protein depletion and plasma volume expansion. These factors can increase pulmonary transvascular fluid filtration which may lead to life-threatening pulmonary edema. We studied the combined effects of plasma protein depletion and plasma volume expansion on lung lymph flow (QL) in awake sheep prepared with chronic lung lymph fistulae. Animals were first chronically protein-depleted by batch plasmapheresis and then infused for 2 hr with either lactated Ringer's (Hypo/LR; n = 7) or 6% hydroxyethyl starch (Hespan) (Hypo/HES; n = 6). Control normoproteinemic animals (Norm/LR; n = 13) only received lactated Ringer's. Hypoproteinemia alone resulted in an average 2-fold increase in QL over normoproteinemic baseline levels (P less than or equal to 0.05). Infusion of LR into hypoproteinemic animals caused a 7.9-fold increase in QL (P less than or equal to 0.05). By comparison, HES infusion under similar hypoproteinemic conditions limited the increase in QL to 3.2-fold over baseline. We attributed this reduced rise in QL to Hespan's high oncotic pressure, which dramatically widened (by 4-5 mm Hg) the pulmonary-to-lymph oncotic pressure gradient. We did not observe this with LR infusion, or in previous studies employing intravenous infusion of plasma protein. Thus, the oncotic pressure of Hespan appears to significantly limit pulmonary fluid filtration during hypoproteinemia compared to LR. We do not believe that these effects are the results of any changes in microvascular porosity.     

A comparison of several hypertonic solutions for resuscitation of bled sheep

Small volumes (4 ml/kg) of 2400 mOsm NaCl restore cardiac output and mean arterial pressure to 80% of baseline after hemorrhage (65% of blood volume) in unanesthetized sheep. An equal volume of normal saline is less effective. To identify an optimal hypertonic solution, we screened six 2400 mOsm solutions in 18 randomized experiments in 8 sheep: NaCl, NaHCO3, NaCl/sodium acetate, NaCl/mannitol, NaCl/6% Dextran 70, and glucose. Cardiovascular function, as determined by cardiac output and mean arterial pressure, was restored best with NaCl, NaCl/NaAc, and NaCl/Dex. These three solutions were then evaluated using 18 sheep in 36 experiments. Following a 1-hr baseline period, the sheep were bled to a mean arterial pressure of 50 mm Hg for 2 hr. One of the solutions was then given in a volume of 4 ml/kg over 2 min and the sheep were monitored for 3 hr. Within 3 min of the infusion, cardiac output increased to greater than 100% of baseline for all three solutions. The NaCl-Dex solution sustained a significantly higher cardiac output over the 3-hr observation period than the other solutions. Plasma volume increased for all solutions following infusion. NaCl-Dex maintained plasma volume significantly better than the other solutions. As a further control, an isotonic solution of 6% Dextran 70 in normal saline was studied. It was not as effective as the hypertonic NaCl-Dex in maintaining cardiac output, mean arterial pressure, or plasma volume. Osmolality increased 10% (309 to 326 mOsm/kg H2O), plasma [NA] increased 7% (151 to 161 meq/liter), and plasma [K] decreased from 3.9 to 2.6 meq/liter following the hypertonic infusions. The sheep appeared to tolerate these electrolyte changes well. We conclude that a single bolus infusion of 2400 mOsm NaCl with 6% Dextran 70 best resuscitates sheep that have been subjected to a moderate degree of hemorrhagic shock compared to several other solutions. Its beneficial effects are caused in part by a sustained reestablishment of plasma volume. More studies are needed to document the safety of dextran in the clinical setting of hemorrhagic shock. Small volumes of hypertonic solutions may be valuable in the initial fluid resuscitation of patients in hemorrhagic shock.     

Small-volume resuscitation with hypertonic saline dextran solution

Small-volume hypertonic resuscitation has been proposed as an effective means for restoration of cardiovascular function after hemorrhage at the scene of an accident. We evaluated the cardiovascular, metabolic, and neurohumoral response of resuscitation after hemorrhage using 200 ml of 2400 mosm sodium chloride, 6% dextran 70. Unanesthetized adult sheep were bled to maintain mean arterial pressure at 50 mm Hg for 3 hours, shed blood volume = 42 +/- 7 ml/kg. The sheep were then treated with a single bolus infusion of hypertonic saline dextran (n = 7) or normal saline solution (control group, n = 7) and then observed for a 30-minute period of simulated patient transport during which no additional fluid was given. Hypertonic saline dextran caused rapid restoration of blood pressure and cardiac output within 2 minutes of infusion. Cardiac output remained at or above baseline level, while both O2 consumption and urine output increased to above baseline level during the 30 minutes of simulated patient transport. By comparison 200 ml of normal saline solution caused only a small increase in blood pressure and no improvement in cardiac output or oxygen consumption. After this 30-minute period, both groups were given lactated Ringer's solution as needed to return and maintain cardiac output at its baseline value. The volume of lactated Ringer's solution required to maintain cardiac output was less in the hypertonic group, 371 +/- 168 ml, only one sixth that of the control group, 2200 +/- 814 ml. In summary after 3 hours of hypovolemia, a small volume of hypertonic saline dextran, about 4 ml/kg, fully restored cardiovascular and metabolic function for at least 30 minutes and significantly lowered the total volume requirements of resuscitation.     

Effect of a hypertonic lactated Ringer's solution on intracranial pressure and cerebral water content in a model of traumatic brain injury

There has recently been an increased interest in the use of hypertonic solutions for fluid resuscitation of trauma victims. In this study, we examined the acute cerebral effects of a hypertonic lactated Ringer's solution (measured osmolality = 469 mOsm/kg) in an animal model of traumatic brain injury. Following the production of a cerebral cryogenic lesion, eight New Zealand white rabbits were randomized to undergo hemodilution with either lactated Ringer's (measured osmolality = 254 mOsm/kg) or hypertonic lactated Ringer's. Over the course of the experiment the lactated Ringer's group required significantly more fluid than the hypertonic group to maintain stable central venous and mean arterial pressure (245 +/- 5 ml vs. 132 +/- 20 ml; p less than 0.0001). Osmolality increased in the hypertonic group by 13.5 +/- 3.3 mOsm/kg whereas it decreased in the lactated Ringer's group by 5.5 +/- 2.6 mOsm/kg. Intracranial pressure increased in both groups over the course of the experiment but the increase in pressure was greater in the lactated Ringer's group than the hypertonic group (9.5 +/- 2.4 mm Hg vs. 1.7 +/- 1.5 mm Hg; p less than 0.001). Brain water content was significantly increased in the region of the lesion as assayed by both the wet/dry weight method and cortical specific gravity determinations, but there was no difference between the two treatment groups. Water content of the nonlesioned hemisphere was significantly less in the hypertonic group. This study suggests that hypertonic saline solutions may be useful for the resuscitation of hypovolemic patients with localized brain injury.     

The effects of hypoproteinemia and volume expansion on lung and soft tissue transvascular fluid filtration

Resuscitation from major trauma or replacement of major operative blood loss frequently results in varying levels of protein depletion and alterations in plasma volume. To assess the importance of these factors on pulmonary and soft tissue transvascular fluid filtration, we compared the effects of hypoproteinemia and plasma volume expansion on the rate of lung and soft tissue transvascular fluid filtration in unanesthetized adult sheep. Ten animals were surgically prepared with chronic lung and soft tissue lymph fistulas. Lung (QL) and soft tissue (Qs) lymph flow rates were used to determine changes in transvascular fluid filtration. Initially, lactated Ringer's solution (LR) was infused to elevate pulmonary arterial wedge pressure of normoproteinemic animals (Norm/LR) 5 mm Hg for 2 1/2 hours. After a plasmapheresis-induced protein depletion of 30% to 35%, similar volume expansions with LR (Hypo/LR) and fresh frozen plasma (Hypo/Plas) were performed. Plasma, lung lymph, and soft tissue lymph oncotic pressures were determined, and transvascular oncotic gradients were calculated. Plasma volume expansion during Hypo/Plas conditions limited (p less than or equal to 0.05, 3 hours after infusion) Qs elevations compared with Hypo/LR expansion. However, there appeared to be no significant advantage with fresh frozen plasma over LR infusion in limiting QL. During fresh frozen plasma infusion, a distinct 10- to 12-hour lag in protein transport into the interstitium was observed in the soft tissue but not the lung microcirculation. The resultant differences in fluid filtration properties were in part the result of significant widening of the oncotic gradient in soft tissue. Plasma protein infusion appeared not to be beneficial over LR in limiting lung transvascular fluid filtration during hypoproteinemic states but significantly decreased soft tissue transvascular fluid flux.     

Hypertonic saline resuscitates dogs in endotoxin shock

In this experiment we determined if infusions of hypertonic saline (HS, 1080 Na meq/liter) could resuscitate dogs in endotoxin shock as effectively as Ringer's lactate (RL, 130 Na meq/liter). Anesthetized dogs received iv 0.5 mg/kg of Escherichia coli endotoxin, and mean arterial pressure (MAP, mm Hg) decreased from 148 +/- 5 to 58 +/- 14 within 30 min. To resuscitate the dogs 13 meq/kg of sodium was intravenously infused over 90 min as either a 10% body weight load of RL (n = 5) or a 1.2% body weight load of HS (n = 5). Both solutions produced an equivalent hemodynamic resuscitation 3 to 4 hr postinfusion with an increase in MAP (RL, 119 +/- 4; HS, 108 +/- 7), the restoration of cardiac outputs to baseline (RL, 2.0 +/- 0.2; HS, 1.9 +/- 0.3 liter/min), and similar renal inulin clearances (RL, 48 +/- 16; HS, 44 +/- 7 ml/min). The net fluid gain (resuscitation fluid volume infused minus urine output as percentage of body weight) was much greater in the RL group (7.2 +/- 1.0%) than in the HS group (0.48 +/- 0.2%). Plasma volume (PV, percentage of body weight) was measured with Evans blue dye in these splenectomized dogs. The increase in PV in the RL dogs (1.25 +/- 0.04%) was slightly greater than the increase in the HS group (0.94 +/- 0.13). Prenodal skin lymph was collected from both hindpaws, and the fractional increase in skin lymph flow after RL (4.5 +/- 2.9) was greater than the increase in the HS group (1.7 +/- 0.3).(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic resuscitation after trauma-hemorrhage and acute fluid replacement improves hepatocellular function and cardiac output.

OBJECTIVE: To determine whether prolonged (chronic) resuscitation has any beneficial effects on cardiac output and hepatocellular function after trauma-hemorrhage and acute fluid replacement. BACKGROUND DATA: Acute fluid resuscitation after trauma-hemorrhage restores but does not maintain the depressed hepatocellular function and cardiac output. METHODS: Male Sprague-Dawley rats underwent a 5-cm laparotomy (i.e., trauma was induced) and were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of maximal bleed-out volume was returned in the form of Ringer's lactate (RL). The animals were acutely resuscitated with RL using 4 times the volume of maximum bleed-out over 60 minutes, followed by chronic resuscitation of 0, 5, or 10 mL/kg/hr RL for 20 hours. Hepatocellular function was determined by an in vivo indocyanine green clearance technique. Hepatic microvascular blood flow was assessed by laser Doppler flowmetry. Plasma levels of interleukin-6 (IL-6) were determined by bioassay. RESULTS: Chronic resuscitation with 5 mL/kg/hr RL, but not with 0 or 10 mL/kg/hr RL, restored cardiac output, hepatocellular function, and hepatic microvascular blood flow at 20 hours after hemorrhage. The regimen above also reduced plasma IL-6 levels. CONCLUSION: Because chronic resuscitation with 5 mL/kg/hr RL after trauma-hemorrhage and acute fluid replacement restored hepatocellular function and hepatic microvascular blood flow and decreased plasma levels of IL-6, we propose that chronic fluid resuscitation in addition to acute fluid replacement should be routinely used in experimental studies of trauma-hemorrhage.     

Kinetics and Extravascular Retention of Acetated Ringer's Solution during Isoflurane or Propofol Anesthesia for Thyroid Surgery

Background: In sheep, isoflurane causes extravascular accumulation of infused crystalloid fluid. The current study evaluates whether isoflurane has a greater tendency than propofol to cause extravascular retention in surgical patients.

Methods: Thirty patients undergoing thyroid surgery lasting for 143 +/- 32 min (mean +/- SD) received an intravenous infusion of 25 ml/kg acetated Ringer's solution over 30 min. Anesthesia was randomized to consist of isoflurane or propofol supplemented by fentanyl. The distribution and elimination of the infused fluid was estimated using volume kinetics based on the fractional dilution of blood hemoglobin over 150 min. Extravascular retention of infused fluid was taken as the difference between the model-predicted elimination and the urinary excretion. The sodium and fluid balances were measured.

Results: The fractional plasma dilution increased gradually to approximately 30% during the infusion and thereafter remained at 15-20%. Urinary excretion averaged 11% of the infused volume. Mean arterial pressure was 10 mmHg lower in the isoflurane group (P < 0.001). The excess fluid volumes in the central and peripheral functional body fluid spaces were virtually identical in the groups. The sum of water losses by evaporation and extravascular fluid retention amounted to 2.0 +/- 2.5 ml/min for isoflurane and 2.2 +/- 2.1 ml/min for propofol. The sodium balance refuted that major fluid shifts occurred between the extracellular and intracellular spaces.     

Thermal skin injury: effect of fluid therapy on the transcapillary colloid osmotic gradient

The effects of fluid therapy on interstitial colloid osmotic and hydrostatic pressures in thermally injured skin were investigated in anesthetized rats subjected to full-thickness scald burns to 40% of the body surface area and resuscitation for 3 hr by either lactated Ringer's or plasma. Interstitial fluid hydrostatic pressure (Pif) was reduced from -2 mm Hg to -20 to -40 mm Hg after injury, which will profoundly increase transcapillary filtration. Following the onset of fluid therapy, Pif increased to slightly positive values. In control, colloid osmotic pressure in plasma (COPp) was 20.6 +/- 0.4 mm Hg and in interstitial fluid (COPif) 13.7 +/- 0.3 mm Hg (means +/- SEM). The transcapillary oncotic pressure gradient (COPgrad = COPp-COPif) was 6.9 +/- 0.4 mm Hg. Following nonresuscitated thermal injury, COPp declined to 18-19 mm Hg (P less than 0.05) and COPif was reduced to 10.4 +/- 0.5 mm Hg (P less than 0.05). Fluid therapy by lactated Ringer's markedly reduced COPp (12.3 +/- 0.3 mm Hg; P less than 0.05), and COPgrad was almost abolished (2.6 +/- 0.7 mm Hg; P less than 0.05). In contrast, plasma infusion maintained COPp, whereas COPgrad increased significantly (11.1 +/- 1.2 mm Hg; P less than 0.05). Noncolloid saline solutions have been preferred for the initial fluid therapy for burns. The present study provides evidence that this will reduce both COPp and COPgrad, a situation in which edema formation will be favored.     

ATP-MgCl2 restores the depressed hepatocellular function and hepatic blood flow following hemorrhage and resuscitation

Although ATP-MgCl2 produces a myriad of beneficial effects following organ ischemia and simple hemorrhagic shock in animal models which involved heparinization and/or blood resuscitation, it is not known whether ATP-MgCl2 has any salutary effect on the depressed active hepatocellular function (AHF) and hepatic microvascular blood flow (HMBF) in a nonheparinized model of trauma and severe hemorrhage in the absence of blood resuscitation. To determine this, rats underwent a midline laparotomy (i.e., trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximum shed blood volume was returned in the form of Ringer's lactate (RL). The animals were then resuscitated with four times the volume of shed blood with RL. ATP-MgCl2, 50 mumoles/kg body weight (BW) each or an equivalent volume of normal saline, was infused intravenously for 95 min during and following crystalloid resuscitation. At 1.5 and 4 hr after resuscitation, AHF (Vmax, maximal velocity of indocyanine green clearance; Km, efficiency of the active transport process) was determined without blood sampling by using an in vivo indocyanine green clearance technique. HMBF was measured with laser Doppler flowmetry. Results indicate that Vmax, Km, and HMBF decreased significantly at 1.5-4 hr after hemorrhage and resuscitation. ATP-MgCl2 infusion restored the depressed Vmax, Km, and HMBF and prevented the occurrence of hepatic edema. The restoration of AHF with ATP-MgCl2 treatment may be due to its direct salutary effect on the active indocyanine green transport process and/or due to improvement in hepatic microcirculation.(ABSTRACT TRUNCATED AT 250 WORDS)     

The hemodynamic consequences of high-dose thiopental anesthesia

The hemodynamic and electroencephalographic effects of a 60 min infusion of thiopental, given at the rate of 1.25 mg X kg-1 X min-1 (total dose 75 mg/kg), were studied in 10 patients without cardiorespiratory disease undergoing surgery for the removal of large and/or deeply seated arteriovenous malformations. Data on heart rate, arterial, right atrial, pulmonary arterial, and pulmonary capillary wedge pressures, thermodilution cardiac output (expressed as cardiac index), the electroencephalogram, arterial blood gases, and serum thiopental concentrations were collected during a sedated, resting control period, and then every 15 min during drug infusion. Lactated Ringer's solution (total volume 1-2 liters) was infused throughout the study period at rates sufficient to maintain pulmonary capillary wedge pressure at control values. In doses sufficient to render the electroencephalogram isoelectric [t approximately equal to 30 min, 37.5 mg/kg cumulative dose, serum concentration 51 +/- 17 micrograms/ml (mean +/- SD)], drug infusion resulted in significant increases in heart rate (to 116% of control), and decreases in arterial pressure (to 87% of control), stroke volume index (to 87% of control), systemic resistance (84% of control), and both left and right ventricular stroke work indices (66% and 69% of control, respectively). Cardiac index was unchanged (following a transient increase at t = 15 min). There were no changes in pulmonary vascular resistance, or blood gases. A large total dose of thiopental (8-11 gm) was needed to maintain electroencephalogram suppression for the remainder of these 10-20 hr procedures, and emergence was slow (48-72 hr). The resultant prolonged ICU support may have contributed to serious postoperative complications in two patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental study of the pressure-volume and pressure-time relations in the completely obstructed pelvis of the porcine kidney

Summary In a series of experiments with pigs the completely obstructed renal pelvis was infused with Ringer's lactate at a constant rate of 2 ml/min. At various pressure levels (lower than 50 mm Hg) the relations pressure vs infused volume and pressure vs actual intrapelvic volume and the effects on the intrapelvic pressure of rapid total or partial extraction of the actual volume were measured. At pressure levels lower than 15–20 mm Hg the P-V relation is exponential; at pressure levels between approximately 20 to 50 mm Hg this relation is linear. In the pressure range from 20 to 50 mm Hg the pressure decays, at a constant or increasing volume, asymptotically to a certain stabilisation value when the infusion is stopped. The relation between stabilised pressure and intrapelvic volume is linear.     

Moderate smoke inhalation produces decreased oxygen delivery, increased oxygen demands, and systemic but not lung parenchymal lipid peroxidation

We studied the first 24-hour lung and systemic physiologic response to a moderate smoke inhalation injury. In addition, we monitored oxidant-induced lipid peroxidation (LP), using malondialdehyde and conjugated dienes. Sixteen adult sheep with lung and soft tissue lymph fistulas were given 20 breaths of smoke while under anesthesia. Eight sheep were given a tidal volume of 5 ml/kg smoke, confining the inflammatory injury to airways only. Eight sheep were given 10 ml/kg smoke after which focal alveolar collapse and a carboxyhemoglobin level of 28% +/- 5% were noted in addition to airways injury. No significant lung or systemic physiologic changes were noted in the 5 ml/kg smoke exposure. However, plasma levels of malondialdehyde increased significantly, indicating that LP had occurred. With the 10 ml/kg smoke exposure, a 50% early decrease in oxygen consumption was noted. At 12 hours, oxygen consumption was then significantly increased by 30% over baseline. Fluid requirements to maintain filling pressures were also significantly increased, comparable to that seen after a 20% total body surface burn. A change in soft tissue permeability was noted with a twofold increase in systemic lymph, which could in part explain the fluid requirements. Lung lymph flow increased by only twofold, and lung water was not increased, whereas arterial partial oxygen pressure decreased from a baseline of 95 +/- 4 mm Hg to 60 +/- 5 mm Hg. Systemic LP was evident when both plasma malondialdehyde and conjugated dienes increased significantly. Liver tissue malondialdehyde at postmortem examination was double the normal level. However, lung parenchymal malondialdehyde was not increased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic function in acute pancreatitis

Acute pancreatitis is often associated with impaired cardiovascular function. This study examined the systemic cardiovascular effect of acute pancreatitis induced by injection of autologous bile (0.5 ml/kg) into the canine pancreatic duct. After acute pancreatitis was induced, eight dogs were given no resuscitation (group 1, untreated pancreatitis), and lactated Ringer's solution was infused in 11 dogs (group II, treated pancreatitis) to maintain mean arterial pressure and pulmonary wedge pressure at control values. In the untreated pancreatitis group, mean arterial pressure, cardiac output, stroke volume, and stroke work values decreased (mean arterial pressure from 101 +/- 4 to 74 +/- 12 mm Hg, cardiac output from 118 +/- 7 to 56.2 +/- 1.1 ml/min/kg; stroke volume from 0.93 +/- 0.08 to 0.22 +/- 0.07 ml/beat/kg; p less than 0.05), whereas heart rate and peripheral resistance increased (heart rate from 125 +/- 7 to 185 +/- 10 beats/min, peripheral vascular resistance from 3130 +/- 410 to 4436 +/- 610 dynes/sec/cm5; p less than 0.05). Although coronary blood flow, endocardial-epicardial flow ratio, and myocardial oxygen delivery values decreased progressively in group I after induction of pancreatitis, these changes did not achieve statistical significance. All indices of cardiovascular function and coronary blood flow remained unchanged in group II. Neither dP/dt max, the maximal rate of left ventricular pressure increase, nor dP/dt at a developed pressure of 40 mm Hg (an index of myocardial contractility minimally affected by changes in preload and afterload) were depressed by bile-induced acute canine pancreatitis in either group. Our data indicate that the detrimental effects of acute pancreatitis on cardiovascular function are related solely to hypovolemia and reduced cardiac filling and not to humoral or reflex effects induced by the disease.     

The use of prostaglandin E1 and Blalock-Taussig shunts in neonates with cyanotic congenital heart disease.

Six unselected neonates with cyanotic congenital heart disease and life-threatening degrees of arterial oxygen desaturation have been managed by a protocol that includes administration of prostaglandin E1 (PGE1) and early Blalock-Taussig shunting. In 5 patients (seven paired observations) partial pressure of arterial oxygen (PaO2) rose from 19 mm Hg to a mean of 32.9 mm Hg within 20 minutes of initiation of PGE1 (0.1 to 0.2 microgram/kg/hr), infused intravenously or through an aortic catheter placed at ductal level or with both methods. The nonresponsive patient was older than the patients showing a positive response (1 month versus 24 to 96 hours). Following catheterization, immediate palliative operation including a Blalock-Taussig shunt was carried out. Although all had a satisfactory PaO2 (mean, 49 mm Hg) postoperatively, the PGE1-nonresponsive patient experienced serious intraoperative bradycardia, hypotension, and acidosis in contrast to the PGE1-responsive group. In this study, the use of PGE1 was not associated with any apparent serious side effects.