Total arteriovenous CO2 removal: simplifying extracorporeal support for respiratory failure.

Background: To reduce the complexity, complications, and cost of conventional extracorporeal membrane oxygenation, we have developed a technique of simplified arteriovenous extracorporeal CO2 removal (AVCO2R) with a low-resistance membrane gas exchanger for total CO2 removal to provide lung rest in the setting of severe respiratory failure.

Methods: We initially used AVCO2R in healthy animals to quantify the gas exchange capabilities of the system and establish ventilator management protocols for the subsequent studies of AVCO2R in a large animal model of respiratory failure secondary to a severe smoke inhalation injury.

Results: In healthy sheep the maximum spontaneous arteriovenous flow ranged from 1,350 to 1,500 mL/min, whereas CO2 removal plateaued at a blood flow of approximately 1,000 mL/min in which 112 +/- 3 mL/min CO2 was removed, allowing an 84% reduction in the minute ventilation of from 6.

Prolonged hemodynamic stability during arteriovenous carbon dioxide removal for severe respiratory failure.

Objective: The effects of prolonged arteriovenous carbon dioxide removal on hemodynamics during severe respiratory failure were evaluated in adult sheep with severe smoke inhalation injury.

Methods: Adult female sheep (n = 6,33.8 +/- 5.

Organ blood flow during arteriovenous carbon dioxide removal.

Animal models of arteriovenous carbon dioxide removal (AVCO2R) have achieved lung rest during treatment of severe respiratory failure, with total CO2 removal at arteriovenous shunt flow rates of 10% to 25% of cardiac output (CO). Previously, no statistically significant changes were reported in heart rate, cardiac output, mean arterial pressure, or pulmonary arterial pressure during prolonged (7 days) AVCO2R with shunt flows to 25% of CO. In this study, to determine the effect of various shunt levels on organ blood flow, colored microspheres were used in a conscious ovine model of AVCO2R.

Cerebral blood flow during experimental endotoxemia in volunteers.

Objective: To measure cerebral blood flow, cerebral metabolic rate for oxygen, cerebral oxygen delivery, and cerebral vascular resistance during experimental endotoxemia in volunteers.

Design: Experimental, prospective study.

Setting: University general clinical research center.

Nitric oxide synthase inhibition restores hypoxic pulmonary vasoconstriction in sepsis.

Hypoxic pulmonary vasoconstriction (HPV) is inhibited by inhaled nitric oxide (NO) in healthy animals and is blunted in endotoxemia. We investigated whether the loss of HPV during sepsis could be reversed by NO synthase (NOS) inhibition. Hypoxic challenges were induced in intubated, awake sheep breathing 100% nitrogen to the left lung and 100% oxygen to the right lung.

Effects of alpha-trinositol on systemic inflammation and renal function in ovine bacterial sepsis.

Neuronally secreted peptides are important mediators of hemodynamic changes in the systemic inflammatory response. The inositol derivative D-myo-inositol[1,2,6]triphosphate (alpha-trinositol) has been demonstrated to be a specific nonpeptide antagonist of vasoconstriction induced by neuropeptide Y. We induced sepsis by a 48 h continuous infusion of Pseudomonas aeruginosa (10(6) colony-forming unit/min intravenously [i.

Pyridoxalated hemoglobin polyoxyethylene conjugate does not restore hypoxic pulmonary vasoconstriction in ovine sepsis.

Objectives: Hypoxic pulmonary vasoconstriction, a protective mechanism, minimizes perfusion of underventilated lung areas to reduce ventilation-perfusion mismatching. We studied the effects of sepsis on hypoxic pulmonary vasoconstriction and attempted to determine whether hypoxic pulmonary vasoconstriction is influenced by pyridoxalated hemoglobin polyoxyethylene conjugate, a nitric oxide scavenger.

Design: Prospective, randomized, controlled experimental study with repeated measures.

Inhalation injury increases the anastomotic bronchial blood flow in the pouch model of the left ovine lung.

Pulmonary parenchymal damage often occurs after airway injury. Bronchial venous drainage empties into the pulmonary microvasculature. We developed an in vivo model to study the bronchopulmonary portal system after smoke inhalation injury.

Acute alterations in growth hormone-insulin-like growth factor axis in humans injected with endotoxin.

The purpose of the present study was to characterize the acute changes in the insulin-like growth factor (IGF) system in humans after administration of endotoxin (lipopolysaccharide; LPS). Escherichia coli LPS (4 ng/kg) was injected intravenously into healthy adults, and serial blood samples were collected for the next 5 h; subjects injected with saline served as time-matched controls. LPS administration resulted in a gradual decrease in the total extractable IGF-I concentration, which was reduced by approximately 20% over the final 2 h of the experiment; levels of free IGF-I were not significantly altered.

A dynamic model of ventricular interaction and pericardial influence.

A mathematical model describing the dynamic interaction between the left and the right ventricle over the complete cardiac cycle is presented. The pericardium-bound left and right ventricles are represented as two coupled chambers consisting of the left and right free walls and the interventricular septum. Time-varying pressure-volume relationships characterize the component compliances, and the interaction of these components produces the globally observed ventricular pump properties (total chamber pressure and volume).

Renal ischemia-reperfusion injury does not induce pulmonary dysfunction in sheep.

It has already been shown that pulmonary injury is induced after intestinal or hind limb ischemia-reperfusion injury. The purpose of this study was to determine the effect of renal ischemia-reperfusion injury on the pulmonary system. We compared the pulmonary effects of 60 and 90 minutes ischemia followed by 24 hour reperfusion in sheep kidneys.

Heparin attenuated neutrophil infiltration but did not affect renal injury induced by ischemia reperfusion.

Although heparin is better known as an anticoagulant, it also has several anti-inflammatory effects. Heparin is known to inhibit neutrophil adhesion, chemotaxis and oxygen free radical production. In addition, heparin is also known to act as an oxygen radical scavenger.

Oxalated pyridoxalated hemoglobin polyoxyethylene conjugate normalizes the hyperdynamic circulation in septic sheep.

Objective: Excessive production of nitric oxide significantly contributes to the hyperdynamic state associated with sepsis. The ability of hemoglobin to scavenge nitric oxide may therefore be beneficial in the treatment of sepsis. In this study, we determined the effects of different doses of the modified human pyridoxalated hemoglobin polyoxyethylene conjugate in an ovine model of hyperdynamic sepsis.

The atrial natriuretic peptide receptor antagonist HS 142-1 improves cardiovascular filling and mean arterial pressure in a hyperdynamic ovine model of sepsis.

Objective: To test whether systemic vascular resistance and mean arterial pressure increase during the administration of the atrial natriuretic peptide antagonist, HS 142-1, in ovine experimental hyperdynamic sepsis.

Design: Prospective trial.

Setting: Research laboratory at a large university medical center.

Nitric oxide and shock.

Shock can be defined as the failure of the circulatory system to provide necessary cellular nutrients, including oxygen, and to remove metabolic wastes. Although it is now recognized that more than 100 different forms of shock exist, this recognition is more a reflection of the widespread use of the term to describe a variety of disease states. For the purpose of this monograph, we concentrate on various forms of cardiovascular shock, in particular, shock that may be linked to inappropriate vasodilation from overproduction of the endogenous vasodilator, nitric oxide.

Significant reduction in minute ventilation and peak inspiratory pressures with arteriovenous CO2 removal during severe respiratory failure.

Objectives: To quantify CO2 removal using an extracorporeal low-resistance membrane gas exchanger placed in an arteriovenous shunt and evaluate its effects on the reduction of ventilatory volumes and airway pressures during severe respiratory failure induced by smoke inhalation injury.

Design: Prospective study.

Setting: Research laboratory.

Beneficial versus detrimental effects of nitric oxide synthase inhibitors in circulatory shock: lessons learned from experimental and clinical studies.

Septic shock is a physiological derangement of the cardiovascular system characterized by pathological vasodilation. Recent studies have established a role for nitric oxide, previously known as endothelium-derived relaxing factor, in the vascular dysfunction of sepsis. This finding suggests that inhibition of nitric oxide synthase (NOS), the enzyme responsible for nitric oxide production, could be a target for therapeutic intervention.

Glucose kinetics in interstitial fluid can be predicted by compartmental modeling.

The purposes of this study were to define in sheep a compartmental model for glucose kinetics in the basal condition and to test the hypothesis that interstitial fluid obtained by sampling thoracic duct lymph (TDL) represents one or more peripheral compartments of the glucose model. A bolus of [6,6-(2)H]glucose was injected in nine animals, followed by frequent sampling of blood and TDL. Linear kinetic modeling has been applied to plasma data, indicating that a three-compartment model adequately describes glucose kinetics.

Inhaled nitric oxide selectively reduces pulmonary hypertension after ovine smoke inhalation but does not improve oxygenation.

Inhaled nitric oxide (NO) is known to selectively reduce pulmonary hypertension and improve the ventilation-perfusion relationship in subjects with lung injury of various origin. However, some forms of lung injury do not react to inhaled NO at all, or show only a reduction in pulmonary arterial pressure. Very little is known about the effects of inhaled NO after smoke inhalation injury.

Unilateral smoke inhalation in sheep: effect on left lung lymph flow with right lung injury.

We previously reported that smoke inhalation to the right lung will result in damage to the air-insufflated left lung. In this study we confirm these findings and determine whether this injury is associated with an elevation in lung lymph flow and pulmonary microvascular permeability to protein as indexed by changes in reflection coefficient. Sheep (n = 12) were surgically prepared by placement of a Swan-Ganz catheter and pneumatic occluders on all pulmonary veins and the left pulmonary artery.

Burn-associated bone disease in sheep: roles of immobilization and endogenous corticosteroids.

To determine the role of immobilization in the pathogenesis of burn-associated bone disease, we selected the sheep as a model to study the effects of burn injury compared with a sham-burned control group. Seven of the sheep were subjected to controlled 40% flame burn, and seven underwent anesthesia with arterial and venous cannulation but without burn. After labeling newly formed bone with tetracycline and calcein, the sheep were killed 2 weeks after burn or sham burn, and the iliac crest and lumbar vertebrae were analyzed for histomorphometry.

The 1996 Moyer Award. Effects of endotoxin on the Th1/Th2 response in humans.

Monocyte/T-cell interactions play a critical role in the systemic response to infection. Distinct patterns of cytokines are produced by two different types of T-helper cells (Th). Th1 cells secrete interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), whereas Th2 cells produce IL-4, IL-5, IL-6, IL-10, and IL-13.

Burn resuscitation: crystalloid versus colloid versus hypertonic saline hyperoncotic colloid in sheep.

Objectives: The present study was undertaken to assess the fluid balance and hemodynamic effects during the first 8 hrs of resuscitation in animals with a large body surface area burn, using lactated Ringer's solution, 6% hetastarch, and hypertonic saline dextran.

Design: A prospective, blinded, controlled, terminal study, using anesthetized animals. The initial baseline period was followed by scald injury, and three different treatment regimens were administered from coded bags to achieve a physiologic end point.