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Biomedical subjects

J C Stothert

Publications and source records attributed to J C Stothert.

At least 19 recordsLinked to original sources

Smoke inhalation causes a delayed increase in airway blood flow to primarily uninjured lung areas.

OBJECTIVE: Single lung inhalation injury causes tissue damage to the contralateral lung. We therefore examined airway blood flow after smoke inhalation in chronic instrumented sheep to get further information about the underlying pathophysiology. DESIGN/PATIENTS: The right lung and lower trachea of 5 animals were smoke-exposed, while their left lung was air-insufflated using a split ventilation technique. Three animals, where both lungs were only air-insufflated, served as controls. Blood flow to the airway was measured using a labeled microsphere technique. All animals were studied for 24 h following smoke inhalation. Then they were sacrificed and their tissues harvested. RESULTS: The airway blood flow to the smoke-exposed lung was elevated 11-fold immediately after inhalation injury. The bronchial blood flow to the air insufflated lung became significantly elevated 24 h post-smoke, although to a lesser extent. The control animals did not show any changes of bronchial blood flow during the observation time. CONCLUSIONS: Damage to one lung can lead to pathophysiologic changes in the contralateral lung. This response appears to be mediated by hematogenous factors.

Analysis of Variance

A noninvasive method for monitoring cerebral perfusion during cardiopulmonary resuscitation.

PURPOSE: This study evaluates the use of transcranial Doppler (TCD) ultrasound in assessing the changes experienced by the cerebral circulation during cardiopulmonary resuscitation (CPR) and compares it with measurements of internal carotid artery (ICA) flow rates (ultrasonic flow-meter measurements) and cerebral blood flow (CBF) (radioactive-microsphere measurements) in a porcine cardiac arrest model undergoing closed chest CPR. METHODS: Sixteen piglets were anesthetized and subjected to TCD monitoring, ICA flow-rate measurements, and CBF measurements during CPR following induction of ventricular fibrillation. A total of 14 comparisons between TCD and CBF measurements, and 36 comparisons between TCD and ICA flow measurements were performed. Correlations were determined using Pearson's method, and the validity of the correlation was determined using Bonferoni's adjusted probabilities. RESULTS: The correlation between mean cerebral blood flow velocity and mean total ICA flow rate was 0.67 (P < .01). The correlation between peak systolic blood flow velocity and CBF was 0.76 (P = .02). CONCLUSIONS: TCD can provide on-line information about cerebral perfusion during CPR.

Animals

Effects of nitric oxide synthesis inhibition in hyperdynamic endotoxemia.

OBJECTIVE: To investigate the effects of N omega-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthesis, on hemodynamics, gas exchange and oxygen transport in an ovine model of hyperdynamic sepsis. DESIGN: Prospective, nonrandomized, controlled study, with repeated measurements. SETTING: University research laboratory. SUBJECTS: Twenty healthy adult sheep (weighing 20 to 45 kg) were divided into two groups of 12 treated sheep and eight control sheep and studied. INTERVENTIONS: Twenty awake, chronically instrumented sheep received a continuous infusion of endotoxin (10 ng/kg/min) over 48 hrs. Twenty-four hours after the start of the endotoxin infusion, 12 sheep (treatment group) received a bolus of the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester (25 mg/kg), while the other eight animals (control group) received the carrier (0.9% NaCl). MEASUREMENTS AND MAIN RESULTS: Twenty-four hours after the start of the endotoxin infusion, both groups exhibited a hyperdynamic state with increased cardiac indices, decreased systemic vascular resistance indices, impaired oxygenation, and increased pulmonary shunt fractions. In both groups, oxygen delivery was significantly increased, while oxygen consumption remained virtually unchanged, resulting in a decreased oxygen extraction ratio. In the control group, the significant alterations in systemic hemodynamics, lung function and oxygen transport persisted for the remainder of the study. Administration of N omega-nitro-L-arginine methyl ester normalized cardiac index and systemic vascular resistance index, increased mean arterial blood pressure, and decreased heart rate. Although oxygen delivery significantly decreased after administration of N omega-nitro-L-arginine methyl ester, oxygen consumption did not change, resulting in a normalization of oxygen extraction ratio. Despite a significant reduction of pulmonary shunt fraction, oxygenation did not improve. Pulmonary arterial pressure and pulmonary vascular resistance index showed a peak 2 hrs after administration of the nitric oxide synthesis inhibitor and then tended to decrease. In contrast, the effects of N omega-nitro-L-arginine methyl ester on the systemic circulation persisted for the remainder of the study. CONCLUSIONS: The data support the assumption that augmented nitric oxide production is a major cause of the hemodynamic alterations seen in hyperdynamic endotoxemia. Administration of the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester normalized the endotoxin-induced hyperdynamic state, but did not impair oxygen consumption, indicating adequate tissue perfusion of metabolically active organs. Inhibition of nitric oxide synthesis may be a therapeutic option in the treatment of hyperdynamic septic patients when conventional therapy fails to maintain a minimum of cardiovascular performance.

Animals

Does positive end-expiratory pressure significantly reduce airway blood flow?

Nutritive (systemic arterial) airway blood flow (mL/min/100 grams tissue) was studied in various size airways at four randomized levels of positive end expiratory pressure (PEEP) in smoke injured and normal lungs. Seven sheep were studied 24 hours after an isolated injury to the left lung using cotton smoke. Radioactive 15-microns microspheres were utilized to measure this airway blood flow. These data demonstrated a marked increase in systemic arterial blood flow to the airways in the injured left lung. Increasing levels of PEEP significantly reduced this hyperemic response. PEEP did not significantly affect the uninjured right lung. Systemic airway blood flow was never reduced to below normal control levels (uninjured) in either lung despite PEEP of up to 20 cm H2O. Severe reduction in airway nutritive flow, and the possibility of airway necrosis, does not appear to occur at PEEP levels of up to 20 cm H2O.

Animals

Postburn gastrointestinal vasoconstriction increases bacterial and endotoxin translocation.

Splanchnic ischemia has been associated with bacterial translocation and increased endotoxin absorption from the gut. To study the effects of major burn on splanchnic circulation, minipigs were randomized to receive 40% flame burn and Parkland resuscitation or sham burn and maintenance fluids. Total and fractionated blood flow, O2 delivery and consumption, mucosal pH of the intestine, and endotoxin levels in the superior mesenteric vein were measured for 48 h, and then abdominal organs were harvested for bacteriological culture and histopathological analysis. Total mesenteric blood flow and fractionated blood flow to the mucosa-submucosa of the jejunum, cecum, and colon decreased 2 and 4 h postburn. Although mesenteric O2 consumption was unchanged, mesenteric O2 delivery and intestinal mucosal pH were decreased during the early postburn period. Concomitantly, endotoxin levels in the superior mesenteric vein were significantly elevated during the first 8 h postburn. The bacteriological cultures of the systemic tissue samples showed increased bacterial translocation in the burn group. After major burns, there is a transient selective splanchnic vasoconstriction, which is associated with intestinal mucosal acidosis and increased incidence of bacterial translocation and endotoxin absorption from the gut.

Animals

Systemic blood flow to sheep lung: comparison of flow probes and microspheres.

Discrepancies exist between experimental measurements of the systemic blood flow to sheep lung by use of microsphere techniques and flow probes on the bronchial artery. In these studies, we simultaneously measured the blood flow through the bronchial artery, using a transit time flow probe, and the systemic blood flow to left lung, using radioactive microspheres. All measurements were made on conscious sheep previously prepared with chronic catheterizations of the left atrium, aorta, and vena cava and a flow probe around the bronchial artery. Inflatable occluder cuffs were placed around the pulmonary and bronchoesophageal arteries. Bronchial artery blood flow in six sheep was 25.3 +/- 5.2 ml/min or 0.4% of the cardiac output. Systemic blood flow to left lung, measured with microspheres, was 54.1 +/- 14.2 ml/min. Calculated systemic blood flow to that portion of sheep lung perfused by the bronchial artery was 127.6 +/- 35.3 ml/min or 1.9% of cardiac output. Occlusion of the bronchoesophageal artery reduced bronchial artery flow to near zero, whereas total systemic blood to the lung was reduced by only 55%. Blood flow to the intraparenchymal cartilaginous airways was reduced 60-90% after occlusion of the bronchoesophageal artery. Sheep, like most mammals, have multiple and complex systemic arterial inputs to the lungs. We conclude that multiple branches of the bronchoesophageal artery provide most but not all of the systemic blood flow to the intraparenchymal cartilaginous airways but that over one-half of the total systemic blood flow to sheep lung comes from sources other than the common bronchial artery.

Animals

Comparison of the pulmonary lymphatic and hemodynamic changes of near-drowning in a sheep model.

The hemodynamic and lung lymph changes following near-drowning (ND) were studied in sheep. Experimental ND was by transtracheal aspiration of 10 ml/kg body weight of either seawater (SW) or freshwater (FW). Extravascular lung water and lung lymph protein flux were significantly increased, but cardiac index was depressed in both groups following ND. Systemic and pulmonary vascular resistances were markedly elevated with FW compared to only a slight rise with SW. Lung lymph oncotic pressure decreased with SW ND from baseline of 9.7 +/- 0.4 to 6.8 +/- 0.63 mm Hg (P < 0.05). In contrast, FW ND increased lung lymph oncotic pressure from 12.8 +/- 0.9 to 16.6 +/- 1.3 mm Hg (P < 0.05). These data suggest that the changes in lung lymph and hemodynamic response to SW and FW ND differ in sheep. The changes are immediate and profound with SW, but slower in onset and less severe with FW. FW ND is associated with hemolysis, which is absent in SW ND.

Animals

Bronchial blood flow during changes in inhaled oxygen and carbon dioxide concentrations in conscious sheep.

Bronchial artery blood flow index (BFI) was measured in an unanesthetized sheep model using a chronically implanted ultrasonic flow probe. The bronchial circulation was monitored during changes of the concentrations of oxygen and carbon dioxide in inhaled air. Control BFI was 15.9 +/- 3.8 ml/min/m2 during normoxic breathing with 0% CO2 (n = 6) and 18.0 +/- 1.6 ml/min/m2 while breathing 28% O2 and 0% carbon dioxide (n = 6). Hypoxia (FIO2 = 0.10) significantly increased BFI to 25.8 +/- 4.9 ml/min/m2 with a decrease in the bronchovascular resistance index (BVRI) from a baseline of 7.85 +/- 1.73 to 4.75 +/- 0.86 mm Hg/(ml/min)/m2. Hyperoxia (FIO2 = 1.0) raised BFI to 30.5 +/- 10.1 ml/min/m2 without a significant decrease in BVRI. Changing the inhaled carbon dioxide concentration from 0 to 10% resulted in a significant increase in BFI from 18.0 +/- 1.6 to 43.6 +/- 10.3 ml/min/m2 and a decrease in BVRI from 5.56 +/- 0.44 to 4.63 +/- 2.18 mmHg/(ml/min)/m2 (not significant). The change in BFI varies directly with lymph flow for hypoxia and hypercarbia. This is consistent with changes in cardiac index, indicating probable changes in surface area being perfused in the lung. Changes in BFI with hyperoxia did not follow changes in systemic vascular resistance or cardiac index. Similarly, lymph flow elevation did not occur during hyperoxia. These data suggest that BFI changes with hyperoxia are not related to changes in total systemic vascular resistance, or cardiac index, and a different mechanism may control bronchovascular flow for this condition.

Animals

Autopsy in general surgery practice.

This study evaluates the impact of the autopsy on a general surgical training program from 1984 through 1988. We have retrospectively examined the charts of all patients who died during this period. Included in this analysis are the records of patients from the general, cardiac, pediatric, and transplant surgery departments during this 5-year period. In all, 628 patients were evaluated. The overall autopsy rate was 73%. The clinical impressions prior to death are correlated with the anatomic diagnoses found during autopsy. Significant diagnostic discrepancies (errors unrecognized and directly related to or associated with the cause of death) were determined. On a yearly basis, diagnostic discrepancies range between 23% to 39%. Gross and histologic examination of surgical patients reveals significant information concerning the cause of death. These data confirm the educational benefit of autopsy despite escalating utilization of sophisticated, noninvasive diagnostic modalities. It is our opinion that the mortality conference, with formal autopsy presentation, is a vital forum for the discussion of patient care and quality assurance issues. Autopsy remains the most specific indicator of errors in diagnosis, management, judgment, and technique in surgical practice today.

Autopsy

Lung edema formation following inhalation injury: role of the bronchial blood flow.

We investigated the contribution of the bronchial blood flow to the lung lymph flow (QL) and lung edema formation after inhalation injury in sheep (n = 18). The animals were equally divided into three groups and chronically prepared by implantation of cardiopulmonary catheters and a flow probe on the common bronchial artery. Groups 1 and 2 sheep were insufflated with 48 breaths of cotton smoke while group 3 received only room air. Just before injury, the bronchial artery of group 2 animals was occluded. The occlusion was maintained for the duration of the 24-h study period. At the end of the investigation, samples of lung were taken for determination of blood-free wet weight-to-dry weight ratio (W/D). Inhalation injury induced a sevenfold increase in QL in group 1 (7 +/- 1 to 50 +/- 9 ml/h; P less than 0.05) but only a threefold increase in group 2 (10 +/- 2 to 28 +/- 7 ml/h; P less than 0.05). The mean W/D value of group 1 animals was 23% higher than that of group 2 (5.1 +/- 0.4 vs. 3.9 +/- 0.2; P less than 0.05). Our data suggest that the bronchial circulation contributes to edema formation in the lung that is often seen after the acute lung injury with smoke inhalation.

Animals

A comparison of transcranial Doppler ultrasound (TCD) and radioactive microspheres in determining cerebral perfusion in normal and low flow states.

We have previously utilized the technique of transcranial Doppler (TCD) ultrasound to determine cerebral perfusion in patients undergoing cardiopulmonary resuscitation (CPR). In order to assess if TCD can reliably measure alterations in cerebral perfusion under conditions of normal and low cardiac outputs, we compared TCD measured blood flow velocities in the middle cerebral artery (MCA) of six piglets with radioactive microsphere determinations of total cerebral perfusion at baseline normal sinus rhythm (NSR), during CPR, and following return of spontaneous circulation (ROSC). Peak systolic and mean blood flow velocities were compared to the microsphere perfusion results on 15 different occasions; six during NSR, five during CPR, and four following ROSC. Although qualitative alterations in TCD measurements reflected changes in microsphere perfusion, we could not find a statistically significant correlation between either peak systolic or mean MCA blood flow velocities and microsphere perfusion measurements either overall or in any subgroup. The possible reasons which may explain the findings are discussed.

Animals

Is emergency department resuscitation of out-of-hospital cardiac arrest victims who arrive pulseless worthwhile?

It is still a common practice to continue unsuccessful field resuscitations in the emergency department (ED) even after prolonged estimated down times. The authors studied patients who arrested in the field and did not regain a pulse before their arrival in the ED to determine if any ever leave the hospital neurologically intact. All cardiac arrests in the urban St Louis area that were brought to our facility over a 2 1/2-year period by advanced life support units (excluding all patients with hypothermia, drug overdose, near drowning, and traumatic cardiac arrest) were reviewed. Of 243 such patients 32 (13%) arrived with a pulse. Twenty-three of these patients were admitted and 10 discharged alive, 7 were neurologically intact. Out of 211 patients who arrived without a pulse, 24 (11%) developed a pulse with further resuscitative efforts in the ED. Eighteen of these patients were admitted but only one was discharged neurologically intact. The only survivor in the group without a pulse arrested while en route to the ED. It is concluded that cardiac arrest victims who arrive in the ED without a pulse on arrival or en route have almost no chance of functional recovery.

Aged

High pressure percutaneous transtracheal ventilation: the use of large gauge intravenous-type catheters in the totally obstructed airway.

Percutaneous transtracheal ventilation using a large gauge intravenous-type catheter can be used successfully in the setting of complete upper airway obstruction in animals. In this study, using a large animal model, satisfactory oxygenation and ventilation was achieved by inversely varying the catheter size and the inspiration to expiration ratio (I:E). Specifically, 30 to 63 kg ruminants with an obstructed upper airway were resuscitated for 30 minutes from a hypoxic, hypercarbic, and acidotic state using 12- and 14-gauge catheters connected to a 50 psi oxygen source via a two-way valve with an I:E of 1:4 and 1:9 seconds, respectively. Shorter expiratory time or increased inspiratory time with these intravenous catheters resulted in significant hemodynamic compromise, barotrauma, inadequate carbon dioxide elimination, acidemia, and frequent death.

Airway Obstruction

The role of autopsy in death resulting from trauma.

This study examined the difference between clinical impressions and autopsy findings in a group of patients dying on a university surgical service after blunt injury, penetrating injury, or thermal burns. Of 215 patients dying between the years 1984 and 1988, 212 were included in this study (autopsy rate, 98.6%). Major discrepancies in clinical diagnosis versus the anatomic diagnosis at autopsy were found to occur in approximately 30% of patients. The incidence of errors in diagnosis which may have impacted on survival in these groups of injured patients was quite low (5.1%). These data support the continued practice of obtaining autopsy in all patients dying from trauma. This information is clinically relevant, and, in today's atmosphere of quality assurance, absolutely necessary for a modern trauma center.

Adult

Bronchial blood flow and eicosanoid blockade following airway acid aspiration.

The systemic circulation to the lung is thought to be an important microvascular exchange region which may contribute to pulmonary edema resulting from airway injury. In a chronic sheep model, we have evaluated the flow through the bronchial artery after airway injury caused by the aspiration of 2.5 ml/kg of 0.1 N hydrochloric acid with and without inhibition of thromboxane synthetase and cyclooxygenase. Cyclooxygenase inhibition with ibuprofen resulted in no rise in bronchial artery blood flow associated with airway acid aspiration (9.8 +/- 1.72 ml/min to 63.7 +/- 8.9 ml/min in the control group versus 11.3 +/- 2.5 ml/min to 10.3 +/- 3.4 ml/min in the ibuprofen group). No difference in bronchial artery blood flow was noted between control acid aspiration and acid aspiration with thromboxane synthetase inhibition. Significant early reduction in lung lymph flow was noted in the cyclooxygenase inhibition group compared to control. These data suggest that inhibition of the cyclooxygenase pathway of eicosanoid production may lessen the injury caused by airway acid aspiration. The decrease in airway blood flow with associated reduction in lymph flow suggests that airway blood flow may be important in the generation of pulmonary edema in this model.

Animals

Intrapulmonary distribution of bronchial blood flow after moderate smoke inhalation.

The systemic blood flow to the airways of the left lung was determined by the radioactive microsphere technique before and 17 h after smoke inhalation in six conscious sheep (smoke group) and six sheep insufflated with air alone (sham group). Smoke inhalation caused a sixfold increase in systemic blood flow to the lower trachea (baseline 10.6 +/- 1.7 vs. injury 60.9 +/- 16.1 ml.min-1.100 g-1) and an 11- to 14-fold increase to the intrapulmonary central airways (baseline range 9.5 +/- 1.9 to 13.5 +/- 3.7 ml.min-1.100 g-1 vs. injury 104.6 +/- 32.2 to 187.3 +/- 83.6 ml.min-1.100 g-1). There was a trend for this hyperemic response to be greater as airway diameter decreased from the trachea to 2-mm-diam central airways. In airways smaller than 2 mm, the hyperemic response appeared to diminish. The total systemic blood flow to whole lung is predominantly to small peripheral airways and showed no significant increase from its baseline level of 17.5 +/- 3.7 ml.min-1.100 g-1 in the lung homogenate. Occlusion of the bronchoesophageal artery decreased central airway blood flow 60-80% and peripheral airway blood flow 40-60% in both the sham and the smoke groups.

Animals

Airway aspiration of hydrochloric acid in sheep.

We have compared the effects of aspiration of 2.5 ml/kg of 0.1 N hydrochloric acid (HCl) on groups undergoing normal saline aspiration (2.5 ml/kg) and a sham control in unanesthetized sheep with chronic lung lymph fistula for up to 148 hr. Significant changes in pulmonary lymph flow and cardiopulmonary variables occurred in the airway acid group within the first 48 hr, as compared to saline and sham control. In the HCl group lymph flow increased from a baseline of 8.5 +/- 1.5 to 21.8 +/- 3.0 ml/hr (mean +/- SEM) at 2 hr. Pulmonary vasoconstriction occurred at this time with significant elevations of lymph thromboxane B2 from a baseline of 400 +/- 11 to 2,090 +/- 690 pg/ml. During the early acid aspiration phase products of lipid peroxidation were noted to increase from 0.29 +/- 0.03 to 0.81 +/- 0.17 absorbance units. Associated with elevated lymph flow was a significant drop in cardiac index in the airway-acid-aspirated group (6.59 +/- 0.52 to 5.53 +/- 0.36 L/min/m2) and a rise in bronchial blood flow from 9.8 +/- 1.7 to 63.7 +/- 8.9 ml/min. These data suggest that a moderate airway acid injury created by 2.5 ml/kg of HCl results in acute pulmonary damage with the release of several potential mediators which may be responsible for the observed effects. The long-term acid-injured animals survived for up to 1 week following the aspiration procedure with evidence of resolution of lung damage by wet-weight dry-weight evaluation of lung (normal lab control = 4.0 +/- 0.2, and 148 hr after acid = 4.5 +/- 0.3) and microscopic evidence of minimal persistent injury. These data document the pulmonary damage and repair resulting from airway acid instillation.

Animals