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Biomedical subjects

P H Breen

Publications and source records attributed to P H Breen.

34 records · Page 2Linked to original sources
PubMed1995

Combined carbon monoxide and cyanide poisoning: a place for treatment.

During fires, victims can inhale significant carbon monoxide (CO) and cyanide (CN) gases, which may cause synergistic toxicity in humans. Oxygen therapy is the specific treatment for CO poisoning, but the treatment of CN toxicity is controversial. To examine the indication for treatment of CN toxicity, we have established a canine model to delineate the natural history of combined CO and CN poisoning. In seven dogs (24 +/- 3 kg), CO gas (201 +/- 43 mL) was administered by closed-circuit inhalation. Then, potassium CN was intravenously (i.v.) infused (0.072 mg.kg-1.min-1) for 17.5 +/- 3.0 min. Cardiorespiratory measurements were conducted before and after these toxic challenges. Despite significant CO poisoning (peak carboxyhemoglobin fractions [COHb] = 46% of total hemoglobin [Hb]; elimination t1/2 = 114 +/- 42 min) with attendant decrease in blood O2 content, CO had essentially little effect on any hemodynamic or metabolic variable. On the other hand, CN severely depressed most hemodynamic and metabolic functions. Compared to baseline values, CN caused significant (P < 0.01) decreases in cardiac output (6.4 +/- 2.0 to 3.1 +/- 0.5 L/min) and heart rate (169 +/- 44 to 115 +/- 29 bpm) and decreases in oxygen consumption (VO2) (133 +/- 19 to 69 +/- 21 mL/min) and carbon dioxide production (VCO2) (128 +/- 27 to 103 +/- 22 mL/min). However, these critical hemodynamic and metabolic variables recovered to baseline values by 15 min after stopping the CN infusion, except lactic acidosis which persisted for at least 25 min after the CN infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Exhaled flow monitoring can detect bronchial flap-valve obstruction in a mechanical lung model.

Flap-valve obstruction to expiratory flow (V) in a major bronchus can result from inspissated secretions, blood, or foreign body. During inhalation, increasing airway caliber preserves inspired V past the obstruction; during exhalation, decreasing airway diameter causes airflow obstruction and even frank gas trapping. We reasoned that the resultant sequential, biphasic exhalation of the lungs would be best detected by measuring exhaled V versus time. Accordingly, we designed an airway obstruction element in a mechanical lung model to examine flap-valve bronchial obstruction. A mechanical lung simulator was ventilated with a pressure-limited flow generator, where f = 10/min, tidal volume = 850 mL, and respiratory compliance = 40 mL/cm H2O. Airway V (pneumotachometer) and pressure (P) were digitally sampled for 1 min. Then, the circumference of the diaphragm in a respiratory one-way valve was trimmed to generate unidirectional resistance to expiratory V. Measurement sequences were repeated after this flap-valve was interposed in the right "main-stem bronchus." Integration of airway V versus time generated changes in lung volume. During flap-valve obstruction of the right bronchus, the V-time plot revealed preservation of peak expired flow from the normal lung, followed by retarded and decreased flow from the obstructed right lung. Gas trapping of the obstructed lung occurred during conditions of decreased expiratory time and increased expiratory resistance. Airway P could not differentiate between bronchial and tracheal flap-valve obstruction because P decreased abruptly in both conditions. The flow-volume loop displayed less distinctive changes than the flow-time plot, in part because the flow-volume loop was data (flow) plotted against its time integral (volume), with loss of temporal data. In this mechanical lung model, we conclude that bronchial flap-valve obstruction was best detected by the flow-time plot, which could measure the sequential emptying of the lungs.

Airway Obstruction↗
PubMed1995

Right atrial bypass model in the dog.

In gas exchange studies addressing the storage and transport of CO2 in dogs, a model in which cardiac output (QT) can be precisely controlled and measured would be beneficial. We identified problems with described extracorporeal circuits and implemented right atrial bypass (RAB) in dogs. In 6 anesthetized (chloralose and urethane), heparinized dogs (mean +/- SD, 24 +/- 4 kg) with open thorax, cannulas were inserted in both vena cavas to drain venous blood return to a reservoir (anaerobic bag or bubble oxygenator). A roller pump then drove blood through a heat exchanger back to the right atrial appendage. After 1.8 +/- 1.4 hour of RAB, physiologic variables remained within reference limits for dogs (QT, 1.5 +/- 0.3 L/min; blood pressure, 92 +/- 25 mm of Hg; arterial PCO2, 35 +/- 4 mm of Hg; PO2, 513 +/- 39 mm of Hg; pH, 7.39 +/- 0.08; and tissue CO2 production, 126 +/- 56 ml/min). To permit study of gas exchange, venous return (and thus, QT) and venous PCO2 and PO2 could be accurately regulated and measured over a wide range. Maintenance of native pulsatile lung perfusion and cardiogenic oscillations minimizes mismatching of pulmonary ventilation and perfusion and facilitates studies addressing pulmonary gas exchange. This RAB model is designed so that investigators can establish the preparation in a few hours.

Animals↗
PubMed1994

Capnometer transport delay: measurement and clinical implications.

The sidestream capnogram is delayed behind real time by transport delay (TD; time to aspirate gas through the sampling tubing) and by the dynamic response (DR) of the measurement cuvette. In six capnometers, we measured TD and DR by plunging the end of the sample tubing into a flask containing CO2 and then digitally analyzing the capnogram. TD ranged from 0.6 to 5.0 s and accounted for 89% or more of the total response time (TD + DR) of the capnometer. TD was generally not reported in the manufacturers' specifications. TD was further prolonged by low aspiration rates or by sampling tube extensions. During a series of quick breaths after endotracheal intubation, long TD can delay the appearance of CO2 and result in a false diagnosis of esophageal intubation. Also, long TD can prolong DR, which can result in underestimation of end-tidal PCO2 during rapid ventilation in pediatric anesthesia.

Blood Gas Monitoring, Transcutaneous↗
PubMed1992

Simple computer measurement of pulmonary VCO2 per breath.

Measurements of the volume of CO2 exhaled per breath (VCO2/br) are preferable to end-tidal PCO2, when the exhaled flow and CO2 waveforms may be changing during unsteady states, such as during alterations in positive end-expiratory pressure or alterations in cardiac output. We describe computer algorithms that determine VCO2/br from digital measurements of exhaled flow (including discontinuous signals common in anesthesia circuits) and CO2 concentration at the airway opening. Fractional concentration of CO2 is normally corrected for dynamic response and transport delay (TD), measured in a separate procedure. Instead, we determine an on-line adjusted TD during baseline ventilation. In six anesthetized dogs, we compared the determination of VCO2/br with a value measured in a simultaneous collection of expired gas. Over a wide range of tidal volume (180-700 ml), respiratory rate (3-30 min-1), and positive end-expiratory pressure (0-14 cmH2O), VCO2/br was more accurate with use of the adjusted TD than the measured TD (P less than 0.05).

Algorithms↗
PubMed1991

Can changes in end-tidal PCO2 measure changes in cardiac output?

In recent studies of cardiopulmonary resuscitation, an increase in end-tidal carbon dioxide tension (PETCO2) signifies an increase in cardiac output (QT) as spontaneous circulation resumes. We hypothesized that changes in QT might generally be measured by changes in PETCO2. In five pentobarbital-anesthetized dogs, we inflated percutaneously inserted vena cava balloons to impede venous return and to decrease QT (measured by pulmonary thermodulation). The PECTCO2 was measured at the airway opening by sidestream infrared capnometry. In 32 vena cava balloon inflation sequences during constant ventilation in five dogs, the percent decrease in PETCO2 directly correlated with the percent decrease in QT (slope = 0.73, R2 = 0.89, P less than 0.001). During decreased QT, reduced CO2 delivery to the lungs decreased alveolar PCO2 to cause part of the decrease in PETCO2. The remaining reduction in PETCO2 resulted from the increase in alveolar dead space (in turn due to lower pulmonary perfusion pressures during reduced QT), which diluted the CO2 from perfused alveolar spaces to further reduce PETCO2. During a sustained reduction in QT, increasing CO2 accumulation in the peripheral tissues and in venous blood began to restore CO2 delivery to the lung and PETCO2 toward baseline levels. Reciprocal changes occurred during increases in QT when the vena cava balloons were deflated. The linear relationship between changes in PETCO2 and QT in animals supports a decision to perform clinical studies necessary to determine whether a change in PETCO2 will be useful as a noninvasive, continuous monitor of a change in QT during anesthesia or intensive care.

Animals↗
PubMed1988

Treatment of canine aspiration pneumonitis: fluid volume reduction vs. fluid volume expansion.

The aspiration of gastric acid causes pulmonary edema and hypoxemia. One approach to the management of this syndrome is to raise cardiac output (Qt) and O2 delivery (QO2) to ensure tissue oxygenation (VO2) at the risk of increasing the edema. Another approach reduces the edema by reducing pulmonary microvascular pressure (Pmv) at the risk of reducing QO2 and VO2. We compared these approaches in 24 anesthetized, ventilated dogs with pulmonary wedge pressure (Ppw), a clinical approximation of Pmv, of 12.5 mmHg. Before and again 1 h after endobronchial instillation of 0.1 N HCl, we measured Qt, QO2, VO2, venous admixture, and in vivo extravascular lung liquid. The dogs were then randomly divided into four equal groups: 1) 12.5 mmHg Ppw, high Qt; 2) 7.5 mmHg Ppw, intermediate Qt; 3) 4.5 mmHg Ppw, low Qt; and 4) 4.5 mmHg Ppw plus dopamine, intermediate Qt. Measured values were followed for 4 more h, after which the lungs were excised to compare wet weight-to-body weight ratios (W/B). When plasmapheresis reduced Ppw at 1 h, edema did not increase further and W/B of groups 2 (21 +/- 3), 3 (18 +/- 3), and 4 (22 +/- 3) were significantly less than in group 1 (27 +/- 3) (P less than 0.001). Although Qt decreased with Ppw, increased hematocrit and reduced venous admixture maintained QO2 in group 2 but not in group 3. In group 4 an intermediate Qt maintained QO2 even at 4.5 mmHg Ppw but edema increased to the group 2 level presumably because Pmv rose with Qt on dopamine. VO2 remained constant over time in each group. These data demonstrate that canine HCl-induced pulmonary edema, measured in vivo or gravimetrically, is very sensitive to reductions in Pmv. Moreover, the lowest Pmv (and QO2) was well tolerated because an O2 supply dependency of VO2 was not observed.

Animals↗
PubMed1987

The effects of indomethacin on edema and gas exchange in canine acid aspiration.

Previous studies have suggested that prostaglandin synthesis inhibition might alter lung water accumulation in low pressure pulmonary edema. Therefore we studied the effects of indomethacin administration on edema formation, hemodynamics, and gas exchange in canine acid aspiration. Fourteen pentobarbital anesthetized dogs received 1 ml/kg of 0.1 N HCl intratracheally and then 7 received indomethacin (5 mg/kg) and 7 served as time controls. Lung liquid was measured in vivo by a double indicator technique and at the end of the experiment by gravimetric determinations. Following HCl administration, venous admixture (Qva/Qt) increased in both groups. Over the succeeding 4 h Qva/Qt decreased after indomethacin administration by 4.1 +/- 14.2%, but increased in the control group by 10.9 +/- 11.5% (P less than 0.05). Cardiac index remained constant in the control group but decreased after indomethacin from 232 +/- 89 ml X kg-1 X min-1 to 167 +/- 75 ml X kg-1 X min-1. Lung liquid accumulation, however, was similar between both groups. We believe that the changes in Qva/Qt associated with indomethacin can be explained by the known observations that decreases in cardiac output are associated with decreases in intrapulmonary shunt.

Analysis of Variance↗
PubMed1987

Canine bronchoconstriction, gas trapping, and hypoxia with methacholine.

The effects of an intravenous methacholine infusion on cardiovascular-pulmonary function were measured in seven mongrel dogs (22.0 +/- 2.8 kg), anesthetized with chloralose and urethan and beta-adrenergically blocked with propranolol. In a volume-displacement plethysmograph, physiological measurements were made at base line and 25 min after establishing a methacholine infusion (0.1-1.0 mg X kg-1 X h-1). Methacholine significantly (P less than 0.05) increased airways resistance (1.9 +/- 0.8 to 8.2 +/- 2.9 cmH2O X l-1 X s), decreased static lung compliance (84.7 +/- 18.5 to 48.2 +/- 9.4 ml/cmH2O), depressed arterial PO2 (81 +/- 17 to 56 +/- 10 Torr), and lowered blood pressure (132 +/- 10 to 69 +/- 18 Torr) and cardiac output (5.7 +/- 1.9 to 4.1 +/- 1.2 l/min). These effects persisted during a further 80 min of methacholine infusion conducted in five of the animals. During the initial 25-min period of methacholine, the end-expired volume (volume-displacement Krogh spirometer) rose in all animals, indicating an increase in functional residual capacity from 997 +/- 115 to 1,623 +/- 259 ml (P less than 0.0005). Analysis of pulmonary pressure-volume curves revealed no change in total lung capacity but an increase in residual volume from 489 +/- 168 to 1,106 +/- 216 ml (P less than 0.001). Thus methacholine caused 617 ml of gas trapping, which was not detected by the Boyle's law principle, presumably because gas was trapped at high transpulmonary pressure. We suggest that intravenous methacholine-induced canine bronchoconstriction, which causes gas trapping and hypoxia, may be a useful animal model of clinical status asthmaticus.

Animals↗
PubMed1986

Artificial ventilation of a canine model of bronchopleural fistula.

The authors studied the abnormalities of gas exchange and lung mechanics in a canine model of bronchopleural fistula during intermittent positive pressure ventilation (IPPV) and high-frequency oscillatory ventilation (HFOV). The left lower lobe bronchus was opened to atmosphere and it was determined that end expired volume was best maintained at frequencies of 45-50 breaths/min. during IPPV. Comparing alternating periods of IPPV and HFOV in six dogs (Group I) at matched airway opening pressure (Pao), we found that Pao2 decreased significantly to 68 +/- 14 mmHg and 69 +/- 24 mmHg, respectively, on opening the fistula. In a second group of six dogs (Group 2), when Pao was increased by additional bias flow into the ventilatory circuit during both IPPV and HFOV, Pao2 increased significantly to 89 +/- 12 mmHg and 87 +/- 8 mmHg, respectively. Repeating Group 2 studies after induction of oleic acid low-pressure pulmonary edema demonstrated that conventional IPPV was associated with large intrapulmonary shunts. HFOV, however, maintained gas exchange at near baseline values. For both Group 1 and Group 2, the calculated gas flow through the fistula was significantly less at all levels of airway pressure during HFOV. The authors conclude that HFOV offers advantages over conventional IPPV in the maintenance of oxygenation and in the reduction of gas leak through the fistula.

Animals↗
PubMed1986

Constant flow ventilation in anesthetized patients: efficacy and safety.

Constant flow ventilation (CFV) maintains normal gas exchange in apneic dogs and has potential clinical application during thoracic surgery or pulmonary edema. We compared CFV and intermittent positive pressure ventilation (IPPV) in five healthy, anesthetized, (fentanyl, diazepam, and nitrous oxide) and paralyzed patients undergoing nonthoracic operations. Constant flow ventilation was delivered at a total flow of 0.9-1.6 L . kg-1 . min-1 (nitrous oxide-oxygen at 1:1) into two tubes of 2.5-3.5 mm inner diameter attached to each side of an 8-9 mm inner diameter orotracheal tube (OTT). Under bronchoscopic guidance, the CFV-OTT was advanced to position each ventilating tube at a mainstem bronchial orifice. Gas exhausted through the OTT lumen. If intrathoracic pressure exceeded a preset limit, a solenoid valve automatically interrupted gas flow to the patient to prevent barotrauma. Compared to IPPV, during CFV for up to 30 min average PaCO2 increased to 69.2 +/- 14.5 from 35.9 +/- 2.9 mm Hg, reflecting a calculated alveolar ventilation (VA) of 46 +/- 22% of the eucapnic level. We suggest that a technique combining CFV at lower flow rates with IPPV may prove clinically useful by allowing decreased tidal volume and inspiratory pressure while maintaining normal VA.

Adult↗
PubMed1985

Increased cardiac output increases shunt: role of pulmonary edema and perfusion.

In low-pressure pulmonary edema increased cardiac output (QT) increases shunt (Qs/QT); we tested whether the mechanism is an increase in extravascular lung water in turn mediated by the accompanying increase in microvascular pressure. In six pentobarbital sodium-anesthetized dogs ventilated with O2 we administered oleic acid into the right atrium. From base line to 2 h post-oleic acid we measured concurrent significant increases in Qs/QT (6-29%, O2 technique) and extravascular thermal volume (ETV, 2.6-7.1 ml/g dry intravascular blood-free lung wt, thermal-green dye indicator technique) that were stable by 90 min. Then, bilateral femoral arteriovenous fistulas were opened and closed in 30-min periods to cause reversible increases in QT and associated Qs/QT. When fistulas were open the time-averaged QT increased from 5.1 to 6.9 min (P less than 0.05), the simultaneous Qs/QT rose from 30.7 to 38.4% (P less than 0.05), but ETV did not increase. We conclude that increasing lung edema does not account for our rise in Qs/QT when QT increased.

Animals↗
PubMed1984

High-frequency ventilation in lung edema: effects on gas exchange and perfusion.

In six open-chest dogs, unilobar pulmonary edema was induced by injection of oleic acid into a lower lobe pulmonary arterial branch. Two hours later, intermittent positive-pressure ventilation (IPPV) and high-frequency oscillatory ventilation (HFOV) at matched mean alveolar pressures (MAP) were compared at 30-min intervals. The edematous lobar venous admixture (Qva/QT) increased by 0.14 (P less than 0.1) and its relative perfusion (QL/QT) decreased by 0.03. (P less than 0.1) during HFOV compared with IPPV. In another six dogs the MAP was increased by 1.5 cmH2O during HFOV; now the edematous lobar Qva/QT decreased by 0.15 (P less than 0.03) and QL/QT increased by 0.03 (P less than 0.03) during HFOV compared with IPPV. Greater MAP during HFOV also improved the edematous lobar ventilation (lobar venous PCO2) during HFOV compared with IPPV. Conceivably, the increase in MAP inflated collapsed, flooded regions, and thereby increased their O2 transfer, perfusion, and ventilation. Whole-lung Qva/QT was similar during IPPV and HFOV in both groups because of the opposing effects of lobar Qva/QT and QL/QT. We conclude that HFOV supports cardiovascular-respiratory function in open-chest unilobar pulmonary edema compared with IPPV at similar MAP; gas exchange and perfusion of edematous units may be sensitive to small changes in MAP, and we detected no intrinsic effects of HFOV on these variables. We speculate that similar beneficial effects in diffuse pulmonary edema may be effected by small variations in MAP during HFOV without the barotrauma side effects sometimes observed when MAP is increased during IPPV.

Animals↗
PubMed1982

How does increased cardiac output increase shunt in pulmonary edema?

In pulmonary edema, the relationship between cardiac output (QT) and shunt (QS/QT) may be due to a diffusion barrier for O2 transfer (incomplete alveolar-capillary equilibration) or to redistribution of increased pulmonary blood flow toward edematous units. We compared transfer of O2 and multiple inert gases in the left (LLL) and right (RLL) lower lobes and in the whole lungs of eight dogs having oleic acid edema in LLL. When mean QT was increased from 3.0 to 5.5 l X min-1 during O2 ventilation, relative perfusion of LLL did not increase but QS/QT increased because LLL shunt increased from 56 to 78%. We conclude that increased pulmonary blood flow is not redistributed toward edematous regions, but we cannot exclude such redistribution within LLL and other slightly edematous lobes. In LLL, inert gas shunt and O2 shunt were not systematically different during O2 ventilation, and lobar venous PO2 measured during air ventilation was not different from that predicted by inert gas transfer. We conclude that diffusion limitation for O2 does not contribute to QS/QT or to the increase in QS/QT when QT increases. Conceivably, increased QT increased QS/QT by increasing edema or hematocrit in edematous regions.

Animals↗
PubMedDate not supplied

Bymixer provides on-line calibration of measurement of CO2 volume exhaled per breath.

The measurement of CO2 volume exhaled per breath (VCO2.br) can be determined during anesthesia by the multiplication and integration of tidal flow (V) and PCO2. During side-stream capnometry, PCO2 must be advanced in time by transport delay (TD), the time to suction gas through the sampling tube. During ventilation, TD can vary due to sample line connection internal volume or flow rate changes. To determine correct TD and measure accurate VCO2.br during actual ventilation. TD can be iteratively adjusted (TDADJ) until VCO2-br/tidal volume equals PCO2 measured in a mixed expired gas collection (PECO2) (J Appl. Physiol. 72:2029-2035, 1992). However. PECO2 is difficult to measure during anesthesia because CO2 is absorbed in the circle circuit. Accordingly, we implemented a bypass flow-mixing chamber device (bymixer) that was interposed in the expiration limb of the circle circuit and accurately measured PECO2 over a wide range of conditions of ventilation of a test lung-metabolic chamber (regression slope = 1.01: R2 = 0.99). The bymixer response (time constant) varied from 18.1 +/- 0.03 sec (12.5 l/min ventilation) to 66.7 +/- 0.9 sec (2.5 l/min). Bymixer PECO2 was used to correctly determine TDADJ (without interrupting respiration) to enable accurate measurement of VCO2.br over widely changing expiratory flow patterns.

Breath Tests↗