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Biomedical subjects

J A Orr

Publications and source records attributed to J A Orr.

At least 19 recordsLinked to original sources
PubMed2002

Role of serotonin in thromboxane A2-induced coronary chemoreflex.

We reported previously that the thromboxane A(2) (TxA(2)) mimetic U-46619 stimulates cardiac vagal afferent nerves, eliciting a reflex decrease in heart rate (HR) and arterial blood pressure (ABP). The present experiments were designed to test the hypothesis that TxA(2) evokes these changes via the release of serotonin [5-hydroxytryptamine (5-HT)] and activation of the 5-HT(3) receptor. Injections of the 5-HT(3) antagonist tropisetron (1 mg of 3-tropanyl-indole-3-carboxylate or ICS-205-930) attenuated the decreases in HR and ABP induced by left atrial injections of U-46619 (20 microg). Tropisetron administration also eliminated the U-46619-induced increase in impulse frequency in a majority of cardiac, vagal afferent units tested. Measurement of serum 5-HT levels revealed an elevation in serum 5-HT levels after U-46619 injection in those rabbits that displayed a significant HR change following injection of U-46619. These results indicate that although other factors may also contribute to these reflex responses, the release of 5-HT and stimulation of the 5-HT(3) receptor plays a significant role in coronary reflexes induced by TxA(2).

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

Effects of intrathecal morphine on the ventilatory response to hypoxia.

BACKGROUND: Intrathecal administration of morphine produces intense analgesia, but it depresses respiration, an effect that can be life-threatening. Whether intrathecal morphine affects the ventilatory response to hypoxia, however, is not known. METHODS: We randomly assigned 30 men to receive one of three study treatments in a double-blind fashion: intravenous morphine (0.14 mg per kilogram of body weight) with intrathecal placebo; intrathecal morphine (0.3 mg) with intravenous placebo; or intravenous and intrathecal placebo. The selected doses of intravenous and intrathecal morphine produce similar degrees of analgesia. The ventilatory response to hypercapnia, the subsequent response to acute hypoxia during hypercapnic breathing (targeted end-tidal partial pressures of expired oxygen and carbon dioxide, 45 mm Hg), and the plasma levels of morphine and morphine metabolites were measured at base line (before drug administration) and 1, 2, 4, 6, 8, 10, and 12 hours after drug administration. RESULTS: At base line, the mean (+/-SD) values for the ventilatory response to hypoxia (calculated as the difference between the minute ventilation during the second full minute of hypoxia and the fifth minute of hypercapnic ventilation) were similar in the three groups: 38.3+/-23.2 liters per minute in the placebo group, 33.5+/-16.4 liters per minute in the intravenous-morphine group, and 30.2+/-11.6 liters per minute in the intrathecal-morphine group (P=0.61). The overall ventilatory response to hypoxia (the area under the curve) was significantly lower after either intravenous morphine (20.2+/-10.8 liters per minute) or intrathecal morphine (14.5+/-6.4 liters per minute) than after placebo (36.8+/-19.2 liters per minute) (P=O.003). Twelve hours after treatment, the ventilatory response to hypoxia in the intrathecal-morphine group (19.9+/-8.9 liters per minute), but not in the intravenous-morphine group (30+/-15.8 liters per minute), remained significantly depressed as compared with the response in the placebo group (40.9+/-19.0 liters per minute) (P= 0.02 for intrathecal morphine vs. placebo). Plasma concentrations of morphine and morphine metabolites either were not detectable after intrathecal morphine or were much lower after intrathecal morphine than after intravenous morphine. CONCLUSIONS: Depression of the ventilatory response to hypoxia after the administration of intrathecal morphine is similar in magnitude to, but longer-lasting than, that after the administration of an equianalgesic dose of intravenous morphine.

Adolescent↗
PubMed2000

Partial CO2 rebreathing indirect Fick technique for non-invasive measurement of cardiac output.

OBJECTIVE: Evaluation in animals of a non-invasive and continuous cardiac output monitoring system based on partial carbon-dioxide (CO2) rebreathing indirect Fick technique. METHODS: We have developed a non-invasive cardiac output (NICO) monitoring system, based on the partial rebreathing method. The partial rebreathing technique employs a differential form of the Fick equation for calculating cardiac output (QT) using non-invasive measurements. Changes in CO2 elimination (deltaVCO2) and partial pressure of end-tidal CO2 (deltaPETCO2) in response to a brief period of partial rebreathing are used to measure pulmonary capillary blood flow (Q(PCBF)). A non-invasive estimate of anatomic and intrapulmonary shunt fraction (Q(S)/Q(T)), based on oxygen saturation from pulse oximetry (SpO2) and inspired oxygen concentration (FIO2), is added to compute total cardiac output [Q(T) = Q(PCBF)/(1 - Q(S)/Q(T))]. The performance of the NICO was compared with iced 5% dextrose bolus thermodilution cardiac output (TDco) measurements in 6 dogs. Cardiac output was varied using dobutamine, and halothane, and by clamping of the inferior vena cava. Two hundred and forty-six (n = 246) paired measurements of TDco and NICO over a range of cardiac outputs (TDco range = 0.60-8.87 l/min) were compared using Bland-Altman analysis and weighted correlation coefficient. RESULTS: The Bland-Altman technique yielded a NICO precision of +/- 0.70 l/min (13.8%) with a mean bias of -0.07 l/min (-1.4%) compared to TDco. The weighted correlation coefficient between TDco and NICO values was: r = 0.93 (n = 246). CONCLUSION: The partial CO2 rebreathing technique for measurement of cardiac output is non-invasive, automated, and based on the well accepted Fick principle. The limits of agreement between NICO and TDco is within the recommended value for NICO to be a clinically acceptable method for cardiac output measurement. The results of this canine study show that NICO performed as well, and in some cases better, than other currently available non-invasive cardiac output techniques over a wide range of cardiac outputs.

Administration, Inhalation↗
PubMed1998

Evaluation in volunteers of the VIA V-ABG automated bedside blood gas, chemistry, and hematocrit monitor.

OBJECTIVE: To evaluate the VIA V-ABG (VIA Medical Corp.) point-of-care blood gas and chemistry monitor in healthy human volunteers, with particular emphasis on the measurement of blood gases. METHODS: Experimental conditions were varied by intermittently subjecting volunteers to either isocapnic hypercapnia (end-tidal (ET), PETCO2 = 50+/-2 mmHg, ETPO2 = 130+/-5 mmHg) or isocapnic hypoxia (PETCO2 = 42+/-2, PETO2 + 45+/-2 mmHg) in addition to room air breathing. Measurements by the VIA V-ABG device were compared with paired samples and measurements performed by two ABL Radiometers (505 and 500). Analysis of results includes bias and precision plots and comparison of results with minimal performance criteria as established by CLIA. RESULTS: Nineteen volunteers yielded 222 matched samples. The range of values were 7.32-7.61 for pH, 20.9-51.6 mmHg for PCO2, 27.9-184.5 mmHg for PO2, 134-141 mmol/l for Na, 3.1-4.1 mmol/l for K, and 30.0-50.4% for hematocrit. Bias and precision (+/-2 sd) for pH was 0.01 and 0.04, for PCO2 was 0.4 and 4.8, for PO2 was 1.0 and 17.0, for Na was -0.3 and 5.2, for K was 0.1 and 0.2, and for Hct was 2.0 and 5.4. CONCLUSIONS: Over the range of blood gas values assessed, blood gas measurements by the VIA V-ABG device were clinically acceptable and met minimal performance criteria utilizing current Medicare CLIA proficiency standards. Performance criteria were also met by the VIA V-ABG device for Na, K, and Hct measurements but the range of values was too narrow to allow characterization of clinical acceptability. The VIA V-ABG device appears to perform well compared with the results which have been published for other point-of-care devices. Comparison between different studies investigating point-of-care devices is difficult due to several factors (range of values measured, comparison device, population studied, etc.). Some of these instruments, including the VIA V-ABG device, may serve quite well as point-of-care devices to perform certain tests at the bedside. Whether or not any of these devices can substitute for traditional laboratory blood gas and chemistry measurements remains an issue that is not adequately studied.

Adult↗
PubMed1997

Stimulation of group III and IV afferent nerves from the hindlimb by thromboxane A2.

These experiments were designed to test the hypothesis that the TxA2 mimetic, U46,619, would stimulate group III and IV afferent nerve endings from the hindlimb of the anesthetized cat. Nerve impulses were recorded from the dorsal rootlets of the L7-S1 segments of the spinal cord, and afferent units identified by measurement of conduction velocities, mechanical probing of hindlimb muscles, and local injection of chemical stimulants (capsaicin and bradykinin). Five of the 15 group III fibers were stimulated by U46,619 (2-10 micrograms injected into the abdominal aorta; mean baseline impulse frequency increasing from 7.3 (+/- 3.2) impulses/s to 16.0 (+/- 3.1)), while 7 of the 12 group IV fibers responded to U46,619 (impulse frequency increasing from 4.3 (+/- 3.2) to 8.8 (+/- 3.6)). The average latency for the response (20-30 s) did not differ between the two groups of afferent fibers. We conclude that group III and IV afferent fibers originating from the skeletal muscle of the hindlimb are stimulated by TxA2 and that the release of TxA2 in skeletal muscle could evoke cardiorespiratory reflexes known to be activated by stimulation of these afferent nerves.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

A preliminary laboratory investigation of air embolus detection and grading using an artificial neural network.

SUMMARY STATEMENT: Processed digitized Doppler signals abstracted from recordings during continuous air infusion in dogs were used to train a neural network to estimate air embolism infusion rates. BACKGROUND: Precordial Doppler is a sensitive technique for detecting venous air embolism during anesthesia, but it requires constant attentive listening. Since neural networks are particularly well suited to the task of pattern recognition, we sought to investigate this technology for detection and grading of air embolism. METHODS: Air was infused into peripheral veins of four anesthetized dogs at rates of 0.025, 0.05, 0.10, 0.25, 0.50 and 1.0 ml-1.kg-1.min-1 while digital recordings of the precordial Doppler ultrasound signal were collected. The frequency content of the recordings was determined by Fourier analysis. The output of the Fourier transform was the input to a neural network. The network was then trained to estimate the air infusion rate. RESULTS: The correlation coefficient between the size of the air embolism and the air infusion rate was greater than r2 = 0.93 for each of the four animals in the study when the network was trained using the data for all four dogs. When the data from a dog was withheld from the training set and used only for testing the correlation coefficients ranged from r2 = 0.75 to r2 = 0.27. For frequencies below 250 Hz, the acoustic energy tended to fall as the air infusion rate increased. The opposite occurred at frequencies above 325 Hz. CONCLUSIONS: Neural network processing of the precordial Doppler signal provides a quantitative estimate of the size of an air embolism.

Anesthesia↗
PubMed1997

TxA2-induced pulmonary artery contraction requires extracellular calcium.

In order to examine the role of extracellular calcium in the pulmonary arterial vasoconstriction that is elicited by thromboxane A2 (TxA2), rabbits were sacrificed and the main trunk of the pulmonary artery removed. Contractile responses of the isolated vessel to the TxA2 mimetic, U46 619, were measured in a temperature controlled (37 degrees C) organ bath. Compared with control responses, U46 619 microM) contractions were nearly eliminated when 1 mM EGTA was added to the buffer. In the presence of normal extracellular calcium concentrations, antagonists of voltage sensitive calcium channels (e.g. verapamil and nifedipine) attenuated the U46 619-induced contractions. These voltage sensitive calcium channel blockers were more effective in eliminating contractile responses to high KCl concentrations (6) or 120 mM KCl). The inability of these calcium channel antagonists to completely eliminate U46 619 responses was confirmed in the anesthetized rabbit where both nifedipine and verapamil failed to block the increase in pulmonary arterial blood pressure resulting from intravenous U46 619 infusion. These results indicate that extracellular calcium is essential for U46 619-induced pulmonary vascular contraction, and that mechanisms in addition to voltage operated calcium channels participate in the movement of extracellular calcium through the plasma membrane.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Clinical analysis of the flexor hallucis brevis as an alternative site for monitoring neuromuscular block from mivacurium.

STUDY OBJECTIVES: To compare the flexor hallucis brevis, which is responsible for flexion of the great toe, to the adductor pollicis as a site for monitoring the onset and recovery from neuromuscular block after an intubating dose of mivacurium chloride. DESIGN: Prospective patient-controlled study. SETTING: University teaching hospital. PATIENTS: 10 ASA physical status I and II adults (age 18 to 55 years, 6 women, 4 men) scheduled for elective procedures requiring muscle relaxation for tracheal intubation. MEASUREMENTS AND MAIN RESULTS: Patients were monitored at the adductor pollicis and the flexor hallucis brevis during the onset and recovery of neuromuscular block, which was administered to facilitate tracheal intubation. All subjects were given mivacurium 0.2 mg/kg over 30 seconds. Their train-of-four (TOF) response was continually monitored at both sites until the patient recovered from the intubating dose to a TOF ratio of 0.75. The time to onset of neuromuscular block, recovery of the first TOF response, and recovery to a TOF ratio of 0.75 were compared between the two monitoring sites using the Wilcoxon signed rank test. Following administration of the intubating dose of mivacurium, the loss of all twitch response occurred 1.2 minutes sooner at the adductor pollicis than at the flexor hallucis brevis (p < 0.02). Reappearance of the first twitch occurred 0.49 minutes slower at the adductor pollicis, although this difference was not statistically significant. The time to recovery to a TOF ratio of 0.75 at the adductor pollicis was slower by 2.83 minutes (p = 0.046). CONCLUSIONS: Due to its lag behind the adductor pollicis, the flexor hallucis brevis is not a good indicator of when to intubate the trachea during the onset of neuromuscular block; however, its faster recovery may make it useful for monitoring deep neuromuscular block intraoperatively or during recovery when the adductor pollicis TOF response still shows complete blockade.

Adolescent↗
PubMed1995

A comparison of dynamic and isometric force sensors for train-of-four measurement using submaximal stimulation current.

OBJECTIVE: We studied the accuracy and repeatability of train-of-four (TOF) ratio measurements made from a dynamic piezoelectric sensor that records movement of the thumb in response to ulnar nerve stimulation compared with an isometric mechanomyogram that measures force of contraction of the adductor pollicis. METHODS: The study involved 10 patients whose level of neuromuscular block was held constant with an intravenous (IV) infusion of vecuronium bromide (0.4 to 1.0 micrograms/kg/min) (Organon, West Orange, NJ). The sensors were attached to opposite arms of each patient and simultaneous measurements of TOF ratio were taken at stimulation current levels of 50, 30, and 20 mA. RESULTS: In comparison to the TOF ratio measured at the maximal stimulation current (50 mA), the TOF ratio from the piezo sensor showed a bias and standard deviation of -0.13 +/- 0.24 when the stimulation current was reduced to 30 mA. At 20 mA, the bias and standard deviation was -0.24 +/- 0.28. The TOF ratio from the mechanomyogram showed a bias and standard deviation of 0.01 +/- 0.07 at 30 mA and 0.0 +/- 0.20 at 20 mA when compared with measurements made when the stimulation current was 50 mA. CONCLUSIONS: Both sensors showed diminished repeatability in TOF measurement with decreasing stimulation current. The data indicate that neither sensor is reliable for general monitoring of neuromuscular block at submaximal current levels. However, the individual patient results showed that some patients could be monitored accurately with both sensors, even at the lowest stimulation current levels.

Electric Stimulation↗
PubMed1995

The time commitment of the community nursing services to Project 2000.

As part of an English National Board funded research study, the authors sent questionnaires to 2500 individuals with community nursing qualifications. The survey was complemented by a series of interviews with community nurse managers. Data indicated that community nurses were spending very considerable amounts of time with students. The number of placements provided per year varied considerably from one respondent to another, as did the average duration of a placement. Community nurses were providing community experience for a variety of types of nursing students, as well as students of other professions, and the time commitment involved placed them under considerable strain. The authors conclude that there is a need to recognise the time given by community nurses to work with students, and the resource implications of this commitment.

Clinical Competence↗
PubMed1994

A breathing circuit alarm system based on neural networks.

OBJECTIVE: The objectives of our study were (1) to implement intelligent respiratory alarms with a neural network; and (2) to increase alarm specificity and decrease false-alarm rates compared with current alarms. METHODS: We trained a neural network to recognize 13 faults in an anesthesia breathing circuit. The system extracted 30 breath-to-breath features from the airway CO2, flow, and pressure signals. We created training data for the network by introducing 13 faults repeatedly in 5 dogs (616 total faults). We used the data to train the neural network using the backward error propagation algorithm. RESULTS: In animals, the trained network reported the alarms correctly for 95.0% of the faults when tested during controlled ventilation, and for 86.9% of the faults during spontaneous breathing. When tested in the operating room, the system found and correctly reported 54 of 57 faults that occurred during 43.6 hr of use. The alarm system produced a total of 74 false alarms during 43.6 hr of monitoring. CONCLUSION: Neural networks may be useful in creating intelligent anesthesia alarm systems.

Anesthesiology↗
PubMed1994

Prostaglandin B2-induced pulmonary hypertension is mediated by TxA2/PGH2 receptor stimulation.

We investigated whether the physiological effects of prostaglandin B2 (PGB2) in the pulmonary circulation might be due to stimulation of thromboxane A2-prostaglandin H2 (TxA2/PGH2) receptors. In seven anesthetized rabbits, intravenous infusion of PGB2 (5.0 micrograms/kg) caused pulmonary hypertension as evidenced by increases in right ventricular systolic blood pressure. The magnitude of the pulmonary hypertension was comparable to that observed after infusion of the TxA2 mimetic U-46619 at a significantly lower dose (0.5 micrograms/kg), indicating that the effects of PGB2 in the intact animal are similar to TxA2 but less potent. Additionally, the TxA2/PGH2-receptor antagonist SQ-29548 blocked the pulmonary blood pressure responses elicited by PGB2. Receptor-binding studies using the TxA2 receptor ligand [3H]SQ-29548 indicated that PGB2 was a potent competitor for TxA2/PGH2 receptor binding. In agreement with the results from the intact animal, however, the efficacy of inhibition with PGB2 was significantly less than that measured for the TxA2 agonist U-46619. All of these results are consistent with the hypothesis that the physiological effects of PGB2 are mediated by stimulation of TxA2/PGH2 receptors.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1994

Mechanisms for the tachypneic response to the thromboxane A2 mimetic U-46,619 in rabbits.

These experiments were designed to determine if intravenous infusion of the thromboxane A2 mimetic, U-46,619, would elicit tachypnea in the rabbit, and if so whether the afferent signal was generated by receptors innervated by myelinated or unmyelinated vagal nerve fibers. Intravenous infusion of U-46,619 (0.5 microgram/kg delivered over 10 s) increased breathing frequency (26%) and right ventricular blood pressure (59%) in the anesthetized rabbit (n = 10). Systemic arterial blood pressure, heart rate, and tidal volume were unaffected by the infusion of U-46,619. When myelinated fiber conduction in the vagus nerve was eliminated by bilaterally cooling the nerve to 6 degrees C, the increase in breathing frequency was only 5% above baseline levels. The tachypneic response to U-46,619 was totally eliminated when both myelinated and unmyelinated fiber conduction was abolished by cooling the vagi to 0 degree C. The increase in right ventricular blood pressure after U-46,619 infusion was unaffected by vagal cooling. Because most (> 80%) of the tachypneic response to U-46,619 was eliminated by blockade of myelinated vagal fiber conduction, we conclude that the tachypneic response to U-46,619 is mediated mostly by receptors innervated by myelinated vagal afferent fibers in the anesthetized rabbit.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1994

Thromboxane A2 mimetic U-46619 induces systemic and pulmonary hypertension and delayed tachypnea in the goat.

Cardiorespiratory variables were measured continuously in five conscious goats before and after the infusion of U-46619 at a dose of either 2, 4, or 6 micrograms.kg-1.5 min-1. Infusion of U-46619 led to immediate increases in pulmonary arterial blood pressure (ABP) that were sustained for up to 15 min after the end of the infusion. Systemic ABP also increased, but the relative increase from control was less than the pulmonary pressor response. At the highest dose, U-46619 elicited a delayed tachypneic response that was greatest several minutes after the infusion was stopped. U-46619 was also infused simultaneously with sodium nitroprusside to clamp ABP pressure at baseline levels to determine whether stimulation of baroreceptors might contribute to the latency of the tachypneic response. Although sodium nitroprusside infusion prevented the increase in ABP, the increase in breathing frequency was still delayed 3-4 min from the start of the infusion. We conclude that U-46619 elicits pulmonary and systemic arterial hypertension in the conscious goat. At the higher dose U-46619 also elicits a delayed tachypnea that remains delayed even if ABP is normal.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1994

An effectiveness study of a new piezoelectric sensor for train-of-four measurement.

We have developed an easy-to-use, noninvasive piezoelectric sensor for quantitative monitoring of neuromuscular block. In a clinical evaluation with 23 patients, the piezo sensor was objectively compared to a mechanomyogram (MMG) for its ability to measure train-of-four (TOF) ratio from the adductor pollicis. After administration of succinylcholine (120-200 mg intravenously [i.v.]) to facilitate intubation, neuromuscular block was maintained with vecuronium by either boluses (1-2 mg i.v.) or an infusion (0.4-1.0 micrograms.kg-1.min-1 i.v.). Paired measurements were made of the TOF ratio from both sensors over a complete range of block levels (8%-100%). The difference in the TOF ratio measurement between the sensors showed a bias of 0.018. The SD of the difference between the sensors was +/- 0.129. The limits of agreement, which define the range in which 95% of the differences between the sensor measurements lie, were from -0.24 to 0.275. The sensitivity of the piezo sensor for detecting recovery based on a TOF ratio greater than 0.70 was shown to be 0.74 with specificity of 0.91. Under the conditions tested, the piezo sensor was not as accurate as the MMG. However, it was able to predict recovery of neuromuscular block with better accuracy than shown previously by manual evaluation of the TOF ratio, making it a reasonable, convenient alternative for quantitative monitoring of recovery from neuromuscular block.

Humans↗
PubMed1993

Integration of monitoring for intelligent alarms in anesthesia: neural networks--can they help?

Although there has been a decrease in the number of anesthesia-related critical incidents, there are still opportunities for further improvement. We discuss the potential of integrated monitoring and artificial neural networks as a means of vigilantly watching for patterns in multiple variables to detect incidents and reduce false alarms. We estimate that half the anesthesia-related events could be detected with integrated monitoring using only 5 variables. A review of research using artificial intelligence/expert systems indicates limited potential for success using these tools alone for integrated monitoring in the operating room. We present artificial neural networks as an approach that is more suited to the type of multivariable monitoring and pattern recognition required. Along with rule-based artificial intelligence, these now have the potential to help develop innovative monitoring in the operating room.

Anesthesiology↗