R. L. Coon

Direct Relaxant Effects of Intravenous Anesthetics on Airway Smooth Muscle

Ketamine, at concentrations achieved with the usual clinical doses, has a direct relaxant effect on airway smooth muscle (ASM).This study investigates the dose-dependent direct relaxation effects of midazolam and propofol on both proximal and distal ASM compared with ketamine. The proximal and distal airways were dissected from eight mongrel dogs and cut into 2-mm rings. The rings were attached to pressure transducers and equilibrated in a Krebs-Ringer bicarbonate bath kept at 37 degrees C, pH 7.4, CO2 37 mm Hg, and PaO2 > 100 mm Hg. Optimal length was determined, a dose-response curve to acetylcholine was established, and the 50% effective dose (ED50) of acetylcholine was calculated. Ketamine, midazolam, or propofol were given in random order to each ring preconstricted with ED50 of acetylcholine in cumulative log incremental doses from 10-6 to 10-4 M. Relaxation response was the tension during anesthetic equilibrium, expressed as a percentage of the tension from ED50 of acetylcholine. The drug vehicles were tested for their effects on the ASM. No bronchorelaxation was seen with any of the intravenous anesthetics at 10-6 M. Ketamine 10-5 M produced a 17.9% +/- 2.1% relaxation in the distal ASM but had no effect on the proximal ASM. Neither propofol nor midazolam affected the ASM at 10-5 M. The distal ASM was significantly (P < 0.005) more sensitive to 10-4 M of all three drugs compared with the proximal ASM. In the proximal ASM, 10-4 M of ketamine, midazolam and propofol reduced ASM tension by 14.9% +/- 4.4%, 19.0% +/- 8.8%, and 14.7% +/- 5.5%, respectively, versus 36.4% +/- 3.2%, 58.6% +/- 6.1%, and 64.4% +/- 9.0% in the distal ASM. The drug vehicles had no effect on the ASM. We conclude that ketamine, midazolam, and propofol have direct relaxant effects on ASM. All three intravenous anesthetics have a greater direct relaxant effect on distal ASM than on proximal ASM. Only ketamine showed significant direct bronchorelaxing effects at concentrations that are likely to be achieved with the usual clinical dosing patterns. (Anesth Analg 1996;83:162-8)

Systemic Arterial Blood pH Servocontrol of Mechanical Ventilation

Servocontrol of mechanical ventilation using systemic arterial blood pH, measured by a dual-function pH/PCO2 intra-arterial sensor, as the controlled variable uas carried out in 30 dogs anesthetized with pentobarbital, 30 mg/kg. The control loop consisted of the animal, an intra-arterial dual-function pH/PCO2 sensor and sensor amplifier, a controller, and a Siemans-Elema 900 servoventilator. The system responded appropriately to changes in set-point pH from 7.30 to 7.50, as well as to infusions of lactic acid, which, with the control loop open, decreased systemic arterial blood pH 0.1 TO 0.2 PH units. Long-term (16 hr) ventilation of one dog with the systemic arterial blood pH servocontrol ventilator was shown to be feasible.

Acute coronary artery occlusion and cardiac sympathetic afferent nerve activity.

Summary Myelinated sympathetic afferent fibers with conduction velocities in the AS range arising from receptors located within the left ventricle responded to acute coronary artery occlusion with an increase in activity. The increase in activity was over 100% above control levels of activity. The increase in afferent nerve activity was directly related to an increase in left ventricular segmental length produced by acute coronary artery occlusion.

Development of Baroreflex Control of Heart Rate in Swine

ABSTRACT: The purpose of this study is to describe the developmental course of arterial baroreflex control of heart rate in swine. Tests of baroreflex function were performed with eight conscious piglets serially over their first 2 mo of life. Systemic blood pressure was raised with phenylephrine (pressor test) and lowered with nitroprusside (depressor test), and stimulus-response curves relating heart rate to mean blood pressure were constructed. Baroreflex sensitivity was determined as the slope of the linear portion of the curve. Baroreflex sensitivity decreased with increasing age. Baroreflex sensitivity was not different between pressor and depressor tests except when the piglets were >52 d old and sensitivity was greater with the depressor test. The heart rates at threshold and saturation, and therefore the heart rate response range, shifted to lower heart rates with increasing age. This shift was more than can be accounted for by the simultaneously decreasing resting heart rate.

Accessory Muscle Activity and Respiration

The relationship between the accessory muscle activity (sternohyoid and sternothyroid) and respiration was studied in canines. These animals do not have an omohyoid muscle such as found in primates. Therefore, chair-trained monkeys that have all three accessory muscles were used in a portion of the study. Findings in canines supported those previously reported. The sternothyroid muscle fired spontaneously with the onset of inspiration, but there was no similar activity in the sternohyoid. The activity of both muscles was observed after sectioning the recurrent laryngeal nerves and inducing hypoxia and hypercarbia. The severely hypoxic animals produced some negligible activity in the sternohyoid muscle. The data obtained from the chair-trained monkeys showed no consistent accessory muscle activity during normal respiration with recordings taken immediately after electrode placement, at 24 hours, and one week later. Respiratory activity was consistent in the omohyoid and sternothyroid but not in the sternohyoid muscle when partial airway obstruction and hypoxia were induced.

Hypocapnic bronchoconstriction and inhalation anesthetics.

The effects of halothane, enflurane, and methoxyflurane on hypocapnic bronchoconstriction (increased airway resistance and decrea ed compliance of the lung) were studied in cico in the isolated left lower lobe of the canine lung. Hypocapnic bronchoconstriction, induced by altering the concentration of CO2 in gas ventilating the lobe, was repeated in the presence and absence of various concentrations of anesthetic gases (halothane: 0.5, 1,0, and 3.0 per cent; enflurane: 1.0, 3.0, and 5.0 per cent; methoxyflurane: 0.25, 0.50, and 1.0 per cent). In the higher concentrations, all three drugs blocked the bronchoconstrictor effect produced when the inspired CO2 was decreased from 5 to 0 per cent. In lower concentrations, halothane was the most effective blocking drug. Propranolol did not affect the ability of the three anesthetics to block hypocapnic bronchoconstriction, nor did the beta-receptor blocking drug sotalol affect the blocking effects of halothane. The ability of these anesthetics to block hypocapnic bronchoconstriction probably is mediated not through an adrenergic mechanism but by one that is nonspecific.

Capnography for detection of endobronchial migration of an endotracheal tube

A patient is described in whom migration of an endotracheal tube into the right main bronchus was suspected when end-tidal carbon dioxide suddenly decreased from 28 to 22 mm Hg. Acute changes with migration of the endotracheal tube into the main bronchus were also studied in an animal experimental model. End-tidal carbon dioxide decreased and tracheal (inflation) pressure increased, with no change in tidal volume. Arterial blood gases showed time-dependent decreases in pH and oxygen tension and an increase in carbon dioxide tension.

Topographical Differences in the Direct Effects of Isoflurane on Airway Smooth Muscle

Volatile anesthetics have a direct relaxant effect on airway smooth muscle, but it is not known whether this effect is similar throughout the bronchial tree. We studied the direct relaxation effect of isoflurane on isolated proximal (outer diameter [OD] 4–6 mm) and distal (OD 0.7–1.5 mm) canine airways precontracted with acetylcholine. Proximal and distal airway rings were suspended in tissue baths and stretched to their optimum length. A dose-response curve was obtained for each airway ring with log increments of acetylcholine. Maximum contraction was reached with 10 −2 mol/L of acetylcholine for the proximal airway smooth muscle (7.0 ± 0.3 g of tension) and 10 −3 mol/L of acetylcholine for the distal airway smooth muscle (2.3 ± 0.1 g of tension). Based on the dose-response curve, the ED50 of acetylcholine was calculated (1.26 ± 0.37 × 10 −4 mol/L for proximal airway smooth muscle; 2.12 ± 1.14 × 10 −5 mol/L for distal airway smooth muscle) and administered to each tissue bath, after which the stabilized response was recorded. A randomly selected dose of isoflurane (1,2, or 2.6 dog minimum alveolar anesthetic concentration [MAC]) was then administered to each bath and the relaxant responses were recorded. The proximal and distal airways relaxed with increased doses of isoflurane in a dose-related manner. The average distal airway relaxation was three times greater than the proximal airway relaxation at all isoflurane levels. The mechanism of this differential response is not known, but may be due to an epithelium dependent effect, sensitivity of contractile elements to Ca2+; and/or differences in ionic fluxes.

Location of lung receptors mediating the breathing frequency response to pulmonary CO2

Pulmonary stretch receptors are thought to mediate the breathing frequency (bf) response to changes in pulmonary CO2. However, the location and distribution of these receptors is disputed. The purpose of this study was to determine what contribution the extrapulmonary receptors make in the pulmonary CO2 bf response. Mongrel dogs were anesthetized and placed on cardiopulmonary bypass. The diaphragm electromyogram was used to monitor respiratory center output and to trigger a ventilator. Exposure of an upper airway segment to CO2 or positive end-expired pressure failed to produce changes in the bf. Denervation of the upper airway down to but not including the hilum caused similar insignificant changes in the CO2 bf response. Lungs collapsed by suction showed minimal Hering-Breuer inhibition when compared with inflated lungs. Bronchial arterial perfusion with hypocapnic followed by hypercapnic blood failed to produce changes in the bf while similar perfusion of the pulmonary arterial system resulted in significant increases in bf. It appears that the receptors mainly responsible for the pulmonary CO2 response are located in the more peripheral regions of the lung.

Depression of baroreflex control of heart rate by halothane in growing piglets

The purpose this study was to examine the effects of halothane on baroreflex control of heart rate in developing swine. Serial tests of baroreflex function were performed over the first 2 months of life in eight piglets in the conscious state and during anesthesia with 0.45, 0.9, and 1.35% halothane. Systemic blood pressure was increased with phenylephrine (pressor test) and decreased with nitroprusside (depressor test), and stimulus-response curves relating mean blood pressure to heart rate were constructed. Baroreflex sensitivity was determined as the slope of the linear portion of the curve. Halothane markedly depressed baroreflex sensitivity at all ages in a dose-dependent manner (conscious greater than 0.45% greater than 0.9%, 1.35%). Increasing age was accompanied by decreasing baroreflex sensitivity in both the conscious and the anesthetized states. The difference in baroreflex sensitivity between conscious and anesthetized states did not change with age for the depressor test (tachycardia response), but it did change with age for the pressor test (bradycardia response). For this test, conscious values converged toward anesthetized values at higher ages; therefore, there was relatively less depression by halothane at older ages. Halothane also decreased resting heart rate and decreased the limits and narrowed the range of the baroreflex heart rate response. Increasing age was accompanied by a decreasing resting heart rate and by decreasing limits and a narrowing range of the baroreflex response. The effect of halothane on heart rate variables was similar at all ages. Halothane decreased resting blood pressure and decreased the lower limit and widened the span of the baroreflex blood pressure range.(ABSTRACT TRUNCATED AT 250 WORDS)