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Biomedical subjects

D F Howland

Publications and source records attributed to D F Howland.

10 recordsLinked to original sources
PubMed1993

Positive end-expiratory pressure-induced, calcium-channel-mediated increases in pulmonary vascular resistance in neonatal lambs.

OBJECTIVES: a) To study the dose response of the calcium-channel-mediated increases in pulmonary vascular resistance with different levels of positive end-expiratory pressure; b) to study the reversibility of the calcium-channel mediated increases in pulmonary vascular resistance after discontinuation of positive end-expiratory pressure; and c) to study the effect of cyclooxygenase and lipoxygenase inhibition on the calcium-channel mediated increases in pulmonary vascular resistance. DESIGN: A prospective, multiexperimental, dose response study. SETTING: Laboratory setting in a university hospital. SUBJECTS: Twenty-three 4- to 10-day-old neonatal lambs. INTERVENTIONS AND MEASUREMENTS: Lungs of neonatal lambs were isolated in situ, and perfused at a constant flow rate, and ventilated at a fixed tidal volume and rate. Mean pulmonary arterial pressure responses to the application and discontinuation of four levels (3.7, 7.4, 11, and 14.7 mm Hg) of positive end-expiratory pressure were studied before and after calcium-channel blockade with verapamil (5 mg) (n = 12). In addition, the mean pulmonary arterial pressure response to 11 mm Hg of positive end-expiratory pressure was studied before and after inhibition of cyclooxygenase with indomethacin (10 mg/kg) (n = 6) and lipoxygenase with diethylcarbamazine (100 mg/kg) (n = 5). RESULTS: The magnitude of the calcium-channel-dependent mean pulmonary arterial pressure response 4 mins after the application of positive end-expiratory pressure was dose related (2.1, 3.0, 4.1, and 5.5 mm Hg with 3.7, 7.4, 11.0, and 14.7 mmHg positive end-expiratory pressure, respectively) and entirely reversible on discontinuation of positive end-expiratory pressure with a time course of 2 to 4 mins. Neither indomethacin nor diethylcarbamazine affected the pulmonary arterial pressure responses to positive end-expiratory pressure. Airway pressure changes with positive end-expiratory pressure were not affected by verapamil, indomethacin, or diethylcarbamazine. CONCLUSIONS: The calcium-channel-mediated pulmonary arterial pressure responses with positive end-expiratory pressure, applied during continuous positive pressure breathing, occur even at low levels of positive end-expiratory pressure, are dose dependent, and are not abolished by treatment with indomethacin or diethylcarbamazine.

Airway Resistance↗
PubMed1991

Cardiac output during liquid (perfluorocarbon) breathing in newborn piglets.

BACKGROUND AND METHODS: Liquid ventilation using perfluorocarbons is a new technique for ventilation of infants with restrictive lung disease. However, this method of ventilation has been shown to impair cardiac output (Qt) in several animal species, casting doubt as to its feasibility. This study tested whether Qt could be maintained during liquid breathing by intravascular volume expansion. Seven piglets were carefully hydrated, instrumented for continuous Qt measurement, and subjected to 2 hr of liquid breathing. PaCO2 was maintained at 40 to 50 torr (5.3 to 6.7 kPa), and PaO2 greater than 80 torr (greater than 10.7 kPa). Additional colloid was given during liquid breathing if Qt decreased to less than 90% of preliquid breathing values. RESULTS: Four piglets maintained Qt throughout the liquid breathing trial with maintenance fluids only. Three piglets each required one 10 mL/kg fluid bolus for Qt 82% to 89% of the baseline value, after which Qt rapidly increased to greater than 90% of baseline. Oxygen consumption and serum lactate levels remained normal throughout liquid breathing. CONCLUSION: Qt is readily maintained during liquid breathing in properly hydrated animals.

Animals↗
PubMed1991

Validity of a disposable end-tidal carbon dioxide detector in verifying endotracheal tube position in piglets.

BACKGROUND AND METHODS: the most reliable methods for confirming endotracheal tube placement are direct visualization of passage through the vocal cords and documentation of CO2 in the expired gas. We evaluated the use of a disposable colorimetric CO2 detector for verifying endotracheal tube position in small animals. The end-tidal CO2 (Petco2) detector was tested in 11 piglets with the endotracheal tube sequentially in the trachea, the esophagus, the esophagus with a carbonated beverage in the stomach, the esophagus after bag-mask ventilation. Endotracheal tube position was confirmed in all cases by direct visualization and capnometry. RESULTS: The Petco2 detector identified the tube placement accurately in all 54 (21 tracheal, 33 esophageal) intubations (p less than .001). CONCLUSIONS: This disposable Petco2 detector is highly sensitive and specific for verifying endotracheal tube placement in this nonarrest piglet model.

Animals↗
PubMed1991

Air trapping causes a Ca2(+)-channel-mediated increase in pulmonary vascular resistance in neonatal lambs.

Air trapping and alveolar hyperinflation may occur during mechanical ventilation in the presence of severe airway obstruction, during fast ventilator rates, and when expiratory time is compromised. Inadvertent positive end-expiratory pressure may occur with air trapping and increased mean airway pressure. The pulmonary artery pressure response to air trapping, produced during volume-regulated time-cycled ventilation, was studied in neonatal lamb lungs, isolated in situ, and perfused at a constant flow rate (50-75 ml.kg-1.min-1), both before and after Ca2(+)-channel blockade with verapamil (5 mg). The hub of the endotracheal tube was narrowed to a 1.5-mm orifice to produce fixed proximal airway obstruction. Air trapping was then produced by lengthening inspiratory time from 25 to 80%, at zero end-expiratory pressure. The magnitude of inadvertent positive end-expiratory pressure due to air trapping was estimated by end-expiratory occlusion pressure. End-expiratory occlusion pressure was 0.20 +/- 0.03 kPa (1.7 +/- 0.2 mm Hg) and 1.60 +/- 0.01 kPa (11.8 +/- 1.0 mm Hg), at 25 and 80% inspiratory times, respectively. On lengthening inspiratory time, mean pulmonary artery pressure (mPpa) increased briskly within 30 s followed by a gradual increase over the next 4 min. Verapamil blunted both the brisk and the gradual increase in mPpa on lengthening inspiratory time. Lengthening inspiratory time increased the mPpa by 2.0 +/- 0.1 kPa (14.7 +/- 0.8 mm Hg) from baseline, and verapamil reduced this increase to 1.3 +/- 0.1 kPa (10.1 +/- 0.6 mm Hg; p less than 0.05 by analysis of variance).(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Obstruction↗
PubMed1990

Systemic heparinization does not prevent clot formation in coil embolization.

Therapeutic transcatheter closure with Gianturco-type steel coils has been applied to a variety of vascular communications in children with congenital heart disease. Vessel closure depends upon successful thrombus formation around the coil. Since systemic anticoagulation with heparin is commonly used during catheterization and cardiac surgery, we studied the effect of systemic heparinization on the efficiency of vessel occlusion by coil embolization in lambs. Catheters inserted in femoral arteries were used to arteriographically locate and size 36 systemic arteries in 9 lambs weighing 4.2 to 7.4 kg. Twenty-four vessels were embolized prior to heparinization with 400 u/kg heparin, IV. Effective anticoagulation was demonstrated by post-heparin activated clotting time (ACT) values greater than 300 sec. Seven vessels (29%) were not successfully coil-embolized because of inadequate coil position or distant embolization of the coil; 17 (71%) of these vessels were shown to be successfully occluded by arteriography 6 to 77 min later. After a period of systemic heparinization ranging from 71 to 159 min, 9/17 arteries remained occluded, 7/17 could not be examined arteriographically due to early demise of the animal, and only 1/17 showed recanalization. A second group of 12 vessels were embolized after heparinization. Eight (75%) were successfully occluded, and 4 (25%) were not successfully coil-embolized because of inadequate coil position or coil embolization to distant arteries. We conclude that systemic heparinization had no measurable effect on occlusion rates in coil-embolized systemic arteries in the lamb. These data support the use of systemic heparinization, when indicated, during or following therapeutic coil embolization in children.

Animals↗
PubMed1990

Airway and alveolar pressures during perfluorocarbon breathing in infant lambs.

Previous studies exploring the utility of liquid breathing using perfluorocarbon have reported proximal airway pressures (Paw) as high as 70 Torr during inspiration, generating concern about the safety of this form of mechanical ventilation. Effects on the pulmonary capillary bed are, however, more likely related to alveolar pressure (PA) than to Paw, and data on PA during liquid breathing are limited. In this study in infant lambs, we reconstructed the pressure waveforms of PA during liquid breathing by using an occlusion technique and compared these with Paw waveforms. Peak PA (18.6 +/- 10.4 Torr) was significantly less than peak Paw (31.5 +/- 10.5 Torr, P less than 0.001), indicating a large resistive pressure drop (14.4 +/- 4.5 Torr) across the bronchial tree. Mean PA (mPA) was very similar to mean Paw (mPaw) [bias = -2.0 Torr, standard error of the average difference = 0.27 Torr, predictive value of mPaw for mPA (r2) = 0.978], suggesting that mPaw, which is easily measured, may be used to estimate mPA during perfluorocarbon liquid breathing. These data show that alveoli do not experience the same large swings in pressure as the proximal airway does during liquid breathing and that simple measurements of mPaw can be used to approximate mPA during liquid breathing.

Animals↗
PubMed1989

Pulmonary vascular resistance after cessation of positive end-expiratory pressure.

This report describes the pulmonary vascular response of infant lamb lung to abrupt cessation of positive end-expiratory pressure (PEEP) during volume-regulated continuous positive-pressure breathing (CPPB). In an intact, endobronchially ventilated preparation, the increase in left lung blood flow (QL) after abrupt cessation of 11 Torr left lung PEEP was found to be gradual, although peak airway pressure (Pmax) fell promptly from 36 to 14 Torr; 49% of the increase in QL occurred greater than 10 s after cessation of PEEP. Recruitment of zone I vasculature that had been created by balloon occlusion of the left pulmonary artery was found to occur promptly after balloon deflation. Isolated neonatal lamb lungs, perfused at constant flow rate, showed similar persistent elevation of pulmonary vascular resistance after cessation of 15 Torr PEEP, although Pmax fell abruptly from 39 to 12 Torr. This hysteresis was eliminated by calcium channel blockade with verapamil, and the magnitude of the change in pulmonary arterial pressure after either application or cessation of PEEP was reduced (25 and 26%, respectively). These observations suggest that, during CPPB, lung stretch alters neonatal pulmonary vascular tone or, by causing calcium channel-dependent lung volume hysteresis, modulates pulmonary vascular resistance. This interaction exaggerates the effect of airway pressure changes on pulmonary vascular resistance during mechanical ventilation.

Animals↗
PubMed1989

Proximal mean airway pressure: a good estimator of mean alveolar pressure during continuous positive-pressure breathing.

Although airway and alveolar pressures are not instantly equal during positive-pressure ventilation, proximal mean airway pressure (Paw) is the simplest available indirect gauge of mean alveolar pressure (Palv). To ascertain the relation of Paw to Palv and the limits of agreement between the two measures, real-time curves of proximal airway pressure (at the hub of the endotracheal tube) and alveolar pressure were generated by repeated airway occlusion at numerous PEEP levels in four groups of ventilated lambs or piglets: normal controls, oleic acid-injured and serotonin stimulated lambs, and preparations with mechanically induced air trapping. From these curves, Paw and Palv were determined. In all groups, Paw proved to be a precise estimator of Palv during volume-regulated, time-cycled, continuous positive-pressure breathing.

Airway Resistance↗
PubMed1985

Pulmonary and systemic vascular effects of SRS-A blockade in conscious lambs.

There is preliminary evidence suggesting that hypoxic pulmonary vasoconstriction may be mediated by slow-reacting substance of anaphylaxis (SRS-A), which is comprised of leukotrienes C4, D4, and E4. We studied the effects of the SRS-A antagonist FPL 57231 (FPL) on the hypoxic pulmonary vasoconstrictor response and on systemic vascular resistance in awake, chronically instrumented young lambs. Two other studies were performed to ascertain whether FPL's vasodilation was specific for hypoxic pulmonary vasoconstriction: the effect of FPL infusion in pulmonary and systemic vascular resistance was measured in six normoxic lambs, and the effect of FPL on 5-hydroxytryptamine (5-HT)-mediated vasoconstriction was determined. In seven lambs, mean pulmonary arterial pressure was 21 mmHg in room air and 28 mmHg in hypoxia (Po2 = 43 Torr). During hypoxia, FPL infusion (2 mg X kg-1 X min-1) reversibly decreased pulmonary arterial pressure to 15 mmHg; pulmonary arteriolar resistance also fell below normoxia levels with FPL. FPL also caused a fall in aortic pressure and systemic vascular resistance in these hypoxic lambs, but the decrease in systemic resistance was less than the fall in pulmonary resistance. beta-Adrenergic blockade using propranolol (1 mg/kg) did not affect the pulmonary vasodilation caused by FPL. In six normoxic lambs, FPL infusion also significantly decreased pulmonary and systemic vascular resistance (29% in each case). These data are consistent with the idea that leukotrienes may be involved in adjusting both pulmonary and systemic vascular tone, but further work is necessary to establish whether FPL's vasodilation is mediated via its leukotriene antagonism or is a nonspecific effect of FPL.

Adrenergic beta-Antagonists↗