Michael G. Levitzky

Chemoreceptor influence on pulmonary blood flow during unilateral hypox1a in dogs

Dogs anesthetized with 30 mg/kg pentobarbital were artificially respired after differential cannulation of the main stem bronchi. Following median sternotomy, blood flow was monitored by electromagnetic flow probes on the left pulmonary artery (QL) and on the pulmonary trunk or aorta, QT. Following 10 min of bilateral 100% O2, QL was 42.5 +/- 7% of QT. When 6% O2, was substituted as the gas mixture inspired by the left lung while the right lung remained on 100% O2, PaO2 was above 70 mm Hg and QL fell to 24.5 +/- 5% of QT. Room air was then used to ventilate the right lung while the left lung remained on 6% O2. This caused PaO2 to fall to 42.3 +/- 3 MM Hg and QL to rise to 38.3 +/- 6% QT. This increase in blood flow to the unilaterally hypoxic lung during systemic hypoxemia did not occur in dogs after peripheral chemoreceptor denervation. Therefore, interference with the local response to alveolar hypoxia during systemic hypoxemia appears to be mediated by the arterial chemoreceptors.

Chemoreceptor stimulation and hypoxic pulmonary vasoconstriction in conscious dogs

Dogs with electromagnetic flow probes implanted on their left (QL) and main (QT) pulmonary arteries, catheters in their left atria and external jugular veins, and chronic tracheostomies were trained to accept Carlens dual-lumen endotracheal tubes into their tracheostomies, thus allowing separate ventilation of the two lungs. Swan-Ganz catheters were inserted through the jugular vein catheters. Pneumotachographs measured air flow to each lung. During bilateral ventilation with room air or O2, QL was about 36% of QT. When the left lung was ventilated with N2 while the right remained on O2, PAO2 was above 90 mmHg and QL fell to about 25% of QT. When the left lung was ventilated with N2 and the right with room air, PAO2 fell below 40 mm Hg and QL increased to control levels. This increase in perfusion of the hypoxic lung during systemic hypoxemia was not seen in dogs after surgical deafferentation of the systemic arterial chemoreceptors, indicating that stimulation of the arterial chemoreceptors may interfere with the hypoxic pulmonary vasoconstriction.

Chemoreceptor stimulation interferes with regional hypoxic pulmonary vasoconstriction

Hypoxemia interferes with the diversion of blood flow away from hypoxic regions of the lung, possibly through activation of the arterial chemoreceptor reflex. The purpose of this study was to determine if selective stimulation of carotid chemoreceptors reduces the diversion of flow (hypoxic vasoconstriction) when normal systemic oxygen levels are present. Chloralose anesthetized dogs were paralyzed and each lung was separately ventilated via a dual-lumen endobronchial tube. Left pulmonary artery (QL) and main pulmonary artery (QT) blood flows were measured with electromagnetic flow probes. Chemoreceptors were stimulated by perfusion of the carotid sinuses with hypoxic, hypercapnic blood. QL/QT averaged 46 +/- 4, 29 +/- 2, and 36 +/- 4% during bilateral O2 ventilation (control), left lung N2 ventilation, and left lung N2 plus chemoreceptor stimulation in dogs treated with the cyclo-oxygenase inhibitor meclofenamate. After vagotomy, QL/QT averaged 45 +/- 4, 27 +/- 3, and 28 +/- 2% during the same conditions. QL/QT decreased significantly from control (P less than 0.05) during left lung N2 alone but did not decrease during left lung N2 plus chemoreceptor stimulation in dogs with intact vagi. In contrast, QL/QT decreased significantly both before and during chemoreceptor stimulation in vagotomized dogs. The same responses were observed in dogs not treated with meclofenamate. These results indicate that selective stimulation of arterial chemoreceptors can interfere with regional hypoxic vasoconstriction and suggest that the vagus nerves may mediate this effect.

Using the pathophysiology of obstructive sleep apnea to teach cardiopulmonary integration

Obstructive sleep apnea (OSA) is a common disorder of upper airway obstruction during sleep. The effects of intermittent upper airway obstruction include alveolar hypoventilation, altered arterial blood gases and acid-base status, and stimulation of the arterial chemoreceptors, which leads to frequent arousals. These arousals disturb sleep architecture and cause hypersomnolence. Chronic intermittent alveolar and systemic arterial hypoxia-hypercapnia can cause pulmonary and systemic hypertension, with effects on the right and left ventricles, and even the renal system. The pathophysiology of OSA can therefore be used to review and integrate many topics in pulmonary and cardiovascular physiology in the context of problem-based learning, a guided discussion, or a formal lecture. The discussion begins with a case scenario, followed by a definition of the disorder, the common symptoms and signs of OSA, and a description of an apneic event. These are related to the physiology of the upper airway in OSA, normal alterations in the respiratory system during sleep, the effects of apnea on gas exchange and arterial blood gases, and the cardiovascular consequences of alterations in alveolar and systemic arterial PO(2) and PCO(2). The treatment of OSA, particularly how the use of continuous positive airway pressure relates to the pathophysiology of the disorder, is discussed briefly.

Pulmonary capillary pressure during acute lung injury in dogs.

Objectives To measure pulmonary capillary pressure and pulmonary artery occlusion pressures both during control conditions and during acute lung injury and to evaluate the effects of inotropic therapy and volume loading on these measurements after lung injury. Design Prospective, randomized, controlled laboratory trial. Setting University research laboratory. Subjects Eighteen heartworm-free mongrel dogs. Interventions Dogs were anesthetized (sodium pentobarbital, 30 mg/kg intravenously), intubated, and mechanically ventilated. A femoral artery and vein and the right external jugular vein were cannulated. After a median sternotomy, two pulmonary artery catheters were inserted via the jugular vein into the left and right lower lobar pulmonary arteries. Oleic acid (0.03 mL/kg) was administered to all dogs via the left pulmonary artery catheter, whereas the right lower lobe served as control. A baseline group of dogs received no further interventions, whereas two additional groups were given dobutamine (30–60 &mgr;g·kg−1·min−1 intravenously) or saline boluses (1–2 L) before measurements were obtained after oleic acid lung injury. Measurements and Main Results Capillary pressure was estimated in both lower lung lobes by using the pulmonary artery occlusion method. Pulmonary capillary and pulmonary artery occlusion pressures were measured before and 2 hrs after oleic acid administration. Left lower lobar capillary pressure increased in all three groups, as did the difference between capillary pressure and pulmonary artery occlusion pressure. Capillary pressure in the control right lower lobe increased significantly only in the saline-loaded dogs, whereas the difference between the right-sided capillary and occlusion pressures increased only in the dogs given dobutamine. Conclusions Oleic acid lung injury increases pulmonary capillary pressure independent of pulmonary artery occlusion pressure. The gradient between the two pressures was not significantly affected by volume loading or dobutamine infusion.

Endothelin produces systemic vasodilation independent of the state of consciousness

The effects of endothelin, ET-1, on pulmonary and systemic hemodynamics were studied in the open chest dog and changes in systemic arterial pressure in dogs under conscious and anesthetized states were compared. Rapid intravenous (IV) bolus injections of ET-1, 100-1,000 nanograms/kg, significantly decreased systemic arterial pressure, and significantly decreased systemic vascular resistance whereas left atrial pressure and pulmonary vascular resistance were not altered. Reductions in systemic arterial pressure in response to bolus injection of ET-1, 100 and 300 nanograms/kg IV, during conscious state and during anesthesia were similar, respectively. The present data suggest that ET-1 dilates the systemic vascular bed independent of the animals state of consciousness. The present data also suggest that when compared to the systemic vascular bed, the pulmonary vascular bed is less responsive to bolus administration of ET-1.

Effect of chemorceptor denervation on the pulmonary vascular response to atelectasis

Six dogs anesthetized with 30 mg/kg pentobarbital were ventilated after differential cannulation of the main stem bronchi. Following sternotomy, blood flow was monitored by electromagnetic flow probes on the left pulmonary artery (QL) and on the pulmonary trunk or aorta (QT). Following 10 min of bilateral 100% O2, QL was 37.4 +/- 5.8% of QT. When left lung atelectasis was induced while the right lung remained on 100% O2, PaO2 remained above 75 mm Hg and QL fell to 26.1 +/- 5.0% of QT. However, when the right lung was ventilated with room air while the left lung remained atelectatic, PaO2 fell to 50.0 +/- 2.6 mm Hg and QL rose to 36.7 +/- 6.2% of QT. Six dogs which had undergone peripheral chemoreceptor denervation prior to these experiments showed a similar decrease in perfusion of the atelectatic left lung when the right lung was ventilated with 100% O2, but did not increase blood flow to the atelectatic lung during systemic hypoxemia. Thus, the increased blood flow to the atelectatic lung which occurs during systemic hypoxemia appears to be mediated by the arterial chemoreceptors.

Hypoxemia and hypoxic pulmonary vasoconstriction: autonomic nervous system versus mixed venous PO2

Hypoxemia interferes with hypoxic pulmonary vasoconstriction (HPV). We investigated the respective roles of the autonomic nervous system and the mixed venous PO2 (PVO2) in the attenuation of HPV by hypoxemia. Pentobarbital-anesthetized dogs had their lungs separately ventilated with a dual-lumen endotracheal tube. Left (Ql) and total (Qt) pulmonary blood flows were determined using electromagnetic flow probes. HPV was initiated by ventilating the left lung with nitrogen for 5-10 min while the right lung received 100% oxygen. The animals were subsequently made hypoxemic by switching the right lung to room air ventilation (5-10 min). Two different protocol groups received either intravenous atropine during hypoxemia (group I) or intravenous propranolol prior to protocol initiation (group II). A third group of dogs (group III) had their mixed venous PO2S maintained above 30 torr during hypoxemia. In response to left lung hypoxia, Ql/Qt decreased from 44 +/- 5, 48 +/- 3 and 46 +/- 2% to 25 +/- 4, 28 +/- 2 and 26 +/- 3% in the three groups, respectively. During hypoxemia Ql/Qt increased to 50 +/- 7 and 47 +/- 3% in groups I and II. In group III dogs, Ql/Qt remained significantly decreased at 31 +/- 3%. Subsequent administration of atropine in group I had no effect on Ql/Qt. We conclude that the loss of flow diversion from a hypoxic lung during hypoxemia may be mediated primarily by a decreased in mixed venous PO2 when PVO2 is allowed to decrease to 15-20 torr.

Effects of expiratory positive airway pressure vs continuous positive airway pressure in conscious, spontaneously breathing dogs.

Abstract The purpose of this study was to compare the cardiopulmonary effects of expiratory positive airway pressure (EPAP) and continuous positive airway pressure (CPAP) in conscious, spontaneously breathing dogs. Nine conscious dogs with electromagnetic flow probes on their pulmonary arteries, catheters in their left atria and pulmonary arteries, and chronic tracheostomies, stood partially supported by slings, and breathed 100% oxygen through endotracheal tubes, pneumotachographs, and nonrebreathing valves which were part of either an EPAP or CPAP system. The effects of EPAP only were studied on four dogs while five were exposed to both EPAP and CPAP. After a 20-min control period, they breathed through either the EPAP or CPAP system for 10 min each under 5-, 10-, 15-, and 20-cm H2O airway pressure. The mean pulmonary artery pressure, mean left atrial pressure, pulmonary vascular resistance, and minute ventilation were found to be significantly higher in the CPAP-treated group. Stroke volume and cardiac output were significantly higher in the EPAP-treated group. Both groups showed a significant carbon dioxide retention.

Continual pulmonary arterial wedge pressure estimated beat-to-beat by a neural network

Pulmonary arterial wedge pressure has been estimated beat-to-beat by an artificial neural network (ANN). Individual beats were parsed from pulmonary arterial pressure recordings obtained in 13 dogs just prior to measurements of conventional occlusive wedge pressure. The beats were resampled and used as inputs to a back-propagation neural network. The network was trained to estimate the wedge pressures obtained immediately after the beats were recorded. The training was done with 80% of all beats and tested on the remaining 20%. Testing on this 20% showed agreement statistics of bias and imprecision of 0.07/spl plusmn/0.70 mmHg. The method clearly demonstrates that it is possible to estimate wedge pressure from individual beats but additional work is needed for practical application.