Bryan E. Marshall

Role of hypoxic pulmonary vasoconstriction in pulmonary gas exchange and blood flow distribution

The regulation of the distribution of ventilation/perfusion ratios by hypoxic pulmonary vasoconstriction contributes to both the efficiency of gas exchange and to pulmonary hemodynamics. In this review, the first of a two part series, are summarized the physiologic principles on which the analysis of ventilation/perfusion ratios and of pressure — flow relationships are based. A new combined analysis is introduced that permits the important contributions of hypoxic pulmonary vasoconstriction to overall gas exchange to be demonstrated in the circumstances of clinical complexity.

Hemodynamic and Metabolic Effects of Hemorrhage in Man, with Particular Reference to the Splanchnic Circulation

1. Eleven normal subjects were studied before and after removal of 15 to 20% of their blood volume within 35 minutes. 2. This amount of blood loss did not produce conspicuous effects upon any of the usually measured circulatory or metabolic parameters. 3. The results suggest that the splanchnic circulation functions as an important blood reservoir in man, that it can be preferentially depleted of blood by a mechanism which does not automatically increase vascular resistance, and that the ability of our subjects to tolerate blood loss was attributable in large part to this response.

Artificial intelligence applications in the intensive care unit

ObjectiveTo review the history and current applications of artificial intelligence in the intensive care unit. Data SourcesThe MEDLINE database, bibliographies of selected articles, and current texts on the subject. Study SelectionThe studies that were selected for review used artificial intelligence tools for a variety of intensive care applications, including direct patient care and retrospective database analysis. Data ExtractionAll literature relevant to the topic was reviewed. Data SynthesisAlthough some of the earliest artificial intelligence (AI) applications were medically oriented, AI has not been widely accepted in medicine. Despite this, patient demographic, clinical, and billing data are increasingly available in an electronic format and therefore susceptible to analysis by intelligent software. Individual AI tools are specifically suited to different tasks, such as waveform analysis or device control. ConclusionsThe intensive care environment is particularly suited to the implementation of AI tools because of the wealth of available data and the inherent opportunities for increased efficiency in inpatient care. A variety of new AI tools have become available in recent years that can function as intelligent assistants to clinicians, constantly monitoring electronic data streams for important trends, or adjusting the settings of bedside devices. The integration of these tools into the intensive care unit can be expected to reduce costs and improve patient outcomes.

Influence of isoflurane on hypoxic pulmonary vasoconstriction in dogs

The authors studied the influence of locally administered isoflurane anesthesia on the pulmonary vascular response to regional alveolar hypoxia (hypoxic pulmonary vasoconstriction [HPV]) over a range of cardiac outputs (COs) in seven mechanically ventilated, closed-chest dogs. The right lung was ventilated with 100% O2 throughout the study. The left lung was ventilated with either 100% O2 (normoxia) or an hypoxic gas mixture (hypoxia). Different alveolar concentrations of isoflurane (0, 1, and 2.5 MAC) were administered to the left lung in a randomized sequence. The CO was altered by opening and closing surgically produced arteriovenous fistulae, at all isoflurane concentrations, and by hemorrhage at 0 MAC isoflurane. The magnitude of the HPV response was measured by differential CO2 elimination in the absence of isoflurane and by venous admixtures in all phases. During normoxia, the left lung effective flow (&OV0422;L%) measured from differential CO2 excretion was 39.9 ± 1.2% of the total blood flow and decreased to 18.8 ± 2.6% when ventilated with the hypoxic gas mixture. Venous admixture (&OV0422;VA/&OV0422;T%) was significantly correlated with &OV0422;L% during hypoxic ventilation in the absence of isoflurane. &OV0422;VA/&OV0422;T% was 22.3 ± 2.7% during hypoxia with normal CO, and it increased significantly to 27.7 ± 1.1% when the CO was increased 43%. It was not significantly altered (23.6 ± 3.6%) when the CO was decreased by 54%. Isoflurane 2.5 MAC significantly increased &OV0422;VA/QT% during hypoxic ventilation of the left lung to 33.9 ± 2.6% with low CO and 35.4 ± 1.7% with normal CO. Isoflurane 1 MAC increased &OV0422;VA/QT% to 27.2 ± 2.7% with normal CO and 28.1 ± 2.6% with high CO. Comparing the effects of the different concentrations of isoflurane on &OV0422;VA/&OV0422;T% during left lung hypoxia under the same conditions of CO, mixed venous and alveolar oxygen tension, and pulmonary artery and pulmonary artery occlusion pressures revealed a significant direct effect of isoflurane dose such that: (% depression of HPV) = [22.8(% alveolar isoflurane) – 5.3]. The ED50 for this response was 2.4% alveolar isoflurane. The authors conclude that isoflurane directly depresses HPV and that secondary influences of the anesthetic action should be considered in the interpretation of the action of inhalational agents on this response in vivo.

Role of hypoxic pulmonary vasoconstriction in pulmonary gas exchange and blood flow distribution. 2. Pathophysiology.

In this review, the second of a two part series, the analytic techniques introduced in the first part are applied to a broad range of pulmonary pathophysiologic conditions. The contributions of hypoxic pulmonary vasoconstriction to both homeostasis and pathophysiology are quantitated for atelectasis, pneumonia, sepsis, pulmonary embolism, chronic obstructive pulmonary disease and adult respiratory distress syndrome. For each disease state the influence of principle variables, including inspired oxygen concentration, cardiac output and severity of pathology are explored and the actions of selected drugs including inhaled nitric oxide and infused vasodilators are illustrated. It is concluded that hypoxic pulmonary vasoconstriction is often a critical determinant of hypoxemia and/or pulmonary hypertension. Furthermore this analysis demonstrates the value of computer simulation to reveal which of the many variables are most responsible for pathophysiologic results.

Effects of Halothane, Enflurane, and Isoflurane on Hypoxic Pulmonary Vasoconstriction in Rat Lungs In Vitro

Rat lungs were ventilated and perfused at a constant rate in vitro. The maximal hypoxic pulmonary vasoconstrictor (HPV) response was recorded by measuring the pulmonary artery pressure change when the inspired oxygen concentration was changed from 21% to 3% (with 5.5% carbon dioxide) in the absence of anesthetic vapor.In different experimental groups, the effects of halothane, enflurane, and isoflurane on HPV were examined. In random order the anesthetics were added to the inspired gas in concentrations of 0.25, 0.5, 1, 1.5, and 2 or 2.5 MAC units. The HPV pressor response to 3% oxygen in the presence of anesthetic agent was expressed as a per cent of the pressure response observed in the absence of anesthetic (R%MAX).All three agents depressed HPV in a dose-related manner. The concentrations in MAC units at which 50% depression of HPV (ED50) occurred was 0.47, 0.60, and 0.56 for halothane, isoflurane, and enflurane, respectively, and neither the ED50 values nor the slopes of these dose response curves were significantly different.It was concluded that these halogenated general anesthetics inhibit HPV with essentially the same potency.

Influence of Mixed Venous Oxygen Tension (PVO2) on Blood Flow to Atelectatic Lung

The influence of mixed venous oxygen tension (PVO2) on blood flow to the atelectatic left lung was studied at normal and reduced cardiac outputs (CO) using extracorporeal veno-venous bypass in six pentobarbital anesthetized, mechanically ventilated dogs. Aortic and left pulmonary artery flows; airway, left atrial, central venous, pulmonary, and systemic arterial pressures; hemoglobin, arterial, and mixed venous blood gases were measured. The blood flow reduction observed in atelectasis was altered by the PVO2. Approximately 50% of blood flow was diverted away from atelectatic lung when PVO2 was low (24 ± 2 mmHg) or normal (46 ± 2 mmHg) (mean left lung blood flow [VL] was 23.2 ± 4.6% with low PVO2 and 19.0 ± 3.4%, with normal PVO2). When PVO2I was increased to greater than 100 mmHg, diversion of blood flow away from atelectatic lung did not occur and VL% was nearly the flow expected for normoxic ventilated left lung (mean VL% = 40.4 ± 5.9%). Shunt (VS/VT%) was significantly greater when PVO2 was high than when it was normal or low (mean VS/VT% = 51.7 ± 5.6%, 31.0 ± 3.1%, 26.0 ± 3.4% with high, normal, and low PVO2, respectively). Mean PVO2 was significantly greater when PVO22 was high than when PVO2 was normal or low, despite the increase in VL% and VS/VT% (PVO2 = 327 ± 25 mmHg, 220 ± 32 mmHg, 115 + 21 mmHg with high, normal, and low PVO2, respectively). A 40% reduction in cardiac output significantly decreased transmural pulmonary artery pressure but did not affect PVO2, VS/VT%i or VL%- The mechanism of blood-flow reduction to atelectatic lung is therefore hypoxic pulmonary vasoconstriction, determined by the PVO2. The contribution of mechanical factors in reducing blood flow to atelectatic lung in the open chest is small

Exercise with Anemia: The Role of the Left-Shifted or Right-Shifted Oxygen-Hemoglobin Equilibrium Curve

Abstract Two patients with similar degrees of anemia, one with a left-shifted and one with a right-shifted oxygen-hemoglobin equilibrium curve, were exercised on a bicycle ergometer. The patient wi...

Pulmonary Blood Pressure and Flow during Atelectasis in the Dog

The purpose of the study was to measure the time course, direction, and magnitude of the hypoxic pulmonary vasoconstriction (HPV) response to atelectasis. Six dogs were anesthetized with pentobarbital. With the chest open, each lung was ventilated separately, Pulmonary blood flow was measured with electromagnetic flow probes. Pulmonary arterial, left atrial, and systemic arterial pressures were measured via indwelling catheters. The right lung was ventilated continuously with 100% O2, while the left lung was either ventilated with 100% O2, (control phase), unventilated (4 hours of atelectasis), or ventilated with a gas mixture containing 4% O2, 3% CO2, and 93% N2 (hypoxia phase). Left lung atelectasis resulted in a reduction of the per cent left lung blood flow from 43 ± 4% (mean ± SE) to 25 ± 7% at 15 min and to 12 ± 1% at 60 min which persisted for the remaining four-hour period. The per cent left lung blood flow was significantly lower (8 ± 1%) and the Pao2 significantly higher (356 ± 38 mmHg) during the maximal response to atelectasis as compared to 15 min of hypoxic ventilation (23 ± 5%; 211 ± 21 mmHg). With atelectasis or hypoxic ventilation, pulmonary perfusion pressure was increased significantly from the control value of 7.9 ± 0.8 mmHg to approximately 11 mmHg.The present study demonstrated that in the open chest model without systemic hypoxemia, the response to acute atelectasis is a regional increase in pulmonary vascular resistance which develops quickly (15 min) and is maximal by 60 min and is maintained thereafter. As a result, there is a sustained diversion of blood flow away from the atelectatic lung and a generalized increase of pulmonary perfusion pressure.

Improvement in Oxygenation by Phenylephrine and Nitric Oxide in Patients with Adult Respiratory Distress Syndrome

Background: Inhaled nitric oxide (NO), a selective vasodilator, improves oxygenation in many patients with adult respiratory distress syndrome (ARDS). Vasoconstrictors may also improve oxygenation, possibly by enhancing hypoxic pulmonary vasoconstriction. This study compared the effects of phenylephrine, NO, and their combination in patients with ARDS. Methods: Twelve patients with ARDS (PaO2 /FIO2 180; Murray score 2) were studied. Each patient received three treatments in random order: intravenous phenylephrine, 50–200 micro gram/min, titrated to a 20% increase in mean arterial blood pressure; inhaled NO, 40 ppm; and the combination (phenylephrine + NO). Hemodynamics and blood gas measurements were made during each treatment and at pre‐ and posttreatment baselines. Results: All three treatments improved PaO2 overall. Six patients were “phenylephrine‐responders” (Delta PaO2 > 10 mmHg), and six were “phenylephrine‐nonresponders.” In phenylephrine‐responders, the effect of phenylephrine was comparable with that of NO (PaO2 from 105 +/‐ 10 to 132 +/‐ 14 mmHg with phenylephrine, and from 110 +/‐ 14 to 143 +/‐ 19 mmHg with NO), and the effect of phenylephrine + NO was greater than that of either treatment alone (PaO2 from 123 +/‐ 13 to 178 +/‐ 23 mmHg). In phenylephrine‐nonresponders, phenylephrine did not affect Pa sub O2, and the effect of phenylephrine + NO was not statistically different from that of NO alone (PaO2 from 82 +/‐ 12 to 138 +/‐ 28 mmHg with NO; from 84 +/‐ 12 to 127 +/‐ 23 mmHg with phenylephrine + NO). Data are mean +/‐ SEM. Conclusions: Phenylephrine alone can improve PaO2 in patients with ARDS. In phenylephrine‐responsive patients, phenylephrine augments the improvement in PaO2 seen with inhaled NO. These results may reflect selective enhancement of hypoxic pulmonary vasoconstriction by phenylephrine, which complements selective vasodilation by NO.