Gas Exchange in the Lung.

Gas exchange in the lung depends on tidal breathing, which brings new oxygen to and removes carbon dioxide from alveolar gas. This maintains alveolar partial pressures that promote passive diffusion to add oxygen and remove carbon dioxide from blood in alveolar capillaries. In a lung model without ventilation and perfusion (V̇AQ̇) mismatch, alveolar partial pressures of oxygen and carbon dioxide are primarily determined by inspiratory pressures and alveolar ventilation. Regions with shunt or low ratios worsen arterial oxygenation while alveolar dead space and high lung units lessen CO2 elimination efficiency. Although less common, diffusion limitation might cause hypoxemia in some situations. This review covers the principles of lung gas exchange and therefore mechanisms of hypoxemia or hypercapnia. In addition, we discuss different metrics that quantify the deviation from ideal gas exchange.

Prospective randomized trial of moderately strenuous aerobic exercise after an implantable cardioverter defibrillator.

BACKGROUND: Despite its salutary effects on health, aerobic exercise is often avoided after receipt of an implantable cardioverter defibrillator (ICD) because of fears that exercise may provoke acute arrhythmias. We prospectively evaluated the effects of a home aerobic exercise training and maintenance program (EX) on aerobic performance, ICD shocks, and hospitalizations exclusively in ICD recipients. METHODS AND RESULTS: A total of 160 patients (124 men and 36 women) were randomly assigned who had an ICD for primary (43%) or secondary (57%) prevention to EX or usual care (UC). The primary outcome was peak oxygen consumption, measured with cardiopulmonary exercise testing at baseline and 8 and 24 weeks. EX consisted of 8 weeks of home walking for 1 h/d, 5 d/wk at 60% to 80% of heart rate reserve, followed by 16 weeks of maintenance home walking for 150 min/wk. Adherence to EX was determined from exercise logs, ambulatory heart rate recordings of exercise, and weekly telephone contacts. Patients assigned to UC received no exercise directives and were monitored by monthly telephone contact. Adverse events were identified by ICD interrogations, patient reports, and medical charts. ICD recipients averaged 55±12 years and mean ejection fraction of 40.6±15.7; all were taking ß-blocker medications. EX significantly increased peak oxygen consumption (EX, 26.7±7.0 mL/kg per minute; UC, 23.9±6.6 mL/kg per minute; P=0.002) at 8 weeks, which persisted during maintenance exercise at 24 weeks (EX, 26.9±7.7 mL/kg per minute; UC, 23.4±6.0 mL/kg per minute; P<0.001). ICD shocks were infrequent (EX=4 versus UC=8), with no differences in hospitalizations or deaths between groups. CONCLUSIONS: Prescribed home exercise is safe and significantly improves cardiovascular performance in ICD recipients without causing shocks or hospitalizations. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00522340.

Total and regional deposition of inhaled aerosols in supine healthy subjects and subjects with mild-to-moderate COPD.

Despite substantial development of sophisticated subject-specific computational models of aerosol transport and deposition in human lungs, experimental validation of predictions from these new models is sparse. We collected aerosol retention and exhalation profiles in seven healthy volunteers and six subjects with mild-to-moderate COPD (FEV1 = 50-80%predicted) in the supine posture. Total deposition was measured during continuous breathing of 1 and 2.9 µm-diameter particles (tidal volume of 1 L, flow rate of 0.3 L/s and 0.75 L/s). Bolus inhalations of 1 µm particles were performed to penetration volumes of 200, 500 and 800 mL (flow rate of 0.5 L/s). Aerosol bolus dispersion (H), deposition, and mode shift (MS) were calculated from these data. There was no significant difference in total deposition between healthy subjects and those with COPD. Total deposition increased with increasing particle size and also with increasing flow rate. Similarly, there was no significant difference in aerosol bolus deposition between subject groups. Yet, the rate of increase in dispersion and of decrease in MS with increasing penetration volume was higher in subjects with COPD than in healthy volunteers (H: 0.798 ± 0.205 vs. 0.527 ± 0.122 mL/mL, p=0.01; MS: -0.271±0.129 vs. -0.145 ± 0.076 mL/mL, p=0.05) indicating larger ventilation inhomogeneities (based on H) and increased flow sequencing (based on MS) in the COPD than in the healthy group. In conclusion, in the supine posture, deposition appears to lack sensitivity for assessing the effect of lung morphology and/or ventilation distribution alteration induced by mild-to-moderate lung disease on the fate of inhaled aerosols. However, other parameters such as aerosol bolus dispersion and mode shift may be more sensitive parameters for evaluating models of lungs with moderate disease.

Visualizing regional myocardial blood flow in the mouse.

RATIONALE: The spatial distribution of blood flow in the hearts of genetically modified mice is a phenotype of interest because derangements in blood flow may precede detectable changes in organ function. However, quantifying the regional distribution of blood flow within organs of mice is challenging because of the small organ volume and the high resolution required to observe spatial differences in flow. Traditional microsphere methods in which the numbers of microspheres per region are indirectly estimated from radioactive counts or extracted fluorescence have been limited to larger organs for 2 reasons; to ensure statistical confidence in the measured flow per region and to be able to physically dissect the organ to acquire spatial information. OBJECTIVE: To develop methods to quantify and statistically compare the spatial distribution of blood flow within organs of mice. METHODS AND RESULTS: We developed and validated statistical methods to compare blood flow between regions and with the same regions over time using 15-µm fluorescent microspheres. We then tested this approach by injecting fluorescent microspheres into isolated perfused mice hearts, determining the spatial location of every microsphere in the hearts, and then visualizing regional flow patterns. We demonstrated application of these statistical and visualizing methods in a coronary artery ligation model in mice. CONCLUSIONS: These new methods provide tools to investigate the spatial and temporal changes in blood flow within organs of mice at a much higher spatial resolution than currently available by other methods.

Comparison of CT-derived ventilation maps with deposition patterns of inhaled microspheres in rats.

PURPOSE: Computer models for inhalation toxicology and drug-aerosol delivery studies rely on ventilation pattern inputs for predictions of particle deposition and vapor uptake. However, changes in lung mechanics due to disease can impact airflow dynamics and model results. It has been demonstrated that non-invasive, in vivo, 4DCT imaging (3D imaging at multiple time points in the breathing cycle) can be used to map heterogeneities in ventilation patterns under healthy and disease conditions. The purpose of this study was to validate ventilation patterns measured from CT imaging by exposing the same rats to an aerosol of fluorescent microspheres (FMS) and examining particle deposition patterns using cryomicrotome imaging. MATERIALS AND METHODS: Six male Sprague-Dawley rats were intratracheally instilled with elastase to a single lobe to induce a heterogeneous disease. After four weeks, rats were imaged over the breathing cycle by CT then immediately exposed to an aerosol of ∼ 1 µm FMS for ∼ 5 minutes. After the exposure, the lungs were excised and prepared for cryomicrotome imaging, where a 3D image of FMS deposition was acquired using serial sectioning. Cryomicrotome images were spatially registered to match the live CT images to facilitate direct quantitative comparisons of FMS signal intensity with the CT-based ventilation maps. RESULTS: Comparisons of fractional ventilation in contiguous, non-overlapping, 3D regions between CT-based ventilation maps and FMS images showed strong correlations in fractional ventilation (r = 0.888, p < 0.0001). CONCLUSION: We conclude that ventilation maps derived from CT imaging are predictive of the 1 µm aerosol deposition used in ventilation-perfusion heterogeneity inhalation studies.

Gas exchange and ventilation-perfusion relationships in the lung.

This review provides an overview of the relationship between ventilation/perfusion ratios and gas exchange in the lung, emphasising basic concepts and relating them to clinical scenarios. For each gas exchanging unit, the alveolar and effluent blood partial pressures of oxygen and carbon dioxide (PO2 and PCO2) are determined by the ratio of alveolar ventilation to blood flow (V'A/Q') for each unit. Shunt and low V'A/Q' regions are two examples of V'A/Q' mismatch and are the most frequent causes of hypoxaemia. Diffusion limitation, hypoventilation and low inspired PO2 cause hypoxaemia, even in the absence of V'A/Q' mismatch. In contrast to other causes, hypoxaemia due to shunt responds poorly to supplemental oxygen. Gas exchanging units with little or no blood flow (high V'A/Q' regions) result in alveolar dead space and increased wasted ventilation, i.e. less efficient carbon dioxide removal. Because of the respiratory drive to maintain a normal arterial PCO2, the most frequent result of wasted ventilation is increased minute ventilation and work of breathing, not hypercapnia. Calculations of alveolar-arterial oxygen tension difference, venous admixture and wasted ventilation provide quantitative estimates of the effect of V'A/Q' mismatch on gas exchange. The types of V'A/Q' mismatch causing impaired gas exchange vary characteristically with different lung diseases.

Stabilized imaging of immune surveillance in the mouse lung.

Real-time imaging of cellular and subcellular dynamics in vascularized organs requires image resolution and image registration to be simultaneously optimized without perturbing normal physiology. This problem is particularly pronounced in the lung, in which cells may transit at speeds >1 mm s(-1) and in which normal respiration results in large-scale tissue movements that prevent image registration. Here we report video-rate, two-photon imaging of a physiologically intact preparation of the mouse lung that is stabilizing and nondisruptive. Using our method, we obtained evidence for differential trapping of T cells and neutrophils in mouse pulmonary capillaries, and observed neutrophil mobilization and dynamic vascular leak in response to stretch and inflammatory models of lung injury in mice. The system permits physiological measurement of motility rates of >1 mm s(-1), observation of detailed cellular morphology and could be applied in the future to other organs and tissues while maintaining intact physiology.

Validation of an axially distributed model for quantification of myocardial blood flow using ¹³N-ammonia PET.

BACKGROUND: Estimation of myocardial blood flow (MBF) with cardiac PET is often performed with conventional compartmental models. In this study, we developed and evaluated a physiologically and anatomically realistic axially distributed model. Unlike compartmental models, this axially distributed approach models both the temporal and the spatial gradients in uptake and retention along the capillary. METHODS: We validated PET-derived flow estimates with microsphere studies in 19 (9 rest, 10 stress) studies in five dogs. The radiotracer, (13)N-ammonia, was injected intravenously while microspheres were administered into the left atrium. A regional reduction in hyperemic flow was forced by an external occluder in five of the stress studies. The flow estimates from the axially distributed model were compared with estimates from conventional compartmental models. RESULTS: The mean difference between microspheres and the axially distributed blood flow estimates in each of the 17 segments was 0.03 mL/g/minute (95% CI [-0.05, 0.11]). The blood flow estimates were highly correlated with each regional microsphere value for the axially distributed model (y = 0.98x + 0.06 mL/g/minute; r = 0.74; P < .001), for the two-compartment (y = 0.64x + 0.34; r = 0.74; P < .001), and for three-compartment model (y = 0.69x + 0.54; r = 0.74; P < .001). The variance of the error of the estimates is higher with the axially distributed model than the compartmental models (1.7 [1.3, 2.1] times higher). CONCLUSION: The proposed axially distributed model provided accurate regional estimates of MBF. The axially distributed model estimated blood flow with more accuracy, but less precision, than the evaluated compartmental models.

A porcine model for initial surge mechanical ventilator assessment and evaluation of two limited-function ventilators.

OBJECTIVES: To adapt an animal model of acute lung injury for use as a standard protocol for a screening initial evaluation of limited function, or "surge," ventilators for use in mass casualty scenarios. DESIGN: Prospective, experimental animal study. SETTING: University research laboratory. SUBJECTS: Twelve adult pigs. INTERVENTIONS: Twelve spontaneously breathing pigs (six in each group) were subjected to acute lung injury/acute respiratory distress syndrome via pulmonary artery infusion of oleic acid. After development of respiratory failure, animals were mechanically ventilated with a limited-function ventilator (simplified automatic ventilator [SAVe] I or II; Automedx, Germantown, MD) for 1 hr or until the ventilator could not support the animal. The limited-function ventilator was then exchanged for a full-function ventilator (Servo 900C; Siemens-Elema, Solna, Sweden). MEASUREMENTS AND MAIN RESULTS: Reliable and reproducible levels of acute lung injury/acute respiratory distress syndrome were induced. The SAVe I was unable to adequately oxygenate five animals with Pao2 (52.0±11.1 torr) compared to the Servo (106.0±25.6 torr; p=.002). The SAVe II was able to oxygenate and ventilate all six animals for 1 hr with no difference in Pao2 (141.8±169.3 torr) compared to the Servo (158.3±167.7 torr). CONCLUSIONS: We describe a novel in vivo model of acute lung injury/acute respiratory distress syndrome that can be used to initially screen limited-function ventilators considered for mass respiratory failure stockpiles and that is intended to be combined with additional studies to definitively assess appropriateness for mass respiratory failure. Specifically, during this study we demonstrate that the SAVe I ventilator is unable to provide sufficient gas exchange, whereas the SAVe II, with several more functions, was able to support the same level of hypoxemic respiratory failure secondary to acute lung injury/acute respiratory distress syndrome for 1 hr.

Testing an exercise intervention to improve aerobic conditioning and autonomic function after an implantable cardioverter defibrillator (ICD).

BACKGROUND: Implantable cardioverter defibrillators (ICDs) are an increasingly common treatment for survivors of sudden cardiac arrest or others with life-threatening ventricular arrhythmias. Health-care providers are often reluctant to prescribe exercise for this group because of the belief that it will provoke ventricular arrhythmias and cardiac arrest; patients are often afraid to exercise because of concern over receiving an ICD shock. A social cognitive theory-driven exercise intervention aimed at stabilizing cardiac arrhythmias and reducing ICD shocks by increasing parasympathetic autonomic nervous system control is described. METHODS: The exercise intervention has two phases that include an 8-week aerobic conditioning component followed by a 16-week exercise maintenance component. The aerobic exercise intervention is expected to have significant impact on cardiopulmonary function, ventricular arrhythmias, cardiac autonomic function, and self-efficacy in persons who have an ICD. The exercise intervention is currently being tested using a randomized clinical trial format, the results of which will be available in 2012. CONCLUSION: The exercise after ICD trial is one of the first clinical trials to test the effects of aerobic exercise on cardiopulmonary outcomes after receiving an ICD for primary or secondary prevention of sudden cardiac arrest.

Mechanical ventilation modulates Toll-like receptor-3-induced lung inflammation via a MyD88-dependent, TLR4-independent pathway: a controlled animal study.

BACKGROUND: Mechanical ventilation augments lung inflammation resulting from exposure to microbial products. The objective of this study was to test the hypothesis that ventilator-associated immune modulation requires MyD88-dependent signaling. Because MyD88 is a critical adapter protein utilized for pro-inflammatory signaling by all Toll-like receptors (TLRs), with the exception of TLR3, as well as by the IL-1 and IL-18 receptors, MyD88 dependence would implicate generation of an endogenous soluble ligand recognized by one or more of these receptors during mechanical ventilation and would provide an opportunity for a potential future therapeutic intervention. METHODS: We compared the effect of mechanical ventilation on lung inflammation and permeability between poly(I:C) exposed mice with or without expression of MyD88. Poly(I:C) is a synthetic ligand for TLR3, the only MyD88-independent TLR, allowing isolation of the effect of MyD88 deletion on ventilator-augmentation of lung inflammation. Lung inflammation was assessed by cytokine concentration in lung tissue homogenate and polymorphonuclear cell (PMN) number in bronchoalveolar lavage fluid (BALF). Lung permeability was assessed by total protein, IgM, and intravenously injected FITC-dextran concentrations in BALF. RESULTS: We found that MyD88 was required for mechanical ventilation augmentation of TLR3-induced lung inflammation and permeability. Because TLR4 is the most commonly reported receptor for endogenous ligands generated during tissue injury, we performed a second experiment comparing wildtype and TLR4-/- mice. We found that mechanical ventilation increased TLR3-mediated inflammation and permeability independent of TLR4. CONCLUSION: These data support the hypothesis that mechanical ventilation with moderate tidal volumes generates an endogenous ligand(s) recognized by MyD88-dependent receptor(s) other than TLR4, and that this mechanism can contribute to the development of ventilator-associated lung inflammation and injury. Identification of these ligands and/or receptors could lead to new pharmacological treatments for ARDS.

The fractal geometry of bronchial trees differs by strain in mice.

Fractal biological structures are pervasive throughout the plant and animal kingdoms, with the mammalian lung being a quintessential example. The lung airway and vascular trees are generated during embryogenesis from a small set of building codes similar to Turing mechanisms that create robust trees ideally suited to their functions. Whereas the blood flow pattern generated by these fractal trees has been shown to be genetically determined, the geometry of the trees has not. We explored a newly established repository providing high-resolution bronchial trees from the four most commonly studied laboratory mice (B6C3F1, BALB/c, C57BL/6 and CD-1). The data fit a fractal model well for all animals with the fractal dimensions ranging from 1.54 to 1.67, indicating that the conducting airway of mice can be considered a self-similar and space-filling structure. We determined that the fractal dimensions of these airway trees differed by strain but not sex, reinforcing the concept that airway branching patterns are encoded within the DNA. The observations also highlight that future study design and interpretations may need to consider differences in airway geometry between mouse strains.NEW & NOTEWORTHY Similar to larger mammals such as humans, the geometries of the bronchial tree in mice are fractal structures that have repeating patterns from the trachea to the terminal branches. The airway geometries of the four most commonly studied mice are different and need to be considered when comparing results that employ different mouse strains. This variability in mouse airway geometries should be incorporated into computer models exploring toxicology and aerosol deposition in mouse models.

lapdMouse: associating lung anatomy with local particle deposition in mice.

To facilitate computational toxicology, we developed an approach for generating high-resolution lung-anatomy and particle-deposition mouse models. Major processing steps of our method include mouse preparation, serial block-face cryomicrotome imaging, and highly automated image analysis for generating three-dimensional (3D) mesh-based models and volume-based models of lung anatomy (airways, lobes, sublobes, and near-acini structures) that are linked to local particle-deposition measurements. Analysis resulted in 34 mouse models covering 4 different mouse strains (B6C3F1: 8, BALB/C: 11, C57Bl/6: 8, and CD-1: 7) as well as both sexes (16 male and 18 female) and different particle sizes [2 µm (n = 15), 1 µm (n = 16), and 0.5 µm (n = 3)]. On average, resulting mouse airway models had 1,616.9 ± 298.1 segments, a centerline length of 597.6 ± 59.8 mm, and 1,968.9 ± 296.3 outlet regions. In addition to 3D geometric lung models, matching detailed relative particle-deposition measurements are provided. All data sets are available online in the lapdMouse archive for download. The presented approach enables linking relative particle deposition to anatomical structures like airways. This will in turn improve the understanding of site-specific airflows and how they affect drug, environmental, or biological aerosol deposition.NEW & NOTEWORTHY Computer simulations of particle deposition in mouse lungs play an important role in computational toxicology. Until now, a limiting factor was the lack of high-resolution mouse lung models and measured local particle-deposition information, which are required for developing accurate modeling approaches (e.g., computational fluid dynamics). With the developed imaging and analysis approach, we address this issue and provide all of the raw and processed data in a publicly accessible repository.

Aerobic Exercise Effects on Quality of Life and Psychological Distress After an Implantable Cardioverter Defibrillator.

PURPOSE: The purpose of this study was to evaluate quality of life (QOL), psychological function, and self-efficacy outcomes in the Anti-Arrhythmic Effects of Exercise After an ICD Trial. METHODS: In the Anti-Arrhythmic Effects of Exercise After an ICD Trial, 160 patients (124 men and 36 women) who had an implantable cardioverter defibrillator for primary (43%) or secondary (57%) prevention were randomized to exercise (EX, n = 84) or usual care (UC, n = 76). The EX consisted of 8 wk of home walking 1 hr/d 5 d/wk, followed by 16 wk of maintenance home walking for 150 min/wk. Adherence was determined from exercise logs, ambulatory HR recordings, and phone calls. Assessments were conducted at baseline, 8, and 24 wk for QOL: Patient Concerns Assessment and Short Form-36; anxiety: State Trait Anxiety Inventory; depression: Physician Health Questionnaire-Depression; and self-efficacy: Self-Efficacy for Walking Scale. RESULTS: Participants averaged 55 ± 12 yr of age with ejection fraction = 40.6 ± 15.7%. The EX significantly decreased depression severity (EX: 1.33 ± 0.64; UC: 1.51 ± 0.86, P = .05) and improved self-efficacy (EX: 7.65 ± 1.97; UC: 6.85 ± 2.40, P = .05) at 8 wk. There were no significant effects at 24 wk. Adherent exercisers had significant improvements in QOL, psychological, and self-efficacy outcomes at 8 and 24 wk compared with those who were nonadherent. There were no implantable cardioverter defibrillator shocks associated with exercise. CONCLUSIONS: The EX conferred significant effects on depression and self-efficacy at 8 wk, without effects on QOL. Adherent exercisers experienced significant improvements in outcomes over those who were nonadherent or received UC.

Regional lung blood flow and ventilation in upright humans studied with quantitative SPECT.

We used quantitative Single Photon Emission Computed Tomography (SPECT) to study the effect of the upright posture on regional lung blood flow and ventilation. Nine (upright) plus seven (prone and supine) healthy volunteers were studied awake, breathing spontaneously. Regional blood flow and ventilation were marked in sitting upright, supine and prone postures using (113m)In-labeled macroaggregates and inhaled Technegas ((99m)Tc); both remain fixed in the lung after administration. All images were obtained while supine. In comparison with horizontal postures, both blood flow and ventilation were greater in caudal regions when upright. The redistribution was greater for blood flow than for ventilation, resulting in decreasing ventilation-to-perfusion ratios down the lung when upright. We conclude that gravity redistributes regional blood flow and ventilation in the upright posture, while the influence is much less in the supine and prone postures.

A perpetual switching system in pulmonary capillaries.

Of the 300 billion capillaries in the human lung, a small fraction meet normal oxygen requirements at rest, with the remainder forming a large reserve. The maximum oxygen demands of the acute stress response require that the reserve capillaries are rapidly recruited. To remain primed for emergencies, the normal cardiac output must be parceled throughout the capillary bed to maintain low opening pressures. The flow-distributing system requires complex switching. Because the pulmonary microcirculation contains contractile machinery, one hypothesis posits an active switching system. The opposing hypothesis is based on passive switching that requires no regulation. Both hypotheses were tested ex vivo in canine lung lobes. The lobes were perfused first with autologous blood, and capillary switching patterns were recorded by videomicroscopy. Next, the vasculature of the lobes was saline flushed, fixed by glutaraldehyde perfusion, flushed again, and then reperfused with the original, unfixed blood. Flow patterns through the same capillaries were recorded again. The 16-min-long videos were divided into 4-s increments. Each capillary segment was recorded as being perfused if at least one red blood cell crossed the entire segment. Otherwise it was recorded as unperfused. These binary measurements were made manually for each segment during every 4 s throughout the 16-min recordings of the fresh and fixed capillaries (>60,000 measurements). Unexpectedly, the switching patterns did not change after fixation. We conclude that the pulmonary capillaries can remain primed for emergencies without requiring regulation: no detectors, no feedback loops, and no effectors-a rare system in biology. NEW & NOTEWORTHY The fluctuating flow patterns of red blood cells within the pulmonary capillary networks have been assumed to be actively controlled within the pulmonary microcirculation. Here we show that the capillary flow switching patterns in the same network are the same whether the lungs are fresh or fixed. This unexpected observation can be successfully explained by a new model of pulmonary capillary flow based on chaos theory and fractal mathematics.

Leading Change and Negotiation Strategies for Division Leaders in Clinical Medicine.

Most physician leaders assume their administrative role based on past achievements but with very little leadership training. In this article, leaders of the Association of Pulmonary, Critical Care, and Sleep Division Directors describe two leadership skills that are often required to effectively lead in a clinical division at an academic or community hospital setting: leading change and negotiation strategy. We adopted our discussion from the business sector and refined the approaches through our own experiences to help division leaders in leading a successful team, whether as a division chief, residency or fellowship program director, or a clinical service director. Leading any change project may include an eight-step process, starting with creating a sense of urgency and completing with anchoring the change to the organizational culture. We then review negotiation strategies, comparing positional bargaining vs principled negotiation, to create more changes and continuing growth for the division. Finally, we discuss the importance of emotional intelligence, exemplary leadership practices, and self-development that the division leader should embrace.

Effects of anemia and hypotension on porcine optic nerve blood flow and oxygen delivery.

BACKGROUND: Perioperative ischemic optic neuropathy occurs after major surgical procedures, which are often associated with hypotension, anemia, or venous congestion. However, the effects of these conditions on optic nerve (ON) blood flow are unknown and cannot be studied adequately in humans. METHODS: Farm-raised pigs were anesthetized with isoflurane, kept normocapnic and normothermic, and subjected to conditions of euvolemic or hypovolemic hypotension (mean arterial pressure 50-55 mm Hg), anemia (hematocrit 17%), venous congestion, and combinations thereof. Control animals were kept euvolemic and normotensive for the entire experiment. Fluorescent microspheres were used to measure cerebral blood flow (CBF) and ON blood flow at baseline and after experimental conditions, and to calculate oxygen delivery (DO2). RESULTS: No significant changes in CBF or ON blood flow or DO2 occurred with euvolemic hypotension (n = 5), compared with controls (n = 12). Hypovolemic hypotension (n = 4) resulted in stable CBF and cerebral DO2, but significant reductions in ON DO2 (P = 0.032). The significant increase in CBF associated with anemia (n = 6) resulted in stable cerebral DO2. In contrast, ON blood flow did not significantly change with anemia, with (n = 5) or without (n = 6) euvolemic hypotension, resulting in significant reductions in ON DO2 (P < 0.01). CONCLUSION: Compensatory mechanisms for porcine CBF maintain stable DO2 under specified conditions of hypotension or anemia, whereas ON compensatory mechanisms were unable to maintain blood flow and to preserve DO2. The authors conclude that the porcine ON is more susceptible to physiologic perturbations than the brain.

Teaching ventilation/perfusion relationships in the lung.

This brief review is meant to serve as a refresher for faculty teaching respiratory physiology to medical students. The concepts of ventilation and perfusion matching are some of the most challenging ideas to learn and teach. Some strategies to consider in teaching these concepts are, first, to build from simple to more complex by starting with a single lung unit and then adding additional units representing shunting, mismatch, and deadspace. Second, use simplified analogies, such as a bathtub, to help students conceptualize new ideas. Third, introduce the concept of alveolar to arterial O(2) differences and the mechanisms for increasing differences as additional lung units are added. Fourth, use the consistent thread of causes of hypoxemia through the lecture to maintain continuity and provide clinical relevance. Finally, use clinically relevant examples at each step and solidify new concepts by discussing differential diagnoses at the end of the lecture(s).