Pulmonary embolization causes hypoxemia by redistributing regional blood flow without changing ventilation

1998 ◽  
Vol 85 (6) ◽  
pp. 2337-2343 ◽  
Author(s):  
William A. Altemeier ◽  
H. Thomas Robertson ◽  
Steve McKinney ◽  
Robb W. Glenny
Keyword(s):  
Blood Flow ◽  
Regional Blood Flow ◽  
Alveolar Ventilation ◽  
Regional Perfusion ◽  
Regional Ventilation ◽  
Fluorescent Microspheres ◽  
Mechanically Ventilated ◽  
Before And After ◽  
Pulmonary Embolization ◽  
Ventilation And Perfusion

To explore mechanisms of hypoxemia after acute pulmonary embolism, we measured regional pulmonary blood flow and alveolar ventilation before and after embolization with 780-μm beads in five anesthetized, mechanically ventilated pigs. Regional ventilation and perfusion were determined in ∼2.0-cm3 lung volumes by using 1-μm-diameter aerosolized and 15-μm-diameter injected fluorescent microspheres. Hypoxemia after embolization resulted from increased perfusion to regions with low ventilation-to-perfusion ratios. Embolization caused an increase in perfusion heterogeneity and a fall in the correlation between ventilation and perfusion. Correlation between regional ventilation pre- and postembolization was greater than correlation between regional perfusion pre- and postembolization. The majority of regional ventilation-to-perfusion ratio heterogeneity was attributable to changes in regional perfusion. Regional perfusion redistribution without compensatory changes in regional ventilation is responsible for hypoxemia after pulmonary vascular embolization in pigs.

Correlation between ventilation and perfusion determinesV˙a/Q˙ heterogeneity in endotoxemia

2000 ◽  
Vol 88 (6) ◽  
pp. 1933-1942 ◽  
Author(s):  
Anthony J. Gerbino ◽  
Steven McKinney ◽  
Robb W. Glenny
Keyword(s):  
Alveolar Ventilation ◽  
Regional Ventilation ◽  
Fluorescent Microspheres ◽  
Mechanically Ventilated ◽  
E Coli ◽  
Ventilation Heterogeneity ◽  
The Impact ◽  
Ventilation And Perfusion

Endotoxin increases ventilation-to-perfusion ratio (V˙a/Q˙) heterogeneity in the lung, but the precise changes in alveolar ventilation (V˙a) and perfusion that lead toV˙a/Q˙heterogeneity are unknown. The purpose of this study was to determine how endotoxin affects the distributions of ventilation and perfusion and the impact of these changes onV˙a/Q˙heterogeneity. Seven anesthetized, mechanically ventilated juvenile pigs were given E. coli endotoxin intravenously, and regional ventilation and perfusion were measured simultaneously by using aerosolized and injected fluorescent microspheres. Endotoxemia significantly decreased the correlation between regional ventilation and perfusion, increased perfusion heterogeneity, and redistributed perfusion between lung regions. In contrast, ventilation heterogeneity did not change, and redistribution of ventilation was modest. The decrease in correlation between regional ventilation and perfusion was responsible for significantly moreV˙a/Q˙ heterogeneity than were changes in ventilation or perfusion heterogeneity. We conclude that V˙a/Q˙heterogeneity increases during endotoxemia primarily as a result of the decrease in correlation between regional ventilation and perfusion, which is in turn determined primarily by changes in perfusion.

Vasomotor tone does not affect perfusion heterogeneity and gas exchange in normal primate lungs during normoxia

2000 ◽  
Vol 89 (6) ◽  
pp. 2263-2267 ◽  
Author(s):  
Robb W. Glenny ◽  
H. Thomas Robertson ◽  
Michael P. Hlastala
Keyword(s):  
Blood Flow ◽  
Gas Exchange ◽  
Regional Blood Flow ◽  
Flow Distribution ◽  
Regional Perfusion ◽  
Vasomotor Tone ◽  
Heterogeneous Distribution ◽  
Mechanically Ventilated ◽  
Before And After ◽  
Spatial Coordinates

To determine whether vasoregulation is an important cause of pulmonary perfusion heterogeneity, we measured regional blood flow and gas exchange before and after giving prostacyclin (PGI2) to baboons. Four animals were anesthetized with ketamine and mechanically ventilated. Fluorescent microspheres were used to mark regional perfusion before and after PGI2 infusion. The lungs were subsequently excised, dried inflated, and diced into ∼2-cm3 pieces ( n = 1,208–1,629 per animal) with the spatial coordinates recorded for each piece. Blood flow to each piece was determined for each condition from the fluorescent signals. Blood flow heterogeneity did not change with PGI2 infusion. Two other measures of spatial blood flow distribution, the fractal dimension and the spatial correlation, did not change with PGI2 infusion. Alveolar-arterial O2 differences did not change with PGI2 infusion. We conclude that, in normal primate lungs during normoxia, vasomotor tone is not a significant cause of perfusion heterogeneity. Despite the heterogeneous distribution of blood flow, active regulation of regional perfusion is not required for efficient gas exchange.

Acetazolamide slows VA/Q matching after changes in regional blood flow

1995 ◽  
Vol 78 (4) ◽  
pp. 1312-1318 ◽  
Author(s):  
E. R. Swenson ◽  
M. M. Graham ◽  
M. P. Hlastala
Keyword(s):  
Regional Blood Flow ◽  
Main Pulmonary Artery ◽  
Inert Gas ◽  
Left Main ◽  
Regional Ventilation ◽  
Mechanically Ventilated ◽  
Gamma Imaging ◽  
Abrupt Changes ◽  
Before And After ◽  
Ventilation And Perfusion

Inhibition of carbonic anhydrase (CA) by acetazolamide increases ventilation-perfusion (VA/Q) heterogeneity (E. R. Swenson, H. T. Robertson, and M. P. Hlastala. J. Clin. Invest. 92: 702–709, 1993), possibly because of slowing of CO2/H(+)-dependent mechanisms of VA/Q matching with temporal fluctuations of regional ventilation and perfusion. To study this concept, we imposed abrupt changes in regional perfusion by lobar or left main pulmonary artery occlusions (PAOs) in anesthetized mechanically ventilated dogs before and after CA inhibition (20 mg/kg iv acetazolamide). The rate of ventilation redistribution and change in VA/Q distributions with changes in perfusion were measured by planar gamma imaging of the lungs during continuous inhalation of 81mKr gas ventilation scanning and the multiple inert-gas elimination technique. PAO for 5 min caused regional Kr activity to fall by 30 +/- 5% (SD) with a half time (t1/2) of 75 +/- 10 s. With release of the occlusion, counts returned to baseline with t1/2 of 79 +/- 12 s. Acetazolamide increased these respective t1/2 values (161 +/- 16 and 180 +/- 17 s). Consistent with these kinetics, VA/Q mismatch was greater with lobar PAO at 2 min but not at 10 min with CA inhibition compared with that caused by lobar PAO alone. Cyclical lobar PAO and release (10 cycles of 1-min occlusion and 1-min release) caused more VA/Q heterogeneity during CA inhibition. The arterial-to-alveolar inert-gas area difference rose minimally from 0.18 to 0.23 (P < 0.05) with cyclical PAO and from 0.24 to 0.48 (P < 0.01) after CA inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Fractal nature of regional ventilation distribution

2000 ◽  
Vol 88 (5) ◽  
pp. 1551-1557 ◽  
Author(s):  
William A. Altemeier ◽  
Steve McKinney ◽  
Robb W. Glenny
Keyword(s):  
Blood Flow ◽  
Regional Blood Flow ◽  
Fractal Dimensions ◽  
Close Correlation ◽  
Aerosol Deposition ◽  
Regional Ventilation ◽  
Significant Difference ◽  
Ventilation Heterogeneity ◽  
Highly Correlated ◽  
Ventilation And Perfusion

High-resolution measurements of pulmonary perfusion reveal substantial spatial heterogeneity that is fractally distributed. This observation led to the hypothesis that the vascular tree is the principal determinant of regional blood flow. Recent studies using aerosol deposition show similar ventilation heterogeneity that is closely correlated with perfusion. We hypothesize that ventilation has fractal characteristics similar to blood flow. We measured regional ventilation and perfusion with aerosolized and injected fluorescent microspheres in six anesthetized, mechanically ventilated pigs in both prone and supine postures. Adjacent regions were clustered into progressively larger groups. Coefficients of variation were calculated for each cluster size to determine fractal dimensions. At the smallest size lung piece, local ventilation and perfusion are highly correlated, with no significant difference between ventilation and perfusion heterogeneity. On average, the fractal dimension of ventilation is 1.16 in the prone posture and 1.09 in the supine posture. Ventilation has fractal properties similar to perfusion. Efficient gas exchange is preserved, despite ventilation and perfusion heterogeneity, through close correlation. One potential explanation is the similar geometry of bronchial and vascular structures.

Endotoxemia increases relative perfusion to dorsal-caudal lung regions

2001 ◽  
Vol 90 (4) ◽  
pp. 1508-1515 ◽  
Author(s):  
Anthony J. Gerbino ◽  
William A. Altemeier ◽  
Carmel Schimmel ◽  
Robb W. Glenny
Keyword(s):  
Spatial Distribution ◽  
Acute Lung Injury ◽  
Gas Exchange ◽  
Lung Injury ◽  
Vascular Response ◽  
Regional Ventilation ◽  
Fluorescent Microspheres ◽  
Mechanically Ventilated ◽  
Ventilation And Perfusion ◽  
Time Point

Changes in the spatial distribution of perfusion during acute lung injury and their impact on gas exchange are poorly understood. We tested whether endotoxemia caused topographical differences in perfusion and whether these differences caused meaningful changes in regional ventilation-to-perfusion ratios and gas exchange. Regional ventilation and perfusion were measured in anesthetized, mechanically ventilated pigs in the prone position before and during endotoxemia with the use of aerosolized and intravenous fluorescent microspheres. On average, relative perfusion halved in ventral and cranial lung regions, doubled in caudal lung regions, and increased 1.5-fold in dorsal lung regions during endotoxemia. In contrast, there were no topographical differences in perfusion before endotoxemia and no topographical differences in ventilation at any time point. Consequently, endotoxemia increased regional ventilation-to-perfusion ratios in the caudal-to-cranial and dorsal-to-ventral directions, resulting in end-capillary Po 2 values that were significantly lower in dorsal-caudal than ventral-cranial regions. We conclude that there are topographical differences in the pulmonary vascular response to endotoxin that may have important consequences for gas exchange in acute lung injury.

Spatial distribution of ventilation and perfusion in anesthetized dogs in lateral postures

2002 ◽  
Vol 92 (2) ◽  
pp. 745-762 ◽  
Author(s):  
Hung Chang ◽  
Stephen J. Lai-Fook ◽  
Karen B. Domino ◽  
Carmel Schimmel ◽  
Jack Hildebrandt ◽  
...  
Keyword(s):  
Blood Flow ◽  
Gas Exchange ◽  
Regional Blood Flow ◽  
Linear Regression Analysis ◽  
Regional Distribution ◽  
Left Lung ◽  
Vertical Gradient ◽  
Fluorescent Microspheres ◽  
Lateral Decubitus ◽  
Ventilation And Perfusion

We aimed to assess the influence of lateral decubitus postures and positive end-expiratory pressure (PEEP) on the regional distribution of ventilation and perfusion. We measured regional ventilation (V˙a) and regional blood flow (Q˙) in six anesthetized, mechanically ventilated dogs in the left (LLD) and right lateral decubitus (RLD) postures with and without 10 cmH2O PEEP. Q˙ was measured by use of intravenously injected 15-μm fluorescent microspheres, and V˙a was measured by aerosolized 1-μm fluorescent microspheres. Fluorescence was analyzed in lung pieces ∼1.7 cm3 in volume. Multiple linear regression analysis was used to evaluate three-dimensional spatial gradients ofQ˙, V˙a, the ratio V˙a/Q˙, and regional Po 2 (PrO2 ) in both lungs. In the LLD posture, a gravity-dependent vertical gradient in Q˙ was observed in both lungs in conjunction with a reduced blood flow and PrO2 to the dependent left lung. Change from the LLD to the RLD or 10 cmH2O PEEP increased localV˙a/Q˙ and PrO2 in the left lung and minimized any role of hypoxia. The greatest reduction in individual lung volume occurred to the left lung in the LLD posture. We conclude that lung distortion caused by the weight of the heart and abdomen is greater in the LLD posture and influences both Q˙ andV˙a, and ultimately gas exchange. In this respect, the smaller left lung was the most susceptible to impaired gas exchange in the LLD posture.

Microsphere maps of regional blood flow and regional ventilation

2007 ◽  
Vol 102 (3) ◽  
pp. 1265-1272 ◽  
Author(s):  
H. Thomas Robertson ◽  
Michael P. Hlastala
Keyword(s):  
Blood Flow ◽  
High Resolution ◽  
Regional Blood Flow ◽  
Alveolar Ventilation ◽  
Regional Ventilation ◽  
Flow Heterogeneity ◽  
Fluorescent Microsphere ◽  
Flow Maps ◽  
Regional Flow ◽  
Alveolar Tissue

Systematically mapped samples cut from lungs previously labeled with intravascular and aerosol microspheres can be used to create high-resolution maps of regional perfusion and regional ventilation. With multiple radioactive or fluorescent microsphere labels available, this methodology can compare regional flow responses to different interventions without partial volume effects or registration errors that complicate interpretation of in vivo imaging measurements. Microsphere blood flow maps examined at different levels of spatial resolution have revealed that regional flow heterogeneity increases progressively down to an acinar level of scale. This pattern of scale-dependent heterogeneity is characteristic of a fractal distribution network, and it suggests that the anatomic configuration of the pulmonary vascular tree is the primary determinant of high-resolution regional flow heterogeneity. At ∼2-cm3 resolution, the large-scale gravitational gradients of blood flow per unit weight of alveolar tissue account for <5% of the overall flow heterogeneity. Furthermore, regional blood flow per gram of alveolar tissue remains relatively constant with different body positions, gravitational stresses, and exercise. Regional alveolar ventilation is accurately represented by the deposition of inhaled 1.0-μm fluorescent microsphere aerosols, at least down to the ∼2-cm3 level of scale. Analysis of these ventilation maps has revealed the same scale-dependent property of regional alveolar ventilation heterogeneity, with a strong correlation between ventilation and blood flow maintained at all levels of scale. The ventilation-perfusion (V̇a/Q̇) distributions obtained from microsphere flow maps of normal animals agree with simultaneously acquired multiple inert-gas elimination technique V̇a/Q̇ distributions, but they underestimate gas-exchange impairment in diffuse lung injury.

Selected Contribution: Redistribution of pulmonary perfusion during weightlessness and increased gravity

2000 ◽  
Vol 89 (3) ◽  
pp. 1239-1248 ◽  
Author(s):  
Robb W. Glenny ◽  
Wayne J. E. Lamm ◽  
Susan L. Bernard ◽  
Dowon An ◽  
Myron Chornuk ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Blood Flow ◽  
Regional Blood Flow ◽  
Regional Perfusion ◽  
Vascular Structure ◽  
Vascular Tree ◽  
Fluorescent Microspheres ◽  
Stepwise Linear Regression ◽  
Gravitational Forces ◽  
Primary Determinant

To compare the relative contributions of gravity and vascular structure to the distribution of pulmonary blood flow, we flew with pigs on the National Aeronautics and Space Administration KC-135 aircraft. A series of parabolas created alternating weightlessness and 1.8-G conditions. Fluorescent microspheres of varying colors were injected into the pulmonary circulation to mark regional blood flow during different postural and gravitational conditions. The lungs were subsequently removed, air dried, and sectioned into ∼2 cm3 pieces. Flow to each piece was determined for the different conditions. Perfusion heterogeneity did not change significantly during weightlessness compared with normal and increased gravitational forces. Regional blood flow to each lung piece changed little despite alterations in posture and gravitational forces. With the use of multiple stepwise linear regression, the contributions of gravity and vascular structure to regional perfusion were separated. We conclude that both gravity and the geometry of the pulmonary vascular tree influence regional pulmonary blood flow. However, the structure of the vascular tree is the primary determinant of regional perfusion in these animals.

Effect of posture on regional gas exchange in pigs

2004 ◽  
Vol 97 (6) ◽  
pp. 2104-2111 ◽  
Author(s):  
William A. Altemeier ◽  
Steve McKinney ◽  
Melissa Krueger ◽  
Robb W. Glenny
Keyword(s):  
Blood Flow ◽  
Gas Exchange ◽  
Oxygen Tension ◽  
Regional Blood Flow ◽  
Flow Distribution ◽  
Regional Ventilation ◽  
Total Blood ◽  
Ventilation Heterogeneity ◽  
Alveolar Oxygen ◽  
Ventilation And Perfusion

Although recent high-resolution studies demonstrate the importance of nongravitational determinants for both pulmonary blood flow and ventilation distributions, posture has a clear impact on whole lung gas exchange. Deterioration in arterial oxygenation with repositioning from prone to supine posture is caused by increased heterogeneity in the distribution of ventilation-to-perfusion ratios. This can result from increased heterogeneity in regional blood flow distribution, increased heterogeneity in regional ventilation distribution, decreased correlation between regional blood flow and ventilation, or some combination of the above (Wilson TA and Beck KC, J Appl Physiol 72: 2298–2304, 1992). We hypothesize that, although repositioning from prone to supine has relatively small effects on overall blood flow and ventilation distributions, regional changes are poorly correlated, resulting in regional ventilation-perfusion mismatch and reduction in alveolar oxygen tension. We report ventilation and perfusion distributions in seven anesthetized, mechanically ventilated pigs measured with aerosolized and injected microspheres. Total contributions of pulmonary structure and posture on ventilation and perfusion heterogeneities were quantified by using analysis of variance. Regional gradients of posture-mediated change in ventilation, perfusion, and calculated alveolar oxygen tension were examined in the caudocranial and ventrodorsal directions. We found that pulmonary structure was responsible for 74.0 ± 4.7% of total ventilation heterogeneity and 63.3 ± 4.2% of total blood flow heterogeneity. Posture-mediated redistribution was primarily oriented along the caudocranial axis for ventilation and along the ventrodorsal axis for blood flow. These mismatched changes reduced alveolar oxygen tension primarily in the dorsocaudal lung region.

Gravity is an important but secondary determinant of regional pulmonary blood flow in upright primates

1999 ◽  
Vol 86 (2) ◽  
pp. 623-632 ◽  
Author(s):  
Robb W. Glenny ◽  
Susan Bernard ◽  
H. Thomas Robertson ◽  
Michael P. Hlastala
Keyword(s):  
Blood Flow ◽  
Pulmonary Blood Flow ◽  
Stepwise Regression ◽  
Regional Blood Flow ◽  
Laboratory Animals ◽  
Pulmonary Perfusion ◽  
Fluorescent Microspheres ◽  
Mechanically Ventilated ◽  
Gravitational Model ◽  
Spatial Coordinates

Original studies leading to the gravitational model of pulmonary blood flow and contemporary studies showing gravity-independent perfusion differ in the recent use of laboratory animals instead of humans. We explored the distribution of pulmonary blood flow in baboons because their anatomy, serial distribution of vascular resistances, and hemodynamic responses to hypoxia are similar to those of humans. Four baboons were anesthetized with ketamine, intubated, and mechanically ventilated. Different colors of fluorescent microspheres were given intravenously while the animals were in the supine, prone, upright (repeated), and head-down (repeated) postures. The animals were killed, and their lungs were excised, dried, and diced into ∼2-cm3 pieces with the spatial coordinates recorded for each piece. Regional blood flow was determined for each posture from the fluorescent signals of each piece. Perfusion heterogeneity was greatest in the upright posture and least when prone. Using multiple-stepwise regression, we estimate that 7, 5, and 25% of perfusion heterogeneity is due to gravity in the supine, prone, and upright postures, respectively. Although important, gravity is not the predominant determinant of pulmonary perfusion heterogeneity in upright primates. Because of anatomic similarities, the same may be true for humans.

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