Effects of age on pulmonary perfusion heterogeneity measured by magnetic resonance imaging.

Normal aging is associated with a decline in pulmonary function and efficiency of gas exchange, although the effects on the spatial distribution of pulmonary perfusion are poorly understood. We hypothesized that spatial pulmonary perfusion heterogeneity would increase with increasing age. Fifty-six healthy, nonsmoking subjects (ages 21-76 yr) underwent magnetic resonance imaging with arterial spin labeling (ASL) using a Vision 1.5-T whole body scanner (Siemens Medical Systems, Erlangen, Germany). ASL uses a magnetically tagged bolus to generate perfusion maps where signal intensity is proportional to regional pulmonary perfusion. The spatial heterogeneity of pulmonary blood flow was quantified by the relative dispersion (RD = SD/mean, a global index of heterogeneity) of signal intensity for voxels within the right lung and by the fractal dimension (D(s)). There were no significant sex differences for RD (P = 0.81) or D(s) (P = 0.43) when age was considered as a covariate. RD increased significantly with increasing age by approximately 0.1/decade until age 50-59 yr, and there was a significant positive relationship between RD and age (R = 0.48, P < 0.0005) and height (R = 0.39, P < 0.01), but not body mass index (R = 0.07, P = 0.67). Age and height combined in a multiple regression were significantly related to RD (R = 0.66, P < 0.0001). There was no significant relationship between RD and spirometry or arterial oxygen saturation. D(s) was not related to age, height, spirometry, or arterial oxygen saturation. The lack of relationship between age and D(s) argues against an intrinsic alteration in the pulmonary vascular branching with age as being responsible for the observed increase in global spatial perfusion heterogeneity measured by the RD.     

Pulmonary blood flow remains fractal down to the level of gas exchange.

The spatial distribution of pulmonary blood flow is increasingly heterogeneous as progressively smaller lung regions are examined. To determine the extent of perfusion heterogeneity at the level of gas exchange, we studied blood flow distributions in rat lungs by using an imaging cryomicrotome. Approximately 150,000 fluorescent 15-microm-diameter microspheres were injected into tail veins of five awake rats. The rats were heavily anesthetized; the lungs were removed, filled with an optimal cutting tissue compound, and frozen; and the spatial location of every microsphere was determined. The data were mathematically dissected with the use of an unbiased random sampling method. The coefficients of variation of microsphere distributions were determined at varying sampling volumes. Perfusion heterogeneity increased linearly on a log-log plot of coefficient of variation vs. volume, down to the smallest sampling size of 0.53 mm(3). The average fractal dimension, a scale-independent measure of perfusion distribution, was 1.2. This value is similar to that of other larger species such as dogs, pigs, and horses. Pulmonary perfusion heterogeneity increases continuously and remains fractal down to the acinar level. Despite the large degree of perfusion heterogeneity at the acinar level, gases are efficiently exchanged.     

Effect of posture on regional gas exchange in pigs.

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.     

Hypoxia and angiotensin II infusion redistribute lung blood flow in lambs

To assess the effects of alveolar hypoxia and angiotensin II infusion on distribution of blood flow to the lung we performed perfusion lung scans on anesthetized mechanically ventilated lambs. Scans were obtained by injecting 1-2 mCi of technetium-labeled albumin macroaggregates as the lambs were ventilated with air, with 10-14% O2 in N2, or with air while receiving angiotensin II intravenously. We found that both alveolar hypoxia and infusion of angiotensin II increased pulmonary vascular resistance and redistributed blood flow from the mid and lower lung regions towards the upper posterior region of the lung. We assessed the effects of angiotensin II infusion on filtration pressure in six lambs by measuring the rate of lung lymph flow and the protein concentration of samples of lung lymph. We found that angiotensin II infusion increased pulmonary arterial pressure 50%, lung lymph flow 90%, and decreased the concentration of protein in lymph relative to plasma. These results are identical to those seen when filtration pressure increases during alveolar hypoxia. We conclude that alveolar hypoxia and angiotensin II infusion both increase fluid filtration in the lung by increasing filtration pressure. The increase in filtration pressure may be the result of a redistribution of blood flow in the lung with relative overperfusion of vessels in some areas and transmission of the elevated pulmonary arterial pressure to fluid-exchanging sites in those vessels.     

Gravity is a minor determinant of pulmonary blood flow distribution

Regional pulmonary blood flow in dogs under zone 3 conditions was measured in supine and prone postures to evaluate the linear gravitational model of perfusion distribution. Flow to regions of lung that were 1.9 cm3 in volume was determined by injection of radiolabeled microspheres in both postures. There was marked perfusion heterogeneity within isogravitational planes (coefficient of variation = 42.5%) as well as within gravitational planes (coefficient of variation = 44.2 and 39.2% in supine and prone postures, respectively; P = 0.02). On average, vertical height explained only 5.8 and 2.4% of the flow variability in the supine and prone postures, respectively. Whereas the gravitational model predicts that regional flows should be negatively correlated when measured in supine and prone postures, flows in the two postures were positively correlated, with an r2 of 0.708 +/- 0.050. Regional perfusion as a function of distance from the center of a lung explained 13.4 and 10.8% of the flow variability in the supine and prone postures, respectively. A linear combination of vertical height and radial distance from the centers of each lung provided a better-fitting model but still explained only 20.0 and 12.0% of the flow variability in the supine and prone postures, respectively. The entire lung was searched for a region of contiguous lung pieces (22.8 cm3) with high flow. Such a region was found in the dorsal area of the lower lobes in six of seven animals, and flow to this region was independent of posture. Under zone 3 conditions, neither gravity nor radial location is the principal determinant of regional perfusion distribution in supine and prone dogs.     

Measurement of bronchial blood flow with radioactive microspheres in awake sheep

Distribution of bronchial blood flow was measured in unanesthetized sheep by the use of two modifications of the microsphere reference sample technique that correct for peripheral shunting of microspheres: 1) A double microsphere method in which simultaneous left and right atrial injections of 15-microns microspheres tagged with different isotopes allowed measurement of both pulmonary blood flow and shunt-corrected bronchial blood flow, and 2) a pulmonary arterial occlusion method in which left atrial injection and transient occlusion of the left pulmonary artery prevented delivery to the lung of microspheres shunted through the peripheral circulation and allowed systemic blood flow to the left lung to be measured. Both methods can be performed in unanesthetized sheep. The pulmonary arterial occlusion method is less costly and requires fewer calculations. The double microsphere method requires less surgical preparation and allows measurement without perturbation of pulmonary hemodynamics. There was no statistically significant difference between bronchial blood flow measured with the two methods. However, total bronchial blood flow measured during pulmonary arterial occlusion (1.52 +/- 0.98% of cardiac output, n = 9) was slightly higher than that measured with the double microsphere method (1.39 +/- 0.88% of cardiac output, n = 9). In another series of experiments in which sequential measurements of bronchial blood flow were made, there was a significant increase of 15% in left lung bronchial blood flow during the first minute of occlusion of the left pulmonary artery. Thus pulmonary arterial occlusion should be performed 5 s after microsphere injection as originally described by Baile et al. (1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Microsphere maps of regional blood flow and regional ventilation.

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 approximately 2-cm(3) 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-microm fluorescent microsphere aerosols, at least down to the approximately 2-cm(3) 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 (VA/Q) distributions obtained from microsphere flow maps of normal animals agree with simultaneously acquired multiple inert-gas elimination technique VA/Q distributions, but they underestimate gas-exchange impairment in diffuse lung injury.     

Inter-Slice Blood Flow and Magnetization Transfer Effects as A New Simultaneous Imaging Strategy

The recent blood flow and magnetization transfer (MT) technique termed alternate ascending/descending directional navigation (ALADDIN) achieves the contrast using interslice blood flow and MT effects with no separate preparation RF pulse, thereby potentially overcoming limitations of conventional methods. In this study, we examined the signal characteristics of ALADDIN as a simultaneous blood flow and MT imaging strategy, by comparing it with pseudo-continuous ASL (pCASL) and conventional MT asymmetry (MTA) methods, all of which had the same bSSFP readout. Bloch-equation simulations and experiments showed ALADDIN perfusion signals increased with flip angle, whereas MTA signals peaked at flip angle around 45°−60°. ALADDIN provided signals comparable to those of pCASL and conventional MTA methods emulating the first, second, and third prior slices of ALADDIN under the same scan conditions, suggesting ALADDIN signals to be superposition of signals from multiple labeling planes. The quantitative cerebral blood flow signals from a modified continuous ASL model overestimated the perfusion signals compared to those measured with a pulsed ASL method. Simultaneous mapping of blood flow, MTA, and MT ratio in the whole brain is feasible with ALADDIN within a clinically reasonable time, which can potentially help diagnosis of various diseases.     

Arterial spin labeling blood flow magnetic resonance imaging for evaluation of renal injury

A multitude of evidence suggests that iodinated contrast material causes nephrotoxicity; however, there have been no previous studies that use arterial spin labeling (ASL) blood flow functional magnetic resonance imaging (fMRI) to investigate the alterations in effective renal plasma flow between normointensive and hypertensive rats following injection of contrast media. We hypothesized that FAIR-SSFSE arterial spin labeling MRI may enable noninvasive and quantitative assessment of regional renal blood flow abnormalities and correlate with disease severity as assessed by histological methods. Renal blood flow (RBF) values of the cortex and medulla of rat kidneys were obtained from ASL images postprocessed at ADW4.3 workstation 0.3, 24, 48, and 72 h before and after injection of iodinated contrast media (6 ml/kg). The H&E method for morphometric measurements was used to confirm the MRI findings. The RBF values of the outer medulla were lower than those of the cortex and the inner medulla as reported previously. Iodinated contrast media treatment resulted in decreases in RBF in the outer medulla and cortex in spontaneously hypertensive rats (SHR), but only in the outer medulla in normotensive rats. The iodinated contrast agent significantly decreased the RBF value in the outer medulla and the cortex in SHR compared with normotensive rats after injection of the iodinated contrast media. Histological observations of kidney morphology were also consistent with ASL perfusion changes. These results demonstrate that the RBF value can reflect changes of renal perfusion in the cortex and medulla. ASL-MRI is a feasible and accurate method for evaluating nephrotoxic drugs-induced kidney damage.     

Steep head-down tilt has persisting effects on the distribution of pulmonary blood flow.

Head-down tilt has been shown to increase lung water content in animals and alter the distribution of ventilation in humans; however, its effects on the distribution of pulmonary blood flow in humans are unknown. We hypothesized that head-down tilt would increase the heterogeneity of pulmonary blood flow in humans, an effect analogous to the changes seen in the distribution of ventilation, by increasing capillary hydrostatic pressure and fluid efflux in the lung. To test this, we evaluated changes in the distribution of pulmonary blood flow in seven normal subjects before and after 1 h of 30 degrees head-down tilt using the magnetic resonance imaging technique of arterial spin labeling. Data were acquired in triplicate before tilt and at 10-min intervals for 1 h after tilt. Pulmonary blood flow heterogeneity was quantified by the relative dispersion (standard deviation/mean) of signal intensity for all voxels within the right lung. Relative dispersion was significantly increased by 29% after tilt and remained elevated during the 1 h of measurements after tilt (0.84 +/- 0.06 pretilt, 1.09 +/- 0.09 calculated for all time points posttilt, P < 0.05). We speculate that the mechanism most likely responsible for our findings is that increased pulmonary capillary pressures and fluid efflux in the lung resulting from head-down tilt alters regional blood flow distribution.     

Effect of furosemide on pulmonary blood flow distribution in resting and exercising horses.

We determined the spatial distribution of pulmonary blood flow (PBF) with 15-micron fluorescent-labeled microspheres during rest and exercise in five Thoroughbred horses before and 4 h after furosemide administration (0.5 mg/kg iv). The primary finding of this study was that PBF redistribution occurred from rest to exercise, both with and without furosemide. However, there was less blood flow to the dorsal portion of the lung during exercise postfurosemide compared with prefurosemide. Furosemide did alter the resting perfusion distribution by increasing the flow to the ventral regions of the lung; however, that increase in flow was abated with exercise. Other findings included 1) unchanged gas exchange and cardiac output during rest and exercise after vs. before furosemide, 2) a decrease in pulmonary arterial pressure after furosemide, 3) an increase in the slope of the relationship of PBF vs. vertical height up the lung during exercise, both with and without furosemide, and 4) a decrease in blood flow to the dorsal region of the lung at rest after furosemide. Pulmonary perfusion variability within the lung may be a function of the anatomy of the pulmonary vessels that results in a predominantly fixed spatial pattern of flow distribution.     

Anatomically based finite element models of the human pulmonary arterial and venous trees including supernumerary vessels.

Studies of the origin of pulmonary blood flow heterogeneity have highlighted the significant role of vessel branching structure on flow distribution. To enable more detailed investigation of structure-function relationships in the pulmonary circulation, an anatomically based finite element model of the arterial and venous networks has been developed to more accurately reflect the geometry found in vivo. Geometric models of the arterial and venous tree structures are created using a combination of multidetector row X-ray computed tomography imaging to define around 2,500 vessels from each tree, a volume-filling branching algorithm to generate the remaining accompanying conducting vessels, and an empirically based algorithm to generate the supernumerary vessel geometry. The explicit generation of supernumerary vessels is a unique feature of the computational model. Analysis of branching properties and geometric parameters demonstrates close correlation between the model geometry and anatomical measures of human pulmonary blood vessels. A total of 12 Strahler orders for the arterial system and 10 Strahler orders for the venous system are generated, down to the equivalent level of the terminal bronchioles in the bronchial tree. A simple Poiseuille flow solution, assuming rigid vessels, is obtained within the arterial geometry of the left lung, demonstrating a large amount of heterogeneity in the flow distribution, especially with inclusion of supernumerary vessels. This model has been constructed to accurately represent available morphometric data derived from the complex asymmetric branching structure of the human pulmonary vasculature in a form that will be suitable for application in functional simulations.     

Longitudinal distribution of vascular compliance in the canine lung

With an isolated perfused canine lung, the compliance of pulmonary circulation was measured and partitioned into components corresponding to alveolar and extra-alveolar compartments. When the lungs were in zone 3, changes in outflow pressure (delta Po) affected all portions of the vasculature causing a change in lung blood volume (delta V). Thus the ratio delta V/delta Po in zone 3 represented the compliance of the entire pulmonary circulation (Cp) plus that of the left atrium (Cla). When the lungs were in zone 2, changes in Po affected only the extra-alveolar vessels that were downstream from the site of critical closure in the alveolar vessels. Thus the ratio delta V/delta Po with forward flow in zone 2 represented the compliance of the venous extra-alveolar vessels (Cv) plus Cla. With reverse flow in zone 2, delta V/delta Po represented the compliance of the arterial extra-alveolar vessels (Ca). The compliance of the alveolar compartment (Calv) was calculated from the difference between Cp and the sum of Ca + Cv. When Po was 6-11 mmHg, Cp was 0.393 +/- 0.0380 (SE) ml X mmHg-1 X kg-1 with forward perfusion and 0.263 +/- 0.0206 (SE) ml X mmHg-1 X kg-1 with reverse perfusion. Calv was 79 and 68% of Cp with forward and reverse perfusion, respectively. When Po was raised to 16-21 mmHg, Cp decreased to 0.225 +/- 0.0235 (SE) ml X mmHg-1 X kg-1 and 0.183 +/- 0.0133 (SE) ml X mmHg-1 X kg-1 with forward and reverse perfusion, respectively. Calv also decreased but remained the largest contributor to Cp. We conclude that the major site of pulmonary vascular compliance in the canine lung is the alveolar compartment, with minor contributions from the arterial and venous extra-alveolar segments.     

Selected contribution: redistribution of pulmonary perfusion during weightlessness and increased gravity.

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 approximately 2 cm(3) 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.     

Role of Rho-kinase signaling and endothelial dysfunction in modulating blood flow distribution in pulmonary hypertension

Rho-kinase-mediated vasoconstriction and endothelial dysfunction are considered two primary instigators of pulmonary arterial hypertension (PAH). However, their contribution to the adverse changes in pulmonary blood flow distribution associated with PAH has not been addressed. This study utilizes synchrotron radiation microangiography to assess the specific role, and contribution of, Rho-kinase-mediated vasoconstriction and endothelial dysfunction in PAH. Male adult Sprague-Dawley rats were injected with saline (Cont-rats) or monocrotaline (MCT-rats) 3 wk before microangiography was performed on the left lung. We assessed dynamic changes in vessel internal diameter (ID) in response to 1) the Rho-kinase inhibitor fasudil (10 mg/kg iv); or 2) ACh (3 μg · kg?1 · min?1), sodium nitroprusside (SNP, 5 μg · kg?1 · min?1), and N(ω)-nitro-l-arginine methyl ester (l-NAME, 50 mg/kg iv). We observed that MCT-rats had fewer vessels of the microcirculation compared with Cont-rats. The fundamental result of this study is that fasudil improved pulmonary blood flow distribution and reduced pulmonary pressure in PAH rats, not only by dilating already-perfused vessels (ID > 100 μm), but also by restoring blood flow to vessels that had previously been constricted closed (ID < 100 μm). Endothelium-dependent vasodilation was impaired in MCT-rats primarily in vessels with an ID < 200 μm. Moreover the vasoconstrictor response to l-NAME was accentuated in MCT-rats, but only in the 200- to 300-μm vessels. These results highlight the importance of Rho-kinase-mediated control and endothelial control of pulmonary vascular tone in PAH. Indeed, an effective therapeutic strategy for treating PAH should target both the smooth muscle Rho-kinase and endothelial pathways.     

Relative contribution of gravity to pulmonary perfusion heterogeneity.

We designed a series of experiments and analyses to quantify the contribution of gravity to pulmonary perfusion heterogeneity. Regional pulmonary perfusion was measured in five anesthetized and ventilated dogs in both supine and prone positions by use of radiolabeled microspheres injected during apnea at functional residual capacity. Measurements of flow were repeated in each position, and the sequence of positions was prospectively designed to nullify any effect of order. The lungs of each animal were excised, perfused with saline until clear, dried at an inflation pressure of 25 cmH2O, and cut into 1.9-cm3 pieces. Each piece was weighed and the radioactivity determined in a scintillation counter. Measurement errors were minimized by excluding lung pieces that had greater than 25% airway and weighed less than 10 mg or greater than 60 mg. Weight-normalized flows in each position and repetition were determined for each lung piece. An analysis of variance model was used to identify the percentage of variation in regional flow that was due to position (supine vs. prone), to random error and time (measurement and repetition), and to structure, where structure was defined as the component of flow that remained constant across position and replication. The contributions of position, error/time, and structure to the total variability of flow across the five dogs were 7.8 +/- 0.6, 8.4 +/- 8.3, and 83.8 +/- 8.4%, (SD), respectively. Because the contribution of position represents the additive effect of gravity between two opposite positions, the contribution of gravity to perfusion heterogeneity in one position may be as little as 4%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Resting State Brain Function Analysis Using Concurrent BOLD in ASL Perfusion fMRI

The past decade has seen astounding discoveries about resting-state brain activity patterns in normal brain as well as their alterations in brain diseases. While the vast majority of resting-state studies are based on the blood-oxygen-level-dependent (BOLD) functional MRI (fMRI), arterial spin labeling (ASL) perfusion fMRI can simultaneously capture BOLD and cerebral blood flow (CBF) signals, providing a unique opportunity for assessing resting brain functions with concurrent BOLD (ccBOLD) and CBF signals. Before taking that benefit, it is necessary to validate the utility of ccBOLD signal for resting-state analysis using conventional BOLD (cvBOLD) signal acquired without ASL modulations. To address this technical issue, resting cvBOLD and ASL perfusion MRI were acquired from a large cohort (n = 89) of healthy subjects. Four widely used resting-state brain function analyses were conducted and compared between the two types of BOLD signal, including the posterior cingulate cortex (PCC) seed-based functional connectivity (FC) analysis, independent component analysis (ICA), analysis of amplitude of low frequency fluctuation (ALFF), and analysis of regional homogeneity (ReHo). Consistent default mode network (DMN) as well as other resting-state networks (RSNs) were observed from cvBOLD and ccBOLD using PCC-FC analysis and ICA. ALFF from both modalities were the same for most of brain regions but were different in peripheral regions suffering from the susceptibility gradients induced signal drop. ReHo showed difference in many brain regions, likely reflecting the SNR and resolution differences between the two BOLD modalities. The DMN and auditory networks showed highest CBF values among all RSNs. These results demonstrated the feasibility of ASL perfusion MRI for assessing resting brain functions using its concurrent BOLD in addition to CBF signal, which provides a potentially useful way to maximize the utility of ASL perfusion MRI.     

Vascular resistance and vasoactivity of gills and pulmonary artery of the salamander,Ambystoma tigrinum

Summary In order to understand the blood flow patterns and their regulation in the gills and pulmonary artery ofAmbystoma tigrinum, the vascular resistance and vasoactivity of the two major branchial perfusion pathways and a vascular plexus in the pulmonary artery were investigated using an isolated-tissue perfusion method. Acetylcholine and epinephrine were both pressor agents in all three vascular segments. Angiotensin II also constricted the branchial respiratory vasculature. Norephinephrine was primarily a vasodilator in the branchial respiratory vasculature, however, it had no effect on the shunt vessels of the gill or the pulmonary arterial plexus. Both gill circulations were insensitive to alterations in CO₂ and pH. Anoxia produced a slight vasodilation of the branchial respiratory vessels but had no effect on the shunt vasculature. Mild hypoxia had no effect on either branchial circulations. The results suggest that: (1) blood flow through the respiratory section of the gill may vary between 8 and 47% of total gill flow, (2) the major perfusion pathway to the lung is probably from the efferent artery of the third gill through the ductus arteriosus and then into the pulmonary artery, (3) O₂, CO₂ and pH exert no local control of branchial perfusion, (4) both cholinergic and adrenergic regulation of branchial and proximal pulmonary arterial vascular resistance is possible, (5) a rise in circulating norepinephrine should increase blood flow to the respiratory section of the gill.Abbreviations AII angiotensin II - ACh acetylcholine - EPi epinephrine - NE norepinephrine     

Regional heterogeneity of myocardial blood flow within the rabbit left ventricle during haemorrhagic hypotension.

Several studies have reported an extensive regional heterogeneity in myocardial blood flow. The reported coefficients of variation for regional myocardial perfusion range from about 0.2 to 0.4 in normotensive animals. The spatial distribution of myocardial perfusion during haemorrhagic hypotension seems not to have been assessed. The goal of the present study was to determine the regional heterogeneity in myocardial blood flow within the rabbit left ventricle during normal conditions and after haemorrhagic hypotension. Radioactive microspheres were infused into the left ventricle in barbiturate anaesthetized rabbits over either 30 or 120 sec. The haemorrhagic hypotension was induced by bleeding, so that mean arterial blood pressure was reduced to about 50% of control. The left ventricles were divided into samples of about 0.025 g each. Regional heterogeneity in the blood flow was expressed as the coefficient of variation corrected for the Poisson distribution of microspheres (CVc). The CVc was 0.37 +/- 0.09 (mean +/- SD) during control and 0.41 +/- 0.11 after bleeding, the CVc obtained after bleeding being somewhat higher than during control (P < 0.05). We obtained a high correlation coefficient (tau about 0.68) between regional perfusion values at control and after bleeding which indicates a stable perfusion pattern within the myocardium. We conclude that the regional distribution of coronary blood flow within the left ventricle is markedly heterogenous during control condition and that this pattern is not changed during haemorrhagic hypotension.     

Regional pulmonary blood flow during 96 hours of hypoxia in conscious sheep

The effects of acute hypoxia on regional pulmonary perfusion have been studied previously in anesthetized, artificially ventilated sheep (J. Appl. Physiol. 56: 338-342, 1984). That study indicated that a rise in pulmonary arterial pressure was associated with a shift of pulmonary blood flow toward dorsal (nondependent) areas of the lung. This study examined the relationship between the pulmonary arterial pressor response and regional pulmonary blood flow in five conscious, standing ewes during 96 h of normobaric hypoxia. The sheep were made hypoxic by N2 dilution in an environmental chamber [arterial O2 tension (PaO2) = 37-42 Torr, arterial CO2 tension (PaCO2) = 25-30 Torr]. Regional pulmonary blood flow was calculated by injecting 15-micron radiolabeled microspheres into the superior vena cava during normoxia and at 24-h intervals of hypoxia. Pulmonary arterial pressure increased from 12 Torr during normoxia to 19-22 Torr throughout hypoxia (alpha less than 0.049). Pulmonary blood flow, expressed as %QCO or ml X min-1 X g-1, did not shift among dorsal and ventral regions during hypoxia (alpha greater than 0.25); nor were there interlobar shifts of blood flow (alpha greater than 0.10). These data suggest that conscious, standing sheep do not demonstrate a shift in pulmonary blood flow during 96 h of normobaric hypoxia even though pulmonary arterial pressure rises 7-10 Torr. We question whether global hypoxic pulmonary vasoconstriction is, by itself, beneficial to the sheep.