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)     

Pulmonary blood flow distribution in anesthetized ponies.

Results of recent investigations in humans and dogs indicate that gravity-independent factors may be important in determining the distribution of pulmonary blood flow. To further evaluate the role of gravity-independent factors, pulmonary blood flow distribution was examined using 15-microns radionuclide-labeled microspheres in five prone ponies over 5 h of pentobarbital sodium anesthesia. The ponies were killed, and the lungs were excised and dried by air inflation (pressure 45 cmH2O). The dry lungs were cut into transverse slices 1-2 cm thick along the dorsal-ventral axis, parallel to gravity. Radioactivity of pieces cut from alternate slices was measured with a gamma well counter. The main finding was a preferential distribution of pulmonary blood flow to dorsal-caudal regions and higher flow in the center of each lung slice when compared with the slice periphery. Flow was lowest in cranial and ventral areas. Differences of +/- 2 SD were observed between core and peripheral blood flow. No medial-lateral differences were found. Pulmonary blood flow distribution did not change over 5 h of anesthesia, and the basic flow pattern was not different in the left vs. right lung. These results suggest that in the intact prone mechanically ventilated pony (inspired O2 fraction greater than or equal to 0.95) factors other than gravity are primary determinants of pulmonary blood flow.     

Pulmonary blood flow distribution measured by radionuclide-computed tomography

Distributions of pulmonary blood flow per unit lung volume were measured with subjects in the prone, supine, and sitting positions by means of radionuclide-computed tomography of intravenously administered 99mTc-labeled macroaggregates of human serum albumin. The blood flow was greater in the direction of gravity in all 31 subjects except one with severe mitral valve stenosis. With the subject in a sitting position, four different types of distribution were distinguished. One type had a three-zonal blood flow distribution as previously reported by West and co-workers (J. Appl. Physiol. 19: 713-724, 1964). Pulmonary arterial pressure and venous pressure estimated from this model showed reasonable agreement with pulmonary arterial pressure and capillary wedge pressure measured by Swan-Ganz catheter in 17 supine patients and in 2 sitting patients. The method makes possible noninvasive assessment of pulmonary vascular pressures.     

Pulmonary blood flow distribution during partial liquid ventilation

Regionalpulmonary blood flow was investigated with radiolabeled microspheres infour supine lambs during the transition from conventional mechanicalventilation (CMV) to partial liquid ventilation (PLV) and withincremental dosing of perfluorocarbon liquid to a cumulative dose of 30 ml/kg. Four lambs supported with CMV served as controls.Formalin-fixed, air-dried lungs were sectioned according to a grid;activity was quantitated with a multichannel scintillation counter,corrected for weight, and normalized to mean flow. During CMV, flow inapical and hilar regions favored dependent lung(P < 0.001), with no gradient acrosstransverse planes from apex to diaphragm. During PLV the gradientwithin transverse planes found during CMV reversed, most notably in thehilar region, favoring nondependent lung(P = 0.03). Also during PLV, flow wasprofoundly reduced near the diaphragm(P < 0.001), and across transverse planes from apex to diaphragm a dose-augmented flow gradient developed favoring apical lung (P < 0.01). Weconclude that regional flow patterns during PLV partially reverse thosenoted during CMV and vary dramatically within the lung from apex todiaphragm.

     

No gravity-independent gradient of blood flow distribution in dog lung

The existence of a major gravity-independent gradient of blood flow in lungs has recently been described based on single photon emission computed tomography after intravenous injection of radioactively labeled macroaggregates. We wanted to test this hypothesis of a major gravity-independent gradient in lung blood flow in experiments with direct measurement of macroaggregate distribution in the dog lung. In six anesthetized (4 prone spontaneously breathing, 2 mechanically ventilated) dogs we injected 111In-labeled albumin macroaggregates intravenously. We killed the dogs, removed, inflated, and froze the lower lobes. We sliced the lobes 1 cm thick and made gamma camera images of the slices. We then cut three or four slices in each lobe into two or three concentric layers and measured the radioactivity per gram of tissue in a well-type gamma counter. In three of the dogs we also labeled the red cells (99mTc) so that blood volume in each sample could be determined. The gamma camera images were acquired on a 64 X 64 matrix with 4 X 4 mm pixels. On the numeric printouts from the individual slices we made two or three concentric layers and calculated activity per pixel in each layer. Neither by the well counting nor by the pixel analysis of the gamma scans did we detect any gravity-independent distribution of blood flow. With the well counting the distribution was the same whether macroaggregate activity was expressed per gram of tissue or per gram of blood-free tissue. We conclude that by direct measurements no major gravity-independent gradient of pulmonary blood flow can be detected in dog lungs.     

Effects of severe reduction in maternal placental blood flow on blood flow distribution in the sheep fetus

To test the hypothesis that fetal lambs are able to maintain oxygen delivery to myocardial, brain and adrenal tissues during reduction in uterine blood flow to 25% of control, we performed experiments on five ewes and their fetuses. A snare occluder was placed around the maternal common hypogastric artery and catheters were placed for measurement of blood pressures, flows, blood gas tensions, pH and oxygen content. After a five day recovery period, control measurements were made. The snare occluder was then closed until the artery was fully occluded. The arterial occlusion caused uteroplacental blood flow to fall to 32 +/- 4% and maternal placental blood flow to fall to 25 +/- 3% of control values. This level of asphyxia was maintained for 19 +/- 3 minutes, when maternal and fetal blood flows were measured again. In response to occlusion, fetal ascending aortic PO2 fell from 21 +/- 2 (SEM) to 13 +/- 2 mmHg (P less than or equal to 0.01), oxygen content from 4.3 +/- 0.3 to 1.4 +/- 0.2 mM (P less than or equal to 0.01) and pH from 7.37 +/- 0.01 to 7.21 +/- 0.05 (P less than or equal to 0.01). PCO2 rose from 48 +/- 1 to 62 +/- 3 mmHg (P less than or equal to 0.01). Fetal arterial blood pressure increased from 51 +/- 3 to 61 +/- 3 mmHg (P less than or equal to 0.001) and heart rate decreased from 172 +/- 10 to 104 +/- 4 beats.min-1 (P less than or equal to 0.01). The heart, brain and adrenals showed vasodilation in response to the asphyxic stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary blood flow distribution after lobar oleic acid injury: a PET study

We evaluated the importance of hypoxic vasoconstriction as a mechanism for pulmonary blood flow reduction during unilobar oleic acid lung injury in dogs. Pulmonary blood flow (PBF) and lung water were measured with positron emission tomography. Data from the injured left (LCL) and right (RCL) caudal lobes were compared in 23 dogs. Six dogs were used to demonstrate that endotoxin (15 micrograms/kg) prevents changes in regional PBF during selective hypoxic ventilation of the LCL. In 17 dogs, oleic acid (OA, 0.015 ml/kg) was injected into the LCL through a balloon-wedged pulmonary arterial catheter. Five dogs received OA only (control group), eight received endotoxin (15 mcg/kg) before OA was administered (endotoxin group), and four were treated with prostaglandin E1 (PGE1) after OA (PGE1 group). The base-line left-to-right PBF ratio (LCL/RCL PBF) was 1.01 +/- 0.11 (SD) for the control group and 1.07 +/- 0.16 for the PGE1 group. One minute after OA, LCL/RCL PBF feel significantly (0.32 +/- 0.15 and 0.32 +/- 0.13 for the control and PGE1 groups, respectively) before any significant increase in lung water was detected. In all 17 dogs that received OA, the LCL/RCL PBF remained severely reduced 60 min after OA compared with base-line values (0.41 +/- 0.15, 0.49 +/- 0.06, and 0.26 +/- 0.13 for the control, PGF1, and endotoxin groups, respectively) despite treatment with endotoxin or PGE1. Lung water measurements obtained 60 min after OA increased significantly (P less than 0.05) in the injured lobe (LCL) but not in the normal lobe (RCL) in all dog groups, whereas PBF to the LCL remained significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)     

Passage of uncharged dextrans from blood to lung lymph in awake sheep

To examine how molecular size alone influences the passage of macromolecules from the pulmonary microcirculation into lymph collected from the caudal mediastinal lymph node of the sheep, we infused polydisperse uncharged [3H]dextrans intravenously at a constant rate over a period of 7.5 h in nine awake sheep with lung lymph fistulas. Lymph and plasma were collected during hours 5.5-7.5 of the infusions, and the [3H]dextrans were separated by molecular sieve chromatography into fractions that ranged from 1.6 to 8.4 nm in effective molecular (Stokes-Einstein) radius. Lymph-to-plasma (L/P) ratios for [3H]dextrans were near 1.0 at 1.6-nm radius, decreased with increasing molecular size, and approached zero at radii above 5.0 nm. We confirmed that these L/P ratios represented steady-state values by extending the duration of the infusion to approximately 30 h in two of the nine sheep and finding that the L/P ratios remained unchanged. These results were consistent with molecular sieving through a homoporous membrane with cylindrical pores of 5.0-nm radius. We also found that the L/P ratio for albumin [0.76 +/- 0.13 (SE)] in five of the same sheep was much higher than that for the [3H]dextran fraction of the same effective molecular radius [0.11 +/- 0.02 (SE)]. These results suggest that the movement of macromolecules from the pulmonary microcirculation into pulmonary lymph collected from the caudal mediastinal node of the sheep is influenced by both molecular size and molecular charge and that, compared with uncharged dextrans, the steady-state passage of anionic endogenous proteins from plasma to lymph is enhanced.     

Changes in blood flow distribution during the perinatal period in fetal sheep and lambs.

We have measured total blood flows and blood flows per 100 g tissue to major tissues at 120 and 140 days gestation in fetal sheep and at 3 and 21 days of age in lambs (gestation period = 144 +/- 2 days). Between 120 and 140 days gestation, flow per 100 g tissue increased by 74, 150, and 317% in the renal, intestinal, and hepatic arterial beds, but no further significant change in flow was observed at 3 or 21 days postpartum. Blood flows per 100 g to cerebral hemispheres and cerebellar tissues also increased dramatically during late gestation (142 and 121%, respectively), but declined sharply by 3 days postpartum (73 and 75%, respectively). Brain blood flows at 21 days postpartum remained substantially below late gestational levels. Adrenal blood flows per 100 g more than doubled during late gestation, fell by more than half at birth, and only partially recovered by 21 days of age. Blood flows to carcass tissues did not change in late gestation, fell at birth, then partially recovered. Pre- and post-natal increases in brain blood flows were almost entirely attributable to increased perfusion rather than tissue growth, whereas large perinatal increases in flow to the diaphragm paralleled tissue growth. Tissue growth and increased perfusion per 100 g contributed almost equally to increased blood flows to kidneys postnatally, and to adrenal glands and the gastrointestinal tract prenatally.     

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 cooling and heating on the regional distribution of blood flow in fetal sheep

This is a study on the effect of cooling and heating amniotic fluid on blood flow to fetal tissues and organs. In 8 unanaesthetized, chronically-catheterised fetal sheep (129-137 days gestation) cold or warm water was passed through tubing encircling the fetus in utero and blood flow was measured using the radionuclide-labelled 15 mu spheres. Following cooling for 30 min, amniotic fluid temperature fell 9.6 degrees C to 29.9 +/- 2.1 degrees C (SEM) fetal arterial temperature fell 2.37 degrees C to 37.30 +/- 0.36, and maternal arterial temperature fell 0.53 degrees C to 38.58 +/- 0.16. Blood flow through the fetal skin fell 60% (P less than 0.01) to 13.6 ml/min per 100 g tissue. Blood flow to the brown fat increased 186% (P less than 0.05) to 99.6 ml/min per 100 g. Following warming for 20 min, fetal temperature rose to 40.43 +/- 0.19 degrees C, and skin blood flow did not change significantly relative to initial control period but rose 200% above that during cooling (P less than 0.01). During both cooling and heating, blood flow to the adrenals rose significantly (P less than 0.05) whereas flow to the carcass, brain, kidneys, and placenta was not altered detectably. Continuous sampling of blood from the inferior vena cava during microsphere injection failed to detect any evidence of arterio-venous shunting through the skin at any temperature studied. Overall, the blood flow responses are consistent with a thermoregulatory role for the skin and brown fat in the near-term fetal sheep.     

Pulmonary blood flow and ventilation-perfusion heterogeneity

We studied the independent influence of changes in perfusion on pulmonary gas exchange in the left lower lobe (LLL) of anesthetized dogs. Blood flow to the LLL (QLLL) was raised 50% (increased QLLL) or reduced 50% (decreased QLLL) from baseline by partial occlusion of the right or left pulmonary artery, respectively. Minute ventilation and alveolar PCO2 of the LLL remained constant throughout the study. We determined ventilation-perfusion distributions of the LLL using the multiple inert gas elimination technique. Increased QLLL impaired LLL pulmonary gas exchange. All dispersion indexes and all arterial-alveolar difference areas increased (P less than 0.01). Decreased QLLL increased the log standard deviation of the perfusion distribution (P less than 0.05) and reduced the log standard deviation of the ventilation distribution (P less than 0.01) but did not affect the dispersion indexes or alveolar-arterial difference areas. We conclude that ventilation-perfusion heterogeneity is increased by independent changes in perfusion from normal baseline blood flow, even when ventilation and alveolar gas composition remain constant.