Gas Washout Research Articles

Assessment of regional myocardial blood flow using the inert gas washout technique.

The measurement of myocardial blood flow in man using the inert gas clearance technique is limited to several approaches and is always linked with invasive procedures. As coronary artery disease, the main object of these investigations, has a regional character, the techniques should be able to detect small differences in flow in the individual myocardial areas perfused by the major coronary branches. Sampling of the radiotracer can take place directly from the coronary sinus blood or the great cardiac vein, or indirectly, from the cardiac tissue by placing a gamma scintillation camera over the heart.

Measurements of the dead space volume.

The "anatomical" dead space is commonly measured by sampling an inert gas (N2) and volume in the exhalation following a large breath of oxygen (VD(F)). It may also be measured from an inert gas washout (VD(O)) that describes both volume and the delivery of VD(O) throughout the expiration. VD(O) is known to increase with age and is enlarged in some obstructive syndromes. VD(O) was appreciably larger than VD(F) in our normal subjects. Both measures increased with lung volume, the increase being entirely due to an increase in the volume of phase I. Physiological dead space (VD(p)) however, did not change significantly with lung volume, showing "alveolar" dead space to diminish as a result. An increase in VD(O) occurred with increasing respiratory frequency that was explained by the increase in volume of phase I. Although an increase in VD(F) occurred with frequency, this was significantly less than that seen by VD(O), i.e., VD(F) did not see the progressive increase in phase I volume with frequency. No lung volume or frequency changes, parasympatholytic or sympathomimetic drugs, or altered patterns of breathing simulated the late delivery of dead space seen in age and some obstructive syndromes.

Characteristics of the washout dead space

The dead space volume was reproducibly measured in normal and diseased lungs by analysis of an inert gas washout. This washout dead space was appreciably larger than that measured by the Fowler technique. In the patients, the washout dead space (V D(0)) formed 72% of the physiological dead space volume, while the Fowler (V D(F)) method accounted for only 50%. The V D(O) increased significantly with age in males, but not in females. V D(F) was not well related to age in this population. V D(O) and V D(F) did not relate to lung volume in these subjects. Although that portion of the dead space delivered in Phase I was significantly greater in males than in females, it was not responsible for the difference in dead space measured by the two techniques. This volume difference was found in that portion delivered late in the breath (Phase III). The nature of this volume is speculative, but may involve a parallel dead space that is measured in addition to the series dead space.

Effect of decompression per se on nitrogen elimination.

The elimination of nitrogen from each of 10 unanesthetized guinea pigs has been monitored after switching to a nitrogen-free breathing mix (normoxic He:O2), either without decompression or on decompression to 2.21 or 1 ATA, following an exposure of 2 h at 4 ATA on normoxic N2;O2. Normoxic conditions were maintained throughout to avoid vasomotor effects of oxygen that could have complicated interpretations derived from previous studies. Results confirmed that inert gas washout rates decrease with decompression per se. This can be explained simply on the basis of the decrease in driving force for nitrogen elimination caused by depositing gas into bubbles where they form in tissue in a somewhat random manner. A very rough estimate shows that about 83% of all body tissue retained its gas in supersaturated solution on decompression to 2.21 ATA but only 79% did so at 1 ATA.

Is inert gas washout from the tissues limited by diffusion?

To determine the extent to which diffusion may limit the exchange of gases stored in the tissues, nine dogs were allowed to breathe an O2-N2-Ar mixture until saturation was achieved; the inspired gas was then changed to one containing neither N2 nor Ar, and the level of these two species in the arterial and in the mixed venous blood was monitored during the washout. A theoretical analysis shows that in a situation where peripheral gas transport is limited entirely by perfusion, the washout curves should be identical, provided concentrations are expressed as a fraction of the initial value. When the process is restricted by diffusion through the tissues, Ar is expected to lag because of its higher molecular weight. In all animals, the rate of elimination of the two tracers was the same, indicating that the time course of storage or release of inert gas from body stores is governed (mainly or entirely) by perfusion.

Renal function and intrarenal hemodynamics in acutely hypoxic and hypercapnic rats

On the basis of microsphere distribution, inert gas washout, and standard clearance data, the effects of acute hypoxia and hypercapnia on the kidney were studied in anesthetized, mechanically ventilated rats. Moderate hypoxia (mean PO2, 48 mm Hg) did not significantly change diuresis, GFR, and tubular sodium rejection. Due to a decrease in renal vascular resistance (R) from 40.1 to 31.8 mm Hg ml-1 min, mean renal blood flow stayed constant in spite of a significant drop in mean arterial blood pressure. Hypoxic changes in R were not accompanied by significant changes in intrarenal distribution of blood flow (IDBF). In severe hypoxia (PO2 less than 45 mm Hg) with oliguria and marked arterial hypotension, R was the lowest of all groups (28.8 mm Hg ml-1 min). Hypercapnia did not significantly change the renal excretory parameters, although an increase in R (without change in IDBF), together with a decrease in MAP caused a marked drop in mean renal blood flow. From these studies we conclude: 1) in the anestheized rat, acute hypoxia caused significant changes in intrarenal hemodynamics without changes in excretory function, 2) hypoxic renal vasodilation persists even in severe hypotension with oliguria and anuria, 3) in acute hypoxia and hypercapnia, changes in renal blood flow and renal vascular resistance are not accompanied by significant changes in IDBF.

Reproducibility of Ventilation Studies

Differences in ventilation patterns were observed in several instances in two consecutive ventilation studies with 127 Xe and 133Xe gas involving a group of 20 patients with COPD and other pulmonary disorders. Included were differences in the distribution of a tracer gas bolus during the initial inspiration, the distribution of gas tracer after equilibration and during gas washout, artifacts external to the lung, and variations in the half-time for gas washout. The observed discrepancies are clinically significant and could lead to erroneous or ambiguous diagnoses.

Continuous distributions of specific ventilation recovered from inert gas washout.

We describe a new technique for recovering continuous distributions of ventilation (V) as a function of tidal ventilation/volume ratio (V/V0) from the nitrogen washout. The analysis yields a continuous distribution of V as a function of V/V0 represented as fractional ventilations of 50 compartments plus dead space. The procedure was verified by recovering known distributions from data to which noise had been added. Using an apparatus to control the subject's tidal volume and FRC, mixed expired N2 data gave the following results: a) the distributions of young, normal subjects were narrow and unimodal with a mean ln standard deviation of 0.56 plus or minus 0.13; b) those of subjects over age 40 were broader (ln SD 0.86 plus or minus 0.19) with more poorly ventilated units; c) patients with pulmonary disease of all descriptions showed enlarged dead space; d) patients with cystic fibrosis showed multimodal distributions with the bulk of the ventilation going to overventilated units; and e) patients with obstructive lung diseases fell into several classes, three of which are illustrated. These results suggest that our approach is well suited for clinical investigation.

Kinetics of Inhaled Krypton in Man

The total body retention of 79Kr and its clearance following a 10-min rebreathing period were measured in vivo in order to refine the dosimetry calculations. Radioactivity in the chest region and in the recirculating krypton-air mixture were measured continuously during rebreathing of the gas mixture and in the first 5 min of the gas washout period using a gamma camera and shielded NaI detector, respectively. Subjects were then counted in the Brookhaven whole-body counter at varying time intervals for up to 55 hr. The retention data of krypton for 16 subjects (12 males, 4 females) were resolved into a five-component exponential curve. The average half-times were 21.5 ± 5.7 sec, 4.74 ± 2.0 min, 0.33 ± 0.11 hr, 2.41 ± 0.95 hr, and 7.0 ± 1.7 hr. The half-time of the long-term component correlated highly with the percentage of total body fat. Internal dose calculations were performed using the MIRD techniques and were compared with previous estimations.

Myocardial blood flow in coronary artery disease: Studies at rest and during stress with inert gas washout techniques

HIS article will review techniques using inert gases that have been utilized to measure average left ventricular and regional myocardial blood flow in man. The development of these techniques has been spurred primarily by the desire to evaluate clinically the disturbances of myocardial blood flow that occur in patients with coronary artery disease. Coronary atherosclerosis is a focal process that affects primarily large epicardial coronary arteries and their major branches and to a lesser extent the smaller intramyocardial vessels.‘,’ Discrete coronary lesions produce alterations in myocardial blood flow both in different regions of the heart (i.e., spatial heterogeneity of blood flow) and also in different layers of the ventricular wall (i.e., transmural heterogeneity of blood flow). In turn, these blood flow alterations in the myocardium may impair cardiac performance. Both global and segmental abnormalities of ventricular contraction are associated with coronary artery disease.” When the blood flow to a region of the myocardium is insufficient to meet the metabolic requirements of the working heart muscle for oxygen, &hernia develops and may produce angina pectoris, myocardial infarction, and/or local abnormalities of cardiac metabolism and function. Coronary arteriography is commonly used to visualize the extent and distribution of coronary artery obstructions. It is a necessary prerequisite to consideration of surgical therapy for angina, infarction, or ventricular failure.+ However, coronary arteriography does not reveal to what degree myocardial blood flow has been compromised by the obstructing lesion. It cannot reveal the presence of small vessel disease (i.e., abnormal vessels < 200~ in diameter) nor the extent

Heterogeneity of flow as an explanation of the multi-exponential washout of inert gas from skeletal muscle

The explanation of the multi-exponential washout of inert gas tracers from skeletal muscle is a source of controversy. The two most likely explanations are a heterogeneous flow pattern and countercurrent shunting of gas. Autoradiographs of canine skeletal muscle obtained after injection of 85Kr indicate that heterogeneous flow is present in this preparation which would cause multi-exponential curves. This finding does not rule out an additional contribution of countercurrent shunting to the shape of the clearance curve.

Quick increase of pulmonary blood flow in response to an acute alveolar hypoxia in human subjects.

The effects of acute alveolar hypoxia on pulmonary blood flow were studied in upright standing human subjects by means of a constant expiration technique combined with continuous analysis of the C2H2 fraction in the expired gas. The subject rapidly and deeply inhaled a gas mixture containing 4.87% C2H2, 0.99% O2, N2 for balance and exhaled the alveolar gas via a constant flow valve. The Po2, of the alveolar gas fell to 37.6+/-5.6 mmHg. The C2H2 curve showed a clear downward inflection 7 to 10 sec after the completion of washout of the dead space gas. This inflection indicates an increase of the C2H2 uptake rate produced by an increase in pulmonary blood flow. The pulmonary blood flow calculated for the time range of 10.0 to 12.5 sec after the establishment of acute alveolar hypoxia (6.5+/-1.11/min) was significantly larger than the blood flow under normoxia (5.5+/-0.91/min). This increase associated with a quick rise in systemic arterial blood pressure which was probably induced by a chemical reflex.

Regional lung function in pulmonary hypertension.

Utilizing 133-xenon gas and a scintillation camera, we examined the distributional relation between ventillation (V) and perfusion (Q) in patients with pulmonary hypertension (PH) comprising mitral stenosis (MS) and left to right shunt disease (shunt). In the case of MS, Q decreased at the dependent part of lung in proportion to the degree of PH, but preserved normal V and resulted in high V/Q value at this region, which was estimated to cause and physiological dead space effect on the gas exchange function. In the case of shunt disease, even with a high degree of PH, reduction of Q at the dependent lung region was not observed with normal preservation of V, thus obviating any type of the V/Q imbalance. Since the washout of xenon gas by resting tidal volume ventilation was observed to be delayed from the dependent lung region, latent ventilatory impairment in this region due to small airway closure at tidal breathing was also suspected.

Regional myocardial blood flow during hyperemia induced by contrast agent in patients with coronary artery disease

Regional myocardial specific blood flow (regional specific flow) was measured at rest and during contrast hyperemia after the intracoronary injection of xenon-133. The changes in regional specific flow were transient, resulting in some compromise in one of the underlying restraints of the inert gas washout method, namely, the presence of a steady state. Therefore, to determine the clinical utility of this technique, regional specific flow values obtained with this method were correlated with the presence and severity of coronary artery disease as assessed from the coronary arteriogram and left ventriculogram. Regional specific flow during contrast hyperemia was 186 ± 11 (mean ± 1 standard error of the mean) ml/min per 100 g in control patients and 115 ± 5 in patients with coronary artery disease. There was an inverse relation between regional specific flow during contrast hyperemia and the percent coronary stenosis when the stenosis was 40 percent or greater ( r = 0.70, P < 0.001). Regional specific flow was significantly less in patients with asynergy (77 ± 10 ml/min per 100 g) than in patients with normal ventricular function (105 ± 5) distal to coronary stenoses of greater than 75 percent. Thus, regional specific flow measured during contrast hyperemia using the xenon washout technique and the Anger camera differentiated patients with normal coronary arteriograms from those with coronary artery disease. With this technique, good correlation was shown between regional specific flow and the percent coronary stenosis and presence of ventricular wall abnormalities. The information obtained with this method may provide prognostic information concerning suitability for surgical intervention.

Analysis of ventilation and performance abnormalities by washout in alveolar air and arterial blood continuous measurement of inert gas

The availability of a rapidly responding arterial catheter and gas analyzer permits the observation of inert gas washout from arterial and alveolar sources. These curves are a logical development of alveolar washout techniques and appear to provide significant new information. While a detailed and formal mathematical treatment of combined alveolar, arterial, and mixed venous washout curves has not yet been derived, inspection and measurement of the y-intercept of the terminal slow space has provided considerable understanding into the distribution of V/Q ratios in the critically ill patient.

Concepts and clinical utilityof the measurement of cerebral blood flow

Within the past several decades, techniques that accurately measure regional cerebral blood flow have been developed. At the present time, the inert gas washout technique using an intraarterial injection of 133Xe with the Anger scintillation camera or multiple probes as the external detector is the most established of these methods. While quantitative measures of cerebral blood flow have been important in elucidating the physiology of cerebral hemodynamics, the techniques are too invasive for routinely screening patients with cerebrovascular disease. As a result, less invasive methods have been sought for diagnostic screening. Because it requires only an intravenous injection of 99mTc-pertechnetate, the radionuclide cerebral angiogram has achieved some popularity as a semiquantitative measure of cerebral hemodynamics, particularly when coupled with static brain scintigraphy. This review examines our current understanding of cerebral hemodynamics and the advantages and limitations of techniques used to measure cerebral blood flow.

Blood Flow in the Small Intestine of Cat and Man as Analyzed by an Inert Gas Washout Technique

Using a recently developed 85Kr-elimination technique, blood flow and flow distribution of the human small intestine have been investigated in patients during abdominal surgery. Total intestinal blood flow was estimated to be 38 +/- 4 ml per min and 100 g of intestinal tissue (mean +/- SE: n = 19), jejunal blood flow being slightly higher than ileal. In 14 of these patients muscularis blood flow was determined to be 21 +/- 2 ml per min and 100 g of muscularis tissue and mucosal-submucosal blood flow was calculated to be 51 +/- 6 ml per min and 100 g of mucosal-submucosal tissue. Seventy-five +/- 3% of total blood flow was distributed to the mucosa-submucosa and the remaining 25 +/- 3% to the muscularis. It was demonstrated that an increasing fraction of flow was diverted to the mucosa-submucosa with enhanced total intestinal blood flow. The human gut exhibited great qualitative and quantitative circulatory similarities with the feline small intestine.

Colonic Blood Flow in Cat and Man as Analyzed by an Inert Gas Washout Technique

An inert gas elimination technique for studying blood flow and flow distribution in the colon was developed on the cat and applied to patients during abdominal surgery. The method involves recording of the elimination of intra-arterially injected 85Kr from a colonic segment whereby the gamma- and beta-radiation of the tracer is registered simultaneously by a scintillation detector and Geiger-Muller tube, respectively. Total blood flow was determined from the recording of gamma-radioactivity using a modification of Zierler's formula, and muscularis blood flow as calculated according to Kety from the mono-exponential elimination recorded by the Geiger-Muller tube. The relative weights of the muscularis and mucosa-submucosa were determined from dissections or histological sections. With these weights and total and muscularis blood flows, flow in the mucosa-submucosa was calculated. Total colonic blood flow was 18 +/- 2 ml per min and 100 g of colonic tissue (mean +/- SE; n = 21). In the muscularis layer blood flow amounted to 11 +/- 1 ml per min and 100 g of muscularis tissue (n = 12), and flow in the mucosa-submucosa was calculated to be 28 +/- 5 ml per min and 100 g of mucosal-submucosal tissue. A major fraction (66 +/- 6%) of total blood flow was distributed to the mucosa-submucosa. As total colonic blood flow was enhanced the increase in flow was diverted only to the mucosa-submucosa. The feline and human large bowel exhibited great qualitative and quantitative circulatory similarities.

Retrograde radioisotope myocardial perfusion patterns in dogs.

A retrograde coronary vein injection technique for concentrating radioisotope in ischemic myocardial regions was evaluated in dogs. Potassium-43 in saline solution was injected into the coronary veins during complete closure of the coronary sinus. In the presence of coronary inflow obstruction, the venous potassium-43 was distributed mainly to the low pressure vessels in ischemic heart regions; i.e., the ratio of potassium-43 in the occluded-to-unoccluded areas ranged from 2:1 to 3:1 thirty seconds after retrograde injections. Krypton-85 in saline solution was injected under pressure into the coronary veins during partial closure of the coronary sinus. In the presence of inflow obstruction, the ratio of krypton-85 in the occluded- to-unoccluded areas ranged from 4:1 to 6:1 sixty seconds after retrograde injections; larger ratios may be expected after rapid washout of gas from the normally perfused region is nearly complete. Myocardial potassium-43 imaging techniques were applied to locate and measure the size of the ischemic heart region as a radioisotopic hot spot. Detection of hypoperfused areas of extremely small size may be accomplished by this technique.

Measuring regional myocardial blood flow with 133Xe and the Anger camera.

Regional myocardial blood flow was measured using the inert gas washout technique and the Anger scintillation camera following injection of 133Xe into the coronary artery. By applying compartmental analysis to 30-minute washout curves, three compartments were delineated, representing blood flow to fat (IIIF) and myocardium (IM and IIM). Regional heterogeneity of flow was a highly sensitive index of coronary artery disease. Functional images delineated areas of altered perfusion better than quadrantic flow values. Gamma camera images of initial xenon distribution identified patients with severely altered flow.