Clinical Science and Molecular Medicine (1917) 52, 343-350.
Comparison of the effects of water immersion and saline infusion on central haemodynamics in man
R. LEVINSON, M. EPSTEIN, M . A. SACKNER A N D R. BEGIN Division of Pulmonary Disease, Department of Medicine. Mount Sinai Medical Center, Miami Beach, Florida, Nephrology Section, Medical Service, Veierans Administraiion Hospiial, and Department of Medicine, University of Miami School of Medicine, Miami, Florida, U.S.A. (Received 27 February 1976; accepted 14 October 1976)
S=m=Y 1. The effects of acute intravenous infusion of 2 litres of saline/l20 min on pulmonary
capillary blood flow (Oc), diffusing capacity per unit of alveolar volume @L/VA), functional residual capacity (FRC), and pulmonary tissue plus capillary blood volume (VTPC) were compared with the changes induced by water immersion to the neck for 4 h. Serial measurements were made at 30 min intervals in five normal subjects, utilizing a non-invasive rebreathing method with a gas mixture containing 0 5 % acetylene, 0.3% C”0, 10% He, 21% O2 and 68.2% N2. 2. Infusion of saline produced a rise in & which was similar to that induced by immersion. This increment in Oc persisted for the 3 h of observation after stopping the infusion, in contrast to the prompt decrease in Qc to pre-study values after cessation of immersion. 3. DLIVA was unaffected by salineadministration in contrast to the marked and prompt increment induced by immersion. 4. Pulmonary tissue plus capillary blood volume was unchanged during both saline administration and immersion, suggesting that neither gradual saline administration nor immersion induces major extravasation of fluid into the pulmonary interstitial space. 5 . The present data indicate that the ‘volume stimulus’ of immersion is similar to that of saline-induced extracellular fluid volume ex-
pansion in normal seated subjects. Immersion may be a preferred investigative approach for assessing the effects of volume expansion in subjects in whom rapid reversibility of the ‘volumestimulus’ is desirable. Key words : diffusion, pulmonary capillary blood flow, saline loading, volume homeostasis, water immersion. Abbreviations: DL, diffusing capacity of lung; FRC, functional residual capacity; VA, alveolar volume; VTPC, pulmonary tissue volume capillary blood volume.
+
Introduction Head-out water immersion results in a significant natriuresis, kaliuresis and diure-sis (Epstein, Duncan & Fishman, 1972; Epstein, Katsikas & Duncan, 1973; Epstein & Saruta, 1971), as well as a suppression of both the renin-aldosterone system and antidiuretic hormone (Epstein, Pins & Miller, 1975; Epstein, Pins, Sancho & Haber, 1975). Previous studies have suggested that these effects are mediated in part by immersioninduced alterations in the lesser circulation, including marked increases in central blood volume, cardiac output and a small increase in the diffusing capacity of the lung (DL) without significant change in pulmonary tissue volume (Arborelius, Balldin, Lilja & Lundgren, 1972; Begin, Epstein, Sackner, Levinson, Dougherty & Duncan, 1976; Echt, Lange & Gauer, 1974; Gauer, Henry & Behn, 1970; Lange, Lange,
Correspondence: Dr Murray Epstein, Veterans Administration Hospital, 1201 N.W. 16th Street, Miami, Flordia 33125, U S A .
343
344
R. Levinson et al.
Echt & Gauer, 1974). Despite the demonstration that immersion provides a 'volume stimulus' without the necessity of increasing total blood volume (Epstein, Pins, Arrington, DeNunzio & Engstrom, 1975), it is unclear whether the magnitude of this stimulus is comparable with that induced by expansion of extracellular volume by saline infusion. Furthermore, since two recent studies suggest that rapid saline administration may cause interstitial pulmonary oedema (Collins, Cochrane, Davis, Benatar & Clark, 1973; Muir, Flenley, Kirby, Sudlow, Guyatt & Brash, 1975), it is important from a clinical standpoint to delineate the relative alterations in pulmonary tissue volume induced by both immersion and saline infusion. The recent development of a rapid, noninvasive, repeatable and reproducible method of measuring central haemodynamics (Sackner, Greeneltch, Heiman, Epstein & Atkins, 1975) has made serial assessment possible without intravascular instrumentation. We have compared the alterations in cardiac output, DL and pulmonary tissue volume induced by headout water immersion with those produced by saline infusion, to assesses the relative effect of these manoeuvres on renal handling of sodium and water.
ature of 34.5 +0.5"C, maintained by two heat exchangers with a combined output of 13 500 BTU/h, controlled by an adjustable temperaturecalibrated control meter with input derived from two thermistors immersed at different water levels. Each subject had previously experienced water immersion to the neck when seated, as described before (Epstein et al., 1972; 1973). After 10 h of overnight fluid restriction, the subject sat quietly for 1 h. At 07.20 hours 400 ml of water was administered orally and at 07.50 hours an additional 300 ml was given. At 08.00 hours venous blood was drawn for determination of serum electrolyte concentrations. After completely emptying his bladder, the subject once again sat for 6 h (08.00-14.00 hours). Two litres of sodium chloride solution (154 mmol/l) containing KCl (5 mmol/l) were infused at a constant rate of 17 ml/min from 09.00 to 11.00 hours; average infusion volume = 2.9 & SEM 0.2% of body weight. Each subject passed urine at hourly intervals during the study, 200 ml of water being given every hour to maintain an adequate urine flow during the study. Sodium and potassium concentrations were measured in the hourly urine collections. Blood was obtained at the beginning and end of each study, and subjects were weighed before and after each study.
Materials and methods Subjects
Rebreathing method
Five healthy male subjects, aged 23-31 years, who had participated in a previous immersion study (Begin et af., 1976), were restudied during infusion of sodium chloride solution (154 mmol/l; saline). Their mean body weight was 7 5 + 5 kg (range 67-77 kg); all were non-smokers and they had no history of hypertension, cardiovascular or respiratory disease, or of diabetes. Significant renal disease was excluded by a normal urine sediment test and creatinine clearance. Results of physical examination, ECG and lung volumes were all normal. Pulmonary closing volume was also normal in the three subjects in whom it was measured.
Pulmonary capillary blood flow (Qc), diffusing capacity per unit of alveolar volume (DL/VA), functional residual capacity (FRC), combined pulmonary tissue and capillary blood volume (VTPC) and O2 consumption (30,) were obtained by a rebreathing method as described in detail by Sackner et al. (1975). This method hinges upon measuring the rate of disappearance from the lung of a soluble gas, acetylene, as a marker of pulmonary capillary blood flow and tissue volume, and of a gas that combines with haemoglobin, carbon monoxide, as an indicator of diffusing capacity. Both of these gases have been utilized by others to measure these variables during a single breath hold. Rebreathing into a bag offers the following advantages: (1) a continuous record of gas disappearance can be recorded before recirculation, whereas repeated breath holds are time-consuming and assume a steady state over
Water immersion Immersion was carried out in a tank (Epstein el al., 1972, 1973), at a constant water temper-
Cardiopulmonary eflects of saline
the relatively long time (30-60 min) necessary to construct a disappearance curve; (2) pulmonary tissue volume is measured with each rebreathing procedure; (3) oxygen consumption is measured simultaneously as an indicator of a steady state. Since high ventilation per se is known to increase cardiac output (Armitage & Arnott, 1949), basal estimates of cardiac output cannot be determined with the method. However, comparisons of pulmonary capillary blood flow by the rebreathing technique with the simultaneously obtained indicator dilution measurement in anaesthetized dogs revealed good agreement. The slope of pulmonary capillary blood flow (cardiac output in normal subjects) as a function of oxygen consumption during exercise up to six times resting oxygen consumption is identical with published values obtained with invasive techniques for measuring cardiac output (Sackner et al., 1975). The rebreathing method should therefore detect changes in pulmonary capillary blood flow in response to a stimulus, as the breathing manoeuvre is the same during each measurement. The test gas mixture contained 0.5 % acetylene, 0.3% Cl8O, 10% He, 21% 0,and 68.2% N2. The subject started to breathe from the rebreathing system at the end of a normal expiration, with six voluntary 2.0-2.5 1 breaths over 15 s with passive expiration to FRC. A mass spectrometer (MGA-1100, PerkinElmer, Pomona, Calif, U.S.A.) sampled the gas mixture at the mouth throughout the procedure, the output being processed by a Linc-8 computer (Digital Equipment Co., Maynard, Mass, U.S.A.), rate of sampling 7/s, each gas fraction being corrected for He dilution. The disappearance of C i 8 0 and acetylene were calculated over the last three
345
breaths (during which He equilibrium was already completed) by using a least-squares fit. The intercept at time zero of acetylene was utilized as a function of the combined pulmonary tissue plus capillary blood volume (VTPC) (Cander & Forster, 1959). In the presentation of results, mean values are given + SEM. Two-factor analysis of variance was used to assess significance of differences in repeated measurements on the same subject, a Newman-Keuls test being then used to determine which of the treatment mean values were significantly different (Snedecor & Cochran, 1967). Differences with P 0.05). Saline infusion resulted in a natriuretic response which was similar to that of immersion. Immersion was associated with a fall of 1.1 f0.2 kg in mean body weight, whereas saline infusion increased mean body weight by 1.5 f 0.2kg (P< 0.05).
+
TABLE1. Effects of immersion on urinary excretory patterns UN.V = urinary sodium excretion; U K V = urinary potassium excretion. None of the differences between the saline and immersion data was statistically significant. Mean results+ SEM (n = 5 ) are shown. Time Group
UN. V (mmol/min) Immersion Saline UKV(mmol/min) Immersion Saline
Pre-study
Ih
87+ 12 as+ 33
137f22 90+ 30
241 29 142+44
300f 31 196+51
307+ 30 210+ 50
170+32 210k46
55f 12 56f 7
aik 24
140+45 aof 17
98+ ia 94+ 13
77+ 16 107+ 19
43+8 90+ 18
so+ a
2h
+
3h
4h
Recovery
VTPC (ml) Immersion Saline O2 consumption (ml/min) Immersion Saline F R C (1 BTPS) Immersion Saline Heart rate (beats/min) Immersion Saline
Group
251+23 235k25
260+17 223f13
60k 3
64+ 3
63+ 3 60+ 2
2.85k 0.22 1.8 1 0.19 3.02f 0.12 3.04*2 0.20
+
674f122 661k61
30 min
657f103 688+75
Pre-study
267228 249f16
632+67 681k90
90 min
251f25 253+22
638+79 699k111
120 min
~~
150 min
271k25 252+17
674+78 660+97
Time ~~
261+20 230+23
698+89 637k114
62+ 2 60+ 4
61+4 60+ 3
60+ 3
64+ 2
62+ 2 59+ 3
63+3 62+ 3
210 min
249+24 231+13
725k130 573+157
240 min
255+19 243+16
7472106 577f131
Recovery
64+ 2 59+ 3
64+ 2 60k 3
62+ 2 62+ 3
1.89f 0.14 1.89+ 0.29 2.92+ 024 2.89*+ 0.13 3.17*+ 0.13 3.03.k 0 1 2
274+25 251+18
642+68 584+140
______
180 min
1.90+ 0.17 1.87f 0.14 I .90+ 0.17 I .84+ 0.17 1.80+ 0.21 3.09*+ 0.17 2.91.k 0.10 2.81*+ 0.12 2.77** 0.14 2.77*+ 0.13
276k32 224+17
624f70 621+115
60 min
~~~
TABLE 2. Comparison of the effects of immersion and saline infusion on pulmonary circulation and function VTPC = pulmonary tissue+capillary volume; FRC = functional residual capacity. Mean r e s u l t s k s ~(n~ = 5) are shown. P
Comparison of the effects of water immersion and saline infusion on central haemodynamics in man
R. LEVINSON, M. EPSTEIN, M . A. SACKNER A N D R. BEGIN Division of Pulmonary Disease, Department of Medicine. Mount Sinai Medical Center, Miami Beach, Florida, Nephrology Section, Medical Service, Veierans Administraiion Hospiial, and Department of Medicine, University of Miami School of Medicine, Miami, Florida, U.S.A. (Received 27 February 1976; accepted 14 October 1976)
S=m=Y 1. The effects of acute intravenous infusion of 2 litres of saline/l20 min on pulmonary
capillary blood flow (Oc), diffusing capacity per unit of alveolar volume @L/VA), functional residual capacity (FRC), and pulmonary tissue plus capillary blood volume (VTPC) were compared with the changes induced by water immersion to the neck for 4 h. Serial measurements were made at 30 min intervals in five normal subjects, utilizing a non-invasive rebreathing method with a gas mixture containing 0 5 % acetylene, 0.3% C”0, 10% He, 21% O2 and 68.2% N2. 2. Infusion of saline produced a rise in & which was similar to that induced by immersion. This increment in Oc persisted for the 3 h of observation after stopping the infusion, in contrast to the prompt decrease in Qc to pre-study values after cessation of immersion. 3. DLIVA was unaffected by salineadministration in contrast to the marked and prompt increment induced by immersion. 4. Pulmonary tissue plus capillary blood volume was unchanged during both saline administration and immersion, suggesting that neither gradual saline administration nor immersion induces major extravasation of fluid into the pulmonary interstitial space. 5 . The present data indicate that the ‘volume stimulus’ of immersion is similar to that of saline-induced extracellular fluid volume ex-
pansion in normal seated subjects. Immersion may be a preferred investigative approach for assessing the effects of volume expansion in subjects in whom rapid reversibility of the ‘volumestimulus’ is desirable. Key words : diffusion, pulmonary capillary blood flow, saline loading, volume homeostasis, water immersion. Abbreviations: DL, diffusing capacity of lung; FRC, functional residual capacity; VA, alveolar volume; VTPC, pulmonary tissue volume capillary blood volume.
+
Introduction Head-out water immersion results in a significant natriuresis, kaliuresis and diure-sis (Epstein, Duncan & Fishman, 1972; Epstein, Katsikas & Duncan, 1973; Epstein & Saruta, 1971), as well as a suppression of both the renin-aldosterone system and antidiuretic hormone (Epstein, Pins & Miller, 1975; Epstein, Pins, Sancho & Haber, 1975). Previous studies have suggested that these effects are mediated in part by immersioninduced alterations in the lesser circulation, including marked increases in central blood volume, cardiac output and a small increase in the diffusing capacity of the lung (DL) without significant change in pulmonary tissue volume (Arborelius, Balldin, Lilja & Lundgren, 1972; Begin, Epstein, Sackner, Levinson, Dougherty & Duncan, 1976; Echt, Lange & Gauer, 1974; Gauer, Henry & Behn, 1970; Lange, Lange,
Correspondence: Dr Murray Epstein, Veterans Administration Hospital, 1201 N.W. 16th Street, Miami, Flordia 33125, U S A .
343
344
R. Levinson et al.
Echt & Gauer, 1974). Despite the demonstration that immersion provides a 'volume stimulus' without the necessity of increasing total blood volume (Epstein, Pins, Arrington, DeNunzio & Engstrom, 1975), it is unclear whether the magnitude of this stimulus is comparable with that induced by expansion of extracellular volume by saline infusion. Furthermore, since two recent studies suggest that rapid saline administration may cause interstitial pulmonary oedema (Collins, Cochrane, Davis, Benatar & Clark, 1973; Muir, Flenley, Kirby, Sudlow, Guyatt & Brash, 1975), it is important from a clinical standpoint to delineate the relative alterations in pulmonary tissue volume induced by both immersion and saline infusion. The recent development of a rapid, noninvasive, repeatable and reproducible method of measuring central haemodynamics (Sackner, Greeneltch, Heiman, Epstein & Atkins, 1975) has made serial assessment possible without intravascular instrumentation. We have compared the alterations in cardiac output, DL and pulmonary tissue volume induced by headout water immersion with those produced by saline infusion, to assesses the relative effect of these manoeuvres on renal handling of sodium and water.
ature of 34.5 +0.5"C, maintained by two heat exchangers with a combined output of 13 500 BTU/h, controlled by an adjustable temperaturecalibrated control meter with input derived from two thermistors immersed at different water levels. Each subject had previously experienced water immersion to the neck when seated, as described before (Epstein et al., 1972; 1973). After 10 h of overnight fluid restriction, the subject sat quietly for 1 h. At 07.20 hours 400 ml of water was administered orally and at 07.50 hours an additional 300 ml was given. At 08.00 hours venous blood was drawn for determination of serum electrolyte concentrations. After completely emptying his bladder, the subject once again sat for 6 h (08.00-14.00 hours). Two litres of sodium chloride solution (154 mmol/l) containing KCl (5 mmol/l) were infused at a constant rate of 17 ml/min from 09.00 to 11.00 hours; average infusion volume = 2.9 & SEM 0.2% of body weight. Each subject passed urine at hourly intervals during the study, 200 ml of water being given every hour to maintain an adequate urine flow during the study. Sodium and potassium concentrations were measured in the hourly urine collections. Blood was obtained at the beginning and end of each study, and subjects were weighed before and after each study.
Materials and methods Subjects
Rebreathing method
Five healthy male subjects, aged 23-31 years, who had participated in a previous immersion study (Begin et af., 1976), were restudied during infusion of sodium chloride solution (154 mmol/l; saline). Their mean body weight was 7 5 + 5 kg (range 67-77 kg); all were non-smokers and they had no history of hypertension, cardiovascular or respiratory disease, or of diabetes. Significant renal disease was excluded by a normal urine sediment test and creatinine clearance. Results of physical examination, ECG and lung volumes were all normal. Pulmonary closing volume was also normal in the three subjects in whom it was measured.
Pulmonary capillary blood flow (Qc), diffusing capacity per unit of alveolar volume (DL/VA), functional residual capacity (FRC), combined pulmonary tissue and capillary blood volume (VTPC) and O2 consumption (30,) were obtained by a rebreathing method as described in detail by Sackner et al. (1975). This method hinges upon measuring the rate of disappearance from the lung of a soluble gas, acetylene, as a marker of pulmonary capillary blood flow and tissue volume, and of a gas that combines with haemoglobin, carbon monoxide, as an indicator of diffusing capacity. Both of these gases have been utilized by others to measure these variables during a single breath hold. Rebreathing into a bag offers the following advantages: (1) a continuous record of gas disappearance can be recorded before recirculation, whereas repeated breath holds are time-consuming and assume a steady state over
Water immersion Immersion was carried out in a tank (Epstein el al., 1972, 1973), at a constant water temper-
Cardiopulmonary eflects of saline
the relatively long time (30-60 min) necessary to construct a disappearance curve; (2) pulmonary tissue volume is measured with each rebreathing procedure; (3) oxygen consumption is measured simultaneously as an indicator of a steady state. Since high ventilation per se is known to increase cardiac output (Armitage & Arnott, 1949), basal estimates of cardiac output cannot be determined with the method. However, comparisons of pulmonary capillary blood flow by the rebreathing technique with the simultaneously obtained indicator dilution measurement in anaesthetized dogs revealed good agreement. The slope of pulmonary capillary blood flow (cardiac output in normal subjects) as a function of oxygen consumption during exercise up to six times resting oxygen consumption is identical with published values obtained with invasive techniques for measuring cardiac output (Sackner et al., 1975). The rebreathing method should therefore detect changes in pulmonary capillary blood flow in response to a stimulus, as the breathing manoeuvre is the same during each measurement. The test gas mixture contained 0.5 % acetylene, 0.3% Cl8O, 10% He, 21% 0,and 68.2% N2. The subject started to breathe from the rebreathing system at the end of a normal expiration, with six voluntary 2.0-2.5 1 breaths over 15 s with passive expiration to FRC. A mass spectrometer (MGA-1100, PerkinElmer, Pomona, Calif, U.S.A.) sampled the gas mixture at the mouth throughout the procedure, the output being processed by a Linc-8 computer (Digital Equipment Co., Maynard, Mass, U.S.A.), rate of sampling 7/s, each gas fraction being corrected for He dilution. The disappearance of C i 8 0 and acetylene were calculated over the last three
345
breaths (during which He equilibrium was already completed) by using a least-squares fit. The intercept at time zero of acetylene was utilized as a function of the combined pulmonary tissue plus capillary blood volume (VTPC) (Cander & Forster, 1959). In the presentation of results, mean values are given + SEM. Two-factor analysis of variance was used to assess significance of differences in repeated measurements on the same subject, a Newman-Keuls test being then used to determine which of the treatment mean values were significantly different (Snedecor & Cochran, 1967). Differences with P 0.05). Saline infusion resulted in a natriuretic response which was similar to that of immersion. Immersion was associated with a fall of 1.1 f0.2 kg in mean body weight, whereas saline infusion increased mean body weight by 1.5 f 0.2kg (P< 0.05).
+
TABLE1. Effects of immersion on urinary excretory patterns UN.V = urinary sodium excretion; U K V = urinary potassium excretion. None of the differences between the saline and immersion data was statistically significant. Mean results+ SEM (n = 5 ) are shown. Time Group
UN. V (mmol/min) Immersion Saline UKV(mmol/min) Immersion Saline
Pre-study
Ih
87+ 12 as+ 33
137f22 90+ 30
241 29 142+44
300f 31 196+51
307+ 30 210+ 50
170+32 210k46
55f 12 56f 7
aik 24
140+45 aof 17
98+ ia 94+ 13
77+ 16 107+ 19
43+8 90+ 18
so+ a
2h
+
3h
4h
Recovery
VTPC (ml) Immersion Saline O2 consumption (ml/min) Immersion Saline F R C (1 BTPS) Immersion Saline Heart rate (beats/min) Immersion Saline
Group
251+23 235k25
260+17 223f13
60k 3
64+ 3
63+ 3 60+ 2
2.85k 0.22 1.8 1 0.19 3.02f 0.12 3.04*2 0.20
+
674f122 661k61
30 min
657f103 688+75
Pre-study
267228 249f16
632+67 681k90
90 min
251f25 253+22
638+79 699k111
120 min
~~
150 min
271k25 252+17
674+78 660+97
Time ~~
261+20 230+23
698+89 637k114
62+ 2 60+ 4
61+4 60+ 3
60+ 3
64+ 2
62+ 2 59+ 3
63+3 62+ 3
210 min
249+24 231+13
725k130 573+157
240 min
255+19 243+16
7472106 577f131
Recovery
64+ 2 59+ 3
64+ 2 60k 3
62+ 2 62+ 3
1.89f 0.14 1.89+ 0.29 2.92+ 024 2.89*+ 0.13 3.17*+ 0.13 3.03.k 0 1 2
274+25 251+18
642+68 584+140
______
180 min
1.90+ 0.17 1.87f 0.14 I .90+ 0.17 I .84+ 0.17 1.80+ 0.21 3.09*+ 0.17 2.91.k 0.10 2.81*+ 0.12 2.77** 0.14 2.77*+ 0.13
276k32 224+17
624f70 621+115
60 min
~~~
TABLE 2. Comparison of the effects of immersion and saline infusion on pulmonary circulation and function VTPC = pulmonary tissue+capillary volume; FRC = functional residual capacity. Mean r e s u l t s k s ~(n~ = 5) are shown. P
