Regulation of sodium excretion in dog, and effects of atrial size and function upon secretion of sodium load - circulatory response to upright til

Abelmann, W. H.

Earley, L. E.

English

Physiological mechanisms and inter-relations between blood volume, blood flow, and electrolyte balanc

NASA Technical Reports Server

THORNDIKE NeMQRIAL UBORATORY 
SECOND AND FOURTH MEDICAL SERVICES 
W V A R D  MEDICAL UNIT 
BOSTON CITY HOSPITAL 
Research Grant NsG 595 
National Aeronautics and Space Administration 
AStudv of mWsiolopical Mechanisms and Inter-Relations 
between Systemic and Regional Blood Volume. Blood 
Flow and Electrolyte Balance 
Walter H. Abelmann, M. D. 
Laurence E. Earley, M. D. 
Interim Progress Report 
December 3, 1966 
GPO PRICE $ 
CFSTI PRICE(S) $ 
Hard copy (HC) ? e m  
Microfiche (MF) 1 6 ~  
ff 653 July 65 
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Abelmann and Earley 
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Renal Hemodivndcs and Sodium Ekcretian 
During the past grant period, laboratory investigations in the 
dog have beencontinued to extend previous observations of relation- 
ships between renal hemodynamics and sodium excretion. 
past year we reported studies demonstrating that the tubular reabsorp- 
tion of sodium relates to the effectiveness with which renal perf’usion 
pressure $8 transmitted along the intrarenal circulation. Renal vaso- 
dilatation alone decreases sodium reabsorption, and increased renal 
perf’usion pressure, in the presence of reduced renal vascular re- 
sistance, a180 reduces sodium reabsorption. 
indicate that renal vascular tone and perfusion pressure could play 
important roles in determining sodium balance, and therefore in regulat- 
ing the extracellular fluid volume. 
During the 
These observations 
Utilizing a technique of diuretic (ethacrynic acid and chlorothiazide) 
induced blockade of distal tubular reabsoqtian, it has been possible 
to localize changes in sodium reabsorption to the proximal tubule. 
Thus the effect of perfusion pressure to alter sodium reabsorption 
occurs in the proximal tubule. 
relationship exists between plasma oncotic (protein) pressure and proximal 
tubular reabsorption. 
ed that proximal tubular reabsorption may relate inversely to the renal 
interstitial volume, and that hydrostatic and oncotic pressures affect 
this mechanism in opposite directions via changes in capillary v d l  
perfusion. 
We have also demonstrated that a direct 
On the basis of these observations it was suggest- 
~~ 
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Abelmk and Earley NsG 595 12/3/66 
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These same l ines  of investigation are being continued t o  explore 
(1 ) The relationships between physiologic renal vascular antoregulation 
and the control of sodium balance, and (2) the extent t o  which  these 
hemodynamically induced changes in  tubular reabsorption and sodium bal- 
ance determine the excretory response t o  volume expansion with (1) water, 
(2) saline, (3) plasma, and ( 4 )  blood, 
D e  Effect of A t r i a l  Fibrillation upon the Excretim of a Sodium Load 
a) Studies in Man 
Investigations of the role of a t r i a l  s ize  and function in the 
Previous reports regulation of sodium excretion have been cmtinged. 
have described our studies of patients with mitral stenosis and a t r i a l  
f ibr i l la t ion,  i n  whom excretion of the sodium load was generally de- 
layed and incmplete but was improved toward normal after cardioverslm 
t o  normal sinus rhythrn. 
A series of patients with coronary or primary myocardial disease 
and a t r i a l  f ibr i l la t ion,  studied recently, have shown similar normal- 
ization of sodium af ter  resti tution of normal sinus rhythm, irrespective 
of heart rate. 
effect of a t r i a l  f ibri l lation, a t  l eas t  in part, i s  hemodynamically 
mediated, the arrhythmia interfering w i t h  the a t r i a l  transport function, 
Current studies are exploring the mediation of t h i s  effect further. 
b) 
Indirect evidence suggests that  the sodium retaining 
rn erimental Studies i n  Dogs 
Further studies of the mechanism by which a t r i a l  f ib r i l l a t ion  
a l te rs  sodium excretion a r e  being carried out i n  the dog, under cir- 
cumstances permitting the control of the variables involved, An electrical  
,e -4 .-  
Abelmann and Earley NSG 595 12/31/66 
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method was developed, permitting a t r i a l  f ibr i l la t ion and defibril lation 
a t  w i l l .  
of alteration of excretion of sodium and water with alteration in a t r i a l  
rhythm, but the findings have not been consistent. 
are  i n  pgress .  
Detdants of the Circulatory Response t o  Upripht T i l t  
Initial studies in the open-chested dog have given evidence 
Further studies 
(3)  
A previous report described the initial studies of the cardio- 
vascular response of patients w i t h  heart disease t o  prolonged up- 
r ight  tilt. 
s t a t i c  tolerance, accompanied by a smaller than normal increase in  
heart rate and diastolic blood pressure and by less narrowing of the 
pulse pressure. 
althaugh it did not correlate w i t h  degree of clinic111 heart failure. 
In general, cardiac patients displayed rather good ortho- 
This response was termed "Heart Failure Responsett, 
Subsequently, in  s ix  subjects and in 34 patients w i t h  cardiovascular 
disease who had supine hemodynamic studies a t  a separate time but in 
a comparable s ta te ,  the responses of heart ra te  and blood pressure were 
analyzed i n  relation t o  hemodynamic variables. 
The response of heart ra te  t o  upright tilt correlated negatively 
and significantly w i t h  right a t r ia l ,  l e f t  a t r i a l ,  and pulmonary arterial 
pressure (R = - 0.4.4, - 0.50, and - 0.LJ respectively); it correlated 
positively and significantly w i t h  cardiac index (R = + 0 . 3 ) .  
response of diastolic pressure to tilt correlated significantly With 
right a t r i a l  pressure (R = - 0.3l) and w i t h  stroke index (R = + 0.39). 
The 
A b e k  and Earley NsG 595 
- 4 -  
12/31/66 
There was no significant correlation w i t h  cardiac rhythm or d ig i ta l i s  
status, 
Prolonged bedrest is knom to resul t  i n  decreased orthostatic tol- 
erance i n  normal subjects, resulting i n  abnormally large increases i n  
heart ra te  and f a l l  in  blood pressure in  response t o  upright tilt, Of 
nine patients with heart disease who were studied a f te r  prolonged bed- 
r e s t  and prior t o  mobilization, both patients i n  congestive heart fa i l -  
ure retained the 'Pneart fa i lure  responsef1 and showed no evidence of 
deconditioning. 
of heart fa i lure  showed an excessive tachycardia and f a l l  i n  blood 
pressure, evidence of deconditioning. 
returned within a week af te r  ambulation. 
Seven patients with wocardial infarcts and no evidence 
Normal orthostatic tolerance 
All of 5 normal subjects responded t o  acute volume depletion by 
intravenous ethaerynic acid with decreased orthostatic tolerance, while 
3 of 4 patients in congestive heart fa i lure  tolerated the upright pos- 
ture relatively w e l l  af ter  double the volume of diuresis. 
It is concluded that patients with heart fa i lure  tend t o  be able 
t o  maintain blood pressure i n  response t o  upright tilt a t  l i t t l e  or  
no increase i n  heart rate, reflecting increased orthostatic tolerance 
or lloverconditioningII. Patients with congestive heart failure may be 
resistant t o  deconditioning by bedrest or by volume depletion. 
These studies serve t o  delineate the role of ventricular f i l l i n g  
pressures and circulating blood volume as determinants of orthostatic 
tolerance. 
c 
, .  
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Abelmazrn and Earley NsG 595 12/31/66 
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Studies of the effects of acute depletion of blood volume and of 
acute expansion of blood volume are i n  progress. 
PUBLICATIONS I N  1966 
1. Abelmann, W. H.: Effect of abnormal circulatory s ta tes  upon response 
t o  upright tilt. Aerospace Med. 21: s5, 1966 (Abstract) 
2. Abelmann, W. H.: Effects of mitral stenosis and a t r ia l  f ibr i l la t ion 
upon sodium excretion. 
Manned Spacecraft Center, February 1966, pp. 103 - 110. Proc. Second Ann. Biomed. Res. Conf., N.A.S.A. 
3. Earley, L. E.: Hemodynamic influences on tubular reabsorption and 
Proc. Second Ann. Bimed. Res. Conf., N.A.S.A. sodium excretion. 
Manned Spacecraft Center, February 1966, pp. 111 - 115. 
4. Earley, I,. E.: Influence of hemodynamic factors on sodium reabsorption. 
Ann. N.Y. Acad. Sci., 312 - 327, 1966. 
5. Earley, L. E. and Friedler, R. M.: The effects. of cmbined renal 
vasodilatation and pressor agents on renal hemodynamics and the 
tubular reabsorption of sodium. J. C l b .  Invest., a: 542 - 551, 
1966. 
6. Earley, L. E., Friedler, R. M. and Martino, J. A.: V r ~ x i m a l ~ ~  tubular 
reabsorption studied during lldistalfl blockade, 
375, 1966 (Abstract). 
C l i n .  Research, l& 
7. Earley, L. E., Martino, J. A. and Friedler, R. M.: Factors affect- 
ing sodium reabsorption by the proximal tubule as determined during 
blockade of d i s t a l  sodium reabsorption. J. C l i n .  Invest. 42: 1668 - 
1684, 1966. 
8. Friedler, R. M., Belleau, L., and Earley, L. E.: Hernodynamically in- 
duced reversal of the sodium retention resulting from acute supra- 
hepatic inferior vena caval constriction. J. Clin. Invest. a: 1009, 
1966 (Abstract). 
9. Friedler, R. M., and Earley, L. E.: Reduced renal concentrating capacity 
during isotonic saline loading. Proc. SOC. Bper. Biol. &Med. 121: 
352 - 357, 1966. 
' , '. 
c 
Abelmann and Fhrley NsG 595 
, L  
12/71/66 
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10. G i r o d ,  C. E. and Abelmann, W. H.: Ekcretian of sodium load by patients 
with m i t r a l  stenosis with observations on the effect of cardioversion. 
C l i n .  Res. 12: 2.47, 1966 (Abstract). 
Ramirez, A. and Abelmann, W. H.: 
ethacrynic acid i n  congestive heart failure. 
and 194, 1966 (Abstract). 
11. HemOdyn&c effects of intravenous 
Circulation &: 111-193 
Mticles  i n  Press 
1. Abelmann, W. H. and Fareeduddin, K.: The circulatory response t o  up- 
r ight  tilt i n  patients w i t h  heart disease. Aerospace M e d .  
Friedler, R. M., Belleau, L. J., Martino, J. A., and Earley, L. E.: 
Hemodynamically induced natriuresis i n  the presence of sodium re- 
tention resulting f r a  auztiriction of the thoracic inferior vena 
cava. J. Lab. & C l i n .  Med. 
2. 
. 


A Study of Physiological Mechanisms and Inter-relations Between Systemic and Regional Blood Volume, Blood Flow and Electrolyte Balance  Interim Progress Report, Jul. 1 - Dec. 31, 1966

- .  
' jr . .  
THORNDIKE MEMORIAL LABORATORY 
SECOND AND FOURTH MEDICAL SERVICES 
WLRVARD MEDICAL UNIT 
BOSTON CITY HQSPITAL 
Research Grant NsG 595 
National Aeronautics and Space Administration 
A Study of Physiolopical Mechanisms and Inter-Relations 
between Systemic and Regional Blood Volume. Blood 
Flow and Electrolyte Balance 
GPO PRICE $ 
Walter H. Abelmann, M.D. 
Laurence E. Earley, M.D. CFSTI PRICE(S) $ 
Hard copy (HC) ,rs e 
.I 
Microfiche (MF) * -  
ff 653 July 86 
Interim Progress Report 
December 31, 1967 
https://ntrs.nasa.gov/search.jsp?R=19680005268 2020-03-12T12:09:49+00:00Z
. .  . ' , , A b e l m  and Earley NsG 595 12/ 3 1/67 
- 1 -  
(1) RePulation of Sodium&cretiQD 
Studies on the mechanisms for  regulating sodium excretion 
have been continued i n  the dog, and recently these projects have 
been extended t o  the human subject. 
two  major areas have been explored and are described below. 
a) 
During the past s i x  mnths 
Earlier studies supported by NsG 595, which have been re- 
viewed i n  previous reports, have led t o  the suggestion 
that  hemodynamic factors (viz., arterial perfusion pres- 
sure, plasma oncotic pressure, and renal vascular resistance) 
may a l t e r  the tubular reabsorption of sodium by intrarenal 
pathways. 
vided evidence that  these physical factors are important 
mediators of the natriuretic response t o  volume expansion, 
and thus, indicating an important physiologic role for non- 
hormonal, physical factors as determinants of sodium excre- 
tion. 
Clearance and micropuncture studies have provided abundant 
data regarding the effects of various maneuvers (volume ex- 
pansion, diuretic infusion, vena caval constriction, etc.) 
on proximal tubular reabsorption of sodium i n  the dog and 
rat .  
tubular anatow of sodium reabsorption i n  the human, and to  
what extent sodium reabsorption by the human nephron resembles 
that  of the dog and ra t .  
A recently completed study i n  the dog has pro- 
b) 
However, vir tual ly  no data has been available on the 
We have utilized the technique of 
. .  I * *  Abelmann and Earley NsG 595 12/31/67 
- 2 -  
diuretic induced lldbstal tubular blockadell, previously de- 
scribed from our laboratory, t o  study sodium reabsorption 
i n  the human. 
d i s t a l  tubular reabsorption of sodium i n  the human resembles 
qualitatively that i n  the r a t  and dog. 
tubular reabsorption of sodium is decreased during I1escapet1 
from a mineralocorticoid and is increased i n  the upright 
position and in  patients with cirrhosis or  congestive heart 
failure. 
The results demnstrate tha t  proximal and 
In  the human proximal 
These general studies are being continued i n  an effor t to  
identify further the role of non-hormnal hemdynamic and physical 
factors 
excretion. 
determinants of normal and abnormal regulation of sodium 
The Effect of A t r i a l  Fibril lation upon the Excretion of a Sodium h a d  
(a) Studies i n  Man 
Investigations of the role of a t r i a l  s ize  and function 
have been continued. As reported previously, i n  patients 
with mitral stenosis and a t r i a l  f ib r i l l a t ion  excretion of 
a sodium load was generally delayed and incomplete, but was 
improved toward normal after cardioversion t o  normal sinus 
rhythm. 
f ib r i l l a t ion  associated with arteriosclerotic heart disease 
disease, thyrotoxicosis, primary myocardial disease and t o  
Extension of these studies t o  patients i n  a t r i a l  
, .  . Abelmann and Earley NsG 595 
- 3 -  
12/31/67 
patients without evidence of heart disease has revealed 
that  generally, retention of a sodium load was l ess  abnormal, 
and no changes were evident a f te r  conversion to  regular sinus 
rhythm. 
In selected patients, these studies included measure 
ments of systemic and renal hemdynamics. 
group is s t i l l  small, the data suggest that  cardioversion 
from atrial. f i b r i l l a t ion  to  sinus rhythm results i n  an in- 
crease i n  cardiac output as well as renal plasma flow, while 
glomerular f i l t r a t i o n  rate  remains unchanged. 
Studies i n  the Dog 
Althoughthis 
A mdel animal has been developed, suitable t o  study 
interrelationships between a t r i a l  arrhythmia, a t r i a l  pressure, 
cardiac output, renal. hemdynamics, and sodium excretion. 
Reversible a t r i a l  f ib r i l l a t ion  as well as reversible mitral 
stenosis can be produced in  th i s  animal. 
out i n  the open-chested an imal  have indicated the desirabi l i ty  
of changing this  mdel  t o  a closed-chest one. 
progress. 
Studies carried 
This is i n  
( 3 )  Determinants of the Circulatory Response to  UpriPht T i l t  
Previous reports have summarized our studies of the toler- 
ance of orthostatic s t ress ,  including the response of heart ra te  and 
blood pressure, i n  a broad sample of patients with cardiovascular 
- .  0 '  Abelmann and Earley NsG 595 12/31/67 
- 4 -  
disease. The increased tolerance of passive upright tilt ob- 
served i n  patients with clinical  as well as subclinical heart 
fa i lure  was attributed primarily to  increased circulating blood 
volume and raised ventricular f i l l ing  pressures. 
by this concept, the "heart failure response1' could be produced 
i n  normal subjects by means of acute expansion of plasma volume. 
Also, patients i n  congestive heart fa i lure  were resis tant  t o  de- 
conditioning by either acute plasma volume depletion o r  prolonged 
bedrest. 
ture,  whether tilt or  s i t t ing ,  was found i n  some patients con- 
valescing from acute myocardial infarction. 
As predicted 
In contrast, a vasodepressor response t o  upright pas- 
Most of these studies had been done i n  unbloody manner, in  
order t o  avoid affecting the phenomenon under study by instru- 
mentation. 
a r t i f i ca l ly  i n  the hea l tw subject or by disease i n  the cardiac 
patient, is the prime determinant of tolerance of orthostatic s t ress  
is now being tested by studying the hemdynamic response t o  ortho- 
s t a t i c  stress i n  selected subjects and patients. 
sults, on the basis of 13 subjects, indeed suggest that a larger 
circulating blood volume, of whatever cause, pernits bet ter  main- 
tanence of cardiac output i n  response t o  orthostatic stress.  
The -thesis that expansion of plasma volume, whether 
Preliminary re- 
The previous recommndation that the role of dehydration i n  
orthostatic intolerance be emphasized stands. 
Public a t  ions 
JL~LY 1 - December 31, 1967 
1. Martino, J . A . ,  and Earley, L.E.: 
on renal hemdynamics and the tubular reabsorption of sodium. 
The effects of infusion of water 


A study of physiological mechanisms and inter-relations between systemic and regional blood volume, blood flow and electrolyte balance  Interim progress report, Jun. 30 - Dec. 31, 1967

A study of physiological mechanisms and inter-relations between systemic and regional blood volume, blood flow and electrolyte balance Interim progress report, Jun. 30 - Dec. 31, 1967

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