Blood pH and carbon dioxide tension effect on performance of heart-lung preparatio

Nejad, N. S.

Ogden, E.

English

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EFFECT OF BLOOD pH AND C02 TENSION ON THE 
PERFORMANCE OF THE HEART-LUNG PREPARATION* 
N. S. Neiad and Eric Ogden 
Bureau of Medicine and Surgery 
MROll.01.2 
Approved by 
t Ashton Graybiel, M. D. 
I Director of Research 
Released by 
Captain J , W. Weaver, MC USN 
Commanding Officer 
I 
I 13 November 1967 
I 
I *This study was supported in part by Ames Research Center, National Aeronautics and Space Administration. 
I 
NAVAL AEROSPACE MEDICAL INSTITUTE 
NAVAL AEROSPACE MEDICAL CENTER 
PENSACOLA, FLORIDA 32512 
https://ntrs.nasa.gov/search.jsp?R=19680006468 2020-03-12T11:59:27+00:00Z
SUMMARY PAGE* 
I 
THE PROBLEM 
To study the direct effect of blood pH and C02 tension on the performance of the 
heart and to separate and identify the effect of blood pC02 and pH on myocardium, an 
isolated heart-lung preparation was chosen i n  preference to an intact animal. This pre- 
paration excludes nervous and humoral influences; thus, the changes observed may be 
ascribed to the direct action of blood pH and blood C 0 2  tension on myocardium find- 
ings. 
FINDINGS 
When the performance of  heart-lung preparations was evaluated by the relation- 
ship between stroke work and left atrial pressure, a change of the C 0 2  content of the 
inspired air from zero to 10 per cent caused a progressive decrease i n  performance. 
The use of HCI or NaHC03 allowed for changing the pH and pC02 of the arterial 
blood separately, Arterial blood pH rather than blood pC02 appeared to be the de- 
cisive factor i n  mediating this change. Whenever a change of inspired air composition 
was made in either direction, the new performance level was preceded by a marked 
Overshoot. A fall i n  arterial pH was accompanied by a slowing of the heart rate. 
- - - - - - - - - -  
"Dr. Ogden i s  at Ames Research Center, NASA, Moffett Field, California. 
The experiments reported herein were conducted according to the principles enun- 
ciated in "Guide for Laboratory Animal Facilities and Care'' prepared by the Committee 
on the Guide for Animal Resources, National Academy of Sciences-National Research 
Counci I. 
ii 
INTRODUCTION 
Jerusalem and Starling (1) as early as 1910 reported that major changes in C 0 2  
in either direction el ici t  cardiac dilation i n  an isolated heart. Since then i t  has been 
reported that while the heart i n  intact animals i s  highly tolerant to severe hypercapnia, 
i t  i s  very sensitive to high pC02 when i t  i s  isolated (2-5). Boniface and Brown (4) 
with the aid of a Cushny myocardiograph measured the effect of carbon dioxide on the 
contractile force of a representative segment of the right ventricle i n  situ. They ob- 
served a pronounced cardiac dilation when the animal was subjected to 30% C02. 
Nahas and Cavert (3) reported acute myocardial failure i n  the heart-lung preparation 
exposed to C 0 2  of 10 per cent or above. 
-- 
The present study examines some effects of moderate elevation of inspired C 0 2  
(0-10%) on cardiac performance, as evaluated by stroke work (SW) and le f t  atrial 
pressure (LAP), in the heart-lung preparation. 
PROCEDURE 
Starling (6) heart-lung preparations (HLP) made from 27 mongrel dogs (9-1 1 kg) 
were ventilated with a pump connected to a spirometer fil led with a gas mixture of 
40% 02, O - l W o  C02, and the balance nitrogen. The preparations were supported by 
a continuous infusion of 590 glucose (10 mg/min), and insulin (0.008 unit/min). Ex- 
pired CO2 and 0 2  were monitored continuously wi th  a Beakman Mode4 LB-I gas ana- 
lyzer and a Model E2 oxygen analyzer, respectively. 
Statham pressure transducers (PR23 and P23Dd) recorded pressures from the left 
atrial appendage and the aortic end of the left subclavian artery. A Shipley-Wilson 
flowmeter (7) was connected in the arterial flowline across the arterial resistance 
ciamp, and the plumonary flow was recorded with a pulsed field electromagnetic flow- 
meter. A portion of the systemic flow was shunted through a modular cuvette for con- 
tinous measurements of p02, pC02, and pH of the arterial blood. Because of the un- 
certainty of the accuracy at very low readings of pC02, a l l  readings of 10 mm Hg or 
less were considered to be i n  the same category, The details of the experimental de- 
sign, instrumentation, and calibrations are described elsewhere (8). 
The recorded changes of C 0 2  tension in the blood, however, did not reach a 
steady state for about 10 minutes because of the slow response time of the instrunent. 
The arterial pC02 was then allowed to remain constant for a period of 15 to25 minutes 
before the inspired C 0 2  concentration was changed again. Measurements were made 
throughout the experiment at one-minute intervals. 
The performance of the heart was evaluated by the relationship between SW and 
mean LAP. The mean left atrial pressure was considered as an index of the f i l l ing 
pressure; the stroke work was considered as an index of performance independent of 
heart rate. 
1 
RESULTS I I 
Figure 1 shows the progressive decrease in  the heart rate as arterial 6 0 2  in- 
creased in 18 separate experiments in response to the changes in inspired C02. In 
these experiments no attempt was made to maintain the blood pH constant. The data 
clearly indicate an inverse relationship between the heart rate and pC02. 
I 
I 
I 
Figure 2 shows the progressive decrease i n  the heart rate as arterial pH i s  lowered I 
in six HLP. In these experiments arterial pC02 was kept constant at or below 10 mm 
Hg. The pH was changed with infusion of 0.5N HCl at the rate of 1.5 cc/min. It i s  
clearly evident that there was an approximately linear relationship between the pH of 
the blood over the range 7.10 to 7.98 and the slowing of the heart rate. It i s  probable 
that the decrease in  the heart rate with a rise i n  arterial pC02 shown in  Figure 1 was 
largely due to pH changes. 
I 
Figure 3 presents data from a single preparation typical of eight experiments 
showing the effect of inhalation of C02. Work curves are shown at arterial pC02 
values of 10, 28, and 52 mm Hg. The performance of the heart was evaluated by 
a comparison of these work curves. Left atrial pressures are plotted against left ven- 
tricular stroke work (i .e., pulmonary flow times the mean aortic pressurebeart rate). 
The workload was varied by changing the flow and keeping the arterial pressure con- 
stant, These graphs show that the work curve was depressed with an increase inarterial 
C 0 2  tension. The optimum work curve i n  a heart-lung preparation appeared to be at 
nearly zero arterial pC02. 
The effect of arterial p c o 2  on LAP at constant stroke work was studied, and data 
from a single preparation typical of five such experiments are shown i n  Figure 4. In 
this preparation the flow was maintained at about 500 cc/min at a mean arterial pressure 
of 80 mm Hg. This graph shows that with increase of pC02 from b l o w  10 mm Hg to 55 
mm Hg, there was an immediate rise i n  LAP from 50 mm H20 to 92 mm H20, followed by 
a drop to a new stable level at 60 mm H20. When the arterial C 0 2  tension was subse- 
quently returned to nearly zero, a rebound i n  LAP (to 40 mm H20) was noted before 
stabilizing at about the previous level. These responses were essentially the same for 
al I five experiments. 
Figure 5 presents data from a single preparation typical of seven experiments on 
seven separate dogs. Both graphs (A and B) show the effect of inhalation of C 0 2  
(4%, 6%, 8%) on stroke work at constant LAP (65 mm H20). On the left hand graph 
(A) the work was computed from the pulmonary flow and the mean aortic pressure; these 
represent the total myocardial work. On the right hand graph (B) the systemic flow was 
used to calculate the stroke work which here represents the effective work of the left 
ventricle, omitting the work involved i n  maintaining the coronary flow. Both graphs 
show a stepwise decline in stroke work with a stepwise increase of pC02 from < 10 to 
75 mm Hg. Recovery i n  performanceoccurred when the pC02 was brought back to< 10. 
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pressure at constant stroke work was recorded when the arterial pC02 and pH were 
separately changed. Figure 6 i s  a detailed presentation of experiment number 1 i n  the I 
series i n  Table I. In Table I only the maximum changes of pH and corresponding LAP , 
are shown; whereas, in Figure 6 the entire experiment i s  plotted. These experiments ~ 
I were carried out i n  an attempt to separate the direct effect of pC02 and pH on the performance of the heart. After the baseline period of the experiment (Figure 6) the 
blood pH was lowered to a value of 7.25 by increasing the arterial pC02 to 55 mm Hg 
by ventilating 890 C02, and this in turn depressed the performance of the heart, as 
indicated by a rise of left atrial pressure from 50 to 117 mm H20. After completion of ~ 
the init ial overshoot, further recovery i n  the heart performance was brought about by 
raising the pH of the blood with continuous infusion of 0.34 NaHC03 at the rate of 
1.5 cc/min. Throughout this period the pC02 was kept at about 55 mm Hg. In the 
next part of this experiment the arterial pC02 was maintained at below 10 mm Hg, 
while the blood pH was lowered by continuous infusion of 0.5N HCl at the rate of 1.5 
cc/min. The left atrial pressure rose from 40 to 105 mm ti20 and was then lowered to 4{ 
mm H20 by continuous infusion of NaHC03. 
Table I presents data obtained from seven experiments i n  which the left atrial 
I 
I , 
Figure 7 presents data obtained from a single preparation typical of four experi- 
I ments (Nos. 4-7) shown i n  Table I. In these experiments the arterial pC02 was kept 
at or below 10 mm Hg. The changes in  blood pH were made with infusion of 0.5N HCl :  
or 0.5M NaHC03 at a rate of 1.5 cc/min. At constant stroke work the left atrial 
pressure was elevated to 85 mm H i 0  as the blood pH was lowered to a final value of7.0) 
The left atrial pressure was subsequently lowered to 33 mm H20 with infusion of NaHCO; 
Table I and Figures 6 and 7 indicate that the performance changes produced by in- 
halation of C 0 2  are more closely related to the consequent changes of blood pH than 
to the direct effect of blood C 0 2  tension. 
I 
DISCUSSION 
The decrease i n  heart rate produced by a change in  arterial C 0 2  tension appears 
to be due to change i n  pH. By evaluating the performance on a stroke work basis, we 
are avoiding the chronotropic effects of temperature. In any case, the heart rate changes 
observed i n  the present study were not sufficient to account for a negative inotropic ef- 
fect shown here. 
There was l itt le difference between the behavior of stroke work calculated with and 
without coronary flow (Figure 5). This suggests that any effect arterial pC02 or pH 
may have on the coronary flow i s  negligible for present considerations. Increasing the 
composition of C 0 2  i n  the inspired air produced progressive deterioration i n  cardiac 
performance as the arterial pC02 rose from near zero to 75 mm Hg. This depression in 
the heart performance i s  reversible. 
Our observations are in sharp contrast to those of Jerusalem and Starling (1) who 
found that there i s  an optimum tension of C 0 2  in the blood at which the heart performs 
8 
Table I 
Effect of Arterial pC02 and pH on Left Arterial Pressure at Constant Work 
~~~~ - 
Trea tmen t Arterial Blood Left Atrial Pressure* 
Experiment Venti lotion Irkusion+ pc02 PH mm H20 
Number %C02*  mm Hg 
1 
0 -- <10 7.95 50 
55 7.25 117 8 
8 NaHC03 55 7.60 40 
0 -- < l o  8.00 40 
0 HCl < l o  7.20 105 
0 NoHC03 <10 7.70 46 
-- 
2 
0 -- 8.00 60 
8 -- 50 7.25 190 
8 NaHC03 50 8.00 45 
0 -- < I O  8.00 45 
0 HCl <10 7.28 120 
0 NaHC03 < 10 8.00 77 
3 
0 -- < 10 8.00 47 
8 -- 55 7.28 117 
8 NaHC03 55 7.95 40 
~~ ~~~ ~ 
0 -- <10 7.90 45 
4 0 HC 1 10 7.00 85 
0 NaHC03 10 7.72 33 
5 
0 -- <10 7.90 53 
0 HCl 10 7.05 165 
0 NaHC03 10 7.80 30 
6 
0 -- 10 7.90 90 
0 HC1 10 7.25 143 
0 NaHC03 10 7.90 67 
7 
0 -- < l o  8.00 60 
0 HC 1 <10 7.43 21 0 
0 NaHC03 < l o  7.86 57 
*A l l  gas mixtures contain 40% 02, zero or 8% C02, balance N2. 
'0.5 N HC1 infusion 1.5 cc/minute 
0.5 M NaHC03 infusion 1.5 cc/minute 
*Note: In this table LAP varies with pH in every case but varies with arterial C 0 2  tension 
only when pH changes. 
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at its maximum. In the present experiments after changes in inspired C 0 2  in  either 
direction the above mentioned inotropic effects appeared dramatically i n  a verymarked 
degree. This i s  considered an overshoot since within five to ten minutes the produced 
inotropic changes diminished and the heart assumed a performance characteristic of the 
new equilibrium level. 
Studies presented here on the negative inotropic effect of C 0 2  inhalation have 
attempted to disassociate the effects of changes in blood pC02 or pH. It appears that 
the performance of the heart regularly increases with increasing pH and diminishes with 
falling pH regardless of the arterial C 0 2  tension. (See Table I.) When the pH i s  
maintained constant either i n  the neighborhood of pH 8.0 or pH 7.0, C 0 2  tension i s  
clearly without inotropic effect. 
Recently i t  was reported that acid pH in  both -- i n  vitro (9) and -- in vivo (10) experi- 
ments inhibits norepinephrine-induced lipolysis; this would reduce the ability to mobi- 
lize fat stored within and around the heart and lungs and thus limit metabolism. This 
phenomenon may well explain the negative inotropic effect observed in our experiments 
at low pH. 
The immediate partial adjustment to hypercapnic depression and the rebound 
phenomenon upon termination of carbon dioxide stress may be accounted for by one or 
both of the following explanations: 
a. Release of endogenous catecholamines while the heart was under C 0 2  stress 
and the persistence of the action of these compounds even after the carbon dioxide 
stress was removed. 
b. A state of ionic disequilibrium due to pH changes across the cell membrane. 
There i s  evidence that the force of contraction i s  a function of the rate of  repolarization 
W'exit) of the membrane (11). The passage of potassium across the cell membrane may 
we l l  be facilitated by pH changes (12). 
12 
REFERENCES 
1. Jerusalem, E., and Starling, E. H., On the significance of carbon dioxide for 
the heart beat. J. Physiol., 40:279-294, 1910. - 3 
2. Brown, E. B., Jr., and Miller, F., Tolerance of the dog heart to carbon dioxide. 
Amer. J. Physiol.,12.550-554, 1952. - -  
3. Nahas, G. G., and Cavert, H. M., Cardiac depressant effect of C 0 2  and i t s  
reversal. Amer. J . Physiol . , 190:483-491, 1957. - -  - 
4. Boniface, K. J., and Brown, J. M., Effect of carbon dioxide excess on con- 
tracti le force of heart, in s i  tu. Amer. J. Physiol . , 172:752-756, 1953. - -  - 
5. Manley, E. S., Jr., Nash, C. B., and Woodbury, R, A., Cardiovascular 
responses to sever hypercapnia of short duration. h e r .  J. Physiol 
640, 1964. 
207:634- - -  I- 
6. Knowlton, F. P., and Starling, E. H., The influence of variations i n  temperature 
and blood-pressure on the performance of the isolated mammalian heart, - J. 
Physiol.,,44:206-219, 191 2. 
7. Shipley, R. E., and Wilson, D., An improved recording rotameter. Proc. SOC. 
Exp. - Biol. - 0 ,  Med _ *  78-724-728, 1951. 
8. Nejad, N. S., and Ogden, E., Effect of temperature change on heart performance 
(heart-lung preparation). -- Proc. SOC. Exg. Biol. Med., in press. 
9. Triner, L., and Nahas, G. G., Acidosiss Effect on lipolytic activity of NE in 
isolated fat cells. Science, 150:1725-1726, - 1965. 
10. Nahas, G. G., and Poyart, C., Effect of arterial pH alterations on metabolic 
activity of norepinephrine. h e r .  J. Physiol.,212:765-772, - 1967. - -  
11. Burgen, A. S. V., and Terroux, K. G., On negative inotropic effect in cat's 
auricle. J. Physiol., 120:449-464, 1953. - - 
12. Fenn, W. O., and Cobb, D. M., Evidence for a potassium shift from plasma to 
muscles in response to an increased carbon dioxide tension. Amer. J. Physiol., 
1 12:41-55, 1935. 
- -  - 
13 
Naval Aerospace Medical Institute 
Pensacola, Florida 32512 
. UNCLASSIFIED 
2 b .  G R O U P  
R E P O R T  D A  r~ 7 8 .  T O T A L  Y O  O F  P A G E S  
13 November 1967 14 
EFFECT OF BLOOD pH AND C 0 2  TENSION ON THE PERFORMANCE OF THE HEART-LUNG 
P RE PARATIO N 
- 
D E S C R I P T I V E  N O T E S  (ripe of reporr and rr ic lu>ivr .  d a l e s )  
A u  r H O R t S )  ( F i r a r  name, middle ~ n i l i a l ,  Ins1 ndme) 
N. S .  Nejad and Eric Ogden 
7b. N O  O F  R E F S  
12 
B C O N T H A C T  O R  G R A N T  h O  
b .  P R O J F C T  N O  MROll .OI  .2 
d.  
911. O R I G I N A T O R ' S  R E P O R T  N U M B E R I S )  
N AMI - 1 025 
9h. O T H E R  R E P O R T  N O I S I  (Any u f h e r  numbers  lhe l  may be as s igned  
l h i s  reporl) 
I S U P P L E h q E N T A Q Y  N O T E S  
Joint report with Ames Research Center, NASA, 
Moffett Field , California 
0 D I S T R I B U T I O N  S T A T E M E N T  
This document has been approved for public release and sale; i t s  distribution i s  unlimited. 
I 2  S P O N S O R I N G  M I L I T A R Y  A C T I V I T Y  
Unclassified 
Security C l a s s i f i c a t i o n  
DD ,',"6t",,1473 ( P A G E  ' )  
S I N  010 1 -  8 0 7 -  6 8 0  1 
Unclassi f i ed 
Security Classification 
K E Y  W O R D S  
Acapnia 
Hypercapnia 
Heart-lung preparation 
Heart rate 
Pulmonary flow 
Systemic flow 
Cardiac work curves 
Performance of the heart 
Arterial blood pCO2 
Arterial blood pH 
HCI 
N a H C 0 3  
L I N K  A 
R O L E  - W T  - 
L I N K  e 
3 O L E  -
Uric lassi fi ed 
W T  - 
L I N K  C 
R O L E  -
(PAGE 2 )  Security Classification 


Effect of Blood Ph and CO2 Tension on the Performance of the Heart-lung Preparation

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