- Email: [email protected]
METABOLIC CHANGES IN DEEP PERFUSION HYPOTHERMIA FOR CARDIAC SURGERY
METABOLIC CHANGES I N DEEP PERFUSION HYPOTHERMIA FOR CARDIAC SURGERY Takeshi Ogata, M.D., John /. Osborn, M.D., William
J. Kerth,
M.D.,
and Frank Gerbode, M.D., Palo Alto and San Francisco, Calif.
W
ITH improved techniques of combining deep hypothermia with extracorporeal circulation, the duration of safe perfusion has increased. However, there have been scattered reports of the development of acidosis during long perfusion and, also, suggestions that induced acidosis during hypothermia might be beneficial.1'2 The following study was designed to investigate metabolic changes during perfusion hypothermia in patients undergoing cardiac surgery. Data bearing on two main questions were obtained: (1) Does metabolic acidosis or tissue anoxia develop during perfusion with hypothermia, and (2) if so, does the induction of acidosis by hydrochloric acid (HC1) (Edmark technique) show objective evidence of benefit? MATERIAL AND METHODS
The observations on which this report is based were carried out on 13 patients undergoing intracardiac surgery at Presbyterian Medical Center, San Francisco, California. All patients had hypothermia induced by blood cooling in the heat-exchanging oxygenator. 3 The patients were included in the study only if they had been cooled to a mean body temperature below 25° C. Seven of these patients served as controls (Group 1) and the other 6 patients received approximately 1 mEq. hydrochloric acid per kilogram of body weight during cooling, with an equivalent amount of intravenous sodium bicarbonate during rewarming. Selection of patients for one group or the other was purely random; the individual making the random selection did not know details of diagnosis or findings. Patient temperature as recorded during perfusion was that of the mixed venous blood issuing from the patient. Samples of mixed venous blood for chemical analysis were obtained from the right atrium immediately before the start of perfusion and every 30 minutes during perfusion, from the venous line of the heart-lung machine. At about 3 hours after operation and again Prom the Departments of Surgery and Pediatrics, Stanford University School of Medicine, Palo Alto, Calif., and The Institute of Medical Sciences, Presbyterian Medical Center, San Francisco 15, Calif. Aided in part by grants from the U. S. Public Health Service. Received for publication Oct. 11, 1962. 610
Vol. 45, No. 5 May, 1963
METABOLIC CHANGES I N H Y P O T H E R M I A
611
at 20 hours after operation, samples of venous blood were obtained from a catheter lying in the inferior vena cava. Blood pH was measured at a temperature of 37° C.4 and was corrected to the original temperature by a factor of 0.015 per degree centigrade. 5 The partial pressure of carbon dioxide was obtained by using the Astrup nomogram,4 after correction of the pH readings for original temperature. That this resulted in a valid measurement of Pco2 at the original temperature was checked by careful equilibration of known samples of blood at known temperatures, with gas of known Pco2Lactate and pyruvate were measured by the method of Priedemann and Haugen. 6 Excess lactate was calculated using the formula described by Huckabee 7 : XL = (Ln - Lo) - (Pn - Po)
^
where XL = excess lactate; Lo and Po = the concentration of lactate and pyruvate in blood at the time of initial sampling; and Ln and Pn = the concentration of these metabolites at each subsequent sampling. Concentrations are expressed in millimols per liter. The pump oxygenator was the heatexchanging, large disc oxygenator which we have described.3 Oxygenator gas was 4 per cent carbon dioxide in oxygen, flowing at 6 L. per minute. RESULTS
Table I and Pig. 1 present the data for mixed venous PCo2- The two groups are rather similar for lowest body temperature reached, for mean PCo2 at lowest point, and for mean PCo2 at the end of perfusion. A rise in P C 0 2 at the end of perfusion over the pre-perfusion values is usual in patients who have undergone hypothermia and is due to decreasing solubility of carbon dioxide with rise in temperature. Three hours after perfusion, the average PCo2 of the patients who received HC1 was lower than that for the controls, but the difference is not statistically significant. Figs. 2 and 3 present detailed data on typical patients from each group to show the usual rate of cooling and warming and the shapes of the curves of the variables involved. Data for mixed venous blood pH are presented in Table I I and Fig. 4. The mean values for patients who did not receive HC1 dropped during perfusion and were still low 3 hours later, whereas the pH of the patients who received HC1 tended to remain almost constant, but, again, the differences are not statistically significant. Blood lactate, pyruvate, and excess lactate were measured in samples taken at the same time as those for pH and PCo2- Data for lactate and for "excess lactate" (see Materials and Methods) are presented in Figs. 5 and 6. It is particularly interesting that neither group of patients showed any important metabolic aeidosis during or after perfusion. There is somewhat more scatter in the group who did not receive HC1 and the values tend to be slightly higher, but, again, the differences are not statistically significant. In analyzing the data on individual patients, it seemed clear that a rise
612
OGATA
J. Thoracic and Cardiovas. Surg.
E T AL.
TABLE I. M E A N S A N D STANDARD DEVIATIONS O F P
C
MEAN
W i t h hydrochloric acid No hydrochloric acid
MEAN
NO. OF CASES
MEAN LOWEST TEMP. (°C.)
6
20.5
47.3 ±
7
22.5
MEAN P c o 2 AT COLDEST
Pco 2 BEFORE PERFUSION
MEAN P c o 2 AT
P c o 2 AT
POINT
END OF PERFUSION
3
HOURS AFTER PERFUSION
9.2
30.6 + 3.6
52.5 ± 3.5
54.1 ± 7.7
40.0 ±10.2
30.7 ± 5 . 3
53.5 ± 7.4
62.8 ± 3.1
BLOOD P. CO. o WITH HCI • WITHOUT HCI -
z0 kjlo ft? lyUl Oft.
K O
k.2 oo a"> ?3
KOO TOO.
KUj XI.
Fig.
*
MEAN
PCoz
KOki
1.
in lactate or excess lactate was more closely related to low blood pressure or perfusion blood flow than to length of perfusion or use of HCI. Figs. 7 and 8 contrast 2 patients with data for temperature, blood pressure, lactate, and excess lactate. Patient W. C. (Fig. 7) underwent a rather prolonged period of perfusion at a blood pressure of only 60 to 65 mm. Hg, at a temperature of 22° C. He showed a marked rise in lactate and excess lactate during this period. Patient E. S. (Fig. 8) was perfused for a similar period at a slightly lower temperature (20° C.) but, at a blood pressure of 75 to 80 mm. Hg, showed no important change in lactate or excess lactate. Patient E. S. (Fig. 8) was one of those who received HCI, but we do not believe that this is the significant difference between these 2 patients. I t appears, from inspection of records of
METABOLIC CHANGES IN HYPOTHERMIA
Vol. 45, No. I May, 1963
613
W.Q. AGE 42 •—• •—• o-—o CMP
pH
•40-i
7. 4 - i
60-.
3S-
7. 3 -
SO-
30-
7. 2 -
40-
25-
r. 1 -
30-
20-
70-
20-
—1
BLOOD BLOOD BLOOD
TEMB pH Pco
PERFUSION
CO
1
-"H
120 TIME-MINUTES
Fig. 2.
individual patients, that, whether they received HC1 or not, a blood pressure of under 80 tended to be associated with an increase in metabolic acidosis, whereas a bloood pressure of over 80 tended to be associated with no important change in lactate or excess lactate. DISCUSSION
In 1961, we reported 2 that the induction of acidosis by intravenous HC1 during deep hypothermia with perfusion (as suggested by Edmark 1 ) increased the incidence of spontaneous defibrillation during warming and appeared, clinically, to benefit the patient. The increase in spontaneous defibrillation E.J.
TEMR
pH
PCOl
T.t-
to -
35 -
7. 3 -
50 -
30 -
7. 2 -
40 -
25 -
7. 1 -
30 -
20 -
7. 0 -
20 -
1
ACE 18 • » • • 0----0
BLOOD BLOOD BLOOD
TEMP pH P,„
Af'
PERFUSION
—\ 60
Pig. 3.
I 120 MINUTES
330
OGATA ET AL.
614 TABLE I I .
With hydrochloric acid No hydrochloric acid
J. Thoracic and Cardiovas. Surg.
M E A N S AND STANDARD DEVIATIONS OF 13 P A T I E N T S COOLED BELOW 25°
C.
NO. OP CASES
MEAN LOWEST TEMP. (°C.)
MEAN p l l BEFORE PERFUSION
MEAN p H AT COLDEST POINT
MEAN p H AT END OF PERFUSION
p H AT 3 HOURS AFTER PERFUSION
6
20.5
7.33 ±.04
7.31 ±.03
7.30 ± .02
7.30 ± .04
7
22.5
7.39 ±.07
7.39 ± .05
7.25 ±.07
7.27 ± .04
r . t6
Be
5r
o Ctt: Iglu
^•5
1-
oo 2r
? L3 1-00
<
hUj
TOO.
Fig.
■*«.
N
XL'0
fSfr h-Okj Till.
4.
in patients receiving HC1 has been confirmed by our further experience, but it has been very difficult to assess clinical benefit. It has been postulated that if induced acidosis benefits patients undergoing deep hypothermia it may be because of the known "shift to the left" of the hemoglobin dissociation curve with a drop in temperature. This " s h i f t " to the left at temperatures where the proportion of oxygen carried by hemoglobin is still important might reduce tissue p 0 2 and lead to metabolic acidosis. The present study was undertaken to try to obtain objective data bearing on this possibility. Huckabee 7 has shown that excess lactate (see Material and Methods for formula) includes only the lactate produced as a result of anaerobic metabolism.
Vol. 45, No. 5 May, 1963
METABOLIC CHANGES I N H Y P O T H E R M I A
LACTATE
mM/i
6ROUP2 (WITH HCI j
3-i
P^
Fig. 5.
mM/i.
EXCESS LACTATE SBOOP2 I WITH HC(J
TIME M I N . 0
30
60
90
BM/L
120
150
GROUP I (WITHOUT
2
Fig. 6.
I MRS. -4FTER PERFUSION
HCI)
615
OGATA E T AL.
616
J. Thoracic and Cardiovas. Surg.
W.C. ACE 33 TEMP.
' BLOOD TEMR ' BLOOD PRESSURE
OP 160
"■\j I PERFUSION TIME MINUTES
120
0
3 MRS. AFTCR PERFUSION
O—O SLOOP m—mEkcESS
mM/ L
LACTATE LACTATE
3 2 1 0 -1
F i g . 7.
E.S. AGE 28
BLOOD TEMP BLOOD PRESSURE
3 HRS AFTCR PERFUSION °"~O BLOOD LACTATE excess LACTATE 160
F i g . 8.
Vol. 45, No. 5 May, 1963
METABOLIC CHANGES I N H Y P O T H E R M I A
617
A rise in excess lactate then indicates a rise in anaerobic metabolism or '' oxygen debt.'' This would appear to be a sensitive technique in the search for oxygen debt, but our data indicated that the patients studied usually did not develop any metabolic acidosis measurable by the methods used, if perfusion pressure and flow were adequate, regardless of whether acidosis was induced with HC1 or not. Such deviations as were observed favored the group who received the HC1, but differences were not significant on a statistical basis. It must be pointed out that this study concerned only patients who were perfused constantly during hypothermia at rather high flows, and does not include data on total or local circulatory arrest. When prolonged interruption of the circulation of the whole body or of the heart alone is to be carried out, the optimal conditions for chemical preparation of the patient may be quite different from when perfusion is continuous. SUMMARY
1. Thirteen patients were studied in detail for metabolic changes during perfusion-induced hypothermia for cardiac surgery. Of these, 6 received intravenous hydrochloric acid to reduce pH during the hypothermia, followed by an equivalent amount of sodium bicarbonate during rewarming. 2. In neither group was there significant rise of lactate or "excess" lactate, so long as perfusion was adequate. The differences which existed favored the patients receiving HC1, but not at the level of statistical significance. 3. Perfusion at temperatures between 20° and 25° C. does not appear to produce metabolic acidosis either during or following the procedure, if perfusion and flow are adequate. Acknowledgment is made and the authors wish to express appreciation to Dr. Kathleen Roberts for providing measurements of serum lactate and pyruvate. REFERENCES 1. Edmark, K. W.: Continuous Blood pH Measurement With Extracorporeal Cooling, Surg. Gynec. & Obst. 109: 743-749, 1959. 2. Osborn. J . J., Gerbode, F., Johnston, J . B., Ross, J., Ogata, T., and Kerth, W. J . : Blood Chemical Changes in Perfusion Hypothermia for Cardiac Surgery, J . THORACIC SURG. 42: 462-476, 1961. 3. Osborn, J . J., Bramson, M. L., and Gerbode, F . : A Rotating Disc Blood Oxygenator and Integral Heat Exchanger of Improved Inherent Efficiency, J . THORACIC SURG. 39: 427-437, 1960. 4. Astrup, P., Jorgensen, K., Anderson, O. S., and Engel, K.: The Acid-Base Metabolism: A New Approach, Lancet 1: 1035-1039, 1960. 5. Severinghaus, J . W . : Oxyhemoglobin Dissociation Curve Correction for Temperature, J . Appl. Physiol. 12: 485-486, 1958. 6.(a) Friedemann, T. E., and Haugen, G. E.: Pyruvic Acid; Determination of Keto Acids in Blood and Urine, J. Biol. Chem. 147: 415-442, 1943. (b) Barker, S. B., and Summerson, W. H . : Colorimetric Determination of Lactic Acid in Biological Material, J . Biol. Chem. 138: 535-554, 1941. 7. Huekabee, W. E . : Abnormal Resting Blood Lactate, Am. J . Med. 30: 833-839, 1961.
J. Kerth,
M.D.,
and Frank Gerbode, M.D., Palo Alto and San Francisco, Calif.
W
ITH improved techniques of combining deep hypothermia with extracorporeal circulation, the duration of safe perfusion has increased. However, there have been scattered reports of the development of acidosis during long perfusion and, also, suggestions that induced acidosis during hypothermia might be beneficial.1'2 The following study was designed to investigate metabolic changes during perfusion hypothermia in patients undergoing cardiac surgery. Data bearing on two main questions were obtained: (1) Does metabolic acidosis or tissue anoxia develop during perfusion with hypothermia, and (2) if so, does the induction of acidosis by hydrochloric acid (HC1) (Edmark technique) show objective evidence of benefit? MATERIAL AND METHODS
The observations on which this report is based were carried out on 13 patients undergoing intracardiac surgery at Presbyterian Medical Center, San Francisco, California. All patients had hypothermia induced by blood cooling in the heat-exchanging oxygenator. 3 The patients were included in the study only if they had been cooled to a mean body temperature below 25° C. Seven of these patients served as controls (Group 1) and the other 6 patients received approximately 1 mEq. hydrochloric acid per kilogram of body weight during cooling, with an equivalent amount of intravenous sodium bicarbonate during rewarming. Selection of patients for one group or the other was purely random; the individual making the random selection did not know details of diagnosis or findings. Patient temperature as recorded during perfusion was that of the mixed venous blood issuing from the patient. Samples of mixed venous blood for chemical analysis were obtained from the right atrium immediately before the start of perfusion and every 30 minutes during perfusion, from the venous line of the heart-lung machine. At about 3 hours after operation and again Prom the Departments of Surgery and Pediatrics, Stanford University School of Medicine, Palo Alto, Calif., and The Institute of Medical Sciences, Presbyterian Medical Center, San Francisco 15, Calif. Aided in part by grants from the U. S. Public Health Service. Received for publication Oct. 11, 1962. 610
Vol. 45, No. 5 May, 1963
METABOLIC CHANGES I N H Y P O T H E R M I A
611
at 20 hours after operation, samples of venous blood were obtained from a catheter lying in the inferior vena cava. Blood pH was measured at a temperature of 37° C.4 and was corrected to the original temperature by a factor of 0.015 per degree centigrade. 5 The partial pressure of carbon dioxide was obtained by using the Astrup nomogram,4 after correction of the pH readings for original temperature. That this resulted in a valid measurement of Pco2 at the original temperature was checked by careful equilibration of known samples of blood at known temperatures, with gas of known Pco2Lactate and pyruvate were measured by the method of Priedemann and Haugen. 6 Excess lactate was calculated using the formula described by Huckabee 7 : XL = (Ln - Lo) - (Pn - Po)
^
where XL = excess lactate; Lo and Po = the concentration of lactate and pyruvate in blood at the time of initial sampling; and Ln and Pn = the concentration of these metabolites at each subsequent sampling. Concentrations are expressed in millimols per liter. The pump oxygenator was the heatexchanging, large disc oxygenator which we have described.3 Oxygenator gas was 4 per cent carbon dioxide in oxygen, flowing at 6 L. per minute. RESULTS
Table I and Pig. 1 present the data for mixed venous PCo2- The two groups are rather similar for lowest body temperature reached, for mean PCo2 at lowest point, and for mean PCo2 at the end of perfusion. A rise in P C 0 2 at the end of perfusion over the pre-perfusion values is usual in patients who have undergone hypothermia and is due to decreasing solubility of carbon dioxide with rise in temperature. Three hours after perfusion, the average PCo2 of the patients who received HC1 was lower than that for the controls, but the difference is not statistically significant. Figs. 2 and 3 present detailed data on typical patients from each group to show the usual rate of cooling and warming and the shapes of the curves of the variables involved. Data for mixed venous blood pH are presented in Table I I and Fig. 4. The mean values for patients who did not receive HC1 dropped during perfusion and were still low 3 hours later, whereas the pH of the patients who received HC1 tended to remain almost constant, but, again, the differences are not statistically significant. Blood lactate, pyruvate, and excess lactate were measured in samples taken at the same time as those for pH and PCo2- Data for lactate and for "excess lactate" (see Materials and Methods) are presented in Figs. 5 and 6. It is particularly interesting that neither group of patients showed any important metabolic aeidosis during or after perfusion. There is somewhat more scatter in the group who did not receive HC1 and the values tend to be slightly higher, but, again, the differences are not statistically significant. In analyzing the data on individual patients, it seemed clear that a rise
612
OGATA
J. Thoracic and Cardiovas. Surg.
E T AL.
TABLE I. M E A N S A N D STANDARD DEVIATIONS O F P
C
MEAN
W i t h hydrochloric acid No hydrochloric acid
MEAN
NO. OF CASES
MEAN LOWEST TEMP. (°C.)
6
20.5
47.3 ±
7
22.5
MEAN P c o 2 AT COLDEST
Pco 2 BEFORE PERFUSION
MEAN P c o 2 AT
P c o 2 AT
POINT
END OF PERFUSION
3
HOURS AFTER PERFUSION
9.2
30.6 + 3.6
52.5 ± 3.5
54.1 ± 7.7
40.0 ±10.2
30.7 ± 5 . 3
53.5 ± 7.4
62.8 ± 3.1
BLOOD P. CO. o WITH HCI • WITHOUT HCI -
z0 kjlo ft? lyUl Oft.
K O
k.2 oo a"> ?3
KOO TOO.
KUj XI.
Fig.
*
MEAN
PCoz
KOki
1.
in lactate or excess lactate was more closely related to low blood pressure or perfusion blood flow than to length of perfusion or use of HCI. Figs. 7 and 8 contrast 2 patients with data for temperature, blood pressure, lactate, and excess lactate. Patient W. C. (Fig. 7) underwent a rather prolonged period of perfusion at a blood pressure of only 60 to 65 mm. Hg, at a temperature of 22° C. He showed a marked rise in lactate and excess lactate during this period. Patient E. S. (Fig. 8) was perfused for a similar period at a slightly lower temperature (20° C.) but, at a blood pressure of 75 to 80 mm. Hg, showed no important change in lactate or excess lactate. Patient E. S. (Fig. 8) was one of those who received HCI, but we do not believe that this is the significant difference between these 2 patients. I t appears, from inspection of records of
METABOLIC CHANGES IN HYPOTHERMIA
Vol. 45, No. I May, 1963
613
W.Q. AGE 42 •—• •—• o-—o CMP
pH
•40-i
7. 4 - i
60-.
3S-
7. 3 -
SO-
30-
7. 2 -
40-
25-
r. 1 -
30-
20-
70-
20-
—1
BLOOD BLOOD BLOOD
TEMB pH Pco
PERFUSION
CO
1
-"H
120 TIME-MINUTES
Fig. 2.
individual patients, that, whether they received HC1 or not, a blood pressure of under 80 tended to be associated with an increase in metabolic acidosis, whereas a bloood pressure of over 80 tended to be associated with no important change in lactate or excess lactate. DISCUSSION
In 1961, we reported 2 that the induction of acidosis by intravenous HC1 during deep hypothermia with perfusion (as suggested by Edmark 1 ) increased the incidence of spontaneous defibrillation during warming and appeared, clinically, to benefit the patient. The increase in spontaneous defibrillation E.J.
TEMR
pH
PCOl
T.t-
to -
35 -
7. 3 -
50 -
30 -
7. 2 -
40 -
25 -
7. 1 -
30 -
20 -
7. 0 -
20 -
1
ACE 18 • » • • 0----0
BLOOD BLOOD BLOOD
TEMP pH P,„
Af'
PERFUSION
—\ 60
Pig. 3.
I 120 MINUTES
330
OGATA ET AL.
614 TABLE I I .
With hydrochloric acid No hydrochloric acid
J. Thoracic and Cardiovas. Surg.
M E A N S AND STANDARD DEVIATIONS OF 13 P A T I E N T S COOLED BELOW 25°
C.
NO. OP CASES
MEAN LOWEST TEMP. (°C.)
MEAN p l l BEFORE PERFUSION
MEAN p H AT COLDEST POINT
MEAN p H AT END OF PERFUSION
p H AT 3 HOURS AFTER PERFUSION
6
20.5
7.33 ±.04
7.31 ±.03
7.30 ± .02
7.30 ± .04
7
22.5
7.39 ±.07
7.39 ± .05
7.25 ±.07
7.27 ± .04
r . t6
Be
5r
o Ctt: Iglu
^•5
1-
oo 2r
? L3 1-00
<
hUj
TOO.
Fig.
■*«.
N
XL'0
fSfr h-Okj Till.
4.
in patients receiving HC1 has been confirmed by our further experience, but it has been very difficult to assess clinical benefit. It has been postulated that if induced acidosis benefits patients undergoing deep hypothermia it may be because of the known "shift to the left" of the hemoglobin dissociation curve with a drop in temperature. This " s h i f t " to the left at temperatures where the proportion of oxygen carried by hemoglobin is still important might reduce tissue p 0 2 and lead to metabolic acidosis. The present study was undertaken to try to obtain objective data bearing on this possibility. Huckabee 7 has shown that excess lactate (see Material and Methods for formula) includes only the lactate produced as a result of anaerobic metabolism.
Vol. 45, No. 5 May, 1963
METABOLIC CHANGES I N H Y P O T H E R M I A
LACTATE
mM/i
6ROUP2 (WITH HCI j
3-i
P^
Fig. 5.
mM/i.
EXCESS LACTATE SBOOP2 I WITH HC(J
TIME M I N . 0
30
60
90
BM/L
120
150
GROUP I (WITHOUT
2
Fig. 6.
I MRS. -4FTER PERFUSION
HCI)
615
OGATA E T AL.
616
J. Thoracic and Cardiovas. Surg.
W.C. ACE 33 TEMP.
' BLOOD TEMR ' BLOOD PRESSURE
OP 160
"■\j I PERFUSION TIME MINUTES
120
0
3 MRS. AFTCR PERFUSION
O—O SLOOP m—mEkcESS
mM/ L
LACTATE LACTATE
3 2 1 0 -1
F i g . 7.
E.S. AGE 28
BLOOD TEMP BLOOD PRESSURE
3 HRS AFTCR PERFUSION °"~O BLOOD LACTATE excess LACTATE 160
F i g . 8.
Vol. 45, No. 5 May, 1963
METABOLIC CHANGES I N H Y P O T H E R M I A
617
A rise in excess lactate then indicates a rise in anaerobic metabolism or '' oxygen debt.'' This would appear to be a sensitive technique in the search for oxygen debt, but our data indicated that the patients studied usually did not develop any metabolic acidosis measurable by the methods used, if perfusion pressure and flow were adequate, regardless of whether acidosis was induced with HC1 or not. Such deviations as were observed favored the group who received the HC1, but differences were not significant on a statistical basis. It must be pointed out that this study concerned only patients who were perfused constantly during hypothermia at rather high flows, and does not include data on total or local circulatory arrest. When prolonged interruption of the circulation of the whole body or of the heart alone is to be carried out, the optimal conditions for chemical preparation of the patient may be quite different from when perfusion is continuous. SUMMARY
1. Thirteen patients were studied in detail for metabolic changes during perfusion-induced hypothermia for cardiac surgery. Of these, 6 received intravenous hydrochloric acid to reduce pH during the hypothermia, followed by an equivalent amount of sodium bicarbonate during rewarming. 2. In neither group was there significant rise of lactate or "excess" lactate, so long as perfusion was adequate. The differences which existed favored the patients receiving HC1, but not at the level of statistical significance. 3. Perfusion at temperatures between 20° and 25° C. does not appear to produce metabolic acidosis either during or following the procedure, if perfusion and flow are adequate. Acknowledgment is made and the authors wish to express appreciation to Dr. Kathleen Roberts for providing measurements of serum lactate and pyruvate. REFERENCES 1. Edmark, K. W.: Continuous Blood pH Measurement With Extracorporeal Cooling, Surg. Gynec. & Obst. 109: 743-749, 1959. 2. Osborn. J . J., Gerbode, F., Johnston, J . B., Ross, J., Ogata, T., and Kerth, W. J . : Blood Chemical Changes in Perfusion Hypothermia for Cardiac Surgery, J . THORACIC SURG. 42: 462-476, 1961. 3. Osborn, J . J., Bramson, M. L., and Gerbode, F . : A Rotating Disc Blood Oxygenator and Integral Heat Exchanger of Improved Inherent Efficiency, J . THORACIC SURG. 39: 427-437, 1960. 4. Astrup, P., Jorgensen, K., Anderson, O. S., and Engel, K.: The Acid-Base Metabolism: A New Approach, Lancet 1: 1035-1039, 1960. 5. Severinghaus, J . W . : Oxyhemoglobin Dissociation Curve Correction for Temperature, J . Appl. Physiol. 12: 485-486, 1958. 6.(a) Friedemann, T. E., and Haugen, G. E.: Pyruvic Acid; Determination of Keto Acids in Blood and Urine, J. Biol. Chem. 147: 415-442, 1943. (b) Barker, S. B., and Summerson, W. H . : Colorimetric Determination of Lactic Acid in Biological Material, J . Biol. Chem. 138: 535-554, 1941. 7. Huekabee, W. E . : Abnormal Resting Blood Lactate, Am. J . Med. 30: 833-839, 1961.