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The relative buffering power of cardioplegic solutions
Volume 93 Number 2 February 1987
5. Cohen MD, Weber TR, Rao Cc. Balloon dilatation of tracheal and bronchial stenosis. Am J Radiol 1984; 142:477-8. 6. Groff DB, Allen JK. Gruentzig balloon catheter dilatation for acquired bronchial stenosis in an infant. Ann Thorac Surg 1985;4:379-81.
Brief communications
°
3 9
Titration of Bicarb-Cardioplegia (conatant C02 content)
30 28 28
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The relative buffering power of cardioplegic solutions
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J. Yasha Kresh, Ph.D., F.A.C.C., Chet Nastala, B.S.,
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P. Carmine Bianchi, Ph.D., Scott M. Goldman, M.D., and Stanley K. Brockman, M.D., FA.C.S., Philadelphia. Pa.
8.5
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7.5
pH
Buffering Power of Bicarb Cardioplegia (3pt deri"· con.tant C02 eeeteet) -1
From the Division of Cardiothoracic Surgery and Department of Pharmacology. Jefferson Medical College, Philadelphia, Pa.
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0
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Those factors that prolong myocardial tolerance to global ischemia constitute an important prerequisite for effective cardioplegia. This study contrasts the relative buffering power of bicarbonate-based and tromethamine-based hyperkalemic crystaUoid cardioplegic solution with histidine protein-type buffer (Bretschneider) solution. In addition, the solutions were compared with titration of whole blood and myocardial muscle homogenate.
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Individual factors that contribute to myocardial protection during prolonged cardiac preservation and cardioplegia, including hypothermia, hyperkalemia, pH buffering, and use of substrates, have not been subjected to systematic biochemically based analysis. The superior buffering capacity of one cardioplegic solution over another has been based on the hypothesis that an absolute desired pH level and associated pKa value are in themselves significant.1,2 Methods. This study contrasts the relative buffering power of bicarbonate-based (NaHC0 3 27 mEq/L) and tromethamine (THAM)-based (27 mliq/L) hyperkalemic crystalloid cardioplegic solution (NaCl 82.5, KCl 30, CaCl 2 1.0, and mannitol 54 mliq/L, and heparin 3000 IV) with protein-type histidine buffer (161 mEq/ L) in ionic solution (K+ 10, Na+, 15, Mg+2 16, Cl" 57, and mannitol 20 mliq/L), For comparison purposes, myocardial tissue was homogenized and titrated. All titrations were performed at 27° C.
Address for reprints: Dr. J.Y. Kresh, Department of Surgery, Division of Cardiothoracic Surgery, Jefferson Medical College, 1025 Walnut St., Philadelphia, Pa. 19107.
0.5
5.5
6.5
7.5
6.5
pH
Fig. 1. Titration and buffering power of bicarbonate-based cardioplegic solution. Buffering power is expressed as the instantaneous (three-point derivative) slope of the titration curve. Note bicarbonate-based solution was titrated at 27 C and constant CO, content. 0
Results. As seen in Figs. 1 and 2, titration using 0.1 to 0.5 rnl HCl solution (0.1 to 0.5N) of bicarbonate-based and THAM-based cardioplegic solutions exhibited a typical sigmoidal curve. The HCl titration of the bicarbonate-based cardioplegic solution was performed at a constant CO 2 content to simulate the conditions of global arrest and anoxia resulting from aortic crossclamping. The buffering power was expressed as the instantaneous slope of the titration: mmol HCI/L/pH. As seen in Fig. 1, the buffering power for the bicarbonate solution ranged from 2 to 15 mmol HCl/L/pH for the corresponding pH values of 8.0 to 6.0, spanning a "window" of maximal value at a pH of 6.3. The buffering power for the THAM-based cardiaplegic solution (Fig. 2) varied from I to 15 mmol HCl/L/pH for a pH range of 8.0 to 6.0, displaying a
The Journal of Thoracic and Cardiovascular Surgery
Brief communications
3 10
Titration of Histidine-Cardioplegia
Titration of Tham Based Cardioplegia 1.0
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Buffering Power of Histidine Card.
Buffering Power of Tham Cardioplegia -1
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Fig. 2. Titration and buffering power of THAM-based cardioplegic solution. Note maximum buffering power occurs at pH of 8.0 (temperature = 27° C).
Fig. 3. Titration and buffering power of histidine-based cardioplegic solution. Note biphasic maximal buffering power (at 8.5 and 6.5).
pronounced shift of the maximal range at pH of 8.0. Note that in both instances, maximal buffering power occurred at the corresponding pKa value of 6.35 for the bicarbonate solution and 8.08 for the THAM solution at 27° C. In contrast, as can be seen in Fig. 3, the histidinebased cardioplegic solution at a similar pH range exhibited a buffering power of 25 mmol HCljLjpH at a pH of 8.0, reaching a maximum of 60 mmol HCl jLjpH at a pH of 6.0, with a much broader range of buffering power greater than 20 mmol HCljLjpH, persisting until a pH of 5.5 was obtained. For comparison, both blood and homogenized canine myocardium were titrated. Glycolysis was arrested with iodoacetate, 2 mmoljL. As seen in Fig. 4, blood was titrated at 27° C in a constant CO 2 environment and pH range of 7.75 to 6.35. The buffering power (slope of titration curve) remained relatively constant at a level of 30 mmol HCljLjpH. The titration of a fresh section of
left ventricular myocardial homogenate exhibited a buffering power of greater than 40 mmol HCljLjpH, independent of the given pH. Similar values (30 to 40) were observed for atrial, right ventricular, and lung homogenate. Discussion. Neither bicarbonate-based nor THAMbased cardioplegic solutions offer significant buffering capacity when compared with myocardial intracellular and whole blood buffers. Furthermore, the buffering power of the crystalloid solutions exhibits a narrow optimal zone beyond which the capacity to counteract acidosis decreases rapidly. The pKa of myocardial homogenate predominantly reflects intracellular buffers and is thus closely related to the imidazole group of histidine, which may explain the beneficial effects of this buffer.t>" Hearts protected with blood-based cardiaplegic solutions have shown superior biochemical and histopathologic outcomes.' In an environment in which an anaerobic substrate is provided, acidosis (pH 6.5 to
Volume 93 Number 2
Brief communications
February 1987
Titration of Lt. Ventricle Homogenate (arrested Ilyeolysis)
60
'0
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buffers. Nevertheless, on-line monitoring of intramyocardial pH3.4 can serve as an index of ischemic stress, providing a measure of the relative effectiveness of the various intraoperative protective schemes applied. REFERENCES
~
20
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31I
6.8
7.2
7.4
....
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"'" ......"
7.6
Bernard M, Menasche P, Canioni P, Fontanarava E, Grousset C, Piwnica A, Cozzone P: Influence of the pH of cardioplegic solutions on intracellular pH, high-energy phosphates, and postarrest performance, J THORAC CARDIOVASC SURG 90:235-242, 1985 2 Vander Woude JC, Christlieb IY, Sicard GA, Clark RE: Imidazole-buffered cardioplegic solution, J THoRAc CARDIOVASC SURG 90:225-234, 1985 3 Tait GA, Booker PO, Wilson GJ, Coles JG, Steward DJ, MacGregor DC: Effect of multidose cardioplegia and cardioplegic solution buffering on myocardial tissue acidosis. J THORAC CARDIOVASC SURG 83:824-829, 1982 4 Walters FJM, Wilson GJ, Steward OJ, Domenech RJ, MacGregor DC: Intramyocardial pH as an index of myocardial metabolism during cardiac surgery, J THoRAc CARDIOVASC SURG 78:319-330, 1979 5 Feindel CM, Tait GA, Wilson GJ, Klement P, MacGregor DC: Multidose blood versus crystalloid cardioplegia, J THORAC CARDIOVASC SURG 87:585-595, 1984 6. del Nido PJ, Wilson GJ, Mickle DAG, Bush BG, Rebeyka 1M, Klement P, Harding R, Tait GA: The role of cardioplegic solution buffering in myocardial protection, J THoRAc CARDIOVASC SURG 89:689-699, 1985
7.6
pH
Fig. 4. Top, Titration (temperature = 27° C) of left ventricular canine myocardium. Glycolysis was arrested with iodoacetate, 2 mmoljL. Bottom. Titration (temperature = 27° C) of blood in a constant CO, environment.
7.0) itself need not be considered detrimental. In fact, a pH of 7.0 is the optimal environment for glutamatecontaining cardioplegic solution.I In general, a more physiologic protein buffer, such as histidine or imidazole, might be superior to the bicarbonate or THAM solutions in stabilizing intracellular pH and the recovery of postischemic biochemical and mechanical parameters.v--" The role of absolute pH value will be dependent on the nature of substrate use, and caution should be exercised in focusing importance on a particular pH value per se.':" In fact, in all physiologic solutions (including those used in poikilothermic vertebrates) the pH rises approximately 0.015 units for each degree Celcius of hypothermia. Consequently, the buffering effect will vary as the perfusate temperature is lowered. Of more importance, the buffering capacity of the solutions tested will be modified further in vivo by intracellular myocardial muscle
Mitral valvuloplasty and repair for infective endocarditis Arlen G. Fleisher, M.D., Ivan David, M.D., Allen Mogtader, M.D., and John E. Hutchinson III, M.D., * New York, N. Y. From the Departments of Cardiothoracic Surgery and Cardiology, St. Luke's-Roosevelt Hospital Center, Amsterdam Ave, at 114th St., New York, N. Y.
The traditional therapy for acute bacterial endocarditis of the mitral valve refractory to medical treatment is valve replacement. Successful valvuloplasty may be feasible in selected cases, in which the infection is limited to a small portion of the mitral valve anulus. The following report describes a case in which valvuloplasty with excision of the affected valve was performed successfully with no recurrence of infection over a 3-year follow-up period. Address for reprints: John E. Hutchinson III, M,D" Director of Cardiothoracic Surgery, Hackensack Hospital, 30 Prospect Ave" Hackensack, N,J. 07601. *Currently Director of Cardiothoracic Surgery, Hackensack Hospital.
5. Cohen MD, Weber TR, Rao Cc. Balloon dilatation of tracheal and bronchial stenosis. Am J Radiol 1984; 142:477-8. 6. Groff DB, Allen JK. Gruentzig balloon catheter dilatation for acquired bronchial stenosis in an infant. Ann Thorac Surg 1985;4:379-81.
Brief communications
°
3 9
Titration of Bicarb-Cardioplegia (conatant C02 content)
30 28 28
I-..
20
22
... :>
18
o
16
'S"
l4
0:
U.
20
--;: 1'0.
...
10.
12 10
10.
The relative buffering power of cardioplegic solutions
....""
)
"""--.,.
J. Yasha Kresh, Ph.D., F.A.C.C., Chet Nastala, B.S.,
-..-..... f-....
o 5.5
0.5
P. Carmine Bianchi, Ph.D., Scott M. Goldman, M.D., and Stanley K. Brockman, M.D., FA.C.S., Philadelphia. Pa.
8.5
6.5
7.5
pH
Buffering Power of Bicarb Cardioplegia (3pt deri"· con.tant C02 eeeteet) -1
From the Division of Cardiothoracic Surgery and Department of Pharmacology. Jefferson Medical College, Philadelphia, Pa.
0
-2
0
-3
0
0
-0
Those factors that prolong myocardial tolerance to global ischemia constitute an important prerequisite for effective cardioplegia. This study contrasts the relative buffering power of bicarbonate-based and tromethamine-based hyperkalemic crystaUoid cardioplegic solution with histidine protein-type buffer (Bretschneider) solution. In addition, the solutions were compared with titration of whole blood and myocardial muscle homogenate.
0
-5 0:
'" ::l :> o
0:
'a"
0
-6 -7
-.
0
-8
0
-10
-11
0
-12
0
0
-13
0
-l4
c
-15
0
-16
Individual factors that contribute to myocardial protection during prolonged cardiac preservation and cardioplegia, including hypothermia, hyperkalemia, pH buffering, and use of substrates, have not been subjected to systematic biochemically based analysis. The superior buffering capacity of one cardioplegic solution over another has been based on the hypothesis that an absolute desired pH level and associated pKa value are in themselves significant.1,2 Methods. This study contrasts the relative buffering power of bicarbonate-based (NaHC0 3 27 mEq/L) and tromethamine (THAM)-based (27 mliq/L) hyperkalemic crystalloid cardioplegic solution (NaCl 82.5, KCl 30, CaCl 2 1.0, and mannitol 54 mliq/L, and heparin 3000 IV) with protein-type histidine buffer (161 mEq/ L) in ionic solution (K+ 10, Na+, 15, Mg+2 16, Cl" 57, and mannitol 20 mliq/L), For comparison purposes, myocardial tissue was homogenized and titrated. All titrations were performed at 27° C.
Address for reprints: Dr. J.Y. Kresh, Department of Surgery, Division of Cardiothoracic Surgery, Jefferson Medical College, 1025 Walnut St., Philadelphia, Pa. 19107.
0.5
5.5
6.5
7.5
6.5
pH
Fig. 1. Titration and buffering power of bicarbonate-based cardioplegic solution. Buffering power is expressed as the instantaneous (three-point derivative) slope of the titration curve. Note bicarbonate-based solution was titrated at 27 C and constant CO, content. 0
Results. As seen in Figs. 1 and 2, titration using 0.1 to 0.5 rnl HCl solution (0.1 to 0.5N) of bicarbonate-based and THAM-based cardioplegic solutions exhibited a typical sigmoidal curve. The HCl titration of the bicarbonate-based cardioplegic solution was performed at a constant CO 2 content to simulate the conditions of global arrest and anoxia resulting from aortic crossclamping. The buffering power was expressed as the instantaneous slope of the titration: mmol HCI/L/pH. As seen in Fig. 1, the buffering power for the bicarbonate solution ranged from 2 to 15 mmol HCl/L/pH for the corresponding pH values of 8.0 to 6.0, spanning a "window" of maximal value at a pH of 6.3. The buffering power for the THAM-based cardiaplegic solution (Fig. 2) varied from I to 15 mmol HCl/L/pH for a pH range of 8.0 to 6.0, displaying a
The Journal of Thoracic and Cardiovascular Surgery
Brief communications
3 10
Titration of Histidine-Cardioplegia
Titration of Tham Based Cardioplegia 1.0
....
22 20
'B
140 130
-..."
14
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12
o
;II
a
110
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pH
or UtraUon)
(apt 4.rtraUYe of titration)
0
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-20
-30 0
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::l
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Buffering Power of Histidine Card.
Buffering Power of Tham Cardioplegia -1
...
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pH
Fig. 2. Titration and buffering power of THAM-based cardioplegic solution. Note maximum buffering power occurs at pH of 8.0 (temperature = 27° C).
Fig. 3. Titration and buffering power of histidine-based cardioplegic solution. Note biphasic maximal buffering power (at 8.5 and 6.5).
pronounced shift of the maximal range at pH of 8.0. Note that in both instances, maximal buffering power occurred at the corresponding pKa value of 6.35 for the bicarbonate solution and 8.08 for the THAM solution at 27° C. In contrast, as can be seen in Fig. 3, the histidinebased cardioplegic solution at a similar pH range exhibited a buffering power of 25 mmol HCljLjpH at a pH of 8.0, reaching a maximum of 60 mmol HCl jLjpH at a pH of 6.0, with a much broader range of buffering power greater than 20 mmol HCljLjpH, persisting until a pH of 5.5 was obtained. For comparison, both blood and homogenized canine myocardium were titrated. Glycolysis was arrested with iodoacetate, 2 mmoljL. As seen in Fig. 4, blood was titrated at 27° C in a constant CO 2 environment and pH range of 7.75 to 6.35. The buffering power (slope of titration curve) remained relatively constant at a level of 30 mmol HCljLjpH. The titration of a fresh section of
left ventricular myocardial homogenate exhibited a buffering power of greater than 40 mmol HCljLjpH, independent of the given pH. Similar values (30 to 40) were observed for atrial, right ventricular, and lung homogenate. Discussion. Neither bicarbonate-based nor THAMbased cardioplegic solutions offer significant buffering capacity when compared with myocardial intracellular and whole blood buffers. Furthermore, the buffering power of the crystalloid solutions exhibits a narrow optimal zone beyond which the capacity to counteract acidosis decreases rapidly. The pKa of myocardial homogenate predominantly reflects intracellular buffers and is thus closely related to the imidazole group of histidine, which may explain the beneficial effects of this buffer.t>" Hearts protected with blood-based cardiaplegic solutions have shown superior biochemical and histopathologic outcomes.' In an environment in which an anaerobic substrate is provided, acidosis (pH 6.5 to
Volume 93 Number 2
Brief communications
February 1987
Titration of Lt. Ventricle Homogenate (arrested Ilyeolysis)
60
'0
"" -. <,
""
30
-.r-,
<,
-,
10
"""",
...
'.6
'.8
8.2
6.'
pH
Titration of Blood
'0
••
s c
:c
.....
""-
30
2.
" "",
Is,
~
e
""" "'I
20
10
,
o 6.2
6.'
6.6
buffers. Nevertheless, on-line monitoring of intramyocardial pH3.4 can serve as an index of ischemic stress, providing a measure of the relative effectiveness of the various intraoperative protective schemes applied. REFERENCES
~
20
'.2
31I
6.8
7.2
7.4
....
Is"
"'" ......"
7.6
Bernard M, Menasche P, Canioni P, Fontanarava E, Grousset C, Piwnica A, Cozzone P: Influence of the pH of cardioplegic solutions on intracellular pH, high-energy phosphates, and postarrest performance, J THORAC CARDIOVASC SURG 90:235-242, 1985 2 Vander Woude JC, Christlieb IY, Sicard GA, Clark RE: Imidazole-buffered cardioplegic solution, J THoRAc CARDIOVASC SURG 90:225-234, 1985 3 Tait GA, Booker PO, Wilson GJ, Coles JG, Steward DJ, MacGregor DC: Effect of multidose cardioplegia and cardioplegic solution buffering on myocardial tissue acidosis. J THORAC CARDIOVASC SURG 83:824-829, 1982 4 Walters FJM, Wilson GJ, Steward OJ, Domenech RJ, MacGregor DC: Intramyocardial pH as an index of myocardial metabolism during cardiac surgery, J THoRAc CARDIOVASC SURG 78:319-330, 1979 5 Feindel CM, Tait GA, Wilson GJ, Klement P, MacGregor DC: Multidose blood versus crystalloid cardioplegia, J THORAC CARDIOVASC SURG 87:585-595, 1984 6. del Nido PJ, Wilson GJ, Mickle DAG, Bush BG, Rebeyka 1M, Klement P, Harding R, Tait GA: The role of cardioplegic solution buffering in myocardial protection, J THoRAc CARDIOVASC SURG 89:689-699, 1985
7.6
pH
Fig. 4. Top, Titration (temperature = 27° C) of left ventricular canine myocardium. Glycolysis was arrested with iodoacetate, 2 mmoljL. Bottom. Titration (temperature = 27° C) of blood in a constant CO, environment.
7.0) itself need not be considered detrimental. In fact, a pH of 7.0 is the optimal environment for glutamatecontaining cardioplegic solution.I In general, a more physiologic protein buffer, such as histidine or imidazole, might be superior to the bicarbonate or THAM solutions in stabilizing intracellular pH and the recovery of postischemic biochemical and mechanical parameters.v--" The role of absolute pH value will be dependent on the nature of substrate use, and caution should be exercised in focusing importance on a particular pH value per se.':" In fact, in all physiologic solutions (including those used in poikilothermic vertebrates) the pH rises approximately 0.015 units for each degree Celcius of hypothermia. Consequently, the buffering effect will vary as the perfusate temperature is lowered. Of more importance, the buffering capacity of the solutions tested will be modified further in vivo by intracellular myocardial muscle
Mitral valvuloplasty and repair for infective endocarditis Arlen G. Fleisher, M.D., Ivan David, M.D., Allen Mogtader, M.D., and John E. Hutchinson III, M.D., * New York, N. Y. From the Departments of Cardiothoracic Surgery and Cardiology, St. Luke's-Roosevelt Hospital Center, Amsterdam Ave, at 114th St., New York, N. Y.
The traditional therapy for acute bacterial endocarditis of the mitral valve refractory to medical treatment is valve replacement. Successful valvuloplasty may be feasible in selected cases, in which the infection is limited to a small portion of the mitral valve anulus. The following report describes a case in which valvuloplasty with excision of the affected valve was performed successfully with no recurrence of infection over a 3-year follow-up period. Address for reprints: John E. Hutchinson III, M,D" Director of Cardiothoracic Surgery, Hackensack Hospital, 30 Prospect Ave" Hackensack, N,J. 07601. *Currently Director of Cardiothoracic Surgery, Hackensack Hospital.