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When and why CPD in continuous warm blood cardioplegia?
Ann Thorac Surg 1993:56:121&20
cations, and whether any further medical or surgical interventions were required. Pulmonary function tests were performed in all patients preoperatively and postoperatively, and pulmonary artery catheters were used in all patients. We have now obtained preliminary results. The expected drop in the white blood cell count does not seem to happen after bypass, and the differential depletion of polymorphonuclear cells did not materialize in the hematologic values of these patient. We found no significant difference in the average length of intermittent positive-pressure ventilation or the incidence of pulmonary complications from the control patients who had undergone CPB before we started using the Pall LG6 filter. Because this filter was introduced in clinical practice only recently, no evaluation of its use has been completed yet. We are interested to hear from other centers about their experience with using this filter.
Khalid Al-Ebrahim, FRCSC Hussein Shafei, FRCSICTh Al-Hada Military Cardiac Centre PO Box 1347 Taif, Saudi Arabia
References 1. Bando KO, Schueler S, Cameron DE, et al. Twelve-hour cardiopulmonary preservation using donor core cooling, leukocyte depletion, and liposomal superoxide dismutase. J Heart Lung Transplant 1991;10:304-9. 2. Royston D, Fleming JS, Desai JB, et al. Increased production of peroxidation products associated with cardiac operation. J Thorac Cardiovasc Surg 1986;91:759-66. 3. Bando KO, Pillai R, Cameron DE, et al. Leukocyte depletion ameliorates free radical mediated lung injury after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1990;99:873-7. 4. Gourlay T, Fleming J, Taylor KM. Laboratory evaluation of the Pall LG6 leukocyte depleting arterial line filter. Perfusion 1992;7:13140.
When and Why CPD in Continuous Warm Blood Cardioplegia? To the Editor: The composition of continuous warm blood cardioplegia (CWBC) that is usually adopted in clinical practice as reported by Lichtenstein and associates (11and Lessana and associates (21 includes both citrate-phosphate-dextrose (CPD) and magnesium (Mg) as in the Fremes solution (Lichtenstein and Salerno) or in the modified low hemodilution technique (Lessana) [3]. The use of these drugs provides a different approach to the physiopathologic and metabolic consequences of CWBC and reperfusion of the injured myocardium. The calcium ions not only are central to normal cardiac function but also have a major role in the response of the myocardium to ischemia and reperfusion. Although the intent of cardioplegic arrest and optimal reperfusion is to prevent an increase in cytosolic calcium concentration, the presence of myocardial ischemia opposes this effect. As intracellular adenosine triphosphate concentration declines, the activity of Na/K increases, facilitating calcium entry via Na/Ca exchange. In addition, without the ability of Na/K adenosine triphosphatase to maintain a normal intracellular potassium concentration, the membrane becomes depolarized, permitting slow-channel calcium influx. The mechanisms that would normally reduce cytosolic calcium, particularly sarcoplasmic reticulum calcium uptake, are impaired because of adenosine triphosphate depletion. Thus, ischemia and reperfusion promotes an increase in cytosolic calcium concentration, myocardial
CORRESPONDENCE
1217
contraction, and further adenosine triphosphate depletion. It would seem reasonable to conclude that the presence of calcium in the solution used to induce ischemic cardiac arrest and reperfusion would be detrimental. The use of CPD in blood cardioplegic reperfusion may help to decrease calcium serum levels and thus the calcium influx. During reperfusion, after ischemic cardiac arrest, CPD and other substrates balanced the ischemic calcium influx, inverting its transmembrane trend. Moreover, the Ca2+ adenosine triphosphatase pumps of the sarcoplasmatic reticulum need magnesium to move calcium from the cytosol into the sarcoplasmic reticulum, and sarcolemmal Na/K adenosine triphosphatase requires Mg to maintain Na and K homeostasis. In addition to its effects on adenosine triphosphatase activity, Mg inhibits the release of Ca from the sarcoplasmic reticulum. Magnesium also contributes to a slower rate of adenosine triphosphate decline, less intracellular Ca accumulation, and less contracture. Magnesium is a readily reversible antagonist to calcium overload. These concepts are well documented by Buckberg [4] and by our clinical practice of warm cardioplegic reperfusion after acute myocardial ischemia and revascularization. However, the use of CWBC for myocardial protection during routine open heart operations involves other considerations regarding the use of CPD and Mg. The strategies of myocardial protection in this case are different. Calcium has a vital role in contractile function and is also an essential structural component of sarcolemma. Although this function is activated by an extracellular concentration of only 50 WmoUL, perfusion of the heart with a solution that has no calcium produces membrane defects that allow massive calcium influx upon reexposure to a calcium-containing medium (or calcium serum correction during aortic cross-clamp release). This phenomenon is called calcium paradox. The use of CPD in CWBC and thus in systemic perfusion may provide a reduction in calcium serum levels and thus may promote calcium paradox. On the other hand, the calcium concentration that produces the least impairment to the enzymatic functions and the best functional recovery with normothermic arrest was 1.2 mmol/L, a concentration within the normal range for plasma-ionized calcium. Furthermore, any event that reduces extracellular Na concentration or increases intracellular Na concentration in respect to the sodium concentration on the other side of the membranes will increase calcium influx. If extracellular Na concentration is not reduced along with extracellular Ca concentration, calcium influx will occur. Moderate reduction of sodium concentration in blood cardioplegia is associated with problems. In the presence of low extracellular Na concentration (30 to 60 mmol/L) and normal extracellular calcium concentration (1.2 mmol/L), potassium-induced deyolarization will produce calcium influx with a resulting contracture and vice versa. However, if calcium is removed from the cardioplegic solution such as blood with CPD, no contracture occurs with the induction of cardioplegia in the presence of a very low sodium concentration. Continuous warm blood cardioplegia (with CPD) is a calciumfree (or very low) and normosodiemic (or moderately low) blood perfusion. In addition, warm cardioplegia is an "aerobic cardioplegia," therefore, theoretically without the ischemia and subsequent reperfusion (calcium influx as consequence of ischemia after reperfusion). Calcium paradox can only become a concern if the heart is perfused with a large enough volume of calcium-free solution or
1218
CORRESPONDENCE
blood with CPD. The importance of the sodium-calcium relationship is one that has received attention in CWBC. On the basis of these considerations CPD is not needed during routine CWBC and justifes the use of Mg as ”physiologic” calcium antagonist. The use of CPD is important in CWBC after acute ischemic injury or coronary occlusion and subsequent reperfusion.
Giorgio Noera, M D , PhD Department of Cardiothoracic S u r g e y University of Modena Via Saragozza 126 41100 Modena Italy References 1. Lichtenstein SV, Salemo T, Slutsky AS. Warm continuous cardioplegia versus intermittent hypothermic protection during CPB. J Cardiothorac Anesth 1990;4:279-81. 2. Lessana A, Romano M, Singh AI, et al. Beyond cold cardioplegia. Ann Thorac Surg 1992;53:666-9. 3. Salemo T, Parenzan L, Bianchi T. In: Associazione per il Progress0 della CardiochirugiaItaliana, ed. Acts of the Symposium on “aerobic cardiac surgery: an update on continuous normothermic blood cardioplegia and normothermic total body perfusion.” Bergamo, Italy: Associazione per il Progresso della Cardiochirugia Italiana, Feb 6, 1993. 4. Buckberg GD. Myocardial temperature management during aortic clamping for cardiac surgery. Protection, preoccupation and perspective. J Thorac Cardiovasc Surg 1991;102:895-903.
Esophageal Exclusion To the Editor: I read with interest the article by Bardini and associates [l] and congratulate them for the results achieved with the 2 cases presented. Double exclusion of the perforated esophagus using absorbable staples may be useful in selected cases. However, the majority of patients with late esophageal perforations wiU require a more aggressive management that includes formal thoracotomy to deal with mediastinitis, pleural cortex, and contamination [2, 31. Rafael Andrade-Alegre, M D Thoracic Surgery Section Santo Tomas Hospital PO Box 957 Panama 1 Republic of Panama
References 1. Bardini R, Bonavina L, Pavanello M, Asolati M, Peracchia A. Temporary double exclusion of the perforated esophagus using absorbable staples. Ann Thorac Surg 1992;54:1165-7. 2. Orringer MB, Stirling MC. Esophagectomy for esophageal disruption. Ann Thorac Surg 1990;49:35-43. 3. Naylor AR, Walker WS, Dark J, Cameron EW. T tube in the management of seriously ill patients with oesophagopleural fistulae. Br J Surg 1990;774&2.
Reply
To the Editor:
We certainly agree with Dr Andrade-Alegre that most patients presenting with late esophageal perforations could benefit from a
Ann Thorac Surg
1993:56121&20
more aggressive management than a double exclusion. This was indeed the case also in our experience. Of 63 patients treated in our institution for a perforation of the intrathoracic esophagus, a double exclusion was performed in 9 (14.2%).We agree with Dr Andrade-Alegre and other authors [l] that this technique should be reserved for patients in whom other approaches are not feasible. When a double exclusion is indicated, the mediastinum should always be drained as stated in our article [2].
Romeo Bardini, M D Luigi Bonavina, M D Maurizio Pavanello, M D Massimo Asolati, M D Alberto Peracchia, M D Department of Surgey University of Padua School of Medicine Via Giustiniani 2 35128 Padua, Italy
References 1. Jones W, Ginsberg R. Esophageal perforation: a continuing challenge. Ann Thorac Surg 1992;53534-43. 2. Bardini R, Bonavina L, Pavanello M, Asolati M, Peracchia A. Temporary double exclusion of the perforated esophagus using absorbable staples. Ann Thorac Surg 1992;54:1165-7.
Device-Supported Myocardial Revascularization To the Editor: We read the article [l] on device-supported myocardial revascularization with great interest and would like to congratulate the authors on their excellent clinical results with coronary operation using bilateral bypass without an oxygenator-a method that was proposed, introduced, and published by us more than 10 years ago [2]. Our experience prompts us to make a few comments that may appear to be pertinent. The first important suggestion is that sophisticated bypass equipment is not a prerequisite of this method. Traditional roller pumps, whether in pulsatile or nonpulsatile mode, can be used with similarly good results [3]. However, we concur with Sweeney and Frazier regarding the need for bilateral rather than left heart bypass as we were able to prove the dependence of the systemic pump’s efficiency on the output of a standby or continuously functioning right-sided pump at an early stage [3]. Sweeney and Frazier found that the balance between right- and left-sided circulation was not always easy to maintain. This problem became apparent in the late 1950s when bilateral bypass was used in combination with deep hypothermic circulatory arrest. A perfectly adequate solution to this problem was found about 30 years ago, and we believe it is still the safest method for bilateral bypass. It consists of a ”double reservoir” system, ie, a shunt between the right and left atrial reservoirs. The right-sided output is set deliberately higher than the required output of the left-sided pump, thereby creating a “left-to-right shunt” to prevent sudden drops in the level of the left atrial reservoir (Fig 1) 141. Finally, we would like to comment on the surgical technical aspects. Sweeney and Frazier (1) used normothermic bypass (2) cannulating the left ventricle, and the peripheral coronary anastomoses were completed (3) on the beating heart (4) placing 5-0 suture loops around the coronary vessels proximally and distally from the anastomosis site. Although the feasibility of their method is well proven and supported by their excellent clinical
cations, and whether any further medical or surgical interventions were required. Pulmonary function tests were performed in all patients preoperatively and postoperatively, and pulmonary artery catheters were used in all patients. We have now obtained preliminary results. The expected drop in the white blood cell count does not seem to happen after bypass, and the differential depletion of polymorphonuclear cells did not materialize in the hematologic values of these patient. We found no significant difference in the average length of intermittent positive-pressure ventilation or the incidence of pulmonary complications from the control patients who had undergone CPB before we started using the Pall LG6 filter. Because this filter was introduced in clinical practice only recently, no evaluation of its use has been completed yet. We are interested to hear from other centers about their experience with using this filter.
Khalid Al-Ebrahim, FRCSC Hussein Shafei, FRCSICTh Al-Hada Military Cardiac Centre PO Box 1347 Taif, Saudi Arabia
References 1. Bando KO, Schueler S, Cameron DE, et al. Twelve-hour cardiopulmonary preservation using donor core cooling, leukocyte depletion, and liposomal superoxide dismutase. J Heart Lung Transplant 1991;10:304-9. 2. Royston D, Fleming JS, Desai JB, et al. Increased production of peroxidation products associated with cardiac operation. J Thorac Cardiovasc Surg 1986;91:759-66. 3. Bando KO, Pillai R, Cameron DE, et al. Leukocyte depletion ameliorates free radical mediated lung injury after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1990;99:873-7. 4. Gourlay T, Fleming J, Taylor KM. Laboratory evaluation of the Pall LG6 leukocyte depleting arterial line filter. Perfusion 1992;7:13140.
When and Why CPD in Continuous Warm Blood Cardioplegia? To the Editor: The composition of continuous warm blood cardioplegia (CWBC) that is usually adopted in clinical practice as reported by Lichtenstein and associates (11and Lessana and associates (21 includes both citrate-phosphate-dextrose (CPD) and magnesium (Mg) as in the Fremes solution (Lichtenstein and Salerno) or in the modified low hemodilution technique (Lessana) [3]. The use of these drugs provides a different approach to the physiopathologic and metabolic consequences of CWBC and reperfusion of the injured myocardium. The calcium ions not only are central to normal cardiac function but also have a major role in the response of the myocardium to ischemia and reperfusion. Although the intent of cardioplegic arrest and optimal reperfusion is to prevent an increase in cytosolic calcium concentration, the presence of myocardial ischemia opposes this effect. As intracellular adenosine triphosphate concentration declines, the activity of Na/K increases, facilitating calcium entry via Na/Ca exchange. In addition, without the ability of Na/K adenosine triphosphatase to maintain a normal intracellular potassium concentration, the membrane becomes depolarized, permitting slow-channel calcium influx. The mechanisms that would normally reduce cytosolic calcium, particularly sarcoplasmic reticulum calcium uptake, are impaired because of adenosine triphosphate depletion. Thus, ischemia and reperfusion promotes an increase in cytosolic calcium concentration, myocardial
CORRESPONDENCE
1217
contraction, and further adenosine triphosphate depletion. It would seem reasonable to conclude that the presence of calcium in the solution used to induce ischemic cardiac arrest and reperfusion would be detrimental. The use of CPD in blood cardioplegic reperfusion may help to decrease calcium serum levels and thus the calcium influx. During reperfusion, after ischemic cardiac arrest, CPD and other substrates balanced the ischemic calcium influx, inverting its transmembrane trend. Moreover, the Ca2+ adenosine triphosphatase pumps of the sarcoplasmatic reticulum need magnesium to move calcium from the cytosol into the sarcoplasmic reticulum, and sarcolemmal Na/K adenosine triphosphatase requires Mg to maintain Na and K homeostasis. In addition to its effects on adenosine triphosphatase activity, Mg inhibits the release of Ca from the sarcoplasmic reticulum. Magnesium also contributes to a slower rate of adenosine triphosphate decline, less intracellular Ca accumulation, and less contracture. Magnesium is a readily reversible antagonist to calcium overload. These concepts are well documented by Buckberg [4] and by our clinical practice of warm cardioplegic reperfusion after acute myocardial ischemia and revascularization. However, the use of CWBC for myocardial protection during routine open heart operations involves other considerations regarding the use of CPD and Mg. The strategies of myocardial protection in this case are different. Calcium has a vital role in contractile function and is also an essential structural component of sarcolemma. Although this function is activated by an extracellular concentration of only 50 WmoUL, perfusion of the heart with a solution that has no calcium produces membrane defects that allow massive calcium influx upon reexposure to a calcium-containing medium (or calcium serum correction during aortic cross-clamp release). This phenomenon is called calcium paradox. The use of CPD in CWBC and thus in systemic perfusion may provide a reduction in calcium serum levels and thus may promote calcium paradox. On the other hand, the calcium concentration that produces the least impairment to the enzymatic functions and the best functional recovery with normothermic arrest was 1.2 mmol/L, a concentration within the normal range for plasma-ionized calcium. Furthermore, any event that reduces extracellular Na concentration or increases intracellular Na concentration in respect to the sodium concentration on the other side of the membranes will increase calcium influx. If extracellular Na concentration is not reduced along with extracellular Ca concentration, calcium influx will occur. Moderate reduction of sodium concentration in blood cardioplegia is associated with problems. In the presence of low extracellular Na concentration (30 to 60 mmol/L) and normal extracellular calcium concentration (1.2 mmol/L), potassium-induced deyolarization will produce calcium influx with a resulting contracture and vice versa. However, if calcium is removed from the cardioplegic solution such as blood with CPD, no contracture occurs with the induction of cardioplegia in the presence of a very low sodium concentration. Continuous warm blood cardioplegia (with CPD) is a calciumfree (or very low) and normosodiemic (or moderately low) blood perfusion. In addition, warm cardioplegia is an "aerobic cardioplegia," therefore, theoretically without the ischemia and subsequent reperfusion (calcium influx as consequence of ischemia after reperfusion). Calcium paradox can only become a concern if the heart is perfused with a large enough volume of calcium-free solution or
1218
CORRESPONDENCE
blood with CPD. The importance of the sodium-calcium relationship is one that has received attention in CWBC. On the basis of these considerations CPD is not needed during routine CWBC and justifes the use of Mg as ”physiologic” calcium antagonist. The use of CPD is important in CWBC after acute ischemic injury or coronary occlusion and subsequent reperfusion.
Giorgio Noera, M D , PhD Department of Cardiothoracic S u r g e y University of Modena Via Saragozza 126 41100 Modena Italy References 1. Lichtenstein SV, Salemo T, Slutsky AS. Warm continuous cardioplegia versus intermittent hypothermic protection during CPB. J Cardiothorac Anesth 1990;4:279-81. 2. Lessana A, Romano M, Singh AI, et al. Beyond cold cardioplegia. Ann Thorac Surg 1992;53:666-9. 3. Salemo T, Parenzan L, Bianchi T. In: Associazione per il Progress0 della CardiochirugiaItaliana, ed. Acts of the Symposium on “aerobic cardiac surgery: an update on continuous normothermic blood cardioplegia and normothermic total body perfusion.” Bergamo, Italy: Associazione per il Progresso della Cardiochirugia Italiana, Feb 6, 1993. 4. Buckberg GD. Myocardial temperature management during aortic clamping for cardiac surgery. Protection, preoccupation and perspective. J Thorac Cardiovasc Surg 1991;102:895-903.
Esophageal Exclusion To the Editor: I read with interest the article by Bardini and associates [l] and congratulate them for the results achieved with the 2 cases presented. Double exclusion of the perforated esophagus using absorbable staples may be useful in selected cases. However, the majority of patients with late esophageal perforations wiU require a more aggressive management that includes formal thoracotomy to deal with mediastinitis, pleural cortex, and contamination [2, 31. Rafael Andrade-Alegre, M D Thoracic Surgery Section Santo Tomas Hospital PO Box 957 Panama 1 Republic of Panama
References 1. Bardini R, Bonavina L, Pavanello M, Asolati M, Peracchia A. Temporary double exclusion of the perforated esophagus using absorbable staples. Ann Thorac Surg 1992;54:1165-7. 2. Orringer MB, Stirling MC. Esophagectomy for esophageal disruption. Ann Thorac Surg 1990;49:35-43. 3. Naylor AR, Walker WS, Dark J, Cameron EW. T tube in the management of seriously ill patients with oesophagopleural fistulae. Br J Surg 1990;774&2.
Reply
To the Editor:
We certainly agree with Dr Andrade-Alegre that most patients presenting with late esophageal perforations could benefit from a
Ann Thorac Surg
1993:56121&20
more aggressive management than a double exclusion. This was indeed the case also in our experience. Of 63 patients treated in our institution for a perforation of the intrathoracic esophagus, a double exclusion was performed in 9 (14.2%).We agree with Dr Andrade-Alegre and other authors [l] that this technique should be reserved for patients in whom other approaches are not feasible. When a double exclusion is indicated, the mediastinum should always be drained as stated in our article [2].
Romeo Bardini, M D Luigi Bonavina, M D Maurizio Pavanello, M D Massimo Asolati, M D Alberto Peracchia, M D Department of Surgey University of Padua School of Medicine Via Giustiniani 2 35128 Padua, Italy
References 1. Jones W, Ginsberg R. Esophageal perforation: a continuing challenge. Ann Thorac Surg 1992;53534-43. 2. Bardini R, Bonavina L, Pavanello M, Asolati M, Peracchia A. Temporary double exclusion of the perforated esophagus using absorbable staples. Ann Thorac Surg 1992;54:1165-7.
Device-Supported Myocardial Revascularization To the Editor: We read the article [l] on device-supported myocardial revascularization with great interest and would like to congratulate the authors on their excellent clinical results with coronary operation using bilateral bypass without an oxygenator-a method that was proposed, introduced, and published by us more than 10 years ago [2]. Our experience prompts us to make a few comments that may appear to be pertinent. The first important suggestion is that sophisticated bypass equipment is not a prerequisite of this method. Traditional roller pumps, whether in pulsatile or nonpulsatile mode, can be used with similarly good results [3]. However, we concur with Sweeney and Frazier regarding the need for bilateral rather than left heart bypass as we were able to prove the dependence of the systemic pump’s efficiency on the output of a standby or continuously functioning right-sided pump at an early stage [3]. Sweeney and Frazier found that the balance between right- and left-sided circulation was not always easy to maintain. This problem became apparent in the late 1950s when bilateral bypass was used in combination with deep hypothermic circulatory arrest. A perfectly adequate solution to this problem was found about 30 years ago, and we believe it is still the safest method for bilateral bypass. It consists of a ”double reservoir” system, ie, a shunt between the right and left atrial reservoirs. The right-sided output is set deliberately higher than the required output of the left-sided pump, thereby creating a “left-to-right shunt” to prevent sudden drops in the level of the left atrial reservoir (Fig 1) 141. Finally, we would like to comment on the surgical technical aspects. Sweeney and Frazier (1) used normothermic bypass (2) cannulating the left ventricle, and the peripheral coronary anastomoses were completed (3) on the beating heart (4) placing 5-0 suture loops around the coronary vessels proximally and distally from the anastomosis site. Although the feasibility of their method is well proven and supported by their excellent clinical