| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Ann Thorac Surg 1998;65:1559-1564
© 1998 The Society of Thoracic Surgeons
a Division of Cardiothoracic Surgery, Saint Louis University Health Sciences Center, St. Mary’s Health Center, St. Louis, Missouri, USA
b Department of Anesthesiology, St. Mary’s Health Center, St. Louis, Missouri, USA
c Division of Cardiothoracic Surgery, Washington University Medical Center at Christian Hospital Northeast, St. Louis, Missouri, USA
Address reprint requests to Dr Fiore, Department of Surgery, St. Louis University Health Sciences Center, 3635 Vista at Grand Blvd, St. Louis, MO 63110-0250
Presented at the Forty-fourth Annual Meeting of the Southern Thoracic Surgical Association, Naples, FL, Nov 6–8, 1997.
 |
Abstract |
|---|
 Top Abstract IntroductionMaterial and methodsResultsCommentDiscussionAcknowledgmentsReferences |
|---|
Methods. Fifty-two patients who required elective myocardial revascularization were prospectively randomized to receive intermittent antegrade tepid (29°C; group T, 25 patients) or cold (4°C; group C, 27 patients) blood cardioplegia.
Results. The two cohorts were similar with respect to all preoperative and intraoperative variables. The mean septal temperature was higher in group T (T, 29.6° ± 1.1°C versus 17.5° ± 3.0°C; p < 0.0001). After reperfusion, group T exhibited significantly greater lactate and acid release despite similar levels of oxygen extraction (p < 0.05). The creatine kinase-MB isoenzyme release was significantly lower in group T (764 ± 89 versus 1,120 ± 141 U · h/L; p < 0.04). Hearts protected with tepid cardioplegia demonstrated significantly increased ejection fraction with volume loading, improvement in left ventricular function at 12 hours, and decreased need for postoperative inotropic support (p < 0.05). The frequency of ventricular defibrillation after cross-clamp removal was lower in this cohort (p < 0.05). There were no hospital deaths, and both groups had similar postoperative courses.
Conclusions. Intermittent antegrade tepid blood cardioplegia is a safe and efficacious method of myocardial protection and demonstrates advantages when compared with cold blood cardioplegia in elective myocardial revascularization.
|
Introduction |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentDiscussionAcknowledgmentsReferences |
|---|
|
Material and methods |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentDiscussionAcknowledgmentsReferences |
|---|
Data recorded included age, sex, history of transmural myocardial infarction, diabetes mellitus, and the extent of coronary artery disease. Major coronary artery stenosis was defined as occlusion of 50% or more of the left main trunk and luminal diameter stenosis of 70% or more of other arteries in any angiographic plane. Regional wall motion abnormality was measured by left ventricular score as defined by the Coronary Artery Surgery Study Group [5].
Operative technique
Cardiopulmonary bypass was established with a single two-stage right atrial cannula. During bypass the hematocrit was maintained between 20% and 25%, pump flows between 2.0 and 2.5 L · min-1 · m-2, and the mean arterial pressure between 50 and 60 mm Hg. Patients were not actively cooled, but their systemic temperature drifted to 32° ± 1°C. A left ventricular vent was not employed. Distal anastomoses were constructed with aortic cross-clamping; proximal anastomoses were performed without global ischemia. Rewarming was commenced during the construction of the last distal anastomosis. Bypass conduits were not perfused with cardioplegia. The volume and temperature of the cardioplegia solution and the rate of infusion were recorded, as were the ventricular septal and nasopharyngeal temperatures (Shiley myocardial temperature probe, DPM; Shiley Inc, Irvine, CA).
Operative variables recorded included cardiopulmonary bypass times, cross-clamp interval, need for inotropic support, number of trials necessary to separate the patient from the extracorporeal circuit, and the number of electric shocks required to achieve ventricular defibrillation. Administration of inotropes was begun if the cardiac index was less than 1.8 L · min-1 · m-2 and the systolic blood pressures less than 80 mm Hg despite an adequate preload.
Cardioplegic groups
The composition of the infusate and its delivery were identical in both groups except for the temperature of the solution. The cardioplegic infusate consisted of a 4:1 dilution of blood to 0.225% normal saline solution (Myotherm Blood Cardioplegia; Avecor Cardiovascular Inc, Plymouth, MN). Additives included 50 mL/L of citrate-phosphate-dextrose and 200 mL/L of THAM (tromethamine). The initial infusion dose was 10 mL/kg and contained 16 ± 1 mEq KCl/L. Reinfusions (5 mL/kg; 8 ± 1 mEq/L of KCl) were performed only at 20-minute intervals. No patient received a terminal "hot shot" of warm cardioplegia. The flow rate sufficient to maintain the aortic root pressure at 70 mm Hg ranged from 200 to 400 mL/min.
Hemodynamic measurements
Heart rate, mean arterial blood pressure, mean pulmonary artery pressure, mean right atrial pressure, and pulmonary capillary wedge pressure were measured. Cardiac output was measured with the thermodilution technique. The derived hemodynamic indices were calculated as follows: 
, 
, and 
. These hemodynamic variables were measured before initiation of cardiopulmonary bypass and at 10 minutes, 1 hour, 4 hours, 12 hours, and 24 hours after cessation of cardiopulmonary bypass.
Creatine kinase measurement
We employed an antibody inhibition technique to measure the release of the MB isoenzyme of creatine kinase (CK). Sequential CK-MB measurements were performed 1, 4, 12, 24, and 48 hours after cross-clamp removal. Integration of the area under the concentration-time curve for CK-MB within the first 48 hours postoperatively allowed calculation of the total release of CK-MB, expressed as units times hours per liter. A transmural myocardial infarction was defined as the appearance of new Q waves or ischemic ST segments changes with a concomitant rise in the level of CK-MB in the first 48 hours.
Oxygen, lactate, and pH assays
Arterial and coronary venous blood samples were obtained simultaneously on bypass before application of the cross-clamp, immediately after cross-clamp removal, 5 minutes and 10 minutes after cross-clamp removal, and 10 minutes after the discontinuation of cardiopulmonary bypass. Coronary venous samples were taken from the coronary sinus, which was cannulated with a 12F pediatric cardiac sump catheter (model 12013; Medtronic-DLP, Grand Rapids, MI).
Blood samples were assayed for the partial pressure of oxygen and carbon dioxide, pH (Acid-Base Laboratory; Radiometer, Copenhagen, Denmark), and oxygen saturation (Co-Oximeter; Instrumentation Laboratory Inc, Lexington, MA). Oxygen content was calculated as follows: 
. Myocardial oxygen extraction was calculated as the arterial oxygen content minus the coronary venous oxygen content. Measurements were made at 37°C and corrected to the myocardial temperature at the time of sampling, which was measured in the left ventricular septum with a temperature probe.
Blood samples for lactate concentration were mixed with a measured volume of 6% perchloric acid. Lactate concentration was measured in the protein-free supernatant by an enzymatic method (Rapid Lactate Stat Pack kit; Calbiochem-Behring, La Jolla, CA). Myocardial lactate extraction was calculated in the same manner as oxygen extraction. Negative lactate values represent net production, whereas positive values represent lactate extraction.
The concentration of hydrogen ion [H+] in the blood sample was determined by converting the measured pH value to 
. Measurements were made at 37°C and corrected to the myocardial temperature at the time of sampling. Myocardial acid production was calculated as the coronary venous effluent [H+] minus the arterial [H+].
Volume loading studies
To assess the state of systolic and diastolic left ventricular performance, volume loading studies were performed immediately after termination of bypass. Normal saline solution was infused after removal of the venous cannula and before protamine was given. Hemodynamic measurements and ejection fraction were assessed before institution of cardiopulmonary bypass and in response to volume loading sufficient to raise the pulmonary capillary wedge pressure by 5 to 8 mm Hg. Patients were ineligible for assessment of left ventricular function if they were receiving inotropes or vasodilators. The stroke index was calculated before and after volume infusion. The ejection fraction was derived from transesophageal echocardiographic sagittal and transverse images of the left ventricle obtained with an Accuson XP-140 (Accuson Inc, Mountain View, CA). The ejection fraction calculation used an off-line system. The area-length formula was employed following recommended guidelines [6]. Analysis was performed by an observer blinded to the randomization. The derived indices were calculated as follows: 
, and 
.
Statistical analysis
Data were analyzed by the StatView IV statistical software package (Brainpower, Inc, Calabasa, CA). Univariate analysis of discrete variables was performed by 
2 analysis or Fisher’s exact test where appropriate. Unpaired Student’s t test or two-factor balanced analysis of variance for repeated measures was used for continuous variables where appropriate. Oxygen extraction, lactate and acid release, and curves describing systolic, diastolic, and myocardial performance were compared by analysis of covariance. Categoric data are displayed as the absolute and percent frequency. Continuous variables are listed as the mean and standard error of the mean or standard deviation as indicated. Statistical significance was assumed at a probability level of less than 0.05.
|
Results |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentDiscussionAcknowledgmentsReferences |
|---|
|
|
At the time of cross-clamp removal, significantly greater acid production was observed in hearts perfused with tepid cardioplegia, but this difference disappeared within 5 minutes, and 10 minutes after separation from the extracorporeal circuit both groups returned to values near those seen before cross-clamping.
Hemodynamic measurements
The hemodynamic measurements of left ventricular function are summarized in Table 3. There were no significant differences between the heart rate, pulmonary capillary wedge pressure, or the mean arterial blood pressure at any time period. The cardiac index was minimally higher in the tepid group, but the difference reached statistical significance only 1 hour after cross-clamp removal. The baseline stroke work index before cardiopulmonary bypass was similar in both groups, as was the reduction in stroke work index 10 minutes after reperfusion. The only significant difference between the groups was noted after 12 hours of reperfusion, at which time hearts protected with tepid blood cardioplegia experienced greater left ventricular stroke work index (p < 0.05). Interestingly, at 24 hours, the stroke work index in the tepid group had significantly exceeded the prebypass value. The improvement in the cold group at this time did not achieve significance, suggesting superior left ventricular performance in the tepid cohort (p < 0.05).
|
Volume loading studies
Monitoring of left atrial pressure revealed that the degree of volume loading performed was similar in the two cohorts (baseline: C, 5.2 ± 1.2 mm Hg, versus T, 5.9 ± 0.6 mm Hg, after volume load: C, 12.0 ± 1.8 mm Hg, versus T, 12.5 ± 0.9 mm Hg; p = not significant). Analysis of covariance did not demonstrate any significant differences in the systolic performance of hearts protected with either cold or tepid blood cardioplegia (Fig 1). The diastolic pressure-volume relation (left atrial pressure versus end-diastolic volume index) and the myocardial performance (cardiac index versus end-diastolic volume index) revealed that the tepid group had improved cardiac function but the differences did not achieve statistical significance. However, the increase in ejection fraction with volume loading was significantly greater in those hearts receiving tepid cardioplegia (baseline: C, 0.58 ± 0.04, versus T, 0.64 ± 0.02, after volume load: C, 0.62 ± 0.02, versus T, 0.68 ± 0.02; p < 0.03).
|
There were no hospital deaths, and no patient required intraaortic balloon pump support for left ventricular dysfunction. Reoperation for bleeding was required in 1 patient, whereas 2 patients (1 in each group) had transient neurologic deficits. No permanent neurologic deficit was identified. No patient had a transmural postoperative myocardial infarction.
|
Comment |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentDiscussionAcknowledgmentsReferences |
|---|
These observations generated an interest in warm (37°C) blood myocardial preservation [10]. The normothermic arrested heart is metabolically balanced in an aerobic environment that permits myocardial resuscitation. However, enthusiasm has been tempered for this technique as disadvantages of warm cardioplegia were gradually enumerated with increasing use [11]. Intermittent antegrade warm cardioplegia cannot be delivered beyond an occluded or critically stenotic coronary artery, which may induce regional anaerobic myocardial metabolism and ischemic injury during cardioplegic arrest. Although retrograde perfusion permits delivery of cardioplegia beyond coronary artery obstructions, protection of the posterior left ventricle and inferior septum may be inadequate and nonnutritive venovenous shunts into thebesian channels may limit retrograde delivery to the right ventricle. Hayashida and co-workers [12] demonstrated that continuous warm retrograde cardioplegia was associated with the greatest lactate and acid release during aortic cross-clamping and significant delay in right and left ventricular function after cross-clamp release. In addition, the greatest depression in high-energy phosphate levels was observed after warm retrograde perfusion. This global ischemic injury may, in part, be related to interruption of cardioplegic flow necessary for proper visualization during coronary bypass anastomoses. In the conventional use of warm cardioplegia with normothermic cardiopulmonary bypass, perfusion at 37°C leads to systemic vasodilatation and hypotension with the potential for cerebral hypoperfusion and central nervous system injury [13].
To avoid the potential hazards of normothermic or hypothermic myocardial preservation, Hayashida and associates [14] subsequently introduced lukewarm or tepid (29°C) cardioplegia. They demonstrated that tepid temperature was associated with reduced oxygen consumption and lactate and acid release compared with warm cardioplegia. They found that tepid cardioplegia conferred improved preservation of left ventricular function.
Our report differs from theirs in that coronary bypass conduits were not perfused, tepid cardioplegia was given only intermittently every 20 minutes without a terminal hot shot, and no attempt was made to introduce catch-up infusions of cardioplegia at any time interval. These modifications simplify the operative procedure and permit a broader clinical application.
Antegrade delivery of cardioplegia, either tepid or cold, resulted in a significant reduction in oxygen extraction immediately after cross clamp removal. This may be due to electromechanical arrest. However, 10 minutes after cessation of cardiopulmonary bypass, hearts receiving tepid cardioplegia had greater ability to extract oxygen when compared with the value seen before cross-clamping, suggesting improved recovery of myocardial aerobic metabolism and preservation of mitochondrial respiratory function in this cohort (p < 0.02).
Neither technique of cardioplegia prevented net myocardial lactate production during global ischemia. After cross-clamp removal, tepid hearts had higher lactate and acid production (washout), which could be an expression of elevated glycolytic activity with anaerobic production of high-energy phosphates. The ability of both groups to extract lactate was not significantly different 10 minutes after reperfusion or separation from cardiopulmonary bypass. This suggests that neither method of myocardial protection provides a truly aerobic environment during global ischemia, as evidenced by similar values of biochemical markers at the time of weaning from cardiopulmonary bypass.
A more sensitive indicator of myocardial preservation is the degree of cellular damage characterized by CK-MB release. The cumulative CK-MB release over 48 hours was significantly higher in those hearts protected with cold blood. This agrees with the work of other investigators and supports the concepts that tepid cardioplegia confers cellular protection and that hypothermia may be associated with increased myocyte necrosis and suboptimal myocardial preservation [15].
These biochemical observations mirrored the hemodynamic performance of the left ventricle. Despite similar preload conditions, the left ventricular stroke work index was consistently higher 12 hours postoperatively in hearts protected with tepid cardioplegia. This may be attributed to a number of factors. The elevated lactate levels noted during reperfusion of tepid hearts may be beneficial. Increased lactate production may be an expression of elevated glycolytic activity or fatty acid oxidation with anaerobic production of high-energy phosphates [16]. The lower CK values in the tepid cohort suggests less myocardial injury, which does contribute to improved ventricular performance. In addition, hearts protected at warmer temperatures may have higher sensitivity to circulating catecholamines, which can enhance left ventricular performance [17]. When compared with tepid or warm methods of myocardial protection, cold cardioplegia has been shown to increase coronary vascular resistance, which could negatively influence myocyte perfusion and subsequent ventricular performance [18].
Differences in ventricular function could not be consistently demonstrated by volume loading studies 10 minutes after termination of cardiopulmonary bypass. The number of patients compared was relatively small, which may have limited the statistical power of the comparison. However, we did demonstrate that the ejection fraction significantly improved with volume loading in hearts protected with tepid blood cardioplegia.
The clinical outcomes for both cohorts were similar. There were no hospital deaths and no patient required intraaortic balloon pump insertion for low cardiac output. However, patients receiving cold blood cardioplegia were more likely to need inotropes postoperatively and experienced a greater frequency of ventricular fibrillation after cross-clamp removal. Hypothermia is known to potentiate ventricular fibrillation after removal of the cross-clamp [19]. Ventricular fibrillation may result in the consumption of high-energy phosphates and is considered undesirable during reperfusion. We have demonstrated that tepid blood cardioplegia is associated with a lower incidence of fibrillation on reperfusion and may allow conservation of myocardial energy stores during the critical period of myocardial recovery.
We believe intermittent tepid blood cardioplegia provides superior myocardial protection during elective revascularization. In our study hemodynamic and clinical differences were demonstrated in a population of patients with mild or no left ventricular dysfunction. However, in patients with acutely ischemic ventricles or those severely compromised from previous myocardial infarction, advantages of tepid blood cardioplegia for myocardial revascularization may be magnified. This study supports continued prospective, randomized trials to determine if tepid or warmer temperatures for blood cardioplegia confer greater myocardial preservation in patients who are at high risk.
|
Discussion |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentDiscussionAcknowledgmentsReferences |
|---|
DR FIORE: Cold blood cardioplegia has been the universal standard method of myocardial protection. However, it is now known that cold blood cardioplegia is associated with a depression in the enzymatic systems responsible for high-energy phosphate production, elevated levels of coronary vascular resistance, and an increase in cellular damage as evidenced by elevated levels of creatine kinase-MB fraction. These observations can be magnified in patients with prolonged cross-clamp times, even if the preoperative ventricular function is normal. It is not surprising that in this study patients receiving cold blood cardioplegia required inotropic support for the first several hours after separation from the extracorporeal circuit. This observation further strengthens our conviction that tepid blood cardioplegia is a superior form of myocardial protection.
DR FRANCIS ROBICSEK (Charlotte, NC): We learned a long time ago that it is difficult to pass cold blood through the coronary circulation. As a matter of fact, deep hypothermic coronary perfusion with undiluted blood, which is not only very viscous but slow to release its oxygen content, may have disastrous consequences. Because of its very high viscosity, giving cardioplegia using 4°C undiluted blood is contraindicated.
I also would like to ask you, did you monitor perfusion pressure in the coronary arteries, and did you measure the amount of cold blood cardioplegia going through? I suspect there is much less volume going through with a much higher resistance and pressure than in normothermic blood.
DR FIORE: We did monitor the pressure in the aorta, which was approximately 70 mm Hg in both groups. The rate of infusion of cardioplegia was approximately 200 mL/min, which also was similar in both groups.
DR ROBICSEK: I believe that using the same perfusion pressure it is impossible to have the same resistance with undiluted blood of 4°C versus 30°C. So the postulate that you have the same blood flow under different temperature extremes at the same pressure sounds to me extremely unlikely.
DR FIORE: Although we did not measure the actual resistance to flow in the coronary arteries, I suspect you are correct, Dr Robicsek; the resistance is higher with 4°C blood than with 30°C blood.
|
Acknowledgments |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentDiscussionAcknowledgmentsReferences |
|---|
|
References |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsCommentDiscussionAcknowledgmentsReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  K. L. Sloots, J. Vinten-Johansen, and G. P. Dobson Warm nondepolarizing adenosine and lidocaine cardioplegia: Continuous versus intermittent delivery J. Thorac. Cardiovasc. Surg., May 1, 2007; 133(5): 1171 - 1178. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Ovrum, G. Tangen, S. Tollofsrud, R. Oystese, M. A. L. Ringdal, and R. Istad Cold blood cardioplegia versus cold crystalloid cardioplegia: A prospective randomized study of 1440 patients undergoing coronary artery bypass grafting J. Thorac. Cardiovasc. Surg., December 1, 2004; 128(6): 860 - 865. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. E. Tan, S. Ahmed, and H. S Paterson Intermittent Tepid Blood Cardioplegia Improves Clinical Outcome Asian Cardiovasc Thorac Ann, June 1, 2003; 11(2): 116 - 121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.-E. Falcoz, D. Kaili, S. Chocron, G. Toubin, M. Puyraveau, J.-F. Viel, and J.-P. Etievent Warm and tepid cardioplegia: Do they provide equal myocardial protection? Ann. Thorac. Surg., December 1, 2002; 74(6): 2156 - 2160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Paparella, T.M. Yau, and E. Young Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update Eur. J. Cardiothorac. Surg., February 1, 2002; 21(2): 232 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chocron, D. Kaili, Y. Yan, G. Toubin, L. Latini, F. Clement, J.-F. Viel, and J.-P. Etievent INTERMEDIATE LUKEWARM (20{degrees}C) ANTEGRADE INTERMITTENT BLOOD CARDIOPLEGIA COMPARED WITH COLD AND WARM BLOOD CARDIOPLEGIA J. Thorac. Cardiovasc. Surg., March 1, 2000; 119(3): 610 - 616. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
