The beneficial effects of systemically administered

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1 Magnesium-Supplemented Warm Blood Cardioplegia in Patients Undergoing Coronary Artery Revascularization Mark Yeatman, FRCS, Massimo Caputo, MD, Pradeep Narayan, FRCS, Attilio A. Lotto, MD, Raimondo Ascione, MD, Alan J. Bryan, FRCS, and Gianni D. Angelini, FRCS Bristol Heart Institute, University of Bristol, Bristol, United Kingdom Background. Although there is growing evidence to suggest that the administration of magnesium (Mg 2 )to patients undergoing coronary artery bypass grafting (CABG) and to patients after myocardial infarction is beneficial, the addition of Mg 2 to cardioplegic solutions remains controversial. The aim of this study was to compare the effects of intermittent warm blood cardioplegia with and without Mg 2 supplementation on the early postoperative clinical outcomes in patients undergoing both elective or urgent CABG. Methods. Four hundred patients undergoing CABG were prospectively randomized to receive either blood cardioplegia without Mg 2 (BC, n 200) or supplemented with Mg 2 (,n 200). Serial plasma Mg 2 concentrations were recorded at base line and postoperatively from days 1 to 4. Results. Patient characteristics were similar and no significant differences were found in early mortality and morbidity in the two groups. Analysis of 178 patients undergoing urgent CABG for unstable symptoms (BC 95, 83) demonstrated a significantly lower requirement for internal defibrillation and temporary epicardial pacing in the group. Furthermore, there was a nearly twofold lower incidence of new postoperative atrial fibrillation in the group compared with the BC group (19% versus 34%, p 0.03). Postoperative plasma Mg 2 levels were consistently lower in those patients who developed new postoperative atrial fibrillation compared with those who did not (p 0.05). Conclusions. The addition of Mg 2 to warm blood cardioplegia resulted in a lower incidence of intraoperative and postoperative arrhythmias in patients undergoing urgent CABG for unstable angina. (Ann Thorac Surg 2002;73:112 8) 2002 by The Society of Thoracic Surgeons The beneficial effects of systemically administered magnesium (Mg 2 ) to patients undergoing both elective [1] and emergency [2] coronary artery bypass graft (CABG) surgery and to patients after myocardial infarction [3] are now well established. However, there is still much debate concerning Mg 2 supplementation of blood-based cardioplegic solutions despite compelling experimental data suggesting a cardioprotective effect [4 7]. The rationale for the cardioprotective effect of Mg 2 during ischemia and reperfusion is mainly based on the concept that it exerts a beneficial effect on calcium (Ca 2 ) transport. Hyperkalemic cardioplegic solutions partially depolarize the membrane and may open the L-type Ca 2 channels. Elevated intracellular Ca 2 levels activate a variety of cellular enzymes and transport systems as well as influencing mitochondrial function and increasing cellular energy demands [8 10]. Mg 2 blocks the L-type Ca 2 channels, reduces Ca 2 loading and energy demands, and preserves myocardial metabolites. Accepted for publication Aug 17, Address reprint requests to Dr Angelini, Bristol Heart Institute, Bristol BS2 8HW, United Kingdom; g.d.angelini@bristol.ac.uk. Recently we [11] have demonstrated that the addition of Mg 2 to intermittent warm blood cardioplegia minimized the ischemic metabolic derangement and reduced the reperfusion-induced injury observed in the hearts of patients undergoing elective CABG. These observations led us to hypothesize that the preservation of intracellular metabolites and of adenosine triphosphate (ATP) levels together with a reduced release of myocardial troponin I, as seen in patients receiving Mg 2 - supplemented cardioplegia, may facilitate recovery after cardiac surgery. The present prospective, randomized, double-blind clinical trial was designed to compare the effects of intermittent warm blood cardioplegia with and without Mg 2 supplementation on the early postoperative clinical outcomes in patients undergoing both elective and urgent CABG. Material and Methods Patient Selection Over a 22-month period (May 1998 to March 2000), 400 patients undergoing first-time CABG were prospectively randomized into one of two groups: (1) intermittent 2002 by The Society of Thoracic Surgeons /02/$22.00 Published by Elsevier Science Inc PII S (01)

2 Ann Thorac Surg YEATMAN ET AL 2002;73:112 8 MAGNESIUM-SUPPLEMENTED WARM BLOOD CARDIOPLEGIA 113 antegrade warm blood cardioplegia (BC group, n 200) and (2) intermittent antegrade warm blood cardioplegia supplemented with Mg 2 ( group, n 200). The randomization sequence was performed by card allocation immediately before surgery, was double blinded, and was strictly respected. Exclusion criteria were repeat operation, emergency life-saving (but not urgent) surgery, valvular heart disease, and renal and hepatic dysfunction. The study protocol was approved by the United Bristol Healthcare Trust Ethics Committee. Anesthesia and Cardiopulmonary Bypass The anesthetic technique was standardized for all patients. This consisted of an oral premedication (20 mg temazepam) followed by total intravenous anesthesia with propofol (3 mg kg 1 h 1 ). Neuromuscular blockade was achieved by administering pancuronium bromide (0.15 mg/kg) or vecuronium (0.15 mg/kg). Intravenous heparin (300 IU/kg) was administered immediately before cannulation for cardiopulmonary bypass (CPB) and additional doses were given to maintain an activated clotting time (ACT) of 480 seconds or greater. Cardiopulmonary bypass was instituted by cannulation of the distal ascending aorta and insertion of a single two-stage cannula into the right atrium. Nonpulsatile flow rates of 2.4 L min 1 m 2 and normothermic temperatures (34 C to 37 C) were used, as previously described [11]. Preparation of the Cardioplegic Solutions The cardioplegic solutions were prepared by mixing whole blood with KCl in the control group (BC) or with a KCl/MgSO 4 solution in the group using the methods described by Calafiore and colleagues [12, 13]. Blood was withdrawn directly from the pump oxygenator using quarter-inch tubing and then reinfused at 34 C to 37 C into the aortic root by means of a roller pump. A syringe pump containing 50 ml KCl (2 mmol/ml; for the BC group) or KCl/MgSO 4 (40 ml of 2 mmol/ml KCl and 10 ml of 2 mmol/ml MgSO 4 ; for the group) was connected to the quarter-inch tubing to deliver the cardioplegic solution. The first dose lasted 2 minutes at a flow rate of 300 ml/min (600 ml overall). The syringe pump rapidly pushed 2 ml of the solution in about 20 seconds and then the flow rate was reduced to 150 ml/h for a final KCl concentration of 20 meq/l in both groups and MgSO 4 concentration of 5 meq/l in the group. After each distal anastomosis (or after 15 minutes of ischemia) a second dose of cardioplegia was administered at a flow rate of 200 ml/min (blood) and 120 ml/h (KCl or KCl/MgSO 4 solutions) for a further 2 minutes. Operative Techniques Distal anastomoses were completed first during a single period of aortic cross-clamping and the proximal anastomoses were performed after removal of the aortic crossclamp and on the beating heart using an aortic sidebiting clamp. At the end of the surgical procedure, protamine sulfate was administered to reverse the heparin effect. Postoperative Management Postoperatively, the lungs were ventilated with 60% oxygen with volume-controlled ventilation and a tidal volume of 10 ml/kg with 5 cm H 2 O of positive endexpiratory pressure. Patients were extubated as soon as they met the following criteria: hemodynamic stability, no excessive bleeding ( 80 ml/h), normothermia, and consciousness with pain control. Potassium and Mg 2 deficiency was promptly treated as necessary to maintain electrolyte balance within the standard normal ranges. Postoperative management (fluid balance, transfusion requirements, and inotropic support, etc) was in accordance with unit protocols as previously described [14]. Data Collection and Definitions Relevant baseline characteristics, intraoperative details, and postoperative clinical outcome data were collected prospectively for each patient randomized into the study. Operative priority was defined as urgent if operation was performed for unstable symptoms requiring in-hospital treatment of angina. Serial plasma Mg 2 concentrations were recorded (at base line and postoperative days 1 to 4) and they were measured as part of the routine clinical care protocol. Various surrogate clinical markers of myocardial preservation were used to detect differences between the study groups and these included defibrillator usage upon removal of the aortic cross-clamp, post-cpb inotropic agents, rates of perioperative myocardial infarction, intraaortic balloon pump usage, the need for temporary pacing (for whatever reason) and the development of new postoperative arrhythmias. Operative mortality was defined as any death that occurred within 30 days of operation. Clinical diagnostic criteria for perioperative myocardial infarction, low cardiac output syndrome, and respiratory tract infection were as defined previously [14]. Ventilatory failure was defined by the requirement for mechanical ventilation of more than 48 hours. Postoperative blood loss was measured as total chest tube drainage starting immediately after closure of the chest in the operating theater. Heart rate and rhythm were continuously monitored and displayed on a screen (Solar 8000 Patient Monitor; Marquette Medical Systems, Milwaukee, WI) during the first 72 hours after surgery. Twelve-lead electrocardiograph (ECG) recordings were performed before surgery, 2 hours after surgery, and then daily thereafter until hospital discharge. After the first 72 hours, trained nurses performed clinical observations every 4 hours. An ECG was recorded on the basis of any clinical suspicion of arrhythmia. In the case of documented arrhythmia, continuous ECG monitoring was restarted. Each episode of arrhythmia was printed out and interpreted by an independent intensive care physician. Atrial fibrillation (AF), atrial flutter, and atrial tachycardia were defined according to Kalman and colleagues [15]. Indications for temporary pacing were made by an independent intensive care unit (ICU) physician, according to the ICU protocol, and included symptomatic bradycardia (unresponsive to

3 114 YEATMAN ET AL Ann Thorac Surg MAGNESIUM-SUPPLEMENTED WARM BLOOD CARDIOPLEGIA 2002;73:112 8 Table 1. Baseline Characteristics Variables BC (n 200) (n 200) p Value BC Urgent (n 95) Urgent (n 83) p Value Age (years) Male gender 157 (78%) 166 (83%) (78%) 63 (76%) 0.8 Body mass index NYHA class I 8 (4%) 11 (5.5%) 28 (29%) 14 (17%) II 45 (22.5%) 33 (16.5%) 32 (34%) 38 (46%) III 80 (40%) 92 (46%) 30 (32%) 24 (29%) IV 67 (33.5%) 64 (32%) 5 (5%) 7 (8%) Extent of coronary artery disease Ejection fraction Good ( 49%) 142 (71%) 149 (74.5%) 60 (63%) 57 (68%) Fair (30% 49%) 48 (24%) 39 (19.5%) 29 (30%) 18 (22%) Poor ( 30%) 10 (5%) 12 (6%) 6 (7%) 8 (10%) Diabetes mellitus Insulin dependent 18 (9%) 5 (2.5%) 11 (12%) 4 (5%) Oral therapy 19 (9.5%) 11 (5.5%) 7 (7%) 4 (5%) Preoperative creatinine ( mol/l) Respiratory diseases Asthma 8 (4%) 8 (4%) 3 (3%) 4 (5%) Chronic obstructive pulmonary disease 10 (5%) 10 (5%) 3 (3%) 5 (6%) Neurologic risk factors Cerebrovascular accident 7 (3.5%) 5 (2.5%) 4 (4%) 3 (4%) Transient ischemic attacks 4 (2%) 8 (4%) 2 (2%) 2 (2%) Peripheral vascular disease 12 (6%) 14 (7%) (8%) 4 (5%) 0.2 Preoperative atrial fibrillation 5 (2.5%) 13 (6.5%) (3%) 4 (5%) 0.6 Euro-score Data are presented as number of observations with percentages in parentheses or as mean SD. BC blood cardioplegia without magnesium supplementation; blood cardioplegia with magnesium supplementation; NYHA New York Heart Association. treatment by drugs), acute conduction disturbances including second- or third-degree atrioventricular block, and bifascicular or trifascicular block. Intraoperative and postoperative outcome data, including major and minor complications and adverse events, were also recorded prospectively. Statistical Analysis Statistical analyses were performed using the Stat-View statistical software package (SAS Institute Inc, Cary, NC). Continuous variables are presented as mean standard deviation and categorical variables presented as either absolute numbers or percentages. Data were checked for normality before statistical analysis. Categorical variables were analyzed using either the 2 test or Fisher s exact test. Normally distributed continuous variables were compared using the unpaired t test and the Mann- Whitney U test was used for those variables that were not normally distributed. Differences between study groups were considered statistically significant when p was less than or equal to After comparison of the two groups as a whole a further subset analysis was made of those patients receiving CABG urgently for unstable symptoms. The rationale for such a comparison was based upon previously published data showing the importance of Mg 2 in acute coronary syndromes managed medically [18]. Results BC Versus The base line characteristics are summarized in Table 1. There were no differences between the two study groups in terms of age, gender, Euro-score and incidence of comorbid conditions. The group had a slightly lower body mass index (BMI) ( versus , p 0.02), a lower incidence of diabetes mellitus (9% versus 19%, p 0.01) and a twofold higher incidence of preoperative AF (7% versus 3%, p 0.05) when compared with the BC group although these differences are relatively small and most likely represent coincidental observations. The intraoperative details are listed in Table 2 and demonstrate that the two groups were comparable in terms of duration of CPB, cross-clamp times, and the number of distal anastomoses performed. After removal of the aortic cross-clamp, 5% of the BC group and 2% of the group required internal defibrillation. The incidence of immediate post-cpb AF,

4 Ann Thorac Surg YEATMAN ET AL 2002;73:112 8 MAGNESIUM-SUPPLEMENTED WARM BLOOD CARDIOPLEGIA 115 Table 2. Intraoperative Data Variables BC (n 200) (n 200) p Value BC Urgent (n 95) Urgent (n 83) p Value Cardiopulmonary bypass time (minutes) Cross-clamp time (minutes) Number of distal anastomosis ST-segment elevation 22 (11%) 12 (6%) (9%) 8 (10%) 0.9 Defibrillation after aortic cross-clamp removal 9 (5%) 3 (2%) (7%) Post-cardiopulmonary bypass arrhythmias Atrial fibrillation 2 (1%) 1 (1%) (1%) 1 (1%) 0.7 Temporary pacing 23 (12%) 18 (9%) (15%) 4 (5%) 0.01 Post-cardiopulmonary bypass inotropic usage Significant 11 (6%) 9 (5%) 8 (8%) 5 (6%) Modest 62 (31%) 60 (30%) 36 (38%) 35 (42%) Post-cardiopulmonary bypass vasodilator usage 53 (27%) 49 (24%) (25%) 28 (34%) 0.2 Data are presented as number of observations with percentages in parentheses or as mean SD. Inotropic requirement: modest 5 7 g kg 1 min 1 of dopamine, 10 g kg 1 min 1 of dobutamine, 0.05 g kg 1 min 1 of adrenaline or noradrenaline; significant inotropic usage exceeding modest or administration of enoximone. Abbreviations as in Table 1. the requirement for temporary pacing and the usage of post-cpb inotropic agents did not differ between the two groups. There was a modest and statistically insignificant difference between the two groups in the prevalence of ST-segment changes during the immediate post-cpb period. The postoperative clinical outcome data are summarized in Table 3, and as can be seen, with the exception of Table 3. Postoperative Data Variables BC (n 200) (n 200) p Value BC Urgent (n 95) Urgent (n 83) p Value Deaths 1 (0.5%) 3 (1.5%) (2%) 0.1 Myocardial infarct 3 (1.5%) 3 (1.5%) (1%) 1 (1%) 0.9 Inotropic requirement Modest 31 (15.5%) 28 (14%) 19 (20%) 13 (16%) Significant 13 (6.5%) 12 (6%) 5 (5%) 9 (10%) Postoperative IABP 9 (4.5%) 7 (3.5%) (6%) 4 (5%) 0.7 Overall postoperative arrhythmias 65 (32.5%) 54 (27%) (38%) 21 (25%) 0.07 Atrial fibrillation 58 (29%) 45 (22%) (34%) 16 (19%) 0.03 Total blood loss (ml) Red blood cell transfusion (units) Platelets transfusion (units) Fresh frozen plasma transfusion (units) Postoperative hemoglobin (g/dl) Reoperation for bleeding 5 (2.5%) 6 (3%) (2%) 4 (5%) 0.1 Neurologic complications Transient ischemic attacks 3 (1.5%) 4 (2%) 0 0 Cerebrovascular accidents 1 (0.5%) 0 1 (1%) 0 Respiratory complications Minor 19 (9.5%) 14 (7%) 9 (9%) 8 (10%) Major 2 (1%) 3 (1.5%) 1 (1%) 2 (2%) Intubation time (hours) ICU stay (days) Hospital stay (days) Data are presented as number of observations with percentages in parentheses or as mean SD. IABP intra-aortic balloon counterpulsation; ICU intensive care unit; Inotropic requirement: modest 5 7 g kg 1 min 1 of dopamine, 10 g kg 1 min 1 of dobutamine, 0.05 g kg 1 min 1 of adrenaline or noradrenaline; significant inotropic usage exceeding modest or administration of enoximone. Abbreviations as in Table 1.

5 116 YEATMAN ET AL Ann Thorac Surg MAGNESIUM-SUPPLEMENTED WARM BLOOD CARDIOPLEGIA 2002;73:112 8 differences achieved statistical significance on the day of operation (p 0.05) but not subsequently. Fig 1. Changes in the postoperative magnesium (Mg 2 ) levels in the blood cardioplegia (BC) without Mg 2 group (open circles) and in the BC with Mg 2 supplementation group (filled circles). *p 0.01 versus BC. (ICU intensive care unit.) total blood loss and high dependancy unit (HDU) length of stay, there were no statistically significant differences between the groups. Although the total postoperative blood loss and total length of HDU stay achieved statistical significance, these changes are small and clinically unimportant. Additionally, the postoperative inotropic requirements, the use of postoperative vasodilators, transfusion requirements, intubation times, total postoperative duration of hospitalization, and incidence of major complications were remarkably similar in both groups. Although there was a trend in the incidence of overall postoperative arrhythmias and in the incidence of new postoperative AF in favor of the group, these changes did not achieve statistical significance. The serial plasma Mg 2 levels for the study groups are shown in Figure 1. Preoperative plasma Mg 2 levels were similar in both groups but plasma Mg 2 levels were significantly lower in the BC group immediately after surgery and at 24 hours postoperatively. These differences had disappeared by postoperative day 2 and beyond (Fig 1). Urgent BC Versus Urgent BC- Mg 2 A relatively high proportion of CABG procedures (178) in both groups were performed urgently on in-hospital patients with unstable symptoms (95 [48%] in the BC group and 83 [41%] in the group; p 0.3). The two groups were well matched in terms of preoperative characteristics (Table 1). The intraoperative data are shown in Table 2 and demonstrate a significantly lower requirement for internal defibrillation after aortic cross-clamp removal as well as a lower requirement for temporary epicardial pacing. Furthermore, there was a nearly twofold lower incidence of new postoperative AF in the group compared with the BC group (19% versus 34%, p 0.03). The serial plasma Mg 2 levels for the patients undergoing urgent CABG are presented in Figure 2, which shows that the postoperative Mg 2 levels were consistently lower in those patients who developed new postoperative AF compared with those who did not. These Comment Although there is growing evidence to suggest that the administration of Mg 2 to patients undergoing CABG [2] and to patients after myocardial infarction [3, 16] is beneficial, the addition of Mg 2 to cardioplegic solutions remains controversial [17, 18]. This is despite the inclusion of Mg 2 in the original cold crystalloid formulations, the rationale for which was based on extensive rat heart studies [4]. The administration of Mg 2 has been shown to be effective in both animal and human models of ischemicreperfusion injury [19, 20]. Thus, Mg 2 increases hemodynamic recovery and reduces reperfusion-induced arrhythmias in ischemic rat hearts [6] and has been shown to increase recovery of human atrial contractile force after brief periods of ischemia [19]. However, the beneficial effects of Mg 2 after ischemia are only apparent when administered before reperfusion and are ineffective when given only during reperfusion [21]. The administration of Mg 2 to patients undergoing coronary artery bypass surgery has also proven effective. Thus Mg 2 supplementation of intermittent cold blood cardioplegia in a recent clinical trial reduced the incidence of ventricular tachyarrhythmias but not the incidence of postoperative AF [22]. Jensen and colleagues [23] were able to demonstrate a reduction in the duration of AF and atrial flutter after intravenous Mg 2 administration during and after CABG. Using a blood-based cardioplegia Caspi and colleagues [2] were also able to show that perioperative administration of MgSO 4 contributed to better myocardial recovery and fewer ventricular tachyarrhythmias after operation. The postulated mechanisms of action of the cardiopro- Fig 2. Serial plasma magnesium (Mg 2 ) levels for the patients undergoing urgent coronary artery bypass graft surgery who developed postoperative atrial fibrillation (open circles) compared with those who did not develop postoperative atrial fibrillation (filled circles). *p 0.05 versus patients who did develop postoperative atrial fibrillation. (ICU intensive care unit.)

6 Ann Thorac Surg YEATMAN ET AL 2002;73:112 8 MAGNESIUM-SUPPLEMENTED WARM BLOOD CARDIOPLEGIA 117 tective benefits of Mg 2 during ischemia-reperfusion injury are mainly thought to be due to the action of Mg 2 in blocking the L-type Ca 2 channels and so limiting the influx of intracellular Ca 2, which occurs during hyperkalemic arrest and subsequent reperfusion [8 10]. Blocking the L-type Ca 2 channels reduces Ca 2 loading and energy demands and preserves myocardial metabolites. Recently we [11] have demonstrated that supplementation of blood cardioplegia with Mg 2 prevents the metabolic derangements after ischemia and reduces the reperfusion injury seen in the hearts of patients undergoing CABG. These observations led us to hypothesize that the preservation of intracellular metabolites and ATP levels together with a reduced release of myocardial troponin I (as seen in patients in which Mg 2 was added to the cardioplegia solution) may facilitate recovery after cardiac surgery. The present study supports the findings of these investigations and provides some interesting insights into both the optimal dose of cardioplegic Mg 2 supplementation as well as the optimum timing of the administered Mg 2. The study demonstrated a lower requirement for defibrillation after removal of the aortic cross clamp, a lower requirement for temporary epicardial pacing and a lower incidence of AF in the Mg 2 supplemented group of patients undergoing urgent but not elective CABG. In addition we observed a decrease in plasma Mg 2 levels during the first 24 to 36 hours after surgery and this decrease was quantitatively greater in the urgent group of patients who developed new postoperative AF. There were no differences in the inotropic requirements or incidence of complications between the two study groups. These results suggest that Mg 2 supplementation of warm blood cardioplegia is beneficial but greater protection may have been afforded by using a higher concentration of Mg 2 in the cardioplegic solution. The St Thomas s II (cold crystalloid) solution contains 15 mmol/l Mg 2 [4] and this was similar to the concentration used by Shakerinia [22]. Our dosing protocol was based on a 4:1 mix of K and Mg 2 and produced an effective Mg 2 concentration of just 5 mmol/l/l. This may have represented a suboptimal concentration for maximum cardioprotection and it is possible that a 15 mmol/l Mg 2 concentration would have produced an even greater clinical impact. The relatively high reductions observed in postoperative arrhythmias in some of the studies using systemically administered Mg 2 suggest that not only is the concentration of the Mg 2 in the cardioplegia important but also suggests that the total amounts of Mg 2 administered may be critical. Thus, Caspi and coworkers [2] and England and associates [24] both continued the Mg 2 supplementation into the postoperative period. Such an approach is logical given the well-demonstrated hypomagnesemia, which is known to follow cardiac surgical procedures [20]. While we accept that total plasma Mg 2 concentrations do not necessarily reflect free ionized Mg 2 concentrations [25], it is interesting that in the present study Mg 2 -deficient cardioplegia resulted in low plasma Mg 2 levels postoperatively and this was found to be a risk factor for the subsequent development of new postoperative AF. It is possible, therefore, that Mg 2 supplementation of blood cardioplegia may reduce postoperative arrhythmias because of two mechanisms: one in limiting Ca 2 -mediated ischemic-reperfusion injury and the other in partially preventing the early postoperative hypomagnesemia encountered after CABG. In summary, it is apparent that the addition of a relatively low amount of Mg 2 (5 mmol/l) to warm blood cardioplegia resulted in some benefit in patients undergoing urgent CABG for unstable angina. This benefit may have been far greater if the dose of Mg 2 had been higher (perhaps optimally around 15 mmol/l). Additional benefit, perhaps, could also be obtained by further doses of systemically administered Mg 2 during the early postoperative period. References 1. Casthely PA, Yoganathan T, Komer C, Kelly M. Magnesium and arrhythmias after coronary artery bypass surgery. J Cardiothorac Vasc Anesth 1994;8: Caspi J, Rudis E, Bar I, Safadi T, Saute M. Effect of magnesium on myocardial function after coronary artery bypass grafting. Ann Thorac Surg 1995;59: Prasad A, Reeder G. Modern adjunctive pharmacotherapy of myocardial infarction. Expert Opin Pharmacother 2000;1: Hearse DJ, Stewart DA, Braimbridge MV. Myocardial protection during ischemic cardiac arrest. The importance of magnesium in cardioplegic infusates. J Thorac Cardiovasc Surg 1978;75: Kronon M, Bolling KS, Allen BS, et al. The relationship between calcium and magnesium in paediatric myocardial protection. J Thorac Cardiovasc Surg 1997;114: Komori S, Li B, Matsumura K, et al. Antiarrhythmic effect of magnesium sulphate against occlusion-induced arrhythmias and reperfusion-induced arrhythmias in anaesthetized rats. Mol Cell Biochem 1999;199: Ichiba T, Matsuda N, Takemoto N, Ishiguro S, Kuroda H, Mori T. Regulation of intracellular calcium concentrations by calcium and magnesium in cardioplegic solutions protects rat neonatal myocytes from simulated ischemia. J Mol Cell Cardiol 1998;30: Tani M. Mechanisms of calcium overload in reperfused ischemic heart. Annu Rev Physiol 1990;52: Jennings RB, Reimer KA. The cell biology of acute myocardial ischemia. Annu Rev Med 1991;42: Minezaki KK, Suleiman M-S, Chapman RA. Changes in mitochondrial-function induced in isolated guinea-pig ventricular myocytes by calcium overload. J Physiol (London) 1994;476: Caputo M, Bryan AJ, Calafiore AM, Suleiman MS, Angelini GD. Intermittent antegrade hyperkalaemic warm blood cardioplegia supplemented with magnesium prevents myocardial substrate derangement in patients undergoing coronary artery bypass surgery. Eur J Cardiothorac Surg 1998;14: Calafiore AM, Teodori G, Mezzetti A, et al. Intermittent antegrade warm blood cardioplegia. Ann Thorac Surg 1995; 59: Mezzetti A, Calafiore AM, Lapenna D, et al. Intermittent antegrade warm cardioplegia reduces oxidative stress and improves metabolism in the ischemic-reperfused human myocardium. J Thorac Cardiovasc Surg 1995;109:

7 118 YEATMAN ET AL Ann Thorac Surg MAGNESIUM-SUPPLEMENTED WARM BLOOD CARDIOPLEGIA 2002;73: Ascione R, Caputo M, Calori G, Lloyd CT, Underwood MJ, Angelini GD. Predictors of atrial fibrillation after conventional and beating heart coronary surgery: a prospective, randomised study. Circulation 2000;102: Kalman JM, Munawar M, Howes LG, et al. Atrial fibrillation after coronary artery bypass grafting is associated with sympathetic activation. Ann Thorac Surg 1995;60: Woods KL. More on intravenous Mg 2 and the unstable coronary artery. Eur Heart J 1997;18: Grigore AM, Mathew JP. Con: magnesium should not be administered to all coronary artery bypass graft surgery patients undergoing cardiopulmonary bypass. J Cardiothorac Vasc Anesth 2000;14: Boyd WC, Thomas SJ. Pro: magnesium should be administered to all coronary artery bypass graft surgery patients undergoing cardiopulmonary bypass. J Cardiothorac Vasc Anesth 2000;14: Lareau S, Boyle A, Deslauriers R, Keon WJ, Kroft T, Labow RS. Magnesium enhances function of postischaemic human myocardial tissue. Cardiovasc Res 1993;27: Haigney MC, Wei S, Kaab S, et al. Loss of cardiac magnesium in experimental heart failure prolongs and destabilizes repolarization in dogs. J Am Coll Cardiol 1998;31: Christensen CW, Rieder MA, Silverstein EL, Gencheff NE. Magnesium sulphate reduces myocardial infarct size when administered before but not after coronary reperfusion in a canine model. Circulation 1995;92: Shakerinia T, Ali IM, Sullivan JA. Magnesium in cardioplegia: is it necessary? Can J Surg 1996;39: Jensen BM, Alstrup P, Klitgard NA. Magnesium substitution and postoperative arrhythmias in patients undergoing coronary artery bypass grafting. Scand Cardiovasc J 1997;31: England MR, Gordon G, Salem M, Chernow B. Magnesium administration and dysrhythmias after cardiac surgery. A placebo-controlled, double-blind, randomised trial. JAMA 1992;268: Altura BM. Introduction: importance of Mg in physiology and medicine and the need for ion selective electrodes. Scand J Clin Lab Invest 1994;217(Suppl):5 9. The Society of Thoracic Surgeons: Thirty-eighth Annual Meeting Mark your calendars for the Thirty-eighth Annual Meeting of The Society of Thoracic Surgeons, which will be held in Fort Lauderdale, Florida, January 28 30, Advance registration forms, hotel reservation forms, and details regarding transportation arrangements, as well as the complete meeting program, have been mailed to Society members. Also, complete meeting information is available on The Society s Website located at Nonmembers wishing to receive information on attending the meeting may contact The Society s Secretary, Gordon F. Murray. Gordon F. Murray, MD Secretary The Society of Thoracic Surgeons 401 N Michigan Ave Chicago, IL Telephone: (312) ; fax: (312) sts@sba.com. website: by The Society of Thoracic Surgeons Ann Thorac Surg 2002;73: /02/$22.00 Published by Elsevier Science Inc