|Year : 2014 | Volume
| Issue : 3 | Page : 362-366
The effects of magnesium sulfate pretreatment on reperfusion injury after coronary artery bypass graft surgery
Mostafa K Abdellatif1, Marwa A Khairy1, Hani A Mabood2
1 Department of Anesthesiology, Intensive Care and Pain Management, Cairo, Egypt
2 Department of Cardiothoracic Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
|Date of Submission||26-Jan-2014|
|Date of Acceptance||30-Apr-2014|
|Date of Web Publication||27-Aug-2014|
Mostafa K Abdellatif
Department of Anesthesiology, Intensive Care and Pain Management, Faculty of Medicine, Ain Shams University, Cairo
Source of Support: None, Conflict of Interest: None
Myocardial ischemia/reperfusion (IR) injury is a complex phenomenon that leads to organ dysfunction and failure after coronary artery bypass graft surgery (CABG). Data from numerous animal experiments and clinical trials suggest that magnesium, a physiological calcium blocker, may be efficacious for the reduction in reperfusion injury. We investigated whether an intravenous administration of magnesium before reperfusion can decrease IR injury after CABG with cardiopulmonary bypass.
Patients and methods
A total of 40 patients undergoing CABG were randomly assigned to a MG group (n = 20) or an NS group (n = 20). The patients in the MG group were administered 25 mg/kg of MgSO 4 mixed in 100 ml normal saline intravenously before reperfusion, and patients in the NS group were administered an equal volume of normal saline. The levels of lactate and pH were measured to assess reperfusion injury at three specific times, which were before induction and after declamping by 10 min and 30 min. To evaluate postoperative other organ dysfunction, alanine aminotransferase and creatinine levels were measured at postoperative day 0.
The blood lactate levels were significantly lower at 10 and 30 min after reperfusion in the MG group compared with the NS group. In addition, postoperative alanine aminotransferase was significantly higher in the NS group than in the MG group.
Magnesium administration before reperfusion of the heart in CABG with cardiopulmonary bypass significantly reduces blood lactate levels. These findings suggest that magnesium treatment may have protective effects on IR injury.
Keywords: coronary artery bypass graft surgery, magnesium sulfate pretreatment, reperfusion injury
|How to cite this article:|
Abdellatif MK, Khairy MA, Mabood HA. The effects of magnesium sulfate pretreatment on reperfusion injury after coronary artery bypass graft surgery. Ain-Shams J Anaesthesiol 2014;7:362-6
|How to cite this URL:|
Abdellatif MK, Khairy MA, Mabood HA. The effects of magnesium sulfate pretreatment on reperfusion injury after coronary artery bypass graft surgery. Ain-Shams J Anaesthesiol [serial online] 2014 [cited 2019 Sep 19];7:362-6. Available from: http://www.asja.eg.net/text.asp?2014/7/3/362/139567
| Introduction|| |
Myocardial ischemia/reperfusion injury (IR) continues to occur after cardiac operations that have been performed in a technically adequate manner; this injury contributes significantly to postoperative morbidity and mortality, despite meticulous adherence to presently known principles of myocardial protection .
Perioperative myocardial IR injury involves the generation of reactive oxygen species on the restoration of oxygen delivery and alterations in intracellular calcium (Ca 2+ ) homeostasis. In addition, the activation of several proinflammatory pathways, including the complement, coagulation, and cytokine cascades, can exacerbate tissue injury and the functional impairment initiated by the original ischemic insult . A significant effort has been made to develop novel surgical techniques and pharmacologic agents that may reduce the generation and subsequent pathophysiological consequences of proinflammatory mediators .
Recent experiments have shown protective effects of magnesium to reduce the reperfusion injury of myocardial infarction, ischemic spinal cord injury, stroke, and during living donor liver transplantation [3-7]. The intravenous administration of magnesium during coronary occlusion has caused a significant reduction in myocardial infarction size . This is because magnesium provides cellular protection during ischemia and reperfusion by stabilizing the cellular transmembrane potential, suppressing excessive calcium influx and reducing cellular energy demand . Magnesium administration also enhances electrophysiological and neurobehavioral recovery and reduces brain infarction after cerebral IR injury . Kaplan et al.  reported that the use of magnesium may have protective effects on reperfusion injuries of the spinal cord in rabbits.
Despite these advances, little is known about the effects of magnesium on reperfusion injury after cardiopulmonary bypass (CPB) during coronary artery bypass graft surgery (CABG) surgery. The primary aim of this study was to evaluate the effects of intravenous magnesium infusion before reperfusion can decrease IR injury after CABG by using blood lactate levels and some clinical parameters, as the intraoperative changes in the blood lactate levels after declamping is a good indicator to reperfusion injury. The secondary objective was to examine the postoperative organ function to detect delayed effects of magnesium.
| Patients and methods|| |
After approval of the institutional ethical committee and obtaining written informed consent, a total of 40 patients of both sexes, who were scheduled for elective CABG using CPB in Ain Shams University Hospitals, were randomly assigned to one of the study groups using a computer-generated list compiled before the start of the study. The inclusion criteria were adult (≥18 years of age) patients. The exclusion criteria included a serum creatinine of greater than 1.5 mg/dl, liver failure [alkaline phosphatase >180 IU/l, alanine aminotransferase (ALT) >35 IU/l, and bilirubin >1.5 mg/dl], pre-existing cardiac arrhythmia, long-term treatment for an arrhythmia, long-term treatment with nifedipine or aminoglycosides, known hypersensitivity to magnesium sulfate, and preoperative magnesium level greater than or equal to 3 mg/dl.
CABG was always performed by the same team of surgeons and anesthesiologists using the same anesthetic and surgical techniques.
Patients were randomized to receive magnesium solution (MG group, n = 20) or normal saline (NS group, n = 20).
Patients in the MG group were administered 25 mg/kg of MgSO 4 mixed in 100 ml normal saline intravenously before reperfusion, and patients in the NS group were administered an equal volume of normal saline. The levels of lactate and pH were measured to assess reperfusion injury at three specific times, which were before induction and after declamping by 10 min and 30 min. To evaluate postoperative other organ dysfunction, ALT and creatinine levels were measured at postoperative day 0.
The mean arterial pressure (MAP) was recorded at three specific times: before induction, after induction, and on bypass. Administration of fluid, vasopressors, and inotropes was guided by hemodynamic monitoring and clinical parameters (central venous pressure: 8-10 mmHg; systolic blood pressure >90 mmHg; heart rate <100 bpm; and urine output: 0.5-1 ml/kg/h). Packed red blood cells were transfused to keep the hematocrit at 30%. Administration of blood and fresh frozen plasma was based on clinical findings by inspection of the surgical field and the medical history of the patient. Sodium bicarbonate was administered if there was metabolic acidosis (pH <7.2 and base excess<−10 mmol/l).
Blood lactate levels were measured using ABL800 FLEX that used a technique based on spectrophotometry analysis, adopting a lactate.
The required sample size was estimated using the G*Power software version 3.1.3 (Heinrich Heine Universitδt, Institut fόr Experimentelle Psychologie, Dόsseldorf, Germany). The primary outcome measure was the difference in serum lactate between the two study groups. Assuming a type I error of 0.05, it was estimated that a sample of 20 patients in each group would achieve a power of 80% to detect a large effect size (d) of 0.8 with regard to the primary outcome of interest.
Statistical analysis was performed on a personal computer using the IBM SPSS statistics version 21 (IBM Corp., Armonk, New York, USA). Categorical data were presented as ratio or as number and percentage, and between-group differences were compared using the Pearson's χ2 -test or the χ2 -test for trends for nominal or ordinal data, respectively. Fisher's exact test was used instead of the χ2 -test if more than 20% of cells in any contingency table had an expected count of less than 5.
Normality of numerical data distribution was tested using the Shapiro-Wilk test. As these data were skewed, they were presented as median and interquartile range, and intergroup differences were compared nonparametrically using the Mann-Whitney U-test. For comparison of repeated within-group measures, the Friedman test was used, with application of the Mann-Whitney U-test as a post-hoc test if a statistically significant difference was detected. To correct for multiple within-group pairwise comparisons, the Bonferroni method was applied. This indicated that to maintain a final type I error of 0.05, an uncorrected two-sided P-value less than 0.017 should be considered statistically significant. For other comparisons, a two-sided P value less than 0.05 was considered statistically significant.
| Results|| |
There was no significant difference between the two groups in terms of age, sex, and associated comorbid diseases such as diabetes mellitus, hypertension, or COPD. No significant difference was found in terms of New York Heart Association classification, American Society of Anesthesiologists-Physical Status classification, or ejection fraction [Table 1].
Baseline hematological and biochemical tests
There was no significant difference between the two groups regarding hemoglobin, serum sodium, and serum potassium [Table 2].
There was no significant difference between the two groups in terms of CPB time, aortic cross-clamping time, MAP before induction, after induction, and average MAP on CPB [Table 3].
Change in serum lactate and pH
The blood lactate levels were similar in all groups at baseline, but significantly increased at 10 and 30 min after reperfusion in both groups. However, significantly higher blood lactate levels were observed in the NS group than in the magnesium-treated group ([Table 4], [Figure 1].
|Figure 1: Box plot showing serum lactate in both the study groups. Circles and asterisks represent outliers and extreme observations, respectively.|
Click here to view
After reperfusion, the pH values significantly decreased compared with the baseline. Significantly lower pH values were observed in the NS group than in the magnesium-treated group (Table 4, [Figure 2].
|Figure 2: Box plot showing pH in both the study groups. Circles and asterisks represent outliers and extreme observations, respectivel y.|
Click here to view
Postoperative organ dysfunction
At postoperative day 0, the serum ALT significantly increased in the NS group than in the magnesium-treated group. There was no significant difference in serum creatinine between the two groups [Table 5].
| Discussion|| |
Molecular and cellular events underlying IR injury are complex, representing the confluence of divergent biological pathways. Ischemia induces accumulation of intracellular sodium, hydrogen, and calcium ions, culminating in tissue acidosis. Reperfusion, in turn, elicits rapid alterations in ion flux .
Accepted approaches to reduce this ischemic insult include local or systemic hypothermia and diastolic arrest with cardioplegia. Administration of magnesium should be added to this list. Timely magnesium administration may provide additional protection from myocardial reperfusion injury when used in conjunction with the currently accepted methods of preservation .
Magnesium is an important cofactor for many enzymatic reactions. It is essential for the production and functioning of ATP, and therefore preserves energy-dependent cellular activity, particularly during ischemic episodes. Magnesium also blocks calcium entry into the cell by acting on voltage receptor and receptor-operated membrane channels . As calcium overload has an important role in the pathogenesis of reperfusion injury , magnesium may provide cellular protection during ischemia.
The purpose of this study was to evaluate whether the administration of magnesium has protective effects against reperfusion injury when administered before declamping during on-bypass CABG.
During IR, injury to the endothelial cell resulted in the inhibition of pyruvate dehydrogenase, and consequently caused anaerobic glycolysis, glycogenolysis, and lactate accumulation [12,13]. Blood lactate levels after declamping may be good marker of reperfusion injury.
In this study, the blood lactate levels were similar in all groups at baseline, but significantly increased at 10 and 30 min after reperfusion in both groups. However, significantly higher blood lactate levels were observed in the NS group than in the magnesium-treated groups. In addition, the MAP values, which are probably the most useful parameters to assess organ perfusion, were adequately maintained in all groups. On the basis of these results, the differences in lactate levels were probably not because of tissue perfusion, but rather correlated with magnesium administration.
After reperfusion, the pH values significantly decreased compared with the baseline. Significantly lower pH values were observed in the NS group than in the magnesium-treated group.
These results came with the results of other studies. In a study conducted by Bariskaner et al. , magnesium treatment significantly suppressed the increase of lactate concentrations, and improved electroencephalogram changes in cerebral IR injury when compared with the untreated group .
In a previous study, Kim et al.  found that magnesium treatment for hepatic IR injury attenuated the increase of lactate levels.
Magnesium may have some organ protection as evident by the results at postoperative day 0; the serum ALT significantly increased in the NS group than in the magnesium-treated group. There was no significant difference in serum creatinine between the two groups.
This study had some limitations. The first limitation was that cytokines or chemokines such as tumor necrosis factor-α, interleukin 1, which are the mediators of myocardial IR injury, were not measured that might give further information on IR injury. The second limitation was that postoperative organ protection of magnesium could be assessed over more than 1 day to add more information.
| Conclusion|| |
Administration of magnesium before reperfusion of the heart in CABG with CPB significantly reduces the blood lactate levels. This result is consistent with those of previous studies [7,14], showing that the administration of magnesium inhibits lactate production after IR injury. These findings suggest that magnesium treatment may have protective effects on IR injury.
| Acknowledgements|| |
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]