Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
Brief Communication
Cardiac Critical Care, Case Report
Cardiac Critical Care, Case Series
Cardiac Critical Care, Editorial
Cardiac Critical Care, Invited Editorial
Cardiac Critical Care, Original Article
Cardiac Critical Care, Point of Technique
Cardiac Critical Care, Review Article
Case Report
Case Report, Cardiac Critical Care
Case Series, Cardiac Critical Care
Editorial
Editorial, Cardiac Critical Care
Invited Editorial, Cardiac Critical Care
JCCC Quiz, Cardiac Critical Care
Legends in Cardiac Sciences
Letter To Editor Response
Letter to Editor, Cardiac Anesthesia
Letter to Editor, Cardiac Critical Care
Letter to the Editor
Narrative Review, Cardiac Critical Care
Original Article
Original Article, Cardiac Critical Care
Original Article, Cardiology
Perspective Insights
Perspective, Cardiac Critical Care
Point of Technique
Point of Technique, Cardiac Critical Care
Point of View, Cardiac Critical Care
Review Article
Review Article, Cardiac Critical Care
Review Article, Cardiology
Review Article, Evidence Based Medicine
Review Article, Invited
Short Communication, Cardiac Critical Care
Surgical Technique
Surgical Technique, Cardiology
Systematic Review
Technical Note
Video Case Report
Video Commentary
Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
Brief Communication
Cardiac Critical Care, Case Report
Cardiac Critical Care, Case Series
Cardiac Critical Care, Editorial
Cardiac Critical Care, Invited Editorial
Cardiac Critical Care, Original Article
Cardiac Critical Care, Point of Technique
Cardiac Critical Care, Review Article
Case Report
Case Report, Cardiac Critical Care
Case Series, Cardiac Critical Care
Editorial
Editorial, Cardiac Critical Care
Invited Editorial, Cardiac Critical Care
JCCC Quiz, Cardiac Critical Care
Legends in Cardiac Sciences
Letter To Editor Response
Letter to Editor, Cardiac Anesthesia
Letter to Editor, Cardiac Critical Care
Letter to the Editor
Narrative Review, Cardiac Critical Care
Original Article
Original Article, Cardiac Critical Care
Original Article, Cardiology
Perspective Insights
Perspective, Cardiac Critical Care
Point of Technique
Point of Technique, Cardiac Critical Care
Point of View, Cardiac Critical Care
Review Article
Review Article, Cardiac Critical Care
Review Article, Cardiology
Review Article, Evidence Based Medicine
Review Article, Invited
Short Communication, Cardiac Critical Care
Surgical Technique
Surgical Technique, Cardiology
Systematic Review
Technical Note
Video Case Report
Video Commentary
Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
Brief Communication
Cardiac Critical Care, Case Report
Cardiac Critical Care, Case Series
Cardiac Critical Care, Editorial
Cardiac Critical Care, Invited Editorial
Cardiac Critical Care, Original Article
Cardiac Critical Care, Point of Technique
Cardiac Critical Care, Review Article
Case Report
Case Report, Cardiac Critical Care
Case Series, Cardiac Critical Care
Editorial
Editorial, Cardiac Critical Care
Invited Editorial, Cardiac Critical Care
JCCC Quiz, Cardiac Critical Care
Legends in Cardiac Sciences
Letter To Editor Response
Letter to Editor, Cardiac Anesthesia
Letter to Editor, Cardiac Critical Care
Letter to the Editor
Narrative Review, Cardiac Critical Care
Original Article
Original Article, Cardiac Critical Care
Original Article, Cardiology
Perspective Insights
Perspective, Cardiac Critical Care
Point of Technique
Point of Technique, Cardiac Critical Care
Point of View, Cardiac Critical Care
Review Article
Review Article, Cardiac Critical Care
Review Article, Cardiology
Review Article, Evidence Based Medicine
Review Article, Invited
Short Communication, Cardiac Critical Care
Surgical Technique
Surgical Technique, Cardiology
Systematic Review
Technical Note
Video Case Report
Video Commentary
View/Download PDF

Translate this page into:

Review Article
5 (
1
); 49-53
doi:
10.1055/s-0041-1723932

Total Intravenous Anesthesia for Myocardial Protection and Preconditioning

Cardiothoracic Sciences Centre, All India Institute of Medical Sciences, New Delhi, India
Address for correspondence Minati Choudhury, MD, PGDip Department of Cardiac Anesthesiology, Cardiothoracic Sciences Centre, All India Institute of Medical Sciences Ansari Nagar, New Delhi 110029 India minati.2002@gmail.com
Licence
This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Disclaimer:
This article was originally published by Thieme Medical and Scientific Publishers Pvt. Ltd. and was migrated to Scientific Scholar after the change of Publisher.

Abstract

Perioperative myocardial injury is common after any major surgical procedure even with best possible anesthesia and surgical management. Organ preservation during surgical procedure prevents morbidity and mortality. The effect of ischemic preconditioning on myocardial as well as other organ protection is well known. A variety of other agents also shown to have preconditioning thus protective effect on myocardium during anesthesia and surgery. The beneficial effect of volatile anesthetic preconditioning is well studied. However, the effect of intravenous anesthetic agents on this context is still way to go. This review is an attempt to look into the latest available research regarding the preconditioning and myocardial protective effect of intravenous anesthetic agents.

Keywords

total intravenous anesthesia
myocardial protection
preconditioning

Introduction

Perioperative myocardial injury is common after cardiac surgery even with best surgical procedure/anesthesia management. However, this injury is common after noncardiac surgery as well. The VISION study group in noncardiac surgery patients also noted that 8% of patients aging more that 45 years suffered from myocardial damage. The incidence of myocardial damage is again more in cases with comorbidities such as diabetes, ischemic heart disease, and/hypertension.

Perioperative organ protection is an important aspect of anesthesia and surgical management, and this is to prevent postoperative morbidity, mortality, and cost of hospital stay. Several methods have been described in literature to reduce organ damage in the perioperative period among which preconditioning is the most important one and considered to be the best.

Myocardial Injury and Preconditioning, General View, and Historical Aspect

Some degree of myocardial injury is inevitable in all kinds of surgery and that is more in cardiac surgical procedures. Surgical trauma, mechanical stress, hemodilution, perfusion temperature, endotoxin release, ischemia-reperfusion injury, blood reaction with foreign material are the major stimulants those can give rise to ischemia, which leads to hypoxia and subsequently dysfunction of mitochondrial electron transport chain dysfunction. There occurs a decrease in adenosine triphosphate (ATP) production, induction of anaerobic metabolism, dysfunction of sodium-potassium pumps, detachment of ribosomes, and a decrease level of antioxidants in the cells. Retention of lactic acid may lead to lactic acidosis. Failure of Na+–K+ ATPase pump and Ca2+ATPase pump leads to accumulation of sodium, hydrogen, and calcium ions in the cell, leading to hyperosmolarity and cellular swelling. Sodium retention decreases cellular pH, leading to the impairment of enzymatic activity and clumping of cellular chromatin. Detachment of ribosome also leads to decrease in protein synthesis. There also occurs limitation of nitric oxide bioavailability followed by apoptosis of cardiac myocytes.

After the reperfusion stage, the restoration of blood flow to ischemic tissue resumes oxygenation. In parallel, there is generation of reactive oxygen species (ROS) due to decrease concentration of antioxidants in the ischemic cells. This leads to endothelial dysfunction, damage to DNA and local inflammatory response. The mitochondrial damage and electrolyte imbalance in this stage promotes the oxidative stress from nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) oxidative system, nitric oxide synthase system and xanthine oxidase system as well as mitochondrial electron transport system. There is activation of inflammatory cascade leading to a cytokine storm, and retention of ROS leading to cellular damage and cell death via mitoptosis, autophagy, necrosis, necroptosis as well as apoptosis. This reperfusion phase is dynamic and sometimes persists for several days.1 Understanding the detailed mechanism of ischemia-reperfusion injury may provide a strong foundation not only for novel therapeutic opportunities, but also for injury prevention.

In literary meaning, preconditioning (PC) is nothing but “adaptation,” in which a living entity is exposed to a form of stress or stimulus or environment to prepare that subject to be more resilient against the stimulus if it is encountered/applied thereafter. The concept of myocardial preconditioning was narrated first by Murray et al way back in 1986. He with his team used ischemia as a stimulus and described ischemic preconditioning (IPC) in dog hearts. In these experiments, one group of dogs was preconditioned with four cycles (5 minutes each) of circumflex artery occlusions, each separated by 5 minutes of reperfusion and followed by continuous 40 minutes occlusion. The control group underwent a single 40 minutes occlusion only. The authors noted a reduction in infarct size (IS) to 25% when compared with the control group (p = 0.001).2

Several cardioprotective strategies like cardioplegia, hypothermia, warm heart surgery, ischemic preconditioning, ischemic postconditioning, remote ischemic preconditioning, use of glucose-insulin in cardioplegia, and nitric oxide-L arginine supplemented cardioplegia are in use.3, 4 The cardio protective effects of volatile anesthetics are widely studied by several authors in the past few decades. These investigators have shown that exposure to volatile anesthetics leads to a variety of changes in the protein structure of the myocardium. These changes in protein structure and their modified distribution after exposure to volatile anesthetic agents can mediate myocardial protection (MP) by preconditioning effect. There exist three windows where MP strategies can be implemented, for example, before ischemia (preconditioning), during ischemia, and after ischemia (postconditioning).5, 8 There is a paucity of literature when myocardial preservation and preconditioning concerned with intravenous anesthetists. Intravenous anesthetics may be the future of cardioprotection; however, it is superiority to volatile anesthetists and other agents as well as ischemic preconditioning are yet to be proved. Fraßdorf et al in one of the reviews narrated the possible protective role of intravenous anesthetics against ischemia and reperfusion injuries.9 The main advantages of APC by anesthetic agents are that, unlike IPC, APC is not selective to myocardium only. The beneficial effects of these agents are for the entire organs of the body. APC is again easy way, less cumbersome because these agents are mandatory during any of the surgical procedures. This review is an attempt to reveal this concept with basic cellular mechanisms and recent trends.

Myocardial Protection and Preconditioning by Intravenous Anesthetic Agents, Mechanisms to Clinical Outcome

One of the frequent challenges of current day anesthesia practice is the prevention and treatment of myocardial ischemia and reperfusion injury. The primary goal in the therapy of myocardial ischemia-related injury is to restore perfusion to the ischemic tissues. The more lethal reperfusion injury can be reduced by modifications of conditions of reperfusion. Among all modifying agents, intravenous anesthetic agents are some. The mechanism involving anesthetic preconditioning (APC) is similar to reperfusion injury salvage kinase (RISK) that of IPC and ischemic postconditioning (IPoC). APC-MP is primarily mediated by RISK and survivor activating factor enhancement (SAFE) pathways. The activation of RISK pathway is via G-protein coupled cell surface receptor and that of SAFE pathway is via TNF-α receptor; both of which inhibit ischemia reperfusion injury (IRI) induced mitochondrial permeability transition pathway (mPTP) opening and activate the opening of KATP channels which subsequently protects cardiomyocyte from IRI induced cell death.

Opioids and Its Derivatives

Previous studies have demonstrated that opioid like agents bestow the ability of cardiac tissue to tolerate periods of ischemia and hypoxia.10 Morphine is one of the first agents to be tested for its cardioprotective effect by Schultz et al. In this experimental model, the authors elicited morphine induced PC by 5 minutes of drug infusion (100 μgm/kg IV) interspersed with 5 minutes drug free periods before the prolonged 30 minutes occlusion. The control group underwent three cycles of IPC. A similar reduction of IS to the area at risk happened in all the subjects. Their results indicate that the effect of morphine induced PC is most likely mediated via an opioid receptor-linked mechanism, which is similar to IPC.11 Murphy et al in one of the prospective randomized studies on coronary artery bypass grafting (CABG) patients, administered either morphine 40 mg or fentanyl 1,000 μgm before CPB. The morphine receivers showed an improvement of myocardial performance index 15 minutes post-CPB and end of surgery when compared with baseline and fentanyl group. However, this study does not comply with the strict definition of preconditioning.12 The protection against IRI to myocardium is offered by opioids mediated via stimulation of generation of ROS, which triggers and enhances the production of endogenous antioxidant enzymes and activates mitochondrial KATP channels, limiting myocardial infarction.13 Previous studies concluded the role of opioids in myocardial hibernation. Both endogenous and exogenous opioid agonists (morphine and remifentanil) reduce myocardial oxidative stress and Ca2+ overload attenuate myocardial IRI in patients undergoing cardiac surgery.12, 13 Qiao et al in one of their initial experimental models show that remifentanil confers MP primarily via activation of JAK2/STAT3 signaling that can function independent of PI3K/AKt activation14

Propofol

The propofol induced myocardial preconditioning is mediated via its ROS scavenging properties, which enhances endogenous myocardial antioxidant capacity and thereby attenuates myocardial IRI. Few of the authors also suggested that propofol-induced MP may partly result from a direct effect on myocardial Ca2+ influx or from inhibition of mPTP. Opening of mPTP uncouples mitochondria and is involved in determining pathways that lead to apoptosis and necrosis.15 Inspite of the fact that propofol protects against IRP when given before onset of ischemia, its administration on reperfusion alone may be ineffective. Administration of propofol (120 µgm/kg/min for 10 minutes) before the commencement of CPB until 15 minutes after aortic cross clamp release, than 60 µgm/kg/min till the end of surgery, significantly attenuated myocardial injury as evidenced by a reduction in cardiac troponin I (CTnI) release as noted by Xia et al.16 Bulow et al compared dexmedetomidine 0.3 µgm/kg/h in patients undergoing on-pump CABG to that with propofol 4 µgmL/min. A reduced oxidative stress markers and inflammatory markers was found with both the drugs.17 The benefits of propofol as APC was demonstrated by several authors; however, few of the trials showed that no difference among patients receiving propofol or sevoflurane and propofol or desflurane in terms of CK-MB, CTnI level, and postoperative recovery parameters.18

Ketamine

While one of the researchers reported that racemic mixture of ketamine blocks IPC of the myocardium, Hanouz et al found that both racemic and S+ isomer of ketamine induced preconditioning effect in isolated human myocardium. Their inference was ketamine-induced preconditioning involved activation of potassium adenosine triphosphate K (ATP) channels and stimulation of α and β adrenergic receptors.19

In another experimental study, the authors found that higher dose of ketamine-xyaline (KX) (K: 200 mg/kg; X: 60 mg/kg or K: 85 mg/kg; X: 15 mg/kg) used to anesthetize guinea pigs led to reduction in myocardial IS and improved hemodynamics after experimental ischemia-reperfusion injury.20

Barbiturates

The ROS scavenging ability of barbiturates has been found in experimental models is lesser than that of propofol. Thiopental is the most potent agent among all the barbiturates for APC when renal, bowel, and neuronal ischemia is concerned, but there is migre literature concerning its effect on myocardial ischemia and reperfusion injury.21

Etomidate

This drug does not have any effect on adhesion of neutrophils to coronary endothelium in postischemic myocardium. There is no clinical report regarding its effect on PC of myocardium.22

Benzodiazepines

The impact of midazolam on ROS formation is much less than that of propofol and there are conflicting reports regarding the effect of benzodiazepines on MP. The following Table 1 enumerates some of the trials narrating the preconditioning effect of intravenous anesthetic agents.

Table 1
The major randomized clinical trials of total intravenous anesthesia in myocardial protection and preconditioning

Reference no.

Induction agents

Test drug for APC

Control drug

Effect

Abbreviations: APC, anesthetic preconditioning; |, decrease; CTnI, cardiac troponin I; CK-MB, creatinine kinase myocardial band; NT-Pro BNP, N-terminal pro-β natriuretic peptide.

17

Sufentanil 0.5–1 µgm/kg followed by 0.5–1 µgm/kg/h

Dexmedetomidine 0.3 µgm/kg/h

Propofol

Oxidative stress and inflammatory markers

23

Midazolam-propofol-fentanyl

Propofol

Sevoflurane

Postoperative lymphedema

24

Institutional protocol

Dexmedetomidine-Lidocaine

Isoflurane

CTnI and CK-MB

25

Fentanyl-Etomidate

Desflurane

Propofol

No difference in cardiac function, CTnI and CK-MB

26

Fentanyl-Midazolam

Sevoflurane

Propofol

No difference in CTnI

27

Etomidate-Midazolam-Fentanyl

Sevoflurane

Propofol

No difference in CTnI, CK-MB, NT-ProBNP, hemodynamics and duration of stay in hospital or intensive care unit

28

Etomidate-Sufentanil

Propofol

-Isoflurane

Midazolam

CTnI is more in Propofol-Isoflurane group

29

Midazolam-Dexmedetomidine-Ketamine

Midazolam

-Dexmedetomidine

-Ketamine

Sevoflurane

CTnI and CK-MB

30

Thiopentone-Fentanyl

Isoflurane

Propofol

Similar in CTnI and CK-MB in both the groups

31

Fentanyl

Remifentanil till sternotomy-propofol

Normal saline till sternotomy-propofol

In CTnI, CK-MB and h-fatty acid binding protein in remifentanyl recievers

32

Midazolam-Sufe

ntanyl

Ketamine

-Sevoflurane

-Fentanyl

Normal saline

Sevoflurane-Fentanyl

No effect on pro-inflammatory cytokine release

33

Opioid-Isoflurane

Morphine

Fentanyl

Inflammatory response

34

Fentanyl-Isoflurane

Fentanyl-Isoflurane

Propofol before aortic cross clamp release till 4 hours after reperfusion

Fentanyl-Isoflurane

Normal before aortic cross clamp release till 4 hours after reperfusion

Free radical mediated lipid peroxidation and decreased systemic inflammation

16

Midazolam-Fentanyl

Propofol

Isoflurane

CTnI and oxidative stress markers

Future Directives

We have achieved a bit in the field of MP and preconditioning by intravenous anesthetic agents. However, we have still miles to go. Volatile anesthetics are the first choice for APC both in noncardiac and cardiac surgical patients. However, there is growing evidence that few of the intravenous agents, especially opioids, propofol, and dexmedetomidine are good anesthetics for APC. Still, there is a lot of doubts that large-scale nonrandomized trials will be performed in the near future to tackle this question. The more challenging situation arises when age, diabetes, and myocardial remodeling diminishes APC. Again, there is significant interference in MP effect between sevoflurane and propofol, which should not be used concomitantly if possible. All the researchers are still waiting for a promising outcome with the best method and magic dose of IV anesthetic agents to provide APC in future.

Conflict of Interest

None declared.

Funding None.

References

  1. , , . Pathophysiology of ischaemia-reperfusion injury. J Pathol. 2000;190(3):255-266.
    [Google Scholar]
  2. , , , . Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986;74(5):1124-1136.
    [Google Scholar]
  3. , , , , , . [Strategy and perspective of myocardial protection during ischaemia and reperfusion, and the role of volatile anaesthetics] Srp Arh Celok Lek. 2007;135:583-588. (9-10)
    [Google Scholar]
  4. , , , . Protective ischaemia in patients: preconditioning and postconditioning. Cardiovasc Res. 2009;83(2):234-246.
    [Google Scholar]
  5. , , , , , , . The cardioprotective effect of sevoflurane depends on protein kinase C activation, opening of mitochondrial K(+)(ATP) channels, and the production of reactive oxygen species. Anesth Analg. 2003;97(5):1370-1376.
    [Google Scholar]
  6. , , . Inhalational anaesthetics and cardioprotection. Handb Exp Pharmacol. 2008;182(182):187-207.
    [Google Scholar]
  7. , , , , . Myocardial preconditioning and cardioprotection by volatile anaesthetics. J Cardiovasc Med (Hagerstown). 2006;7(2):86-95.
    [Google Scholar]
  8. , , , et al . Cardiac protection by volatile anesthetics in non-cardiac surgery? A meta-analysis of randomized controlled studies on clinically relevant endpoints. HSR Proc Intensive Care Cardiovasc Anesth. 2009;1(4):34-43.
    [Google Scholar]
  9. , , , . Anaesthesia and myocardial ischaemia/reperfusion injury. Br J Anaesth. 2009;103(1):89-98.
    [Google Scholar]
  10. , , . Delta-1 opioid receptor dependence of acute hypoxic adaptation. J Pharmacol Exp Ther. 1994;268(1):74-77.
    [Google Scholar]
  11. , , , , . Evidence for involvement of opioid receptors in ischemic preconditioning in rat hearts. Am J Physiol. 1995;268:H2157-H2161. (5 Pt 2)
    [Google Scholar]
  12. , , , , , . Opioids and cardioprotection: the impact of morphine and fentanyl on recovery of ventricular function after cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2006;20(4):493-502.
    [Google Scholar]
  13. , , , et al . Mechanism of preconditioning by isoflurane in rabbits: a direct role for reactive oxygen species. Anesthesiology. 2002;97(6):1485-1490.
    [Google Scholar]
  14. , , , et al . Remifentanil preconditioning reduces postischemic myocardial infarction and improves left ventricular performance via activation of the Janus activated kinase-2/signal transducers and activators of transcription-3 signal pathway and subsequent inhibition of glycogen synthase kinase-3beta in rats. Crit Care Med. 2016;44(3):e131-e145.
    [Google Scholar]
  15. , , , . Mitochondrial permeability transition and oxidative stress. FEBS Lett. 2001;495:12-15. (1-2)
    [Google Scholar]
  16. , , , . Large-dose propofol during cardiopulmonary bypass decreases biochemical markers of myocardial injury in coronary surgery patients: a comparison with isoflurane. Anesth Analg. 2006;103(3):527-532.
    [Google Scholar]
  17. , , , et al . Dexmedetomidine decreases the inflammatory response to myocardial surgery under mini-cardiopulmonary bypass. Braz J Med Biol Res. 2016;49(4):e4646.
    [Google Scholar]
  18. , , . Peri-operative anaesthetic myocardial preconditioning and protection - cellular mechanisms and clinical relevance in cardiac anaesthesia. Anaesthesia. 2015;70(4):467-482.
    [Google Scholar]
  19. , , , et al . Ketamine preconditions isolated human right atrial myocardium: roles of adenosine triphosphate-sensitive potassium channels and adrenoceptors. Anesthesiology. 2005;102(6):1190-1196.
    [Google Scholar]
  20. , , , et al . High doses of ketamine-xylazine anesthesia reduce cardiac ischemia-reperfusion injury in guinea pigs. J Am Assoc Lab Anim Sci. 2011;50(3):349-354.
    [Google Scholar]
  21. , , , , , . Effects of propofol on ischemia and reperfusion in the isolated rat heart compared with thiamylal. Jpn Heart J. 2001;42(2):193-206.
    [Google Scholar]
  22. , , , , , , . The effects of thiopentone, etomidate, ketamine and midazolam on several bactericidal functions of polymorphonuclear leucocytes in vitro. Eur J Anaesthesiol. 1995;12(2):141-146.
    [Google Scholar]
  23. , , , et al . Propofol provides more effective patients undergoing off-pump coronary artery bypass graftsurgery. J Cardiothorac Vasc Anesth. 2015;29:1172-1179.
    [Google Scholar]
  24. , , , et al . A comparison among infusion of lidocaine and dexmedetomidine alone and in combination in subjects undergoing coronary artery bypass graft: a randomized trial. Contemp Clin Trials. 2014;39(2):303-309.
    [Google Scholar]
  25. , , , , , , . Comparison of haemodynamics and myocardial injury markers under desflurane vs. propofol anaesthesia for off-pump coronary surgery. A prospective randomised trial. Anaesthesiol Intensive Ther. 2014;46(1):4-13.
    [Google Scholar]
  26. , , , et al . Myocardial protection during off pump coronary artery bypass surgery: a comparison of inhalational anesthesia with sevoflurane or desflurane and total intravenous anesthesia. Ann Card Anaesth. 2013;16(1):4-8.
    [Google Scholar]
  27. , , , et al . Cardioprotective effect of sevoflurane and propofol during anaesthesia and the postoperative period in coronary bypass graft surgery: a double-blind randomised study. Eur J Anaesthesiol. 2012;29(12):561-569.
    [Google Scholar]
  28. , , , et al . A comparative study of cardioprotective effect of three anesthetic agents by measuring serum level of troponin-T after coronary artery bypass grafting. Int Cardiovasc Res J. 2012;6(3):70-74.
    [Google Scholar]
  29. , , , et al . Comparison of the effects of ketamine-dexmedetomidine and sevoflurane-sufentanil anesthesia on cardiac biomarkers after cardiac surgery: an observational study. Physiol Res. 2012;61(1):63-72.
    [Google Scholar]
  30. , , , , , , . Myocardial protection with isoflurane during off-pump coronary artery bypass grafting: a randomized trial. J Cardiothorac Vasc Anesth. 2011;25(1):59-65.
    [Google Scholar]
  31. , , , , . Remifentanil reduces the release of biochemical markers of myocardial damage after coronary artery bypass surgery: a randomized trial. J Cardiothorac Vasc Anesth. 2010;24(5):790-796.
    [Google Scholar]
  32. , , , , , , . Effect of low-dose ketamine on inflammatory response in off-pump coronary artery bypass graft surgery. Br J Anaesth. 2009;102(1):23-28.
    [Google Scholar]
  33. , , , , , . The effects of morphine and fentanyl on the inflammatory response to cardiopulmonary bypass in patients undergoing elective coronary artery bypass graft surgery. Anesth Analg. 2007;104(6):1334-1342.
    [Google Scholar]
  34. , , , , , , . The effects of propofol on neutrophil function, lipid peroxidation and inflammatory response during elective coronary artery bypass grafting in patients with impaired ventricular function. Br J Anaesth. 2006;97(6):825-831.
    [Google Scholar]
Show Sections