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Myocardial conditioning techniques in off-pump coronary artery bypass grafting

  • Marco Moscarelli1, 2Email author,
  • Prakash P Punjabi1,
  • Gamov I Miroslav1,
  • Paolo Del Sarto2,
  • Francesca Fiorentino1 and
  • Gianni D Angelini1, 3
Journal of Cardiothoracic Surgery201510:7

https://doi.org/10.1186/s13019-014-0204-7

Received: 20 October 2014

Accepted: 26 December 2014

Published: 20 January 2015

Abstract

Off-pump coronary artery bypass surgery by avoiding cardioplegic arrest seems to reduce the risk of ischemic myocardial injury. However, even short-term regional ischemic periods, hemodynamic instability and arrhythmias associated with the procedure can be responsible for myocardial damage. Conditioning, a potential cardio-protective tool during on-pump cardiac surgery, has hardly been investigated in the context of off-pump surgery. There are virtually no large trials on remote ischemic preconditioning and the majority of reports have focused on central ischemic conditioning. Similarly, volatile anesthetic agents with conditioning effect like ischemic preconditioning have been shown to reduce cardiac injury during on-pump procedures but have not been validated in the off-pump scenario. Here, we review the available evidence on myocardial conditioning, either with ischemia/reperfusion or volatile anesthetic agents in patients undergoing off-pump coronary artery surgery.

Keywords

Off-pump coronary artery bypass Ischemic preconditioning Volatile anaesthetics

Review

Conditioning is an umbrella definition that consists of pre-conditioning, per-conditioning and post-conditioning [1]. Conditioning can be elicited remotely (e.g. at the level of a limb) [2] or centrally (e.g. at the level of the heart) [3]. Stimulus normally consists of an ischemic period followed by reperfusion [4], but other triggers like pain-stimulus [5], hyperbaric oxygen [6] and most importantly methods such as volatile anesthetics [7] have been advocated as being equally effective. Conditioning has been experimented in cardiac surgery mainly in the form of remote ischemic preconditioning (RIPC) and the majority of the largest trials have been in on-pump CABG patients (ONCAB) [8] or during valve surgery [9]. RIPC seems to lowers troponin release in patients undergoing ONCAB (‘proof of concept’), but still unclear is if this leads to any better clinical outcome. RIP Heart-Study will recruit over 2000 on-pump patients and will include as primary outcomes all-cause mortality, non-fatal MI, any new stroke and/or acute renal failure [10] and the ERICCA [11] trial will establish if there would be better clinical outcome in on-pump high-risk patients. However, it is still an open question whether conditioning has potential benefits in patients undergoing OPCAB in terms of lowering troponin release and improving clinical outcomes. Ischemia during OPCAB can happen in 10% of cases [12] with ST segment elevation in up to 40% of patients [13]. Although the use of intra-coronary shunts can reduce the ischemic time, even short-term regional ischemic periods or heart manipulations can result in myocardial injury [14], and subsequent arrhythmias and/or hemodynamic instability which can lead even to conversion to ONCAB [15].

Several reports on the use of volatile anesthetics cardio-protective agents in ONCAB surgery have suggested a similar ischemic preconditioning effect. However, only small trials have investigated the effect of anaesthetic preconditioning in OPCAB. The use of alternative methods such as adenosine, hyperbaric oxygen or temperature in OPCAB is also yet to be validated. Optimizing protection of the heart from ischemia/reperfusion injury (I/R) during OPCAB is, therefore, a worthwhile goal.

Ischemic conditioning in OPCAB

Although there are evidences supporting the benefits of ischemic preconditioning (IP) in terms of cardio-protection, its adoption in OPCAB has been relatively limited (Table 1) with just few studies published so far.
Table 1

Studies including ischemic conditioning

Author, date, journal and country study type

Patient group

Type of conditioning

Outcomes

Key results

Comments

Joung et al. (2013) Korean J Anestesiol, Korea [16] Prospective controlled randomized trial

Seventy OPCAB

RIPC 4 cycles of 5 min ischemia and 5 min of reperfusion before coronary artery anastomoses

Six cognitive function test day 1 after surgery

Post-operative cognitive dysfunction was 28.6% (10 pts) and 31.4% (11 pts) in RIPC and Control group respectively

RIPC did not reduce incidence of post-op cognitive dysfunction after OPCABG during the immediate post-op period

35 RIPC

35 Control

Forouzannia et al. (2013) J The Univ Heart Ctr, Iran [17] Prospective controlled randomized trial

Sixty OPCAB

Adenosine.

Post-op EF

IP and adenosine did not elicit statistically significant EF preservation compared to the control group

No difference found in post-op EF and enzymes release in between groups. Incidence of arrhythmias was higher in the IP group but did not reach statistical significance

20 Adenosine

IP induced with twice 2 min LAD occlusion followed 3 min reperfusion before the first anastomosis

Arrhythmias

20 IP

Troponin/CK-MB

20 Control

Hong et al. (2012) Circulation Journal, Japan [18] Prospective controlled randomized trial

Seventy OPCAB

Lower limb 4 cycles of 5 min ischemia and 5 min of reperfusion before anastomoses (RIPC) and after anastomoses (RIPostC)

Troponin release

RIPC + RIPostC significantly reduced postoperative serum troponin I levels

RIPC + RIPostC decreased postoperative myocardial enzyme elevation by almost half postoperatively in patients undergoing OPCAB

35 RIPC + RIPpostC

35 Control

Hong et al. (2010)] Anaesth Intensive Care, Korea [19] Prospective randomized controlled trial

130 OPCAB

Upper limb 4 cycles of 5 min ischemia and 5 min of reperfusion after anesthesia

Troponin release

Troponin release was lower in the RIPC group but was not statistically significant

RIPC did not reduce significantly post-operative myocardial enzyme release

65 RIPC

65 Control

Succi et al. (2010) Arq Bras Cardiol, Brasil [20] Prospective controlled randomized trial

Forty OPCAB

IP induced with twice 1 min LAD occlusion followed 2 min reperfusion before the anastomosis

Intra-op EF (measured pulsed Doppler of the descending thoracic aorta)

Acceleration of the aortic blood flow with no differences in between groups; IP group maintained left ventricular contractility during the entire procedure while the control group presented significant reduction in left ventricular contractility

IP prevented the decrease in left ventricular contractility during off-pump myocardial revascularization surgery

0 IP

20 Control

Drenger et al. (2008) Journal of Cardiothoracic and Vascular Anesthesia, Israel [21] Prospective controlled randomized trial

Twenty five OPCAB

IP induced with single 5 min LAD occlusion followed by 5 min reperfusion 1.6% ENF started 15 min before LAD occlusion

Myocardial metabolism

Lactate production in the ENF group decreased significantly compared with control and IP groups. Oxygen utilization in the control was 44% higher than the other two groups. Early recovery of anterior wall hypokinesis in both study group

Application of methods such as IP or volatile anesthesia appeared to reduce the metabolic deficit

8 Control

9 IP

8 Enflurane

Wu et al. (2003) Journal of Cardiothoracic and Vascular Anesthesia, Finland [22] Prospective controlled randomized trial

Thirty two OPCAB

IP induced with twice 2 min LAD occlusion followed 3 min reperfusion before the first anastomosis

Incidence of post-operative arrhythmias

IP suppressed the HR elevation during the time of myocardial ischemia and reperfusion and significantly reduced the incidence of VT after surgery. Incidence of SVT during 2 to 24 hours after surgery was lower in the IP patients but incidence of SVES, VES, and AF were similar between the 2 groups

Arrhythmia was a common phenomenon during and after OPCAB procedure; IP protocol significantly suppressed HR elevation, episodes of SVT, and incidence of VT after surgery but incidence of post-op AF was similar in between groups

16 IP

16 Control

Doi et al. (2003) Jpn J Thorac Cardiovasc Surg, Japan [23] Prospective observational study

Forty-five OPCAB (MIDCAB)

IP induced with 5 min vessel occlusion followed 5 min reperfusion before anastomosis

phiL/phiT, QT, JT dispersions before, during and after IP and during and after coronary anastomosis

Anisotropy was exaggerated during the 5-minute coronary occlusion; during anastomosis, conduction velocities were decreased, but showed no further deterioration; QT and JT dispersions were improved by reperfusion

Anisotropy and dispersions were minimized after IP, therefore IP demonstrated antiarrhythmic protective effects on the human myocardium

Laurikka et al. (2003) Chest, Finland [14] Prospective controlled randomized trial

Thirty-two OPCAB

IP induced with cycle of twice 2 min LAD occlusion followed 3 min reperfusion before the first anastomosis

Myocardial performance

IP group had complete recovery of mean after the operation; in the control subjects, mean SVI showed a significant reduction postoperatively

IP tended to decrease the immediate myocardial enzyme release, prohibited the postoperative increase in HR, and enhanced the recovery of SVI

16 IP

16 Control

Matsumoto et al. (2001) Kyobu Geka, Japan [24] Retrospective observational study

Forty-three OPCAB

IP induced with twice 5 min vessel occlusion followed 5 min reperfusion before anastomosis Allopurinol preoperatively and nicorandil intraoperatively;

Myocardial tissue oxygen saturation

Troponin level was statistically significant lower in the IP group

On day 1 post op, the increase in the mean HR was also significantly lower in the IP group

Significant amelioration of post-ischemic recovery in the IP + pharmacological preconditioning

Concomitant use of IP and KATP opener, oxidative radical scavenger both ameliorated cardiac dysfunction during ischemia in anastomotic occlusion of the coronary artery and improved the post-ischemic functional recovery

12 IP

29 IP+pharmacological

Post-ischemic functional recovery

van Aarnhem et al. (1999) Eur J Cardiothorac Surg, The Netherlands [12] Retrospective observational study

Two-hundred OPCAB

IP induced with 5 min of local coronary artery occlusion and 5 min of reperfusion before anastomosis

Ischemia during temporary coronary artery occlusions

Ischemia (defined as defined as > 1 mm S-T segment) occurred during 35 (10%) temporary coronary artery occlusions

Temporary segmental occlusion was safe before anastomosis in OPCAB; shunts were used in critical ischemia

Ischemic dysfunction was precipitated by the 5-min LAD occlusion, as shown by the increase in LVWMS and PA pressure. However, a 5-min coronary occlusion and the resulting ischemia did not alter regional LV systolic function during subsequent ischemia

There were no perioperative MI/no conversion to ONCAB LVWMS decreased significantly after first cycle but improved after IP No significant differences in pulmonary artery pressures were after IP and during anastomosis

Malkowski (1998) J Am Coll Cardiol (USA) [13] Prospective observational study

Seventeen OPCAB (MIDCAB)

IP induced with 5 min of local coronary artery occlusion and 5 min of reperfusion

LVWMS

PA systolic and diastolic pressure

AF: Atrial fibrillation; IP: Ischemic preconditioning; I/R: Ischemia reperfusion; LAD: Left anterior descending artery; LVWMS: Left ventricle wall motion score; MIDCAB: Minimally invasive direct coronary artery bypass grafting; ONCAB: On-pump CABG; OPCAB: Off-pump CABG; phiL/phiT: Ratio of longitudinal to transverse conduction velocity PostC: Postconditioning; RIPC: Ischemic remote preconditioning; SVI: Stroke volume index; SS: Sevoflurane.

Malkowsky et al. [13] induced IP with 5 minutes of local coronary artery occlusion and 5 minutes of reperfusion in a series of 17 single vessel OPCAB patients. Left anterior descending artery (LAD) occlusion/reperfusion increased left ventricle wall motion score (LVWMS) and pulmonary pressure (PA). However, subsequent ischemia during the construction of the anastomosis did not alter the regional LV systolic function. van Aarnhem et al. [12] retrospectively reviewed a cohort of 200 OPCAB patients in whom ischemic preconditioning was used before anastomosis by occluding the vessel for 5 minutes and then allowing 5 minutes of reperfusion. They reported a 10% incidence of-intra operative ischemia (defined as 1 mm ST segment elevation) but no perioperative myocardial injury. Intra–coronary shunts were used in case of critical ischemia and no conversion to ONCAB was observed. Laurikka et al. [14] showed that IP, induced with two cycles of 2 minutes left anterior descending artery occlusion (LAD) followed by 3 minutes of reperfusion before the first coronary artery anastomosis, decreased the immediate myocardial enzyme release, reduced the post-operative increase in HR, and enhanced the recovery of volume index after surgery. Doy et al. demonstrated that a single cycle of 5 minutes of central I/R attenuated ischemia-induced electrophysiological changes in patients undergoing MIDCAB [23]. Wu et al. [22] reported that IP, induced by to cycles of 2 minutes occlusion of LAD followed by reperfusion, led to a positive suppression of HR and reduced the incidence of supra-ventricular and ventricular arrhythmias, although the incidence of post-operative atrial fibrillation (AF) remained similar between preconditioned and non-preconditioned groups. Drengen et al. [21] compared prospectively a cohort of patients preconditioned with a single cycle of 5 minutes of LAD occlusion followed by 5 minutes of reperfusion and a cohort preconditioned with 1.6% enflurane with a non-preconditioned group. They reported a significant reduction of metabolic deficit in both the IP and volatile groups compared to the non-preconditioned group [21]. Hong et al. [19] carried out a prospective controlled randomized trial on RIPC in patients undergoing OPCAB. Remote ischemic preconditioning was elicited with 4 cycles of 5 min upper limb ischemia and 5 min of reperfusion after anesthesia. Troponin release was lower in the RIPC group but did not reach statistical significance (p = 0.172) [19]. Succi et al. [20] reported that IP, induced only by 1 minutes of LAD occlusion followed by 2 minutes of reperfusion before anastomosis prevented decrease in left ventricular contractility Hong et al. [18] used both RIPC and postconditioning (PostC) in a cohort of 35 OPCAB patients. Ischemic remote preconditioning and PostC were elicited with 4 cycles of 5 minutes of ischemia and 5 minutes of reperfusion of the lower limb before and after anastomosis. They reported a significant decrease in post-operative myocardial enzymes. Forouzinna et al. [17] prospectively compared patients preconditioned either with adenosine or with 2 cycles of 2 minutes of LAD occlusion followed by reperfusion with a non preconditioned control group. They reported no differences in terms of post-operative EF and enzyme release but the incidence of post-operative AF was higher in the IP group although it did not reach statistical significance. A recent pilot study by Jung et al. focusing on neurological outcome did not show any benefits of RIPC in patients undergoing OPCAB in terms of cognitive outcomes [16].

Volatile anesthetic agents conditioning in OPCAB

Several reports investigating the potential use of volatile anesthetics as preconditioning agents in OPCAB (Table 2) have reported rather different results. Sevoflurane was found to reduce troponin release in three trials [25-27], although Orriach et al. used sevoflurane as well as post-conditioning agent, extending its administration during the first post-operative hours [25]. No differences in troponin release were reported by other authors when sevoflurane was compared to desflurane and propofol [28], to propofol in a remifentanil-based anesthesia regime [29,30] and to isoflurane alone [31,32]. Sevoflurane was also showed to have several other benefits: better antioxidative properties than propofol [33], reduced incidence of arrhythmias compared to desflurane [34], better preservation of cardiac function compared to control and to propofol [35,36] and to reduced NBP release and plasma protein A release when compared to propofol [37]. Isoflurane was reported to reduce troponin release when compared to propofol [38] but no differences were found when compared to sevoflurane [31,32]. Other authors on the contrary did not find differences in terms of troponin release when it was compared to a propofol group of patients [39]. Desflurane was reported to improve LSWI when compared to a propofol anesthetic regime, although no differences in troponin release were observed [40], and moreover was found to be less effective in reducing incidence of arrhythmias than sevoflurane [34]. Guarracino et al. observed a significant reduction in troponin release in a cohort of 57 patients anesthetized with desflurane [41]. Finally, remifentanil was found to have a preconditioning effect by lowering troponin release [42], however no differences were reported when was associated with sevoflurane and compared to propofol [30].
Table 2

Studies including anaesthetics agents

Mroziński et al. (2014) Anaesthesiol Intensive Ther, Poland [40] Prospective randomized open-label trial

Sixty OPCAB 28 Propofol 32 Desflurane

DES PP

Assessment of hemodynamic function and myocardial injury markers

DES group demonstrated improved stability, expressed as LVSWI; no differences in myocardial injury in between groups

No difference reported between DES and PP in major haemodynamic parameters, myocardial injury markers and the long-term outcome; DES might accelerate LVSWI recovery

Orriach et al. (2013) J Crit Care, Spain [25] Prospective randomized trial

Sixty OPCAB

SS and PP (intra-op and post op as postconditioning)

BNP Troponin release Need for inotropic drugs

SS group had reduced BNP, troponin release and number of inotropic drugs Compared to S-P and P-P groups

SS administration in OR and CICU, decreased troponin release compared with SS intra-op, but both were a better option to decrease troponin level when compared to PP

20

Sevoflurane/Sevoflurane (S-S)

20 Sevoflurane/Propofol (S-P) 20 Propofol/Propofol (P-P)

Wang et al. (2013) Scand Cardiovasc J, China [26] Prospective randomized controlled trial

Forty-eight OPCAB

SS

BNP

SS significantly decreased post-surgical troponin levels No significant differences in BNP level among groups

SS exerted significant myocardial protective effect; BNP could not predict myocardial protective effect of SS in OPCAB

20 Sevoflurane

 

Troponin release

20 Control

Suryaprakash et al. (2013) Ann Card Anaesth, India [28] Prospective randomized trial

One hundred thirty

SS

Troponin release

Changes in troponin levels at all time intervals were comparable in the three groups

No difference found in myocardial protection with SS or DES or PP

nine OPCAB

DES

48 Sevoflurane

PP

52 Desflurane

39 Propofol

Tempe et al. (2011) J Cardiothorac Vasc Anesth, India [38] Prospective randomized trial

Forty-five OPCAB

ISO

Troponin release

Troponin release in the PP group was significantly higher than the ISO group at 6 and 24 hours after surgery

ISO provided protection against myocardial damage by lowering levels of troponin-T

Isoflurane

PP

Propofol

Ballester et al. (2011) Eur J Anaesthesiol, Spain [33] Prospective controlled randomized trial

Thirty-eight OPCAB

SS

Markers of lipoperoxidation (F2-isoprostanes) and nitrosative stress (nitrates/nitrites) measured in coronary sinus blood

F2-isoprostanes concentrations were significant lower in the SS group at all different time point

SS showed better antioxidative properties than PP

20 Sevoflurane

PP

18 Propofol

Kim et al. (2011) Anaesth Intensive Care, Korea [29] Prospective randomized controlled trial

Ninety-four OPCAB

SS

CK MB and troponin release

No statistically differences in between groups in terms of CK-MB and troponin release at different end points

SS and PP had similar CK-MB and troponin values

47 Sevoflurane

PP

47 Propofol

(both in a remifentanil based anesthesia)

Hammerling et al. (2010) Ann Card Anaesth Canada [34] Prospective double blinded trial

Forty OPCAB

SS

Incidence of arrhythmias

Supraventricular tachycardia occurred only in the DES-group, AF was significantly more frequent in the DES group versus SEVO-group

SS found to be more advantageous than DES, as it was associated with less AF or supraventricular arrhythmias

20 Sevoflurane

DES

20 Desflurane

Xu (2009) J South Med Univ, China [42] Prospective controlled randomized trial

Twenty four OPCAB

REMI

Troponin release

Statistically significant reduction of troponin level in the REMI group

Troponin levels of REMI preconditioning group were markedly decreased after the operation in comparison with those of the control group

12 Remifentanil

12 Control

Drenger et al. (2008) Journal of Cardiothoracic and Vascular Anesthesia, Israel [21] Prospective controlled randomized trial

Twenty five OPCAB

IP induced with single 5 min LAD occlusion followed by 5 min reperfusion 1.6% ENF started 15 min before LAD occlusion

Myocardial metabolism

Lactate production in the ENF group decreased significantly compared with control and IP groups. Oxygen utilization in the control group was 44% higher than the other two groups Early recovery of anterior wall hypokinesis in both study groups

Application of methods such as IP or volatile anesthesia appeared to reduce the metabolic deficit

8 Control

9 IP

8 Enflurane

Hemmerling (2008) European Journal of Anaesthesiology, Canada [31] Prospective randomised trial

Fourty OPCAB

SS

Troponin/CK-MB

No differences in terms of enzymes release, heart contractility and haemodynamic values Extubation time was significantly shorter with SS compared to ISO

SS and ISO provided the same ischaemic cardio-protective effects; SEVO allowed a more rapid recovery from anaesthesia

20 Sevoflurane

ISO

LVWM abnormalities time to extubation/respiratory functions haemodynamic parameters

20 Isoflurane

Huseidzinović et al. (2007) Croat Med J, Croatia [35] Prospective randomised controlled trial

32 OPCABG

SS

Acceleration of aortic blood flow, CI, HR, mean arterial pressure, and central venous pressure at different time points

SS group showed better CI values at the beginning of ischemia and 15 minutes after ischemia; in the PP group acceleration decreased and remained lower 15 minutes after sternal closure while was increased in the SS group

Cardiac function was better preserved in patients with SS than with PP

16 Sevoflurane

16 Control

Venkatesh et al. (2007) Ann Card Anaesth, India [32] Prospective randomized

Forty OPCAB

SS

Haemodynamic effects amount of analgesia needed postoperative recovery

No differences identified in terms of haemodynamic parameters, depth of anesthesia, and quantity of agent needed; time of awakening and subsequent extubation were significantly less with SS

SS and ISO could both safely used in OPCAB; awakening and extubation time were significantly lower with SS.

20 Isoflurane

ISO

20 Sevoflurne

Lucchinetti et al. (2007) Anesthesiology, Switzerland [37] Prospective randomised trial

20 OPCAB

SS

Troponin, NBP and associate pregnancy-associated plasma protein A release Gene expression profile (atrial biopsies)

NPB and protein A were decrease in SS group; Echo showed preserved post-op LV function in SS group.

SS gene regulatory control of myocardial substrate metabolism predicted postoperative cardiac function in OPCAB patients

10 Propofol

PP

10 Sevoflurane

Guarracino et al. (2006) Journal of Cardiothoracic and Vascular Anesthesia, Italy [41] Prospective randomised trial

One hundred twelve

DES

Troponin release

Post-op peak troponin was significantly lower in DES group

Myocardial damage measured by cardiac troponin release could be reduced by DES during OPCAB

OPCAB

PP

57 Desflurane

(in addition to opiate-based anesthesia)

55 Propofol

Law-Koune (2006) J Cardiothorac Vasc Anesth, France [30] Prospective randomized trial

Eighteen OPCAB

SS-REMI

Troponin release

No difference in troponin release

Study did not support cardio-protective effects of SS

9 Sevoflurane-remifentanil

PP-REMI

9 Propofol-remifentanil

Bein et al. (2005) Anesth Analg, Germany [43] Prospective randomized trial

Fifty-two OPCAB (MIDCAB)

SS

Myocardial function

Myocardial performance index and early to atrial filling velocity ratio in the PP group deteriorated significantly whereas there was no change in the SS group

In patients undergoing MIDCAB surgery, SS preserved myocardial function better than PP

26 Sevoflurane

PP

26 Propofol

 

Kendall (2004) Anaesthesia, UK [39] Prospective randomized trial

Thirty OPCAB

PP

Troponin release

No significant difference in between groups

No support of ISO as cardioprotective agent was reported

10 Propofol

ISO

10 Isoflurane

ISO/high thoracic epidural analgesia

10 Isoflurane and high thoracic epidural analgesia

Conzen et al. (2003) Anesthesiology, Germany [27] Prospective randomized trial

Twenty OPCAB

SS

Troponin release

Troponin increased significantly more in the PP group rather than in the SS group

Patients receiving SS had less myocardial injury during the first 24 post-op hours than patients with PP

10 Sevoflurane

10 Propofol

AF: Atrial fibrillation; BNP: Brain natriuretic peptide ONCAB: On pump Coronary Artery By-pass Grafting; OPCAB: Off pump Coronary Artery By-pass Grafting; DES: Desflurane IP: Ischemic preconditioning; LAD: Left anterior descending artery; LVWMS: Left ventricle wall motion score; MIDCAB: Minimally invasive direct coronary artery bypass grafting; PostC: Postconditioning; SS: Sevoflurane.

Alternative way to standard conditioning in OPCAB

There have been few reports on the use of adenosine as preconditioning agent in OPCAB. Forouzinna et al. [17] reported no differences between preconditioned and non preconditioned groups in terms of EF and troponin release. Li et al. [6] randomized a small number of patients to on and off-pump to be preconditioned with the use of hyperbaric oxygen (HBO). Patients in the preconditioning group underwent HBO for 70 min/daily for 5 consecutive days before surgery. Preconditioning with HBO resulted in both cerebral and cardiac protective effects as determined by biochemical markers of neuronal and myocardial injury and clinical outcomes in patients undergoing ONCAB while no benefits were observed in the OPCAB group. Matsumoto et al. [24] reviewed a cohort of 48 OPCAB patients. Among them, the subgroup treated with IP plus allopurinol and nicorandil had an improved post-ischemic functional recovery after surgery.

Myocardial conditioning in cardiac surgery can be achieved in different ways. The most used are central or remote preconditioning and volatile anesthetics, while adenosine or other pharmacological agents less frequently used. Ischemic conditioning was first reported in 1986 [4] and conditioning by volatile anesthetic with halothane in 1976 [44]. Although different, both techniques share probably some common mechanisms of action and, most importantly, can be used simultaneously. Both have been frequently utilized in ONCAB [45], but with regard of OPCAB surgery no large trials have been published so far evaluating their effect on troponin [19] or clinical outcomes. Moreover, according to clinical trial.gov [46], while there are different trials in different phases, registered and ongoing, investigating the effect of RIPC in ONCABG (isolated or plus/minus valve surgery) the only trial aiming to compare the effect of RIPC on ON and OFF-pump CABG is the RIP-CON study, expected to report in June 2015 [47]. Small trials are present in the literature, focusing on the effect of RIPC on different subsystem outcomes. Joung et al. [16] randomised 70 OPCAB patients to RIPC and control with cognitive function as primary end points. Hong et al. reported no differences in terms of troponin release in OPCAB after RIPC [19]. Same Authors [18], however, studied the effect of RIPC and PostC together and they observed, this time, a reduction of troponin release in a series of OPCAB. All the other trials [13,14,17,20-22,48] carried out in OPCAB with conditioning used ‘central preconditioning’, hence eliciting protection by cycles of occlusion/reperfusion at the level of targeted vessel. All of them led to different and non-homogeneous results. Central remote ischemic preconditioning has been, however, fairly dismissed in on pump cardiac surgery and during interventional cardiology procedure for its impracticality and its high level of invasiveness [2,3,49]. It is important to stress that some of the RIPC and central IP trials did not state the type of anesthesia used [13,23], or deliberately used propofol as anesthetic maintenance [12,16-18,20], while very few did not use it [19,21,22]. Recently it has been reported that propofol may inhibit preconditioning effect, and large trials have intentionally avoided it use [50].

Since the first report in 1976 [44] volatile anaesthetics have been frequently used as conditioning techniques in ONCAB. Two large meta-analyses from 2006 [51,52] have suggested that there was a significant difference in in patients who received volatile agents in terms of reduced troponin release, improved CI, less use of inotropes and reduced need of mechanical ventilation. However they did not point out any differences with regards of mortality, LOS and myocardial infarction rate. Moreover a relatively recent review [53] has reported that sevoflurane had beneficial effects only in naïve patients with no previous exposures to episode of angina. Although there is sufficient evidence to support the use of volatile agents during cardiac surgery and taking into account their feasibility to be used as pre, per and post conditioning with the potential to prolong the protective effect [25], no large trials have been set in place in order to identify potential benefits in patients undergoing OPCAB. Up till now there are 17 trials comparing different volatile anesthetics vs propofol or vs control or volatiles among themself but the vast majority of them were underpowered and led to conflictive results (Table 2). Sevoflurane is proven to reduce troponin level after on-pump surgery but its effect is still unclear in the off-pump scenario. With regard to OPCAB, sevoflurane was found to preserve cardiac function in three studies [35,37,54], to reduce troponin release in two studies [26,27], to have antioxidant properties in one [33] and to prevent incidence of arrhythmias in one [34]. On the contrary sevoflurane did not show any better troponin reduction when compared to other agents in four studies [28-31]. Only Orriach et al. used sevoflurane during and after the operation as post-conditioning and reported a significant reduction in troponin release [25].

Conclusions

Although OPCAB is thought to reduce the extent of general ischemia, ischemic cardiac insult can be found in up to 10% of the patients [12]. Data coming from the largest pooled analysis on mainly on-pump experience reported a trend toward a consistent reduction of almost a half of MI in RIPC groups [55]; hence there may be the theoretical potential to translate the same advantage to off-pump patients. However, up till now there are no strong evidences supporting the use of ischemic preconditioning, either central or remote, in OPCAB patients.

In terms of volatile anaesthetics, taking into account all the trials, we can conclude here that has not yet been demonstrated if they can reduce troponin level after off-pump surgery. Other forms of conditioning used in OPCAB such as adenosine/HBO/pharmacological have been used and some times in association with IP, but led to different conclusions. Conditioning, either elicited by ischemia/reperfusion or by volatile agents, may theoretically be a valid method to increase cardiac protection in off-pump surgery, but further trials are definitely needed.

Abbreviations

AF: 

Atrial fibrillation

BNP: 

Brain natriuretic peptide

CABG: 

Coronary Artery By-pass Grafting

DES: 

Desflurane

HBO: 

Hyperbaric oxygen

IP: 

Ischemic preconditioning

I/R: 

Ischemia reperfusion

LAD: 

Left anterior descending artery

LVWMS: 

Left ventricle wall motion score

MIDCAB: 

Minimally invasive direct coronary artery bypass grafting

ONCAB: 

On-pump CABG

OPCAB: 

Off-pump CABG

phiL /phiT: 

Ratio of longitudinal to transverse conduction velocity

PostC: 

Postconditioning

RIPC: 

Ischemic remote preconditioning

SVI: 

Stroke volume index

SS: 

Sevoflurane

TIVA: 

Total intra-venous anesthesia

Declarations

Authors’ Affiliations

(1)
NHLI, Hammersmith Hospital, Imperial College London
(2)
Fondazione Monasterio, Ospedale Pasquinucci
(3)
Bristol Heart Institute, University of Bristol

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