Recent publications have described the association of the MECC with minimal activation of inflammation and coagulopathy, less hemodilution with low blood transfusion, and a low incidence of cerebral stroke [8, 20, 21]. The SIRS is a complex multifactorial syndrome that is known to be ­associated with ECC. The SIRS to ECC is initiated by many aggressive factors, including surgical trauma, blood contact with nonendothelial surfaces, cardioplegia, and ischemia-reperfusion injury [22–24]. Several blood elements, such as neutrophils, monocytes, endothelial cells, platelets, and complement proteins, are involved in the SIRS. When activated, these blood components release cytotoxic and vasoactive substances, produce inflammatory and inhibitory cytokines, and express cell receptors interacting with specific cellular substance [24]. Therefore, when the SIRS has been initiated, several inflammatory mediators, including anti- and proinflammatory cytokines, could be associated with a worse postoperative course.

Cytokines are small proinflammatory peptides strongly involved in the myocardial stunning process and in multiorgan failure syndrome [23]. Important cytokines involved in the SIRS are interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and soluble CD 40 ligand (sCD40L).

IL-1β is produced mainly by monocytes. This cytokine derives from IL-1 by the action of the IL-1β-converting enzyme. An increase of IL-1β was found after ECC with a peak concentration after 24 h [5].

IL-6 is produced and released by the monocytes and endothelial cells following a stimulus by IL-1 and TNF-α. IL-6 has its peak concentration a few hours after the end of ECC and gradually decreases within the following 24 h [5, 10, 16]. The IL-6 concentration also increases after major noncardiac operations, and the peak concentration occurs 6–24 h after the end of the operation.

TNF-α is a cytokine produced by neutrophils and monocytes. A significant increase of TNF-α was shown after removal of the cross clamp, and a peak concentration is reached 24 h after the end of ECC. TNF-α has a negative inotropic effect, and the myocardium is a major source after ischemic reperfusion injury.

sCD40L is produced by activated platelets and upregulates the expression of inflammatory adhesion receptors including E-selectin, VCAM-1, tissue factor, and matrix metalloproteinases [25]. Furthermore, sCD40L has been described as a major mediator of vascular inflammation [26]. Plasma levels of CD40L increased within 1 h on ECC and increased by fourfold after 2 h [25]. A high preoperative level of CD40L was associated with a high risk of postoperative atrial fibrillation in patients who underwent off-pump myocardial revascularization [27].

At this time, there are not many publications comparing MECC to off-pump surgery, and obviously many further ­randomized studies are needed to verify the superiority of one technique over the other. The few studies available did not identify significant differences between the two techniques in terms of hospital mortality, neurocognitive disturbance, triggering of SIRS, blood loss and transfusion requirements, and rate of postoperative atrial fibrillation.

In-hospital mortality did not differ among the different studies. Puehler et al. [9] did not find significant in-hospital mortality in patients undergoing CABG with MECC or cECC or off-pump surgery. Each group had 558 patients, and overall in-hospital mortality in the MECC group was 3.22 % compared to the off-pump group, which was 3.76 %. However, in a subgroup of an emergent population, the in-hospital mortality of the MECC group was significantly lower than that of the off-pump group (5.6 and 10.7 %, respectively). However the in-hospital mortality ranged between 0 and 5.4 % in the different studies [8, 16, 19, 28].

SIRS, hemolysis, and coagulopathy are among the most studied events in the studies comparing MECC to off-pump surgery. Wippermann et al. [16] reported no significant changes in prothrombin fragment 1.2 levels, interleukin 6 releases, and plasmin-antiplasmin complex levels between the MECC and off-pump groups over the immediate postoperative course. Instead, they found a significant difference when these two groups were compared to cECC patients. Van Boven et al. [29] reported no differences in serum concentrations of malondialdehyde, allantoin/urate ratios, and lung epithelium-specific proteins (CC16) in MECC compared to off-pump patients. The release of these biomarkers was higher in cECC patients, and they speculated that the oxidative stress parameters showed a tendency toward improved global organ protection in MECC and off-pump patients compared to cECC patients.

Mazzei et al. [13] compared interleukin 6 and serum S-100 protein levels between MECC and off-pump surgery in a prospective randomized trial. No differences were reported in terms of release of these biomarkers over a 24 h period, and this evidence suggests that off-pump surgery and MECC with cardioplegic arrest should be considered equivalent tools.

Recently, Formica et al. [8] in a prospective randomized study evaluated the release of tumor necrosis factor-α and interleukin 6 in a group of patients operated on with MECC compared to off-pump surgery. They observed a higher release of interleukin 6 in off-pump surgery than in MECC surgery 24 h after the operation, whereas levels of tumor necrosis factor-α were not different in the two groups. Moreover, the authors observed no difference in the cardiac release of these cytokines in the two groups. The authors suggested that, according to their findings, MECC can be used extensively in all patients with multivessel disease in whom off-pump surgery could have more operative risks.

Neurocognitive disturbance and cerebrovascular events such as stroke/transient ischemic attack can seriously complicated the postoperative course of patients undergoing coronary surgery. It has been recognized that off-pump surgery is associated with a lower incidence of cerebral stroke when compared to CABG with ECC, above all in patients who have undergone off-pump surgery with the no-touch aorta technique. At this time, no reports exist showing evidence of an increased rate of neurological sequelae in MECC patients. However, neurological complications are always caused by multifactorial events such as micro- and macroembolizations, cerebral hypoperfusion, cerebrovasculopathy, and carotid disease, and for this reason, it is not possible to find a direct correlation between MECC and postoperative neurological outcome.

At the present time, few studies study have primarily investigated the incidence of postoperative atrial fibrillation (AF) in MECC compared to off-pump surgery. In their study, Panday et al. [30] reported a lower incidence of postoperative AF in the MECC and off-pump groups (25 and 21.7 %, respectively) compared to the cECC group (35.6 %). Other authors reported a very low incidence of postoperative atrial fibrillation without differences in the MECC, off-pump, and cEE groups (3.6, 3.9, and 5.4 %, respectively) [9]. Formica et al. [8] reported no significant difference in the incidence of AF, but the rate of AF in the MECC group was higher than in the off-pump group (40 and 23.3 %, respectively; p  =  0.9). Postoperative AF is considered a multifactorial complication in which hypoglycemia due to hemodilution, release of proinflammatory cytokines, need for blood, and advanced age can be associated with the development of this event.

Completeness of revascularization, reoperation for graft failure, and composite outcome at midterm are considered some of the main weaknesses of off-pump surgery. Some recent large trials compared off-pump surgery to cECC and reported survival of less than 10 years for off-pump surgery [31], more early reinterventions after the off-pump procedure [32], fewer grafts performed, poorer long-term graft patency, and increased incidence of composite outcome (death and major cardiac events) in off-pump surgery [3]. These results have led to less acceptance of off-pump surgery worldwide. Formica et al. [8] reported fewer grafts performed and less use of bilateral internal arteries in off-pump surgery compared to MECC. Other authors reported similar findings [13, 19, 33]. With MECC surgery, the incidence of complete revascularization and total arterial myocardial revascularization is higher because, like with cECC, the handling of the heart during coronary anastomosis is safer with the MECC even in unstable patients with a dilated and dysfunctional left heart. Currently, only one randomized trial has focused on 1-year follow-up in MECC and off-pump patients. In this trial, the authors reported no difference in the incidence of death and recurrence of angina in both groups, and the incidence of both events was low [13].

Perioperative blood transfusions are one of the most common events that physicians encounter clinically. Among the factors that increase the incidence of the red cell requirement, the most reported include advancing age, redo surgery, the preoperative use of anti-platelet agents, preoperative hemodilution, and other non-cardiac causes such as renal dysfunction and lessr impairment [34, 35]. Off-pump CABG has been reported to significantly reduce the mean blood loss and transfusion requirement when compared to cECC [36]. One of the aims of the MECC circuit is to reduce hemodilution and thereby to reduce the need for transfusions. Analysis of the data presently available has shown no significant difference in the mean blood loss or number of patients transfused when MECC is compared to OPCAB [8, 9, 36]. Interestingly, Gerritsen et al. [37] reported a significantly lower blood loss with MECC compared to off-pump surgery. This is most likely because of the different antiplatelets/anticoagulation therapy strategies applied in cardiac units, the variation in anticoagulation strategies employed by the different units, and the more aggressive approach to anticoagulation that is applied by this group.