**4. Clinical application of miniaturized extracorporeal circulation**

Clinical experience with the MECC is rapidly increasing over the last 10 years. Several reports describe the application of MECC in isolated CABG operation; however some reports describe the use of this strategy during aortic valve replacement operation, mitral valve surgery, ascending aorta operation.

#### **4.1 Miniaturized extracorporeal circulation and isolated CABG operation**

Different studies have reported the use of MECC compared to conventional ECC strategy in isolated CABG to demonstrate a clinical superiority of the MECC versus ECC. Actually no clinical benefits of MECC were reported in terms of early mortality and in terms of neurological or renal impairment. The most important differences between MECC and standard ECC that were reported regard the impact of SIRS, the myocardial protection and hemodilution.

Many Authors have conducted randomized studies to compare MECC system with conventional ECC in patients undergoing isolated CABG operations. Fromes et al. (Fromes 2002) reported a series of 60 patients divided into two groups. They demonstrated that in both MECC and standard ECC groups the monocyte count drops following the initiation of bypass and then increases again during the next 24 hours. The drop in monocyte count was greater in standard ECC group probably as a consequent major hemodilution Moreover the MECC group had reduced release of IL-6, TNF-α, neutrophil elastase and S100B. No differences were found in IL-1β or β-thromboglobulin in both groups. In this study Fromes et al measured the release of cytokines at six interval points during and after extracorporeal circulation up to 24 hours postoperatively. Van Boven et al. (Van Boven et al. 2004) measured the levels of malondialdehyde (MDA) and allantoin/urate ratio in 184 patients divided in MECC and standard ECC. They can demonstrate a reduced release of MDA and allantoin/urate ratio in MECC patients. Moreover a significant blood transfusion rate was described in the MECC group. They found also reduced levels of oxidative stress in the MECC patients following the release of the aortic cross clamp. In a cohort of 400 patients, Remady et al. (Remady 2007) demonstrated a higher CRP levels in the standard ECC patients, at 24 and 48 hours, a less hemodilution and a reduced need for blood product transfusion in MECC patients, a higher evidence of focal neurological and renal impairment in standard ECC and a lower release of troponine in MECC groups. In another randomized trial, Skrabal et al (Skrabal et al. 2007) reported lower myocardial damage with lower levels of creatine-kinase MB and troponine T in patients operated on with MECC system. In a prospective randomized multicenter study (El-Essawi et al. 2010), comparing MECC system with conventional ECC, the Authors found statistical differences in need of total transfusion and blood product transfusion. Moreover a lower incidence rate of postoperative atrial fibrillation was detected in MECC group. In a big series of 1.053 patients operated on with the MECC system, Immer et al (Immer et al. 2007) reported a reduced troponine level release, a

adenine dinucleotide phosphate (NADPH), oxidase, superoxide dismutase and nitric oxide dismutase. When the aortic cross clamp is removed, myocardial ischemia is followed by reperfusion, which generates oxidative stress with production of reactive oxidants (O2-,

Clinical experience with the MECC is rapidly increasing over the last 10 years. Several reports describe the application of MECC in isolated CABG operation; however some reports describe the use of this strategy during aortic valve replacement operation, mitral

Different studies have reported the use of MECC compared to conventional ECC strategy in isolated CABG to demonstrate a clinical superiority of the MECC versus ECC. Actually no clinical benefits of MECC were reported in terms of early mortality and in terms of neurological or renal impairment. The most important differences between MECC and standard ECC that were reported regard the impact of SIRS, the myocardial protection and

Many Authors have conducted randomized studies to compare MECC system with conventional ECC in patients undergoing isolated CABG operations. Fromes et al. (Fromes 2002) reported a series of 60 patients divided into two groups. They demonstrated that in both MECC and standard ECC groups the monocyte count drops following the initiation of bypass and then increases again during the next 24 hours. The drop in monocyte count was greater in standard ECC group probably as a consequent major hemodilution Moreover the MECC group had reduced release of IL-6, TNF-α, neutrophil elastase and S100B. No differences were found in IL-1β or β-thromboglobulin in both groups. In this study Fromes et al measured the release of cytokines at six interval points during and after extracorporeal circulation up to 24 hours postoperatively. Van Boven et al. (Van Boven et al. 2004) measured the levels of malondialdehyde (MDA) and allantoin/urate ratio in 184 patients divided in MECC and standard ECC. They can demonstrate a reduced release of MDA and allantoin/urate ratio in MECC patients. Moreover a significant blood transfusion rate was described in the MECC group. They found also reduced levels of oxidative stress in the MECC patients following the release of the aortic cross clamp. In a cohort of 400 patients, Remady et al. (Remady 2007) demonstrated a higher CRP levels in the standard ECC patients, at 24 and 48 hours, a less hemodilution and a reduced need for blood product transfusion in MECC patients, a higher evidence of focal neurological and renal impairment in standard ECC and a lower release of troponine in MECC groups. In another randomized trial, Skrabal et al (Skrabal et al. 2007) reported lower myocardial damage with lower levels of creatine-kinase MB and troponine T in patients operated on with MECC system. In a prospective randomized multicenter study (El-Essawi et al. 2010), comparing MECC system with conventional ECC, the Authors found statistical differences in need of total transfusion and blood product transfusion. Moreover a lower incidence rate of postoperative atrial fibrillation was detected in MECC group. In a big series of 1.053 patients operated on with the MECC system, Immer et al (Immer et al. 2007) reported a reduced troponine level release, a

H2O2, NO and HOCl) by the action of the four enzymes.

valve surgery, ascending aorta operation.

hemodilution.

**4. Clinical application of miniaturized extracorporeal circulation** 

**4.1 Miniaturized extracorporeal circulation and isolated CABG operation** 

reduced postoperative release of IL-6 and also a low incidence of postoperative atrial fibrillation and an early extubation time. Similar results were already reported by others (Wiesenack 2004). In some prospective randomized trials comparing MECC and OPCAB, some Authors did not find dramatic difference between the two techniques. In particular Mazzei et al. (Mazzei et al. 2007) comparing 150 MECC patients with 150 OPCAB patients, found that the mortality and morbidity had not significant difference and the release of IL-6 and S-100 protein were similar in both groups as wel as the length of stay and the use of blood product. In a recent prospective randomized study (Formica et al.2009) we wanted to study the inflammatory response and the myocardial damage in two groups of patients operated either with MECC or with OPCAB technique. We can demonstrate that the releases of cardiac TNF-α and IL-6 from coronary sinus were similar in both groups during the operative period and that the hemoglobin levels were higher in MECC GROUP than in OPCAB after 24 hours. Moreover the production of blood lactate from coronary sinus did not reach statistical difference in both groups. Other Authors (Reber et al. 2010) have observed in a retrospective study that MECC system can guarantee a more complete revascularization compared to OPCAB. In a recent publication (Puelher et al 2011), the outcome of 2243 patients underwent CABG operation with MECC were reported. They found a 30-mortality of 2.3%, and a very low incidence of blood transfusion, need for inotropic support, renal substitute therapy, release of myocardial necrosis enzymes and neurological dysfunction. The rate of conversion from the MECC was extremely low (0.4%).

Other Autrhors (Anastasiadis et al 2011a) have reported better neurocognitive outcome in MECC system compared to conventional ECC on the day of discharge and at 3 months.

#### **4.2 Miniaturized extracorporeal circulation and aortic valve replacement**

The first application of MECC for aortic valve replacement (AVR) was reported by Remady et al (Remady et al. 2004). They applied the MECC system in 45 patients requiring isolated AVR or associated with CABG. The Authors reported a very low 30-day mortality and morbidity incidence rate and considered the MECC system a new cardiopulmonary concept safe and reliable in aortic valve surgery too. Since than few Authors reported the use of MECC for AVR. In a prospective randomized study Remady et al (Remady 2004) reported better clinical results with reduced myocardial damage, good preservation of renal function and better platelets count in MECC group compared than standard ECC group. In another prospective randomized study conducted on a total of 40 patients, Castiglioni et al (Castiglioni et al. 2007) reported better clinical data with lower hemodilution, lower intraoperative blood transfusion and lower postoperative bleeding in the MECC group compared to standard ECC. Furthermore they reported a lower release of troponine in MECC patients than standard ECC groups.

#### **4.3 Miniaturized extracorporeal circulation and other surgical applications**

At the best of our knowledge no other surgical application of MECC are schematically reported in the literature. Some reports (Anastasiadis et al 2011b; Palombo et al. 2004) described the use of MECC in elective thoracoabdominal aortic surgery. They described only 7 cases without any complications. We used the MECC system in few case of CABG associated with mitral valve annuloplasty and in 5 cases of kidney cancer and inferior vena

Miniaturized Extracorporeal Circulation 143

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cava metastathic thrombosis. In this operation, we used the MECC system to cool the patients during the isolation of renal tumor mass. The two surgical equips could work contemporaneously. Once the patients reaches the body temperature of 20 °C, the MECC system was converted in a standard ECC to drained all the blood and arrested the systemic circulation. Once the thrombus was from the inferior vena cava and the vessel was sutured, we restarted the systemic circulation and the standard ECC was converted in MECC system. We preferred to use this strategy to reduce the risk of bleeding from the abdomen, which is very high in such tumoral pathologies.
