Efficacy of Pulsatile Flow Perfusion in Adult Cardiac Surgery: Hemodynamic Energy and Vascular Reactivity.

Background: The role of pulsatile (PP) versus non-pulsatile (NP) flow during a cardiopulmonary bypass (CPB) is still debated. This study's aim was to analyze hemodynamic effects, endothelial reactivity and erythrocytes response during a CPB with PP or NP. Methods: Fifty-two patients undergoing an aortic valve replacement were prospectively randomized for surgery with either PP or NP flow. Pulsatility was evaluated in terms of energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE). Systemic (SVRi) and pulmonary (PVRi) vascular resistances, endothelial markers levels and erythrocyte nitric-oxide synthase (eNOS) activity were collected at different perioperative time-points. Results: In the PP group, the resultant EEP was 7.3% higher than the mean arterial pressure (MAP), which corresponded to 5150 ± 2291 ergs/cm3 of SHE. In the NP group, the EEP and MAP were equal; no SHE was produced. The PP group showed lower SVRi during clamp-time (p = 0.06) and lower PVRi after protamine administration and during first postoperative hours (p = 0.02). Lower SVRi required a higher dosage of norepinephrine in the PP group (p = 0.02). Erythrocyte eNOS activity results were higher in the PP patients (p = 0.04). Renal function was better preserved in the PP group (p = 0.001), whereas other perioperative variables were comparable between the groups. Conclusions: A PP flow during a CPB results in significantly lower SVRi, PVRi and increased eNOS production. The clinical impact of increased perioperative vasopressor requirements in the PP group deserves further evaluation.

Impact on Renal Function and Hospital Outcomes of an Individualized Management of Cardiopulmonary Bypass in Congenital Heart Surgery: A Pilot Study.

During cardiopulmonary bypass (CPB), high flows can allow an adequate perfusion to kidneys, but, on the other hand, they could cause emboli production, increased vascular pressure, and a more intense inflammatory response, which are in turn causes of renal damage. Along with demographic variables, other intra-operative management and post-operative events, this might lead to Acute kidney injury (AKI) in infants undergoing cardiac surgery. The aim of our study was to investigate if a CPB strategy with flow requirements based on monitoring of continuous metabolic and hemodynamic parameters could have an impact on outcomes, with a focus on renal damage. Thirty-four consecutive infants and young children undergoing surgery requiring CPB, comparable as for demographic and patho-physiological profile, were included. In Group A, 16 patients underwent, for a variable period of 20 min, CPB aiming for the minimal flow that could maintain values of MVO2 > 70% and frontal NIRS (both left and right) > 45%, and renal NIRS > 65%. In Group B, 18 patients underwent nominal flows CPB. Tapered CPB allowed for a mean reduction of flows of 34%. No difference in terms of blood-gas analysis, spectroscopy trend, laboratory analyses, and hospital outcome were recorded. In patients developing AKI (20%), renal damage was correlated with demographic characteristics and with renal NIRS during the first 6 h in the ICU. A safe individualized strategy for conduction of CPB, which allows significant flow reduction while maintaining normal hemodynamic and metabolic parameters, does not impact on renal function and hospital outcomes.

Cerebral perfusion strategy in a challenge cerebral vessels debranching.

We present a case of antegrade cerebral perfusion based on a circuit with a centrifugal pump for general open-heart surgery to achieving cerebral protection during a challenging hybrid aortic arch repair.

Selective Cerebro-Myocardial Perfusion in Complex Neonatal Aortic Arch Pathology: Midterm Results.

Aortic arch repair in newborns and infants has traditionally been accomplished using a period of deep hypothermic circulatory arrest. To reduce neurologic and cardiac dysfunction related to circulatory arrest and myocardial ischemia during complex aortic arch surgery, an alternative and novel strategy for cerebro-myocardial protection was recently developed, where regional low-flow perfusion is combined with controlled and independent coronary perfusion. The aim of the present retrospective study was to assess short-term and mid-term results of selective and independent cerebro-myocardial perfusion in neonatal aortic arch surgery. From April 2008 to August 2015, 28 consecutive neonates underwent aortic arch surgery under cerebro-myocardial perfusion. There were 17 male and 11 female, with median age of 15 days (3-30 days) and median body weight of 3 kg (1.6-4.2 kg), 9 (32%) of whom with low body weight (<2.5 kg). The spectrum of pathologies treated was heterogeneous and included 13 neonates having single-stage biventricular repair (46%), 7 staged biventricular repair (25%), and 8 single-ventricle repair (29%). All operations were performed under moderate hypothermia and with a "beating heart and brain." Average cardiopulmonary bypass time was 131 ± 64 min (42-310 min). A period of cardiac arrest to complete intra-cardiac repair was required in nine patients (32%), and circulatory arrest in 1 to repair total anomalous pulmonary venous connection. Average time of splanchnic ischemia during cerebro-myocardial perfusion was 30 ± 11 min (15-69 min). Renal dysfunction, requiring a period of peritoneal dialysis was observed in 10 (36%) patients, while liver dysfunction was noted only in 3 (11%). There were three (11%) early and two late deaths during a median follow-up of 2.9 years (range 6 months-7.7 years), with an actuarial survival of 82% at 7 years. At latest follow-up, no patient showed signs of cardiac or neurologic dysfunction. The present experience shows that a strategy of selective and independent cerebro-myocardial perfusion is safe, versatile, and feasible in high-risk neonates with complex congenital arch pathology. Encouraging outcomes were noted in terms of cardiac and neurological function, with limited end-organ morbidity.

Improved Outcome of Cardiac Extracorporeal Membrane Oxygenation in Infants and Children Using Magnetic Levitation Centrifugal Pumps.

Extracorporeal membrane oxygenation (ECMO) has traditionally been and, for the most part, still is being performed using roller pumps. Use of first-generation centrifugal pumps has yielded controversial outcomes, perhaps due to mechanical properties of the same and the ensuing risk of hemolysis and renal morbidity. Latest-generation centrifugal pumps, using magnetic levitation (ML), exhibit mechanical properties which may have overcome limitations of first-generation devices. This retrospective study aimed to assess the safety and efficacy of veno-arterial (V-A) ECMO for cardiac indications in neonates, infants, and children, using standard (SP) and latest-generation ML centrifugal pumps. Between 2002 and 2014, 33 consecutive neonates, infants, and young children were supported using V-A ECMO for cardiac indications. There were 21 males and 12 females, with median age of 29 days (4 days-5 years) and a median body weight of 3.2 kg (1.9-18 kg). Indication for V-A ECMO were acute circulatory collapse in ICU or ward after cardiac repair in 16 (49%) patients, failure to wean after repair of complex congenital heart disease in 9 (27%), fulminant myocarditis in 4 (12%), preoperative sepsis in 2 (6%), and refractory tachy-arrhythmias in 2 (6%). Central cannulation was used in 27 (81%) patients and peripheral in 6. Seven (21%) patients were supported with SP and 26 (79%) with ML centrifugal pumps. Median duration of support was 82 h (range 24-672 h), with 26 (79%) patients weaned from support. Three patients required a second ECMO run but died on support. Seventeen (51%) patients required peritoneal dialysis for acute renal failure. Overall survival to discharge was 39% (13/33 patients). All patients with fulminant myocarditis and with refractory arrhythmias were weaned, and five (83%) survived, whereas no patient supported for sepsis survived. Risk factors for hospital mortality included lower (<2.5 kg) body weight (P = 0.02) and rescue ECMO after cardiac repair (P = 0.03). During a median follow-up of 34 months (range 4-62 months), there were three (23%) late deaths and two late survivors with neurological sequelae. Weaning rate (5/7 vs. 21/26, P = NS) and prevalence of renal failure requiring dialysis (4/7 vs. 13/26, P = NS) were comparable between SP and ML ECMO groups. Patients supported with ML had a trend toward higher hospital survival (1/7 vs. 12/26, P = 0.07) and significantly higher late survival (0/7 vs. 10/26, P = 0.05). The present experience shows that V-A ECMO for cardiac indications using centrifugal pumps in infants and children yields outcomes absolutely comparable to international registry (ELSO) data using mostly roller pumps. Although changes in practice may have contributed to these results, use of ML centrifugal pumps appears to further improve end-organ recovery and hospital and late survival.

Continuous Metabolic Monitoring in Infant Cardiac Surgery: Toward an Individualized Cardiopulmonary Bypass Strategy.

Cardiopulmonary bypass (CPB) in infants is associated with morbidity due to systemic inflammatory response syndrome (SIRS). Strategies to mitigate SIRS include management of perfusion temperature, hemodilution, circuit miniaturization, and biocompatibility. Traditionally, perfusion parameters have been based on body weight. However, intraoperative monitoring of systemic and cerebral metabolic parameters suggest that often, nominal CPB flows may be overestimated. The aim of the study was to assess the safety and efficacy of continuous metabolic monitoring to manage CPB in infants during open-heart repair. Between December 2013 and October 2014, 31 consecutive neonates, infants, and young children undergoing surgery using normothermic CPB were enrolled. There were 18 male and 13 female infants, aged 1.4 ± 1.7 years, with a mean body weight of 7.8 ± 3.8 kg and body surface area of 0.39 m(2) . The study was divided into two phases: (i) safety assessment; the first 20 patients were managed according to conventional CPB flows (150 mL/min/kg), except for a 20-min test during which CPB was adjusted to the minimum flow to maintain MVO2>70% and rSO2>45% (group A); (ii) efficacy assessment; the following 11 patients were exclusively managed adjusting flows to maintain MVO2>70% and rSO2>45% for the entire duration of CPB (group B). Hemodynamic, metabolic, and clinical variables were compared within and between patient groups. Demographic variables were comparable in the two groups. In group A, the 20-min test allowed reduction of CPB flows greater than 10%, with no impact on pH, blood gas exchange, and lactate. In group B, metabolic monitoring resulted in no significant variation of endpoint parameters, when compared with group A patients (standard CPB), except for a 10% reduction of nominal flows. There was no mortality and no neurologic morbidity in either group. Morbidity was comparable in the two groups, including: inotropic and/or mechanical circulatory support (8 vs. 1, group A vs. B, P = 0.07), reexploration for bleeding (1 vs. none, P = not significant [NS]), renal failure requiring dialysis (none vs. 1, P = NS), prolonged ventilation (9 vs. 4, P = NS), and sepsis (2 vs. 1, P = NS). The present study shows that normothermic CPB in neonates, infants, and young children can be safely managed exclusively by systemic and cerebral metabolic monitoring. This strategy allows reduction of at least 10% of predicted CPB flows under normothermia and may lay the ground for further tailoring of CPB parameters to individual patient needs.

Hemoglobin Concentration Affects Electroencephalogram During Cardiopulmonary Bypass: An Indication for Neuro-Protective Values.

Hemodilution during cardiopulmonary bypass (CPB) is widely used to decrease transfusion and improve microcirculation but has drawbacks, such as diminished hemoglobin levels. Among others, reduced brain oxygenation accounts for neurological adverse outcomes after CPB. The aim of the present study was to ascertain if and how continuous electroencephalogram (EEG) during CPB is affected by hematocrit level and what should be the minimum value to avoid significant frequency band shifts on the EEG. A comparative study design was used with 16 subjects undergoing elective mitral valve repair/replacement. EEG was continuously recorded during the surgical procedure (from anesthesia induction to 20 min after CPB end). Data were marked at relevant time points (T0: before CPB start; T1: after 30 min from CPB beginning; T2: at CPB end), and the following 2 min EEG analyzed with a fast Fourier transform to obtain relative power for delta, theta, alpha, and beta bands. A general linear model for repeated measure was used to study interactions of time (T0, T1, and T2, EEG frequency band, and topographical distribution. The relative powers for each electrode were calculated and represented using topographic maps. Power spectrum differences between time points (T2-T1; T2-T0; T1-T0) were calculated for each electrode, and differences >10%, considered indicative of neuronal sufferance, were included in further analysis. Cutoff hemoglobin values that maximize the proportion of correctly classified EEG band shifts were obtained by previous definition were obtained. At T2, diffuse EEG slowing in delta and theta bands was detected; a minor slowing over anterior regions was evident at T1 for the theta band. Decrements in EEG power greater than 10% were detected only for the delta band at T2. Hemoglobin concentration levels at which no slowing increase was evident were 9.4 mg/dL (Ht: 28.2%) at T1 and 9.2 mg/dL (Ht: 27.6%) at T2. EEG burst-suppression pattern related to a lesser degree of slowing at T2. In conclusion, we propose hemoglobin cutoff levels that prevent EEG slowing indicative of neuronal sufferance. In addition, burst-suppression EEG patterns offer higher central nervous system protection as measured on EEG.

Oxygenator Is the Main Responsible for Leukocyte Activation in Experimental Model of Extracorporeal Circulation: A Cautionary Tale.

In order to assess mechanisms underlying inflammatory activation during extracorporeal circulation (ECC), several small animal models of ECC have been proposed recently. The majority of them are based on home-made, nonstandardized, and hardly reproducible oxygenators. The present study has generated fundamental information on the role of oxygenator of ECC in activating inflammatory signaling pathways on leukocytes, leading to systemic inflammatory response, and organ dysfunction. The present results suggest that experimental animal models of ECC used in translational research on inflammatory response should be based on standardized, reproducible oxygenators with clinical characteristics.

Pulsatile cardiopulmonary bypass and renal function in elderly patients undergoing aortic valve surgery†.

OBJECTIVES: To evaluate if pulsatile cardiopulmonary bypass (CPB) has any protective influence on renal function in elderly patients undergoing aortic valve replacement (AVR). METHODS: Forty-six patients (≥ 75 years old) with aortic valve stenosis underwent AVR with either pulsatile perfusion (PP) or non-pulsatile perfusion (NP) during CPB. Haemodynamic efficacy of the blood pump during either type of perfusion was described in terms of the energy equivalent pressure and the surplus haemodynamic energy. Urine samples were collected before surgery, at sternum closure, and at 2 and 18 h of intensive care unit stay to detect acute kidney injury markers. Perioperative urine levels of N-acetyl-ß-D-glucosaminidase (NAG), kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin (NGAL) were assessed together with plasma creatinine, creatinine clearance (CCr) and 24-h haemodynamic monitoring. Normally distributed continuous variables were described as mean ± standard deviation and non-normally distributed data were presented as the median [25th-75th percentiles]. RESULTS: PP was characterized by a significantly higher amount of surplus haemodynamic energy transferred to the patients (P < 0.001), with lower mean systemic vascular resistance during CPB (P = 0.020) and during 18 h postoperatively (group-P = 0.018). No difference was found between pre- and postoperative CCr in the PP group (71 ± 23 vs 60 ± 35 ml/min, P = 0.27), while its statistically significant perioperative decrement was observed in the NP group (67 ± 24 vs 45 ± 15 ml/min, P < 0.001). The PP group showed significantly lower urinary levels of NAG at 18 h postoperatively (P = 0.008), and NGAL at sternum closure (P = 0.010), 2 h (P < 0.001) and 18 h (P = 0.015) postoperatively. CONCLUSIONS: Short-term PP in elderly patients showed higher safety for renal physiology than NP, resulting in better maintenance of glomerular filtration and lower renal tissue injury.

Pulsatile flow decreases gaseous micro-bubble filtering properties of oxygenators without integrated arterial filters during cardiopulmonary bypass.

OBJECTIVES: Cardiopulmonary bypass (CPB) has a risk of embolic injury with an important role of gaseous micro-bubbles (GMBs), coming from CPB-circuit. Pulsatile perfusion (PP) can provide specific conditions for supplementary GMB-activity with respect to non-pulsatile (NP). We aimed to test GMB-filtering properties of three modern oxygenators under pulsatile and non-pulsatile conditions. METHODS: Seventy-eight patients undergoing on-pump myocardial revascularization were randomized prospectively into three equal groups according to the oxygenator model used during CPB. Terumo Capiox-FX25, Sorin Synthesis or Maquet Quadrox-i-Adult membrane oxygenators were tested. Each group was divided equally to undergo PP or NP. GMBs were counted by means of a GAMPT-BCC200 bubble-counter with two probes placed at preoxygenator and arterial post-filter positions. Results were evaluated in terms of GMB-volume, GMB-number, amount of large over-ranged GMBs, a series of filtering indices and major neurological outcomes. RESULTS: PP decreased GMB-filtering properties of the tested oxygenators. Those with integrated filters (CAPIOX-FX25 and SYNTHESIS) did not show significant differences between perfusion groups, while QUADROX-i oxygenator with external arterial filter showed significantly higher GMB-volume (P < 0.001), GMB-number (P < 0.001) and amount of over-ranged bubbles (P < 0.001) detected in arterial line during PP. Despite the differences in filtering capacity of all circuits with both types of perfusion, no important differences in clinical outcomes and major neurological events were observed. CONCLUSIONS: Pulsatile flow decreases gaseous micro-bubble filtering properties of oxygenators without integrated arterial filters during CPB. PP requires specially designed circuit components to avoid the risk of additional GMB delivery.

Gaseous micro-emboli activity during cardiopulmonary bypass in adults: pulsatile flow versus nonpulsatile flow.

Cardiopulmonary bypass (CPB) has a risk of cerebral injury, with an important role of gaseous micro-emboli (GME) coming from the CPB circuit. Pulsatile perfusion is supposed to perform specific conditions for supplementary GME activity. We aimed to determine whether pulsatile CPB augments production and delivery of GME and evaluate the role of different events in GME activity during either type of perfusion. Twenty-four patients who underwent on-pump coronary artery bypass grafting surgery at the University of Verona were divided equally into two groups-pulsatile perfusion (PP) group and nonpulsatile perfusion (NP) group. The circuit included a JostraHL-20 roller pump set in pulsatile or nonpulsatile mode, an open Sorin Synthesis membrane oxygenator with integrated screen-type arterial filter, and phosphorylcholine-coated tubes. Hemodynamic flow evaluation was performed in terms of energy equivalent pressure and surplus hemodynamic energy (SHE). GME were counted by means of a GAMPT BCC200 bubble counter (GAMPT, Zappendorf, Germany) with two probes placed at postpump and postarterial filter positions. Results were evaluated in terms of GME number, GME volume, number of over-ranged GME from both probes, and series of filtering indexes. In PP mode, the pump produced and delivered along the circuit significantly higher amounts of SHE than in NP mode. At the venous postpump site, GME number was significantly higher during PP but no difference was found in terms of GME volume or number of over-ranged bubbles. No significant difference in GME number, GME volume, or number of over-ranges was found at the postarterial filter site. Filtering indexes were similar between the two groups. Neither type of perfusion was shown to contribute to excessive GME production during the most important perfusionist manipulation. Pulsatility leads to GME increment by splitting and size diminishing of the existing bubbles but not by additional gas production. PP augmented GME number at the venous postpump site, while mean volume remained comparable with NP. Sorin Synthesis oxygenator showed high efficacy in GME removal during either type of perfusion. Supplementary GME production and delivery during typical perfusionist manipulations did not depend on perfusion type.

Comparison between D901 Lilliput 1 and Kids D100 neonatal oxygenators: toward bypass circuit miniaturization.

Progress in biomaterial technology and improvements in surgical and perfusion strategy ameliorated morbidity and mortality in pediatric cardiac surgery. In this study, we describe our clinical experience comparing performance of two neonatal oxygenators. From January 2002 to March 2011, 159 infants with less than 5 kg body weight underwent heart surgery. Ninety-four patients received a D901 Lilliput 1 oxygenator with standard bypass circuit (group A), while 65 received a D100 Kids with miniaturized bypass circuit (group B). Miniaturization consisted in shortened arterial, venous, cardioplegia, and pump-master lines. Priming composition consisted in Ringer's acetate solution with addition of albumin and blood, with target hematocrit of 24% or greater. In group B cardiopulmonary bypass (CPB) was vacuum-assisted and started with an empty venous line. Modified ultrafiltration and Cell-Saver blood infusion was routinely applied in both groups. Average ± standard deviation (SD) age at repair was 37 ± 38 days in group A and 59 ± 60 days in group B (P = 0.005). Average ± SD weight, height, and body surface area were 3.5 ± 0.7 kg, 52 ± 4 cm, and 0.22 ± 0.03 m(2) , respectively, in group A, and 3.7 ± 1 kg, 53 ± 5 cm, and 0.23 ± 0.02 m(2) , respectively, in group B (P = not significant [NS]). Male sex was predominant (55 vs. 58%, P = NS). Priming volume was 524 ± 67 mL (group A) and 337 ± 53 mL (group B) (P = 0.001). There were no statistical differences in hemoglobin at the start, during, and at the end of CPB, but group A required higher blood volume added to the prime (111 ± 33 vs. 93 ± 31 mL, P = 0.001). In group B, two surgical procedures were completed in total hemodilution. In group B, CPB time and aortic cross-clamp time were shorter than in group A (106 ± 52 vs. 142 ± 78 min and 44 ± 31 vs. 64 ± 31 min, respectively, P = 0.001). There were 16 hospital deaths in group A and 4 in group B (P = 0.04). Durations of mechanical ventilation and intensive care unit stay were 5.3 ± 3.2 vs. 4.1 ± 3.2 days (P = 0.02) and 6.5 ± 4.9 vs. 5.1 ± 3 days (P = 0.03), respectively. There were significant differences in inotropic score (1083 ± 1175 vs. 682 ± 938, P = 0.04) and blood postoperative transfusion (153 ± 226 vs. 90 ± 61 mL, P = 0.04). Twenty-seven patients in group A and 10 in group B presented with major adverse postoperative complications (P = 0.04). Use of neonatal oxygenators with low priming volume, associated with a miniaturized bypass circuit, seems to be a favorable strategy to decrease postoperative morbidity after cardiac surgery in neonates and infants.

Leukocyte filtration of blood cardioplegia attenuates myocardial damage and inflammation.

OBJECTIVES: Leukocyte filtration of blood cardioplegia (cLkF) is postulated to reduce ischaemia-reperfusion myocardial injury. Contradictory results have been published and few studies have addressed perioperative cytokine leakage and haemodynamic status after LkF. METHODS: Thirty patients undergoing isolated aortic valve replacement were randomized to cLkF (cLkF-Group) or to standard cold blood cardioplegia (S-Group). Troponin I (TnI) and lactate were sampled from the coronary sinus at reperfusion. Peripheral TnI and lactate were collected preoperatively at admission, and in the intensive care unit (ICU) at 8, 12, 36 and 60 h postoperatively. Cardiac index (CI), indexed systemic vascular resistances, cardiac cycle efficiency (CCE) and central venous pressure (CVP) were registered preoperatively, at admission to the ICU and at the 6th, 12th, 18th, 24th and 36th postoperative hour. IL-6, IL-8, TNF-alpha and IL-10 were sampled preoperatively, at reperfusion, on admission to the ICU and the 6th, 18th and 24th postoperative hours. RESULTS: The cLkF group showed lower TnI (2.4 ± 0.4 vs. 5.1 ± 0.8 µg/l, P = 0.0001) and lactate (0.9 ± 0.1 vs. 1.6 ± 0.2 mmol/l, P = 0.0001) from the coronary sinus at reperfusion. TnI levels (group-P = 0.0001, group time-P < 0.0001) and lactate (group time-P = 0.001) remained lower postoperatively after cLkF. Ventricular defibrillation at aortic declamping was less common in the cLkF-Group (33.3% vs. S-Group: 93.3%; P = 0.002). Cytokines demonstrated significant postoperative leakage (time-P = 0.0001 in both groups for IL-6, IL-8, TNF-alpha, IL-10), with lower pro-inflammatory (IL-6 group-P = 0.0001, group time-P = 0.0001; IL-8 group-P = 0.0001, group time-P = 0.007; TNF-alpha group-P = 0.0001; group time-P = 0.012) and higher anti-inflammatory cytokine secretion after cLkF (IL-10 group-P = 0.005). Perioperative haemodynamic indices proved to be similar between the two groups (group-P = NS for CI, SVRI, CCE and CVP). CONCLUSIONS: cLkF during blood cardioplegia attenuates myocardial ischaemia/reperfusion injury and reduces perioperative leakage of TnI, lactate and pro-inflammatory cytokines. These data did not result in a better haemodynamic status.

"Polarizing" microplegia improves cardiac cycle efficiency after CABG for unstable angina.

BACKGROUND: Myocardial protection during coronary artery bypass grafting (CABG) for unstable angina (UA) still represents a major challenge, ought to the risk for further ischemia/reperfusion injury. Few studies investigate the biochemical, hemodynamic and echocardiographic results of microplegia (Mic) in UA. METHODS: Eighty UA-patients undergoing CABG were randomized to Mic (Mic-Group) or standard 4:1 blood Buckberg-cardioplegia (Buck-Group). Troponin-I and lactate were sampled from coronary sinus at reperfusion (T1), and from peripheral blood preoperatively (T0), at 6 (T2), 12 (T3) and 48 (T4) hours. Cardiac index (CI), indexed systemic vascular resistances (ISVR), Δp/Δt, cardiac cycle efficiency (CCE), and central venous pressure (CVP) were collected preoperatively (T0), and since Intensive Care Unit (ICU)-arrival (T1) to 24h (T5). Echocardiographic E-wave (E), A-wave (A), E/A, peak early-diastolic TDI-mitral annular-velocity (Ea), and E/Ea investigated the diastolic function and Wall Motion Score Index (WMSI) the systolic function, preoperatively (T0) and at 96h (T1). RESULTS: Mic-Group showed lower troponin-I and lactate from coronary sinus (p=.0001 for both) and during the postoperative course (between-groups p=.001 and .0001, respectively). WMSI improved only after Mic (time-p=.001). Higher CI Δp/Δt and CCE (between-groups p=.0001), with comparable CVP and ISVR (p=N.S.) were detected after Mic. Diastolic function improved in both groups, but better after Mic (between-groups p=.003, .001, and .013 for E, E/A, and Ea, respectively). Mic resulted in lower transfusions (p=.006) and hospitalization (p=.002), and a trend towards lower need/duration of inotropes (p=.04 and p=.041, respectively), and ICU-stay (p=.015). CONCLUSION: Microplegia attenuates myocardial damage in UA, reduces transfusions, improves postoperative systo-diastolic function, and shortens hospitalization.

Cardioprotective effect of δ-opioid receptor agonist vs. mild therapeutic hypothermia in a rat model of cardiac arrest with extracorporeal life support.

BACKGROUND: To compare the effect of δ-opioid receptor agonist, d-Ala2-d-Leu5 enkephalin (DADLE) with normothermic control and therapeutic hypothermia on post resuscitation myocardial function in a model of extracorporeal life support (ECLS). METHODS: Ventricular fibrillation (VF) was induced in male Wistar rats. After 10 min of untreated VF, venoarterial ECLS was instituted for 60 min. At the beginning of ECLS animals were randomized to three groups of ten: normothermia, hypothermia (32 °C) and DADLE intravenous infusion (1 mg/kg/h). Cooling to 32 °C or normothermia or drug infusion lasted for the entire ECLS. Plasma samples and myocardial biopsies were obtained and left-ventricular (LV) function was assessed by a conductance catheter at baseline and after weaning from ECLS. RESULTS: DADLE administration resulted in a significantly enhanced recovery of LV systolic function expressed by slope of the LV end-systolic pressure volume relationship (Ees) and preload recruitable stroke work (PRSW) than hypothermia and normothermia. LV stiffness indicated by end-diastolic pressure volume relationship (EDPVR) was significantly lower after DADLE administration (P<0.01). LV relaxation described by Tau was preserved after DADLE treatment but not after normothermia or mild hypothermia (P<0.01). Plasma lactate concentrations were lower in DADLE group (P<0.05). DADLE and not conventional hypothermia significantly increased phosphorylation of the kinases ERK1 and 2 (3.9±0.3 and 3.1±0.5 vs. 0.4±0.1 and 0.3±0.1-fold of baseline levels) (P<0.001). Both DADLE and hypothermia but not normothermia increase phosphorylation of Akt. CONCLUSIONS: DADLE was more effective than mild therapeutic hypothermia in recovering myocardial function and activation of the pro-survival kinases Akt and ERK after ECLS.

Clinical evaluation of new generation oxygenators with integrated arterial line filters for cardiopulmonary bypass.

New generation oxygenators with integrated arterial line filters have been marketed to improve the efficacy of cardiopulmonary bypass (CPB). Differences in designs, materials, coating surfaces, pore size of arterial filter, and static prime exist between the oxygenators. Despite abundant preclinical data, literature lacks clinical studies. From September 2010 to March 2011, 80 consecutive patients were randomized to CPB using Terumo Capiox FX25 (40 patients, Group-T) or Sorin Synthesis (40 patients, Group-S) oxygenators. Pressure drop and gas exchange efficacy were registered during CPB. High-sensitivity C-reactive protein (hs-CRP), white blood cells (WBCs), fluid balance, activated clotting time, international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, platelets (PLTs), serum albumin, and total proteins were measured perioperatively at different timepoints. Clinical outcome was recorded. Repeated measure analysis of variance and nonparametric statistics assessed between-groups and during time differences. The two groups showed similar baseline and intraoperative variables. No differences were recorded in pressure drop and gas exchange (group-P and group*time-P = N.S. for all) during CPB. Despite similar fluid balance (P = N.S. for static/dynamic priming and ΔVolume administered intraoperatively), Group-T showed higher hs-CRP (group-P = 0.034), aPTT (group-P = 0.0001), and INR (group-P= 0.05), with lower serum albumin (group-P = 0.014), total proteins (group-P = 0.0001), fibrinogen (group-P = 0.041), and PLTs (group-P = 0.021). Group-T also showed higher postoperative bleeding (group-P = 0.009) and need for transfusions (P = 0.008 for packed red cells and P = 0.0001 for fresh frozen plasma and total transfused volumes). However, clinical outcome was comparable (P = N.S. for all clinical endpoints). Both oxygenators proved effective and resulted in comparable clinical outcomes. However, Sorin Synthesis seems to reduce inflammation and better preserve the coagulative cascade and serum proteins, resulting in lower transfusions and post-CPB inflammatory response.

Selective pulmonary pulsatile perfusion with oxygenated blood during cardiopulmonary bypass attenuates lung tissue inflammation but does not affect circulating cytokine levels.

OBJECTIVE: Improved respiratory outcome has been shown after selective pulsatile pulmonary perfusion (sPPP) during cardiopulmonary bypass (CPB). No contemporary study has analysed the impact of sPPP on alveolar and systemic inflammatory response in humans. METHODS: Sixty-four patients undergoing a coronary artery bypass graft (CABG) were randomized to sPPP or standard CPB (32 patients each). An alveolar-arterial oxygen gradient (A-aDO(2)) was measured preoperatively (T0), at ICU arrival (T1), 3 h postoperatively (T2) and postextubation (T3). The bronchoalveolar lavage (BAL) was collected at T0, T1 and T2. White blood cells (WBCs), neutrophils, mononucleates and lymphocytes in BAL infiltrates were compared between the two groups. A cytokine assay for interleukin-1 (IL-1), IL-8, tumour necrosis factor alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1), growth regulated oncogene-alpha (GRO-α) and interferon (IFN)-γ was collected from the BAL and peripheral blood at the same time-points. Repeated-measure analysis of variance and non-parametric statistics were used to assess the between-group and during time differences. RESULTS: The two groups proved comparable for perioperative variables. A-aDO(2) proved better after sPPP (group-P = 0.0001; group time-P < 0.0001). BAL infiltrates after sPPP showed lower WBCs, neutrophils and lymphocytes (group-P = 0.0001, group time-P = 0.0001 for all) together with higher mononucleates (group-P = 0.0001, group time-P = 0.0001). Proinflammatory cytokines and chemokine MCP-1 were lower in BAL after sPPP (group-P = 0.005, 0.034, 0.036 and 0.005, and group time-P = 0.001, 0.009, 0.001 and 0.0001 for IL-1, IL-8, TNF-α and MCP-1, respectively), whereas the immune modulator IFN-γ significantly augmented after sPPP (time-P = 0.0001) but remained stable after the standard CPB (time-P = 0.101, group-P = 001, group time-P = 0.0001). Indeed, serum cytokines were not different in the two groups during the study (P = NS at single time-points and as a function of time). CONCLUSIONS: sPPP attenuates alveolar inflammation, as demonstrated by the lower neutrophilic/lymphocytic alveolar infiltration, and the secretion of anti-inflammatory rather than proinflammatory mediators.

Levosimendan is superior to epinephrine in improving myocardial function after cardiopulmonary bypass with deep hypothermic circulatory arrest in rats.

OBJECTIVE: To investigate effects of epinephrine and levosimendan on cardiac function after rewarming from deep hypothermia. METHODS: Forty-five male Wistar rats (400-500 g) underwent cardiopulmonary bypass and were cooled to a core temperature of 13°C to 15°C within 30 minutes. After 15 minutes of deep hypothermic circulatory arrest, they were randomly assigned to treatment with levosimendan (12 µg/kg; infusion of 0.2 µg · kg(-1) · min(-1)) (n = 15) or epinephrine (0.1 µg/kg; infusion of 0.1 µg · kg(-1) · min(-1)) (n = 15) or saline as control (n = 10). The rewarming lasted 60 minutes. Systolic and diastolic function was evaluated at different preloads with a conductance catheter, including the slope of the end-systolic pressure-volume relation (ESPVR) and end-diastolic pressure-volume relationship (EDPVR), preload recruitable stroke work, first derivative of left ventricular pressure (+dP/dt), and its relation to end-diastolic volume, as well as the time constant of left ventricular relaxation (Tau) and maximal slope of the diastolic pressure decrement (-dP/dt). Plasma lactate levels were collected. RESULTS: Stroke volume, ejection fraction and +dP/dt were significantly higher in the levosimendan-treated group than in the epinephrine group. The slope values of preload recruitable stroke work, ESPVR, and the relation of +dP/dt to end-diastolic volume were significantly higher, indicating a better contractility and increased systolic function. -dP/dt was significantly higher in the levosimendan group (3468 ± 320 vs 1103 ± 101 mm Hg/s; P < .01). Left ventricular stiffness expressed by EDPVR and relaxation (Tau) were significantly improved in levosimendan-treated group. Plasma lactated concentrations were lower in levosimendan group (2.03 ± 1.27 vs 4.64 ± 1.02; P < .05). CONCLUSIONS: Levosimendan has better inotropic and lusitropic effects than epinephrine during rewarming from deep hypothermic circulatory arrest with cardiopulmonary bypass.

Selective cerebro-myocardial perfusion in complex congenital aortic arch pathology: a novel technique.

Simultaneous cerebro-myocardial perfusion has been described in neonatal and infant arch surgery, suggesting a reduction in cardiac morbidity. Here reported is a novel technique for selective cerebral perfusion combined with controlled and independent myocardial perfusion during surgery for complex or recurrent aortic arch lesions. From April 2008 to April 2011, 10 patients with arch pathology underwent surgery (two hypoplastic left heart syndrome [HLHS], four recurrent arch obstruction, two aortic arch hypoplasia + ventricular septal defect [VSD], one single ventricle + transposition of the great arteries + arch hypoplasia, one interrupted aortic arch type B + VSD). Median age was 63 days (6 days-36 years) and median weight 4.0 kg (1.6-52). Via midline sternotomy, an arterial cannula (6 or 8 Fr for infants) was directly inserted into the innominate artery or through a polytetrafluoroethylene (PTFE) graft (for neonates <2.0 kg). A cardioplegia delivery system was inserted into the aortic root. Under moderate hypothermia, ascending and descending aorta were cross-clamped, and "beating heart and brain" aortic arch repair was performed. Arch repair was composed of patch augmentation in five, end-to-side anastomosis in three, and replacement in two patients. Average cardiopulmonary bypass time was 163 ± 68 min (71-310). In two patients only (one HLHS, one complex single ventricle), a period of cardiac arrest was required to complete intracardiac repair. In such cases, antegrade blood cardioplegia was delivered directly via the same catheter used for selective myocardial perfusion. Average time of splanchnic ischemia during cerebro-myocardial perfusion was 39 ± 18 min (17-69). Weaning from cardiopulmonary bypass was achieved without inotropic support in three and with low dose in seven patients. One patient required veno-arterial extracorporeal membrane oxygenation. Four patients, body weight <3.0 kg, needed delayed sternal closure. No neurologic dysfunction was noted. Renal function proved satisfactory in all, while liver function was adequate in all but one. The present experience suggests that selective and independent cerebro-myocardial perfusion is feasible in patients with complex or recurrent aortic arch disease, starting from premature newborn less than 2.0 kg of body weight to adults. The technique is as safe as previously reported methods of cerebro-myocardial perfusion and possibly more versatile.