Validation of a new model of selective antegrade cerebral perfusion with circulatory arrest in rats.

Background: Selective antegrade cerebral perfusion (SACP) is adopted as an alternative to deep hypothermic circulatory arrest (DHCA) during aortic arch surgery. However, there is still no preclinical evidence to support the use of SACP associated with moderate hypothermia (28-30°C) instead of DHCA (18-20°C). The present study aims to develop a reliable and reproducible preclinical model of cardiopulmonary bypass (CPB) with SACP applicable for assessing the best temperature management.

Nitric Oxide in Selective Cerebral Perfusion Could Enhance Neuroprotection During Aortic Arch Surgery.

Background: Hypothermic circulatory arrest (HCA) in aortic arch surgery has a significant risk of neurological injury despite the newest protective techniques and strategies. Nitric oxide (NO) could exert a protective role, reduce infarct area and increase cerebral perfusion. This study aims to investigate the possible neuroprotective effects of NO administered in the oxygenator of selective antegrade cerebral perfusion (SCP) during HCA.

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

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. Fifty-two patients undergoing an aortic valve replacement were prospectively randomized for surgery with either PP or NP flow.

Slow versus fast rewarming after hypothermic circulatory arrest: effects on neuroinflammation and cerebral oedema.

Objectives: Among the factors that could determine neurological outcome after hypothermic circulatory arrest (HCA) rewarming is rarely considered. The optimal rewarming rate is still unknown. The goal of this study was to investigate the effects of 2 different protocols for rewarming after HCA on neurological outcome in an experimental animal model.

Cardioprotective Effects of Sphingosine-1-Phosphate Receptor Immunomodulator FTY720 in a Clinically Relevant Model of Cardioplegic Arrest and Cardiopulmonary Bypass.

FTY720, an immunomodulator derived from sphingosine-1-phosphate, has recently demonstrated its immunomodulatory, anti-inflammatory, anti-oxidant, anti-apoptotic and anti-inflammatory properties. Furthermore, FTY720 might be a key pharmacological target for preconditioning. In this preclinical model, we have investigated the effects of FTY720 on myocardium during reperfusion in an experimental model of cardioplegic arrest (CPA) and cardiopulmonary bypass.

Peptidomimetic Targeting of Cavβ2 Overcomes Dysregulation of the L-Type Calcium Channel Density and Recovers Cardiac Function.

Background: L-type calcium channels (LTCCs) play important roles in regulating cardiomyocyte physiology, which is governed by appropriate LTCC trafficking to and density at the cell surface. Factors influencing the expression, half-life, subcellular trafficking, and gating of LTCCs are therefore critically involved in conditions of cardiac physiology and disease.

Methods: Yeast 2-hybrid screenings, biochemical and molecular evaluations, protein interaction assays, fluorescence microscopy, structural molecular modeling, and functional studies were used to investigate the molecular mechanisms through which the LTCC Cavβ2 chaperone regulates channel density at the plasma membrane.

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.

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.

G-CSF displays restricted ability to promote Sca-1(+) cardiac stem cell proliferation in vitro.

Granulocyte colony-stimulating factor (G-CSF) is a controversial chemical in cardiac cell therapy. Myocardial homing of mobilized bone marrow-derived cells is thought to play a critical role in observed G-CSF-induced cardiac repair; meanwhile, the activation of proliferative potential of cardiac stem cells (CSCs) residing in the heart is a significant challenge. The present study aims to investigate whether G-CSF receptor is expressed in adult resident Sca-1(+) CSCs and determine the effect of G-CSF treatment on the proliferation of CSCs.

Diabetic hearts have lower basal urocortin levels that fail to increase after cardioplegic arrest: association with increased apoptosis and postsurgical cardiac dysfunction.

Objectives: The present study investigated the cardioprotective role of urocortin (Ucn) and its relationship with protein kinase C (PKC)ε and PKCδ in patients with (DMPs) and without (NDMPs) diabetes mellitus after on-pump cardiac surgery (OPCS). The molecular mechanisms responsible for the reported worse outcomes of DMP after OPCS remain unknown.

Methods: Two sequential biopsy specimens were obtained from the right atrium of 27 DMPs and 22 NDMPs before and after cardiopulmonary bypass.

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.

Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest.

Introduction: Rewarming from deep hypothermic circulatory arrest (DHCA) produces calcium desensitization by troponin I (cTnI) phosphorylation which results in myocardial dysfunction. This study investigated the acute overall hemodynamic and metabolic effects of epinephrine and levosimendan, a calcium sensitizer, on myocardial function after rewarming from DHCA.

Methods: Forty male Wistar rats (400 to 500 g) underwent cardiopulmonary bypass (CPB) through central cannulation and were cooled to a core temperature of 13°C to 15°C within 30 minutes.

Targeting urocortin signaling pathways to enhance cardioprotection: is it time to move from bench to bedside?

Despite the exponential growth in medical knowledge, cardiovascular diseases (CVDs) contribute to more than one-third of worldwide morbidity and mortality. A range of therapies already exist for established CVDs, although there is significant interest in further understanding their pathogenesis. The urocortins (Ucns) are peptide members of the corticotrophin-releasing factor family, a group of evolutionary conserved peptides with homologues in fish, amphibians and mammals and considered to play a pivotal role in energy homeostasis and local tissue repair.

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.

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.

Increased expression of adenosine triphosphate-sensitive K+ channels in mitral dysfunction: mechanically stimulated transcription and hypoxia-induced protein stability?

Objectives: The aim of this study was to test whether adenosine triphosphate-sensitive K(+) (KATP) channel expression relates to mechanical and hypoxic stress within the left human heart.

Background: The KATP channels play a vital role in preserving the metabolic integrity of the stressed heart. However, the mechanisms that govern the expression of their subunits (e.

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.

Preservation of endothelium nitric oxide release by pulsatile flow cardiopulmonary bypass when compared with continuous flow.

The aim of this work is to analyze endothelium nitric oxide (NO) release in patients undergoing continuous or pulsatile flow cardiopulmonary bypass (CPB). Nine patients operated under continuous flow CPB, and nine patients on pulsatile flow CPB were enrolled. Plasma samples were withdrawn for the chemiluminescence detection of nitrite and nitrate.

Warm-blood cardioplegic arrest induces selective mitochondrial translocation of protein kinase Cepsilon followed by interaction with 6.1 inwardly rectifying potassium channel subunit in viable myocytes overexpressing urocortin.

Objective: This study investigates the cardioprotective role and mechanism of action of urocortin in patients undergoing cardiac surgery, with respect to protein kinase Cepsilon expression, activation, and relocation.

Background: Cardioplegic arrest and subsequent reperfusion inevitably expose the heart to iatrogenic ischemia/reperfusion injury. We previously reported that iatrogenic ischemia/reperfusion injury caused myocyte induction of urocortin, an endogenous cardioprotective peptide.

Validation of a rat model of cardiopulmonary bypass with a new miniaturized hollow fiber oxygenator.

Cardiopulmonary bypass (CPB) is an essential component of cardiac surgery, with still unknown device/patient interactions. To evaluate the response of CPB to hemodynamic, biochemical, inflammatory, as well as thermo-pharmacodynamic interactions, a novel miniaturized oxygenator with controlled and standardized specifications has been developed together with an improved surgical central cannulation technique. A hollow-fiber small priming volume (6.