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Myocardial function after polarizing versus depolarizing cardiac arrest with blood cardioplegia in a porcine model of cardiopulmonary bypass.

ABSTRACT: Potassium-based depolarizing St Thomas' Hospital cardioplegic solution No 2 administered as intermittent, oxygenated blood is considered as a gold standard for myocardial protection during cardiac surgery. However, the alternative concept of polarizing arrest may have beneficial protective effects. We hypothesize that polarized arrest with esmolol/adenosine/magnesium (St Thomas' Hospital Polarizing cardioplegic solution) in cold, intermittent oxygenated blood offers comparable myocardial protection in a clinically relevant animal model.Twenty anaesthetized young pigs, 42 ± 2 (standard deviation) kg on standardized tepid cardiopulmonary bypass (CPB) were randomized (10 per group) to depolarizing or polarizing cardiac arrest for 60 min with cardioplegia administered in the aortic root every 20 min as freshly mixed cold, intermittent, oxygenated blood. Global and local baseline and postoperative cardiac function 60, 120 and 180 min after myocardial reperfusion was evaluated with pressure-conductance catheter and strain by Tissue Doppler Imaging. Regional tissue blood flow, cleaved caspase-3 activity, GRK2 phosphorylation and mitochondrial function and ultrastructure were evaluated in myocardial tissue samples.Left ventricular function and general haemodynamics did not differ between groups before CPB. Cardiac asystole was obtained and maintained during aortic cross-clamping. Compared with baseline, heart rate was increased and left ventricular end-systolic and end-diastolic pressures decreased in both groups after weaning. Cardiac index, systolic pressure and radial peak systolic strain did not differ between groups. Contractility, evaluated as dP/dtmax, gradually increased from 120 to 180 min after declamping in animals with polarizing cardioplegia and was significantly higher, 1871 ± 160 (standard error) mmHg/s, compared with standard potassium-based cardioplegic arrest, 1351 ± 70 mmHg/s, after 180 min of reperfusion (P = 0.008). Radial peak ejection strain rate increased and the load-independent variable preload recruitable stroke work was increased with polarizing cardioplegia after 180 min, 64 ± 3 vs 54 ± 2 mmHg (P = 0.018), indicating better preserved left ventricular contractility with polarizing cardioplegia. Phosphorylation of GRK2 in myocardial tissue did not differ between groups. Fractional cytoplasmic volume in myocytes was reduced in hearts arrested with polarizing cardioplegia, indicating reduction of cytoplasmic oedema.Polarizing oxygenated blood cardioplegia with esmolol/adenosine/magnesium offers comparable myocardial protection and improves contractility compared with the standard potassium-based depolarizing blood cardioplegia.

SUBMITTER: Aass T

PROVIDER: S-EPMC4913873 | biostudies-other | 2016 Jul

REPOSITORIES: biostudies-other

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Myocardial function after polarizing versus depolarizing cardiac arrest with blood cardioplegia in a porcine model of cardiopulmonary bypass.

Aass Terje T Stangeland Lodve L Moen Christian Arvei CA Salminen Pirjo-Riitta PR Dahle Geir Olav GO Chambers David J DJ Markou Thomais T Eliassen Finn F Urban Malte M Haaverstad Rune R Matre Knut K Grong Ketil K

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 20160202 1

<h4>Objectives</h4>Potassium-based depolarizing St Thomas' Hospital cardioplegic solution No 2 administered as intermittent, oxygenated blood is considered as a gold standard for myocardial protection during cardiac surgery. However, the alternative concept of polarizing arrest may have beneficial protective effects. We hypothesize that polarized arrest with esmolol/adenosine/magnesium (St Thomas' Hospital Polarizing cardioplegic solution) in cold, intermittent oxygenated blood offers comparable ...[more]

PMID: 26843432

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Project description:ObjectivesThis study investigated whether the novel St. Thomas' Hospital polarizing cardioplegic solution (STH-POL) with esmolol/adenosine/magnesium offers improved myocardial protection by reducing demands for high-energy phosphates during cardiac arrest compared to the depolarizing St. Thomas' Hospital cardioplegic solution No 2 (STH-2).MethodsTwenty anaesthetised pigs on tepid cardiopulmonary bypass were randomized to cardiac arrest for 60 min with antegrade freshly mixed, repeated, cold, oxygenated STH-POL or STH-2 blood cardioplegia every 20 min. Haemodynamic variables were continuously recorded. Left ventricular biopsies, snap-frozen in liquid nitrogen or fixed in glutaraldehyde, were obtained at Baseline, 58 min after cross-clamp and 20 and 180 min after weaning from bypass. Adenine nucleotides were evaluated by high-performance liquid chromatography, myocardial ultrastructure with morphometry.ResultsWith STH-POL myocardial creatine phosphate was increased compared to STH-2 at 58 min of cross-clamp [59.9 ± 6.4 (SEM) vs 44.5 ± 7.4 nmol/mg protein; P < 0.025], and at 20 min after reperfusion (61.0 ± 6.7 vs 49.0 ± 5.5 nmol/mg protein; P < 0.05), ATP levels were increased at 20 min of reperfusion with STH-POL (35.4 ± 1.1 vs 32.4 ± 1.2 nmol/mg protein; P < 0.05). Mitochondrial surface-to-volume ratio was decreased with polarizing compared to depolarizing cardioplegia 20 min after reperfusion (6.74 ± 0.14 vs 7.46 ± 0.13 µm 2 /µm 3 ; P = 0.047). None of these differences were present at 180 min of reperfusion. From 150 min of reperfusion and onwards, cardiac index was increased with STH-POL; 4.8 ± 0.2 compared to 4.0 ± 0.2 l/min/m 2 ( P = 0.011) for STH-2 at 180 min.ConclusionsPolarizing STH-POL cardioplegia improved energy status compared to standard STH-2 depolarizing blood cardioplegia during cardioplegic arrest and early after reperfusion.

Project description:BACKGROUND:The use of cardioplegia solutions as a myocardial protection technique is essential during cardiac surgery with cardiopulmonary bypass. The del Nido cardioplegia solution (DNS) has been widely used as a myocardial preservation technique for pediatric patients undergoing cardiac surgery with cardiopulmonary bypass. Its unique pharmacological features have created growing interest for adult cardiac surgery, especially for elderly patients or those with ventricular dysfunction who are more prone to ischemia-reperfusion injury. Ever since its implementation, several retrospective studies have been published to validate the efficacy, safety, and efficiency of DNS in adult patients undergoing coronary revascularization, valve replacement, or combined procedures. Recently, a meta-analysis based on nine retrospective studies was published claiming the noninferiority of DNS compared to other conventional cardioplegia solutions. Few prospective randomized studies have been conducted whose primary outcome was the assessment of DNS clinical efficacy compared to other solutions commonly used in adult patients. OBJECTIVE:The aim of this randomized clinical trial is to assess the benefits of DNS compared to Cardi-Braun blood cardioplegia solution in clinical and biochemical terms regarding myocardial protection during adult cardiac surgery. METHODS:This is the protocol of a controlled, randomized, single-center clinical trial carried out at the Puerta de Hierro Majadahonda University Hospital in Spain. A total of 474 participants over the age of 18 years undergoing elective cardiac surgery with cardiopulmonary bypass will be assigned to groups by simple randomization to receive either DNS or Cardi-Braun blood cardioplegia solution. The primary outcome will be the differences between groups in myocardial protection in biochemical terms (ie, perioperative troponin levels) and clinical terms (ie, presence of the composite variable acute cardiovascular event). The clinical trial will be carried out under conditions of respect for the fundamental rights of the person and the ethical principles that affect biomedical research with human beings, as well as in accordance with international recommendations contained in the Declaration of Helsinki and its subsequent revisions. RESULTS:The inclusion process started in 2018. Data cleaning and analyses are expected to take place in the fall of 2020 and the results are expected in January 2021. CONCLUSIONS:This study is particularly relevant as it will be one of the first to analyze the clinical effects of del Nido cardioplegia on the basis of direct myocardial protection parameters. In light of published studies, carrying out prospective studies based on primary clinical objectives with a larger sample, high-risk patients, and longer cardiopulmonary bypass times continues to be necessary. We believe that our study addresses an important gap in the knowledge of del Nido cardioplegia in adult patient cardiac surgery and will be able to clarify the possible benefits of this method in a large population of patients undergoing these procedures. TRIAL REGISTRATION:European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) 2017-005144-14; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2017-005144-14+; ClinicalTrials.gov NCT04094168; https://clinicaltrials.gov/ct2/show/NCT04094168. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):DERR1-10.2196/17826.

Project description:BackgroundBlood-based cardioplegia is the standard myocardial protection strategy in pediatric cardiac surgery. Custadiol (histidine-tryptophan-ketoglutarate), an alternative, may have some advantages but is potentially less effective at myocardial protection. This study aimed to test whether custadiol is not inferior to blood-based cardioplegia in pediatric cardiac surgery.MethodsThe study was designed as a randomized controlled trial with a blinded outcome assessment. All pediatric patients undergoing cardiac surgery with cardiopulmonary bypass and cardioplegia, including neonates, were eligible. Emergency surgery was excluded. The primary outcome was a composite of death within 30 days, an ICU stay longer than 5 days, or arrhythmia requiring intervention. Secondary endpoints included total hospital stay, inotropic score, cardiac troponin levels, ventricular function, and extended survival postdischarge. The sample size was determined a priori for a noninferiority design with an expected primary outcome of 40% and a clinical significance difference of 20%.ResultsBetween January 2018 and January 2021, 226 patients, divided into the Custodiol cardioplegia (CC) group (n = 107) and the blood cardioplegia (BC) group (n = 119), completed the study protocol. There was no difference in the composite endpoint between the CC and BC groups, 65 (60.75%) vs. 71 (59.66%), respectively (P = 0.87). The total length of stay in the hospital was 14 (Q2-Q3: 10-19) days in the CC group vs. 13 (10-21) days in the BC group (P = 0.85). The inotropic score was not significantly different between the CC and BC groups, 5 (2.6-7.45) vs. 5 (2.6-7.5), respectively (P = 0.82). The cardiac troponin level and ventricular function did not differ significantly between the two groups (P = 0.34 and P = 0.85, respectively). The median duration of follow-up was 32.75 (Q2-Q3: 18.73-41.53) months, and there was no difference in survival between the two groups (log-rank P = 0.55).ConclusionsCustodial cardioplegia is not inferior to blood cardioplegia for myocardial protection in pediatric patients. Trial registration The trial was registered in Clinicaltrials.gov, and the ClinicalTrials.gov Identifier number is NCT03082716 Date: 17/03/2017.

Project description:Identification of microRNAs (miRNA) associated with cardiopulmonary bypass, cardiac arrest and subsequent myocardial ischemia/reperfusion may unravel novel therapeutic targets and biomarkers. The primary aim of the present study was to investigate the effects of cardiopulmonary bypass and temperature of cardioplegic arrest on myocardial miRNA profile in pigs' left ventricular tissue. We employed next-generation sequencing to analyse miRNA profiles in the following groups: (1) hearts were arrested with antegrade warm St Thomas Hospital No. 2 (STH2) cardioplegia (n = 5; STH2-warm, 37 °C) and (2) cold STH2 (n = 6; STH2-cold, 4 °C) cardioplegia. Sixty min of ischemia was followed by 60 min of on-pump reperfusion with an additional 90 min of off-pump reperfusion. In addition, two groups without cardiac arrest (off-pump and on-pump group; n = 3, respectively) served as additional controls. STH2-warm and STH2-cold cardioplegia revealed no hemodynamic differences. In contrast, coronary venous creatine kinase-myocardial band (CK-MB) levels were significantly lower in pigs receiving STH2-warm cardioplegia (p < 0.05). Principal component analysis revealed that cardiopulmonary bypass and cardioplegic arrest markedly affected miRNAs in left ventricular tissue. Accordingly, ssc-miR-122, ssc-miR-10a-5p, ssc-miR-193a-3p, ssc-miR-499-3p, ssc-miR-374a-5p, ssc-miR-345-5p, ssc-miR-142-3p, ssc-miR-424-5p, ssc-miR-545-3p, ssc-miR-30b-5p, ssc-miR-145-5p, ssc-miR-374b-5p and ssc-miR-139-3p were differently regulated by cardiopulmonary bypass (false discovery rate (FDR) < 0.05 versus off-pump group). However, only ssc-miR-451 was differently expressed between STH2-warm and STH2-cold (FDR < 0.05). These data demonstrate for the first time that cardiopulmonary bypass and temperature of cardioplegic solution affected the expression of miRNAs in left ventricular tissue. In conclusion, specific miRNAs are potential therapeutic targets for limiting ischemia-reperfusion injury in patients undergoing cardiac surgery.

Dataset Information

Myocardial function after polarizing versus depolarizing cardiac arrest with blood cardioplegia in a porcine model of cardiopulmonary bypass.

Publications

Myocardial function after polarizing versus depolarizing cardiac arrest with blood cardioplegia in a porcine model of cardiopulmonary bypass.

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