Dataset Information

Myocardial energy metabolism and ultrastructure with polarizing and depolarizing cardioplegia in a porcine model.

ABSTRACT:

Objectives

This 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).

Methods

Twenty 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.

Results

With 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.

Conclusions

Polarizing STH-POL cardioplegia improved energy status compared to standard STH-2 depolarizing blood cardioplegia during cardioplegic arrest and early after reperfusion.

SUBMITTER: Aass T

PROVIDER: S-EPMC5848816 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Publications

Myocardial energy metabolism and ultrastructure with polarizing and depolarizing cardioplegia in a porcine model.

Aass Terje T Stangeland Lodve L Chambers David J DJ Hallström Seth S Rossmann Christine C Podesser Bruno K BK Urban Malte M Nesheim Knut K 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 20170701 1

<h4>Objectives</h4>This 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).<h4>Methods</h4>Twenty anaesthetised pigs on tepid cardiopulmonary bypass were randomized to cardiac arrest for 60 min with antegrade freshly mixed, r ...[more]

PMID: 28329148

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Project description:ObjectivesPotassium-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.MethodsTwenty 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.ResultsLeft 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.ConclusionsPolarizing oxygenated blood cardioplegia with esmolol/adenosine/magnesium offers comparable myocardial protection and improves contractility compared with the standard potassium-based depolarizing blood cardioplegia.

Project description:Ethnopharmacological relevance: Shexiang Baoxin Pill (SBP) is a traditional formulation of a Chinese patent medicine, which has been commonly used for the treatment of cardiovascular disease (CVD) in China since the 1980s. Previous clinical studies have shown that SBP is safe and effective in patients with CVD, but the mechanism of the therapeutic effect is still poorly understood and requires further research. Aim of the study: This study aims to comprehensively understand the effects and the underlying mechanisms of SBP for CVD treatment by analyzing the whole proteome of myocardial infarction (MI) model rats with or without SBP treatment. Materials and methods: We evaluated the therapeutic effects of SBP on myocardial infarction model (MI) rats by performing the echocardiography analyses after 15-day treatment. And the label-free quantitative proteomic approach was utilized to investigate the whole proteome of the rat heart tissues from MI group (MI rats, n=3), SBP group (MI rats treated with SBP, n=3) and SOG group (sham operated rats, n=3) on the operation day (Day 0) and 15 days after operation (Day 15), respectively. The differentially expressed proteins were subsequently analyzed with bioinformatical methods such as KEGG pathway enrichment analysis, gene ontology (GO)-annotation analysis and protein-protein interaction (PPI) network analysis. Finally, the expression levels of two promising proteins were validated by immunoblotting. Results: The echocardiography analyses show SBP significantly improved the left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) of MI rats. Additionally, 134 proteins were differentially expressed both between SBP/MI and SOG/MI, and 15 proteins were found closely related to CVD. The pathway enrichment and GO-annotation analysis of these differentially expressed proteins revealed that the proteins involved in cellular mitochondrial energy metabolism processes, such as fatty acid beta-oxidation and aerobic respiration, were significantly regulated under SBP treatments, of which fatty acid-binding protein 3 (FABP3) and myoglobin (MB) was significantly down-regulated in MI model group compared with SOG group and was returned to the basal level by SBP treatment. Expression levels of these two proteins were confirmed by immunoblotting experiments. Conclusions: These results we obtained in current study probably demonstrated that the cardio-protective effects of Shexiang Baoxin Pill might be achieved through the regulation of energy metabolism homeostasis in cardiac tissue.

Dataset Information

Myocardial energy metabolism and ultrastructure with polarizing and depolarizing cardioplegia in a porcine model.

Objectives

Methods

Results

Conclusions

Publications

Myocardial energy metabolism and ultrastructure with polarizing and depolarizing cardioplegia in a porcine model.

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