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Differential neuronal vulnerability varies according to specific cardiopulmonary bypass insult in a porcine survival model.

ABSTRACT: We investigated whether the degree of vulnerability of different areas in the developing brain varies according to the specific mechanism of the insults caused by cardiopulmonary bypass.A meta-analysis of 2 experimental studies (n = 80) was conducted. The end points of the otherwise identical studies were tissue oxygen index in the first experiment, whereas cerebral microvessel vasoconstriction and inflammatory response of endothelial cells were directly visualized in the second study. We assigned ultra-low flow bypass at 25 °C for 60 minutes as control; circulatory arrest at 25 °C for 60 minutes as ischemic stress under circulatory arrest (ischemia-CA); and ultra-low flow bypass at 34 °C for 60 minutes as the stress under ultra-low flow bypass (ischemia-ULF). Histologic neuronal damage was the primary outcome. Secondary measures included neurologic recovery.Vasoconstriction after ischemia and inflammation after bypass were independent predictors of severe histologic damage. The caudate nucleus was significantly vulnerable to ischemia-CA and was significantly influenced by vasoconstriction. In contrast, the hippocampus was significantly vulnerable to ischemia-ULF. The different forms of ischemic insults did not influence Purkinje cells, whereas Purkinje damage significantly correlated with inflammation. Tissue oxygen index had the ability to differentiate accurately regional damage. Neurologic recovery under ischemia-CA was significantly worse compared with ischemia-ULF. Neurologic recovery correlated with neuronal damage in the caudate nucleus, but it did not correlate with damage in the hippocampus.Neuronal vulnerability in different areas of the developing brain varies according to mechanisms of bypass-induced ischemic stress. Certain regional damage may not be apparent in assessing acute neurologic recovery.

SUBMITTER: Ishibashi N

PROVIDER: S-EPMC2917514 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Differential neuronal vulnerability varies according to specific cardiopulmonary bypass insult in a porcine survival model.

Ishibashi Nobuyuki N Iwata Yusuke Y Okamura Toru T Zurakowski David D Lidov Hart G W HG Jonas Richard A RA

The Journal of thoracic and cardiovascular surgery 20101201 6

<h4>Objective</h4>We investigated whether the degree of vulnerability of different areas in the developing brain varies according to the specific mechanism of the insults caused by cardiopulmonary bypass.<h4>Methods</h4>A meta-analysis of 2 experimental studies (n = 80) was conducted. The end points of the otherwise identical studies were tissue oxygen index in the first experiment, whereas cerebral microvessel vasoconstriction and inflammatory response of endothelial cells were directly visuali ...[more]

PMID: 20434176

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Project description: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.

Dataset Information

Differential neuronal vulnerability varies according to specific cardiopulmonary bypass insult in a porcine survival model.

Publications

Differential neuronal vulnerability varies according to specific cardiopulmonary bypass insult in a porcine survival model.

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