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31P-n.m.r. studies on cerebral energy metabolism under conditions of hypoglycaemia and hypoxia in vitro.

ABSTRACT: A system has been developed for performing 31P-n.m.r. studies on cerebral tissues superfused in vitro, and gives results comparable with those reported from studies in vivo. Under optimal superfusion conditions [10 mM-glucose and O2/CO2 (19:1)] the tissue concentrations of phosphocreatine and ATP were calculated to be approx. 3.1 and 1.3 mumol/g respectively. When the glucose of the superfusing medium was lowered to 0.5 mM, slightly decreased sugar phosphate peaks were observed, but there was no detectable change in [ATP] or [phosphocreatine]. At 0.2 mM-glucose, significantly decreased concentrations of phosphocreatine and ATP were observed. Substitution of pyruvate plus malate for glucose did not decrease levels of phosphocreatine and ATP. When the superfusing medium was gassed with air/CO2 (19:1; 'mild hypoxia'), there was an appreciable fall in sugar phosphates and phosphocreatine with no detectable effect on ATP. In the presence of N2/CO2 (19:1; 'severe hypoxia', since O2 was not completely excluded), concentrations of phosphocreatine fell considerably, but with little effect on ATP. The results demonstrate the feasibility of studying cerebral energy metabolism in vitro using the non-invasive 31P-n.m.r. technique and are discussed in relation to the sensitivity of cerebral tissues to metabolic insults in vitro and in vivo.

SUBMITTER: Cox DW

PROVIDER: S-EPMC1152055 | biostudies-other | 1983 May

REPOSITORIES: biostudies-other

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Project description:BACKGROUND:The heart's energy demand per gram of tissue is the body's highest and creatine kinase (CK) metabolism, its primary energy reserve, is compromised in common heart diseases. Here, neural-network analysis is used to test whether noninvasive phosphorus (31P) cardiovascular magnetic resonance spectroscopy (CMRS) measurements of cardiac adenosine triphosphate (ATP) energy, phosphocreatine (PCr), the first-order CK reaction rate kf, and the rate of ATP synthesis through CK (CK flux), can predict specific human heart disease and clinical severity. METHODS:The data comprised the extant 178 complete sets of PCr and ATP concentrations, kf, and CK flux data from human CMRS studies performed on clinical 1.5 and 3 Tesla scanners. Healthy subjects and patients with nonischemic cardiomyopathy, dilated (DCM) or hypertrophic disease, New York Heart Association (NYHA) class I-IV heart failure (HF), or with anterior myocardial infarction are included. Three-layer neural-networks were created to classify disease and to differentiate DCM, hypertrophy and clinical NYHA class in HF patients using leave-one-out training. Network performance was assessed using 'confusion matrices' and 'area-under-the-curve' (AUC) analyses of 'receiver operating curves'. Possible methodological bias and network imbalance were tested by segregating 1.5 and 3 Tesla data, and by data augmentation by random interpolation of nearest neighbors, respectively. RESULTS:The network differentiated healthy, HF and non-HF cardiac disease with an overall accuracy of 84% and AUC?>?90% for each category using the four CK metabolic parameters, alone. HF patients with DCM, hypertrophy, and different NYHA severity were differentiated with ~?80% overall accuracy independent of CMRS methodology. CONCLUSIONS:While sample-size was limited in some sub-classes, a neural network classifier applied to noninvasive cardiac 31P CMRS data, could serve as a metabolic biomarker for common disease types and HF severity with clinically-relevant accuracy. Moreover, the network's ability to individually classify disease and HF severity using CK metabolism alone, implies an intimate relationship between CK metabolism and disease, with subtle underlying phenotypic differences that enable their differentiation. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT00181259.

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31P-n.m.r. studies on cerebral energy metabolism under conditions of hypoglycaemia and hypoxia in vitro.

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