Biomedical subjects

L Demaison

Publications and source records attributed to L Demaison.

26 records · Page 2Linked to original sources

PubMed1987

A new experimental model for studies of drug actions on myocardial metabolism. Application to a study of the influence of POCA.

In order to study myocardial metabolism by external detection, quantitative information on the metabolism of a gamma-emitting iodinated fatty acid (IHA) was obtained from time-activity curves of radioactivity in different compartments. A 4-compartment mathematical model was then developed; compartments 0, 1, 2, and 3 correspond respectively to vascular IHA, intracellular IHA, esterified forms, and iodide resulting from mitochondrial oxidation of IHA. We applied this model to a study of the influence of an inhibitor of fatty acid oxidation, POCA (2-[5(4 chlorophenyl) pentyl]-oxirane-2-carboxylate). Isolated rat hearts were perfused for 20 min with Krebs liquid containing increasing concentrations of POCA. IHA was then injected as a bolus at the entrance of the coronary network. The level of cardiac radioactivity was recorded for 30 min and the division into the 4 compartments was simulated at different concentrations of POCA. The drug appeared to increase the myocardial retention of IHA and slow down the speed of degradation and storage; the variations were dose-dependent. These results correspond to those obtained by intracellular analysis. The proposed method, which is reliable and sensitive, is an interesting experiment for pharmacological studies of cardiac metabolism.

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PubMed1986

Mathematical model of the metabolism of 123I-16-iodo-9-hexadecenoic acid in an isolated rat heart. Validation by comparison with experimental measurements.

The aim of the present study was to demonstrate that it is possible to estimate the intracellular metabolism of a fatty acid labelled with iodine using external radioactivity measurements. 123I-16-iodo-9-hexadecenoic acid (IHA) was injected close to the coronary arteries of isolated rat hearts perfused according to the Langendorff technique. The time course of the cardiac radioactivity was measured using an INa crystal coupled to an analyser. The obtained curves were analysed using a four-compartment mathematical model, with the compartments corresponding to the vascular-IHA (O), intramyocardial free-IHA (1), esterified-IHA (2) and iodide (3) pools. Curve analysis using this model demonstrated that, as compared to substrate-free perfusion, the presence of glucose (11 mM) increased IHA storage and decreased its oxidation. These changes were enhanced by the presence of insulin. A comparison of these results with measurements of the radioactivity levels within the various cellular fractions validated our proposed mathematical model. Thus, using only a mathematical analysis of a cardiac time-activity curve, it is possible to obtain quantitative information about IHA distribution in the different intracellular metabolic pathways. This technique is potentially useful for the study of metabolic effects of ischaemia or anoxia, as well as for the study of the influence of various substrates or drugs on IHA metabolism in isolated rat hearts.

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PubMed1985

Do iodinated fatty acids undergo a nonspecific deiodination in the myocardium?

The intracellular and subcellular distribution of 16-(123I)-iodo-9-hexadecenoic acid were studied in isolated rat hearts, perfused with or without glucose. At various time intervals after injection, cardiac lipids were extracted and the activity was determined for all fractions and all lipid classes. The total cardiac activity was maximal within 1 min postinjection and most of the activity was in the aqueous phase. The presence of glucose in the perfusion medium induced an increase of total cardiac and organic fraction activities. In the latter fraction, activity was very low for FFA, but high for triglycerides (TG), and especially polar lipids. The presence of an exogenous substrate, led to a more active esterification of fatty acids. Coronary effluent analysis showed, in the hydrophilic phase, a lower activity spike in the presence than in the absence of glucose. In the mitochondrial fraction most activity occurred in the organic phase, especially as polar lipids. In the nonmitochondrial fraction, activity was much higher in the aqueous phase. At 90 s postinjection of 1-14C-palmitic acid, over 80% of the myocardial activity was found in the hydrophilic fraction, which indicates, as for the iodo-fatty acid (IFA), an immediate and important oxidation, especially without glucose. These data seem to prove that IFA is taken up by the myocardial cell, subsequently enters the mitochondria and, without an early deiodination, is oxidized with iodide release. Changes in IFA metabolism, consecutive to modifications of glucose concentration in the perfusion medium can be observed by external detection of the myocardial activity curve. Omega-Iodinated fatty acids do not undergo a nonspecific deiodination and are therefore well suited for an external study of myocardial metabolism.

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PubMed1985

Influence on the myocardial and blood activity course of the characteristics of the labelled fatty acid injected i.v. into mice.

In order to choose a labelled fatty acid (FA) for the external study of myocardial metabolism, FAs that are different in chain length, saturation, nature and position of the radioactive label, are injected i.v. into mice. Myocardial and blood activities are measured at various times p.i. It appears that hexadecanoic and hexadecenoic acids, iodine labelled in omega position, have the highest maximal myocardial activity among all the FAs studied. Furthermore, the myocardial and blood time-activity course is similar for both FAs. As unsaturated FAs have apparently a higher myocardial fixation in man than the saturated ones, 123I 16 iodo-9 hexadecenoic acid has been selected and seems well suited for the study of myocardial metabolism.

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PubMed1985

Kinetics of (16 123I) iodohexadecenoic acid metabolism in the rat myocardium, influence of glucose concentration in the perfusate and comparison with (1 14C) palmitate.

External counting, intracellular and subcellular distribution of (16 123I) iodohexadecenoic acid are studied on isolated rat hearts perfused with or without glucose. The presence of an exogenous substrate reduces the fatty acid oxidation and induces an increase of total cardiac and organic fraction activities. In this fraction, activity is very low for free fatty acids, but high for triglycerides and especially for polar lipids. The presence of an exogenous substrate leads to a more active esterification of fatty acids. Coronary effluents analysis shows, in the hydrophilic phase, a lower activity rebound in the presence of glucose. In the mitochondrial fraction, activity is mostly in the organic phase, as polar lipids especially. In the non-mitochondrial fraction, activity is much higher in the aqueous phase. 90 s p.i. of (l 14C) palmitic acid, over 80% of the myocardial activity is found in the hydrophilic fraction, which indicates--as for the iodo fatty acid (IHA)--an immediate and important oxidation, especially without glucose. These data seem to prove that IHA is taken up by the myocardial cells, enters the mitochondria where it is, without an early deiodination, oxidized with iodide release. IHA metabolic changes can be seen on the external detection myocardial activity curve. Omega iodinated fatty acids do not undergo a nonspecific important deiodination and are therefore well adapted to an external study of myocardial metabolism.

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PubMedDate not supplied

Cellular and mitochondrial energy metabolism in the stunned myocardium.

The influence of cardiac stunning on the oxidation of fatty acids and the oxidative phosphorylation in mitochondria was investigated. Rat hearts were perfused for 15 min according to the working mode with a Krebs-Henseleit buffer containing glucose (11 mM). The hearts were then maintained in normoxic conditions (C group) or subjected to a 15-min global no-flow normothermic ischemia followed by a 30-min reperfusion (R group). Throughout the perfusion, the aortic and coronary flows, and the heart rate and oxygen consumption were monitored. At the end of the perfusion procedure, a bolus of 1-14C palmitate was injected in the coronary arterial bed to evaluate the fatty acid oxidation. Two sub-populations of mitochondria were isolated from each heart by either mechanical (ME mitochondria) or enzymic (EE mitochondria) extraction and their respiration properties were evaluated. Furthermore, the mitochondrial energy production (ATP and creatine phosphate) was assessed. During ischemia, the aortic flow was suppressed and recovered only to approximately 50% of the preischemic value during reperfusion. This mechanical stunning was associated with an important reduction of the stroke volume (-37%, p < 0.01) and a slight decrease in heart rate (-20%, p < 0.001). At the end of reperfusion, the beta-oxidation rate constituted 55 +/- 1.7% of the cell palmitate and was similar to that assessed in the C group. The oxygen consumption was decreased to 216 +/- 31.0 microL O2/min/gww and the venous O2 concentration increased to 5.1 +/- 0.572 microL O2/mL (instead of 2.9 +/- 0.342 microL O2/mL in the C group), although due to large SD, only the latter was statistically significant. A decrease in metabolic efficiency (42 +/- 14.4 vs 106 +/- 16.8 mL/microL O2 in the C group) and an increase in palmitate oxidation to oxygen consumption ratio (77 +/- 10.1 vs 47.6 +/- 4.25% beta-oxidized palmitate/microL O2 in the C group) were observed. This increased fatty acid contribution in the oxidation metabolism could be responsible for some oxygen wasting and could contribute to decrease the energy available for the contraction despite the normal cardiac oxygen uptake. Furthermore, the respiration parameters of the mitochondria were similar in the C and R groups when glutamate (20 mM) or palmitoylcarnitine (25 microM) were used as substrate. ME mitochondria of R group displayed a reduced rate of ATP production (118 +/- 29.5 vs 180 +/- 14.5 nmoles/min/mg proteins in the C group) without altered creatine phosphate production. The presence of calcium in the medium (10(-5) M) provoked a decrease in ATP production.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗

PubMedDate not supplied

Effect of dietary polyunsaturated fatty acids on contractile function of hearts isolated from sedentary and trained rats.

Moderate physical training induced a decrease in arterial blood pressure in fish oil-fed rats as compared to sunflower seed oil-fed rats. The purpose of this study was to determine if these changes were due to modifications of the left ventricular function of the heart. Forty rats were fed a semi-purified diet containing either 10% sunflower seed oil or 10% fish oil (EPAX 3000TG, Pronova). Each dietary group was assigned to two sub-groups, one being constituted by sedentary animals and the other by trained animals. Training was achieved by daily running for 60 minutes at moderate intensity for three weeks. At the end of the training period, the animals were sacrificed and their hearts were immediately perfused according to the working mode. The phospholipid fatty acid composition and parameters of the left ventricular function were determined. Feeding fish oil markedly reduced the proportion of n-6 polyunsaturated fatty acids (PUFA, 18:2 n-6, 20:4 n-6, 22:4 n-6 and 22:5 n-6) in cardiac phospholipids. The n-6 PUFA were replaced by n-3 PUFA (mainly docosahexaenoic acid). In sedentary animals, the fluid dynamic (aortic and coronary flow, cardiac output) was not modified by the diet. The heart rate was reduced (-10%) in n-3 PUFA-rich hearts. Physical training did not markedly alter the polyunsaturated fatty acid profile of cardiac phospholipids. Conversely, it reduced the heart rate, aortic flow and cardiac output (-11, -21 and -14%, respectively) at a similar extent in the two dietary groups. In a second set of experiments, the training period was repeated in animals fed a commercially available diet (A103, UAR) which simultaneously provided n-6 and n-3 fatty acids. In these dietary conditions, neither the aortic flow nor the heart rate was decreased by physical exercise. These results suggest that both n-6 and n-3 PUFA in the diet are necessary to ensure a good cardiac adaptation to moderate physical training. Furthermore, the fish oil-induced decrease in arterial blood pressure in trained animals was not related to changes in cardiac contractility, but to a decrease in vascular resistances. Moderate physical training + dietary n-3 PUFA might be used to prevent hypertension and cardiovascular diseases.

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PubMedDate not supplied

Individual effects of dietary EPA and DHA on the functioning of the isolated working rat heart.

The aim of this study was to evaluate the effects of dietary pure eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the physiology of the heart in normoxic conditions and during postischemic reperfusion. These effects were compared with those of dietary n-6 polyunsaturated fatty acids (PUFA). Rats were fed a diet containing either sunflower seed oil (75 g x kg(-1), SSO group), or a mixture of EPA (20:5 n-3) ethyl ester and SSO (10:90, EPA group), or a mixture of DHA (22:6 n-3) ethyl ester and SSO (10:90, DHA group), or a mixture of EPA + DHA ethyl esters and SSO (4.2:5.8:90, e+D group) for 6 weeks. The hearts were then perfused according to the working mode. The perfusion was maintained either in normoxic conditions or stopped for 17 min (global zero-flow ischemia) and restored for 33 min (reperfusion). The aortic and coronary flows, aortic developed pressure, and electrocardiogram were continuously monitored. When rats were fed a diet containing either EPA and (or) DHA, the n-6/n-3 PUFA ratio of cardiac phospholipids decreased. The proportion of arachidonic acid was reduced more with DHA than dietary EPA. In the EPA group, the percentage of DHA was lower than in the DHA group, but the percentage of EPA and docosapentaenoic acid (22:5 n-3) was higher. These changes in membrane fatty acid composition altered the cardiac function. In normoxic conditions, the coronary flow was higher in the SSO group than in the DHA and EPA groups. The heart rate was lower in the DHA and e+D groups than in the EPA and SSO groups. The aortic flow, cardiac output, and aortic developed pressure were not affected. During postischemic reperfusion, the recovery of aortic flow, coronary flow, and aortic developed pressure was similar in the four groups. A slightly improved recovery of cardiac function was noticed in the EPA group, but the difference was not significant. Feeding rats 5% fish oil + 5% SSO instead of 10% SSO for 8 weeks increased the incorporation of EPA in cardiac phospholipids and favored the recovery (+120%) of aortic flow during postischemic reperfusion. In conclusion, the beneficial effect of dietary fish oil on the recovery of cardiac pump activity during reperfusion was not observed with DHA or EPA alone. It appears to be positively related to the accumulation of EPA in membrane phospholipids. The dietary conditions favouring EPA accumulation remain to be determined.

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