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Biomedical subjects

D Feuvray

Publications and source records attributed to D Feuvray.

At least 37 records · Page 2Linked to original sources
PubMed1993

Skinned cardiac fibres of diabetic rats: contractile activation and effects of 2,3-butanedione monoxime (BDM) and caffeine.

OBJECTIVE: The aim was to examine contractile properties of skinned cardiac fibres from rats with streptozotocin induced diabetes and to compare the effects of two agents, caffeine and 2,3-butanedione monoxime (BDM), on myocardial contractile characteristics of normal and diabetic cardiac fibres. METHODS: Small fibre bundles dissected from papillary muscles of the left ventricle were chemically skinned by exposure to Triton X-100. The tension-pCa (pCa = -log10 [Ca2+]) relationships were determined under isometric conditions. RESULTS: In skinned fibres from diabetic rats maximum Ca2+ activated force was unchanged in comparison with normal rats, but a significant, though small, increase in the Ca2+ sensitivity [pCa for one half maximal activation (pCa50)] of contraction was shown. Caffeine (5-20 mM) increased Ca2+ sensitivity in a dose dependent manner and to the same extent in the two groups of preparations. Up to 10 mM caffeine, maximum force was not affected. On the other hand, BDM (2 and 5 mM) decreased Ca2+ sensitivity in both normal and diabetic fibres, but the rightward shift of the tension-pCa relationship induced by BDM was more pronounced in diabetic than in normal fibres: pCa50 was 5.55(SEM 0.02), 5.51(0.01), and 5.46(0.01) in normal fibres, and 5.62(0.01), 5.51(0.02), and 5.45(0.02) in diabetic fibres for 0, 2, and 5 mM BDM, respectively. Maximum tension was similarly decreased by BDM in the two groups of fibres. CONCLUSIONS: (1) No change is induced by diabetes in the site of action of caffeine; (2) some drugs that affect myofilament Ca2+ sensitivity, such as BDM, may act differently in diabetic and control myocardium.

Animals↗
PubMed1993

Calcium and potassium currents in ventricular myocytes isolated from diabetic rats.

1. The whole-cell voltage-clamp technique was applied to ventricular myocytes isolated from normal and streptozotocin-induced diabetic rat hearts to investigate the contribution of the calcium current and of the calcium-independent potassium currents to diabetes-induced alterations of the action potential. 2. In single calcium-tolerant isolated myocytes diabetes induced a lengthening of the action potential similar to that previously described in intact ventricular muscles. 3. Only L-type calcium current was present both in normal and diabetic cells. Inactivation of ICa was described in both preparations by two exponentials, whose time constants were not modified by diabetes. 4. Calcium current density-voltage relationships and steady-state inactivation curves were not significantly affected by diabetes. 5. Potassium background inward rectifier current was not modified by diabetes. 6. Calcium-independent outward potassium current inactivated, in both cell types, according to a biexponential process whose time constants were not affected by diabetes. 7. The transient outward potassium current density was significantly reduced by diabetes whereas neither the voltage dependence of the inactivation nor the time dependence of recovery from inactivation was modified. 8. A 4-aminopyridine-insensitive potassium current was also reduced by diabetes. 9. Our results show that in isolated ventricular myocytes the lengthening of the action potential induced by diabetes results mainly from a decrease of the transmembrane calcium-independent potassium permeability.

4-Aminopyridine↗
PubMed1991

Intracellular sodium activity in papillary muscle from diabetic rat hearts.

In quiescent papillary muscles isolated from hearts of rats with streptozotocin-induced diabetes resting intracellular sodium activity (aiNa) was about 56% greater than in muscles from controls. An intracellular acid load induced by the NH4+ method caused a rise in aiNa whose maximum amplitude was similar in both groups of muscles. However, the half-time to maximum amplitude was increased by about 56% in diabetic muscles. These results are consistent with a diabetes-induced decrease in the activity of the sarcolemmal Na(+)-H+ exchange.

Animals↗
PubMed1990

Intracellular pH and role of Na+/H+ exchange during ischaemia and reperfusion of normal and diabetic rat hearts.

STUDY OBJECTIVE: The aim was to investigate the role of intracellular pH (pHi) and ion exchange on the functional recovery of perfused hearts isolated from normal (N) rats either receiving or not receiving amiloride (an Na+/H+ exchange inhibitor), and from STZ induced diabetic (D) rats with decreased Na+/H+ exchange activity. DESIGN: Working heart preparations were submitted to a zero flow ischaemic period of 30 min at 37 degrees C and then reperfused for 30 min. The time course of pHi decline during ischaemia and of recovery on reperfusion was followed by means of 31P-NMR. MEASUREMENTS AND MAIN RESULTS: In N hearts without amiloride, ischaemia caused a progressive decrease in pHi. This was slightly, although not significantly, more abrupt in N hearts receiving amiloride. D hearts showed a slower fall in pHi, but the mean value reached after 30 min did not differ significantly from that of normal hearts. pHi recovery on reperfusion was markedly slower in the D hearts compared to N hearts. The mean value reached after 30 min did not differ significantly from that of N hearts. pHi recovery was also markedly slower in N hearts exposed to amiloride during both ischaemia and reperfusion. The higher functional recovery on reperfusion, as assessed by the recoveries of aortic flow and stroke volume, was observed for those hearts with slower pHi recovery. Improved recoveries of aortic flow and stroke volume as compared to normal non-treated hearts were 34% and 21% for the diabetic hearts, and 22% and 40% for the normal hearts receiving amiloride. CONCLUSIONS: The comparison of data from diabetic rat hearts with reduced activity of the Na+/H+ exchange process v normal hearts with pharmacological block of the exchanger provide support for a critical role of the Na+/H+ exchanger in the initial stage of reperfusion.

Amiloride↗
PubMed1990

Decreased sensitivity of contraction to changes of intracellular pH in papillary muscle from diabetic rat hearts.

1. The relationship between intracellular pH (pHi) and contractile activity was investigated in papillary muscles isolated from right ventricle of normal and streptozotocin (STZ)-induced diabetic rats. pHi changes induced by 20 mM-NH4Cl were recorded with H(+)-sensitive microelectrodes. 2. An increase in pHi of approximately 0.20 pH units on exposure to NH4Cl led to an increase of the maximum developed tension, which was 707.8 +/- 57.5% (mean +/- S.E. of mean, n = 10) of control in normal muscles and 271 +/- 16.3% (n = 10) in diabetic muscles. On the other hand, acidosis induced by NH4Cl withdrawal was associated with a fall in developed tension to 48.2 +/- 6.7% of control in diabetic muscles, as compared to 79.2 +/- 8% in normal muscles. 3. The decrease in tension associated with acidosis was rapidly followed (in approximately 2 min) by a transient redevelopment of force, which peaked at 80.2 +/- 8.6% of control in the diabetic muscles as compared to 153.5 +/- 11.7% in normal papillary muscles. The peak of this secondary positive inotropy coincided in both groups of muscles with the maximum decrease of pHi, i.e. -0.40 +/- 0.02 and -0.28 +/- 0.04 pH units in diabetic and normal muscles, respectively. 4. Caffeine (10 mM), which had a marked positive inotropic effect in both groups of muscles, abolished the transient recovery of tension occurring after NH4Cl withdrawal. Ryanodine (2 microM) which had a marked negative inotropic effect on both normal and diabetic papillary muscles, also suppressed the transient recovery of tension. 5. The presence of amiloride (1 mM) during acidosis induced by NH4Cl withdrawal abolished the observed differences in developed tension, in particular the transient recovery of tension, between normal and diabetic muscles, as it abolished the differences in the amplitude of pHi decrease and in the time course of pHi recovery. 6. The presence of 2',4'-dichlorobenzamil amiloride (40 microM) significantly and similarly delayed and reduced the amplitude of transient recovery of tension in both normal and diabetic papillary muscles. 7. We conclude that STZ-induced diabetes induces a decrease in pHi sensitivity of contractile force. This may be the consequence of a change in sarcoplasmic reticulum (SR) composition and function, and may also indirectly result from changes in Na(+)-H+ exchange activity, particularly during intracellular acidosis.

Amiloride↗
PubMed1989

Influence of intracellular pH on mitochondrial calcium during ischaemia of the isolated rat heart.

Under physiological conditions cardiac mitochondria seem to play a minor role in maintaining intracellular Ca2+ homoeostasis. However, under conditions of cellular Ca2+ overload, mitochondria may accumulate large amounts of Ca2+. Using transmission and analytical electron microscopy, we investigated, in globally ischaemic rat heart preparations, the influence of intracellular pH on the development of Ca2+-containing intramitochondrial inclusions. We confirmed that under these experimental conditions Ca2+ was a major element of mitochondrial inclusions. The size of these inclusions increased with external Ca2+ concentration. An intracellular alkalinization, produced by addition of 20 mM NH4Cl to the perfusate prior to ischaemia, inhibited the formation of such inclusions. On the other hand, a pre-ischaemic intracellular acidification, produced by the addition and subsequent withdrawal of the 20 mM NH4Cl, increased the number of inclusions present at the end of an ischaemic episode. The presence of amiloride (10(-3) M), prior to and during ischaemia, increased the number of inclusions. These data suggest that cytoplasmic pH may be an important factor in mitochondrial Ca2+ accumulation in pathological conditions.

Amiloride↗
PubMed1988

Intracellular pH regulation in papillary muscle cells from streptozotocin diabetic rats: an ion-sensitive microelectrode study.

Intracellular pH regulation was studied in papillary muscle from STZ-induced diabetic rat hearts. In control bicarbonate solution there was no difference between the steady-state pHi values recorded from diabetic or normal papillary muscle. The addition of insulin had no effect on the pHi of either group. The amplitude of NH4+-induced alkalinization and the time course of recovery from alkalinization were similar in both normal and diabetic muscles. In both preparations, the recovery from alkalinization was similarly delayed by the disulfonic stilbene DIDS. This suggests the participation of a Cl-/HCO3- exchange in the recovery from alkalosis in rat myocardial cells that is not changed by diabetes. On the other hand, the amplitude of the acidification induced by the withdrawal of NH4+ was markedly increased in diabetic papillary muscles as compared to normal muscles. Moreover, there was a marked slowing down of the recovery from acidosis in the diabetics. The amplitude of NH+4 withdrawal-induced acidification was increased equally by amiloride in both normal and diabetic muscles. These findings suggest that diabetes is associated with a change in the activity of the amiloride-sensitive Na+/H+ exchange.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1988

[Intermediate myocardial metabolism. Changes in ischemia, diabetes and hyperthyroidism].

Long-chain free fatty acids (FFA) are oxidized, in preference to carbohydrates, by a myocardium with normal oxygen supply. Their utilization is increased in diabetes and most probably also in hyperthyroidism, since in both cases plasma FFA concentrations are augmented. Under conditions of ischaemia, the long-chain fatty acid esters of coenzyme A (CoA) and carnitine accumulate in cells. This accumulation depends on the degree of coronary blood flow reduction, being very high in moderate ischaemia and much reduced when the coronary flow is nul. The accumulation of acyl-CoA and acylcarnitine in ischaemic myocardium is amplified by diabetes. The presence in the cells of these amphophilic compounds (notably acylcarnitine) in high concentrations has been associated with changes in the structure and properties of mitochondrial and sarcolemmal membranes. Finally, the accumulation of glycolysis end-products (e.g. lactates and protons) may condition the degree of functional recovery from global and total ischaemia. In this respect, recently obtained in vitro data show that a decrease in cellular pH may be one of the determinant factors in reperfusion.

Coronary Disease↗
PubMed1986

Reduction of ischemia-induced acyl carnitine accumulation by TDGA and its influence on lactate dehydrogenase release in diabetic rat hearts.

The contribution of long-chain acyl carnitine to increase enzyme release during ischemia was investigated both in normal and diabetic rat hearts. 2-Tetradecylglycidic acid (TDGA) was used to inhibit acyl carnitine formation. Isolated working-heart preparations were perfused with glucose (11 mM) and palmitate (0.1 mM) in control and mild ischemic conditions. Ischemia induced lactate dehydrogenase (LDH) release from both normal and diabetic hearts, but the release was higher from the diabetics over a 15-min ischemic period. The ischemia-induced tissue accumulation of long-chain acyl carnitine also was greater in diabetic hearts compared with normal hearts. When TDGA was provided in the perfusate 10 min before the addition of palmitate, levels of acyl carnitine were significantly reduced (by approximately 80%) in the ischemic tissue of both groups of hearts. Similarly, LDH release from ischemic hearts was markedly decreased in the presence of TDGA. A positive correlation was shown between LDH release over the ischemic period and the tissue levels of acyl carnitine at the end of ischemia. Significant improvement in mechanical function with TDGA was only observed in ischemic diabetic hearts. There was absolutely no difference in high-energy compounds under a given perfusion condition, either with or without TDGA, between normal and diabetic hearts. It is concluded that lessening the accumulation of fatty acid intermediates, such as acyl carnitine, may be important to prevent or to limit the loss of sarcolemmal integrity under ischemic conditions, especially in diabetic hearts.

Acetylcarnitine↗
PubMed1985

Abnormal cardiac rhythm in diabetic rats.

A significant occurrence of abnormal rhythm was observed in perfused working hearts of diabetic rats. The incidence of arrhythmias was 19/51 in diabetics as compared with 2/38 in normal controls. In considering possible pathogenetic mechanisms, conduction system defects appear to merit particular attention.

Animals↗
PubMed1984

Lipid intermediates in chronically volume-overloaded rat hearts. Effect of diffuse ischemia.

Tissue contents of intermediates of fatty acid metabolism were determined in isolated volume-overloaded rat hearts, 3 months after creation of an aorto-caval fistula. In the absence of any modification of blood carnitine, tissue levels of total carnitine were reduced by 33% in overloaded hearts compared to normal hearts. Total tissue CoA was unchanged. Fifteen minutes of whole-heart ischemia (i.e. a 50% reduction in coronary flow) did not increase levels of long-chain acyl esters of CoA and carnitine of the overloaded myocardium, in the presence of glucose as the only exogenous substrate. This was associated with lower than normal levels of long-chain acyl carnitine under normoxic conditions. The addition of exogenous palmitate (1.5 mM) resulted in an ischemia-induced accumulation of long-chain acyl-CoA and acyl carnitine in the overloaded heart although to a smaller extent than in the normal heart under similar perfusion conditions.

Acyl Coenzyme A↗
PubMed1984

[Metabolism of long chain fatty acids in the normal and pathologic heart: effects of ischemia].

Long-chain free fatty acids which, in well-oxygenated hearts are the preferred metabolic fuel, are detrimental to cardiac function under ischemic conditions. A number of metabolic products accumulate in the cell during ischemia, among which are the long-chain acyl esters of CoA and carnitine. The presence of exogenous fatty acids during ischemic perfusion results in higher tissue levels of acyl carnitine. Diabetic hearts also have higher tissue levels of long-chain acyl-CoA and acyl carnitine. Moreover the increase of these long-chain acyl esters during ischemia is greater than in the normal hearts. The rise in long-chain acyl carnitine levels in the ischemic tissue correlates with the appearance of amorphous densities in the mitochondria and with structural alteration of the inner mitochondrial membrane. Accumulation of intermediates of fatty acid metabolism likely to contribute to cellular damage during ischemia.

Acyl Coenzyme A↗
PubMed1983

Ultrastructural, functional, and metabolic correlates in the ischemic rat heart. Effects of free fatty acid.

A study correlating functional, metabolic, and ultrastructural changes in the ischemic myocardium was conducted on isolated working rat hearts, both in the presence and absence of fatty acid. Glucose alone (11 mM) or glucose plus palmitic acid (1.5 mM) were used as metabolic substrates. A 60-min period of whole-heart ischemia resulted in a more dramatic morphological alteration in those hearts receiving palmitate than in those receiving no palmitate. In ischemic hearts receiving palmitate, intramitochondrial amorphous densities of both rounded and elongated types were observed. These densities did not develop in hearts receiving glucose alone over the same period of ischemia. Such morphological alterations were associated with a more severe deterioration of mechanical function in the presence of palmitate. Biochemical determinations of fatty acid derivatives showed increased tissue levels of acyl esters of CoA and carnitine in ischemic hearts, but levels of long-chain acyl carnitine were much higher in those ischemic hearts receiving palmitate. Furthermore, from the data obtained on isolated mitochondria, it appeared that the mitochondrial level of long-chain acyl carnitine was approximately four times higher in the ischemic hearts receiving palmitate than in those receiving no palmitate. This great rise in mitochondrial levels of long-chain acyl carnitine correlated with modifications of the mitochondrial structure and with the appearance of amorphous densities.

Acyl Coenzyme A↗
PubMed1981

Structural, functional, and metabolic correlates in ischemic hearts: effects of substrates.

The ultrastructure, function, and metabolism of isolated rat hearts perfused under control or ischemic conditions were investigated. Either both glucose (11 mM) or glucose and palmitic acid (1.5 mM) were used as metabolic substrates. A 60-min period of whole-heart ischemia, i.e., a 60% initial reduction in coronary flow, resulted in a more dramatic morphological alteration in those hearts receiving palmitate compared to those receiving glucose as the only substrate. In ischemic hearts receiving palmitate, intramitochondrial osmiophilic amorphous densities of both rounded and elongated types were observed. These amorphous densities did not develop in ischemic hearts receiving glucose alone over the same period of ischemia. Such morphological alterations were associated with a more severe deterioration of mechanical function in the presence of palmitate. Both ischemic conditions resulted in increased tissue levels of acyl esters of CoA and carnitine, but the rise in levels of long-chain acyl carnitine was about two times greater in those ischemic hearts receiving palmitate.

Acyl Coenzyme A↗