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H M Piper

Publications and source records attributed to H M Piper.

170 records · Page 10Linked to original sources
PubMedDate not supplied

The role of Na+/H+ exchange in ischemia-reperfusion.

In ischemia the cytosol of cardiomyocytes acidifies; this is reversed upon reperfusion. One of the major pH(i)-regulating transport systems involved is the Na+/H+ exchanger. Inhibitors of the Na+/H+ exchanger have been found to more effectively protect ischemic-reperfused myocardium when administered before and during ischemia than during reperfusion alone. It has been hypothesized that the protection provided by pre-ischemic administration is due to a reduction in Na+ and secondary Ca2+ influx. Under reperfusion conditions Na+/H/ exchange inhibition also seems protective since it prolongs intracellular acidosis which can prevent hypercontracture. In detail, however, the mechanisms by which Na+/H+ exchange inhibition provides protection in ischemic-reperfused myocardium are still not fully identified.

Acidosis↗
PubMedDate not supplied

Calcium and sodium control in hypoxic-reoxygenated cardiomyocytes.

When oxygen-deprived cardiomyocytes become energy depleted, they accumulate Na+ and Ca2+ in the cytosol. Influx of Ca2+ via the Na+/Ca2+ exchange mechanism seems to contribute to the development of Ca2+ overload, but Ca2+ overload may eventually also occur when this route is blocked. Hypoxic-reoxygenated cardiomyocytes in a state of severe overload of Na+ and Ca2+ can rapidly re-establish a normal cation control when oxidative energy production is re-initiated. The recovery of cellular Ca2+ control may be divided into three stages: first, sequestration of large amounts of Ca2+ into the sarcoplasmic reticulum; second, oscillatory movement of Ca2+ from and back into the sarcoplasmic reticulum and gradual extrusion across the sarcolemma; third, re-establishment of constant low cytosolic Ca2+ concentrations. When the Na+/Ca2+ exchanger is inhibited, extrusion of Ca2+ from the cells' interior is impaired and oscillatory Ca2+ movements between cytosol and sarcoplasmic reticulum continue for long time. Thus, the functions of the sarcoplasmic reticulum and the Na+/Ca2+ exchanger are of crucial importance for the recovery of Ca2+ control in reoxygenated cardiomyocytes. In re-energized cardiomyocytes, a persistent elevation of the cytosolic Ca2+ concentration provokes maximal force development and consecutive mechanical cell injury ("oxygen paradox"). This injury can be prevented when the contractile machinery is inhibited during the initial phase of reoxygenation as long as necessary for the re-establishment of a normal cytosolic Ca2+ control.

Animals↗
PubMedDate not supplied

A new method for studying the incorporation of nonesterified fatty acids into cardiac lipids by using deuterium-labelled palmitate.

A new method for measuring the incorporation of exogenous fatty acids into myocardial lipids of working rat hearts using deuterium-labelled palmitate has been developed. After perfusing isolated hearts, the fatty acid composition of triglycerides, diglycerides, monoglycerides, cholesterol esters, and nonesterified fatty acids (NEFA) was measured by a mass fragmentographic method. Hearts perfused only with 5 mM glucose and 1 mM lactate perfusion as basic substrates showed a significant decrease of triglyceride content, while the other lipids were not found to be significantly reduced. The fatty acid composition of all lipids were not affected. An addition of D31-palmitate complexed to albumin at a molar ratio of 5:1, caused a dose-dependent incorporation into triglycerides and diglycerides which suggested saturation kinetics. The tissue content of nonesterified D31-palmitate was found to be linearly related to its concentration in the perfusate. It may be of note that the concentration of the other NEFA was significantly affected neither by a fatty-acid-free perfusion nor by a perfusion with D31-palmitate. A significant incorporation of the supplied fatty acid into cholesterol esters and monoglycerides could not be detected.

Animals↗
PubMedDate not supplied

The role of fatty acids in ischemic tissue injury: difference between oleic and palmitic acid.

Guinea pig hearts were subjected to low-flow perfusion (0.3 ml/g fresh weight/min) with an oxygen depleted perfusate. Fatty acids (palmitic or oleic acid), added to the perfusate, accelerated in a dose-dependent manner the anoxic decay of creatine phosphate and ATP, impaired lactate production and augmented enzyme release (lactate dehydrogenase, malate dehydrogenase). Palmitic and oleic acid, however, differed distinctly in their deleterious effect, this being greater for oleic acid. After 60 min anoxic low-flow perfusion with 11 mM glucose and 0.2 mM of either fatty acid, complexed in 5:1 molar relationship to albumin, the creatine phosphate content with palmitate is 39% greater than with oleate, the ATP content 23%, lactate production 15% greater, and release of malate dehydrogenase 24% lower, but the elevated contents of long-chain acyl CoA and acyl carnitine are not significantly different for the two fatty acids. These results accord with earlier experiences on subcellular systems showing that the physicochemical effects of the oleyl residue are more harmful than those of the palmityl residue.

Adenosine Triphosphate↗
PubMedDate not supplied

Myocardial fatty acid oxidation: evidence for an albumin-receptor-mediated membrane transfer of fatty acids.

Using a computer-assisted working rat heart preparation, which allows continuous registration of the respiratory quotient, it was tested which parameters determine fatty acid oxidation in the myocardium. Supplying albumin and palmitate in different concentrations the rate of fatty acid oxidation was measured. The UFA concentrations were calculated using stepwise equilibrium constants. When keeping constant the NEFA/albumin ratio and raising total NEFA concentration, an increase in fatty acid oxidation was found showing a saturation curve. Increasing NEFA at constant albumin concentration, however, results in a linear increase in fatty acid oxidation. Keeping constant the total NEFA concentration elevation of albumin shows an inhibitory effect. These results suggest the existence of a receptor for albumin on heart cell surface, which mediates uptake of albumin-bound NEFA. An additional supply of glucose and lactate does not show any effect on these relations. Acetate and dichloroacetate, an activator of the pyruvate dehydrogenase, are found to be competitive inhibitors of fatty acid oxidation.

Albumins↗
PubMedDate not supplied

A new method for continuous measuring of respiratory quotient in a computer-assisted working heart preparation.

A method was developed for continuous monitoring of the respiratory quotient (RQ) and the ratio of O2-consumption to O2-demand (EQ) in an isolated working rat heart preparation. The RQ allows to get informations about substrates actually oxidized in the myocardium. The EQ is a parameter which behaves reciprocally to the ATP/O of the oxidized substrates during steady state and additionally it allows monitoring of a transitory oxygen debt. For registration of RQ the arterio-venous O2-difference and the CO2-release are measured. As the CO2-production is very small compared with arterial CO2- and HCO-3 -concentrations when using a bicarbonate buffer for perfusion, a bicarbonate-free perfusion-fluid is used. In a portion of coronary effluent the pH is lowered to shift the CO2/HCO-3 -equilibrium to the side of dissolved CO2. Then the pCO2 is measured with a CO2-Nelectrode. Additionally, ventricular pressure, cardiac input and coronary flow are continuously registrated. All data are fed via an AD-converter into an LSI 11-computer. Heart rate, maximum ventricular pressure, dP/dtmax, oxygen demand after Bretschneider's formula, RQ and EQ are calculated. The advantages of the system described are demonstrated with two examples.

Animals↗
PubMedDate not supplied

Significance of nitric oxide and peroxynitrite in permeability changes of the retinal microvascular endothelial cell monolayer induced by vascular endothelial growth factor.

Reactive oxygen species (ROS) play an important role in signaling pathways stimulated by growth factors in vascular cells. We investigated whether vascular endothelial growth factor (VEGF), which is upregulated in diabetic retinopathy and atherosclerosis, is able to enhance production of ROS, and if so, whether ROS modulate endothelial permeability. ROS levels in bovine retinal microvascular endothelial cells (BMEC) were measured by the oxidation of 2', 7'-dichlorodihydrofluorescein (DCHF), and permeability was examined by monitoring the passage of albumin through BMEC monolayers. VEGF stimulated oxidation of DCHF in BMEC, an effect which was inhibited by superoxide dismutase (SOD) and the nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), but not by D-NAME. Urate, a scavenger of peroxynitrite, attenuated the VEGF-induced oxidation of DCHF. VEGF elicited a significant increase in the macromolecule permeability of BMEC monolayers within 30 min. SOD did not modify the basal or the VEGF-stimulated hyperpermeability, but the combination of SOD and VEGF induced a transient reduction in permeability after 10 min. L-NAME, but not D-NAME, enhanced VEGF-induced hyperpermeability without affecting basal values. Urate did not modify the VEGF-induced changes in permeability. In conclusion, VEGF stimulates oxidation of DCHF, which most likely represents peroxynitrite formation, and induces an increase in permeability of BMEC monolayers. Activation of NO synthase seems to counteract this stimulatory effect of VEGF on endothelial permeability.

Animals↗