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E Gerlach

Publications and source records attributed to E Gerlach.

116 records · Page 7Linked to original sources
PubMedDate not supplied

Postischemic dysfunction of the heart induced by small numbers of neutrophils via formation of hypochlorous acid.

The role of polymorphonuclear neutrophils (PMN) in the injury of the heart following ischemia and reperfusion is still controversial. The aim of this study was to investigate whether small numbers of PMN may cause myocardial dysfunction in an isolated system, how the resulting loss of function can be characterized and whether the formation of hypochlorous acid (HOCl) can be responsible for the PMN-mediated effect. Isolated working guinea pig hearts were subjected to a 90% reduction of coronary flow for 30 min, with or without intracoronary infusion of homologous PMN (approximately 1-2 x 10(5) cells/min, i.e. about 5-10% of normal blood count). This ischemia was followed by a 15 min reflow period in a non-working ("Langendorff") mode before work was resumed. In hearts perfused only with buffer, post-hypoxic heart function recovered to 75-80% of the initial value. Inclusion of unstimulated PMN did not further attenuate cardiac function. However, cardiac output was decreased to 42% of the initial value, provided thrombin (0.3 U/ml) and H2O2 (10(-5) M) were also present, and the retained PMN (about 10% of those infused) were additionally stimulated during reflow by application of FMLP (10(-6) M for 1 min). In these instances, coronary flow at any time of the experiment and release of lactate or purines during ischemia and reflow did not differ significantly between hearts perfused with or without PMN. There was no substantial release of myoglobin in controls and in PMN-treated hearts. Inotropic stimulation of the hearts with noradrenaline or exogenous Ca2+ caused a sustained increase in contractile force. However, the response was significantly reduced in PMN-perfused hearts in comparison to control hearts. The myocardial contents of high-energy phosphates with and without inotropic stimulation proved to be identical irrespective of whether experiments had been performed in the absence or presence of PMN. A similar loss of myocardial function as mediated by PMN could be produced by infusing chemically generated hypochlorous acid (HOCl, 5 x 10(-7) M for 10 min). Strikingly, that portion of the infused HOCl which actually reacted with cardiac tissue was comparable to the amount shown to be generated by stimulating 10(6) PMN retained in the coronary system (about 7 nmoles). Supplementing the perfusate with the scavengers L-methionine (10(-4) M) or uric acid (5 x 10(-4) M) prevented the attenuation of heart function provoked by PMN. The results indicate that small numbers of PMN, sufficiently activated, can depress cardiac function after 30 min of ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

Changes of myocardial adenine nucleotide and protein synthesis during development of cardiac hypertrophy.

1. Studies on three models of cardiac hypertrophy (aortic constriction, application of isoproterenol, daily administrations of 3,3'5-triiodo-L-thyronine, respectively) reveal that the enhancement of de novo synthesis of adenine nucleotides occurs very early during the development of cardiac hypertorphy and always precedes the increase of protein synthesis. Therefore, it seems likely that the accelerated synthesis of adenine nucleotides is an important factor among those metabolic processes involved in the stimulation of protein synthesis in the hypertrophying heart. 2. As far as the mechanism for the observed enhancement of adenine nucleotide synthesis is concerned, it has been demonstrated that the available pool of 5-phosphoribosyl-l-pyrophosphate, an essential precursor substance of de novo synthesis, is increased in the hypertrophying heart due to isoproterenol and 3,3'5-triiodo-L-thyronine, respectively.

Adenine Nucleotides↗
PubMedDate not supplied

The vascular endothelium: a survey of some newly evolving biochemical and physiological features.

The morphological, biochemical and functional characterization of the vascular endothelium has become possible through the broad use of electron microscopic methods, the successful elaboration and application of techniques for the isolation and cultivation of endothelial cells in vitro and through sophisticated studies on vessel and organ preparations, both in vitro and in vivo. In this survey emphasis is placed on certain methodological aspects of endothelial cell culture as well as on biochemical, physiological and pathophysiological features of the vascular endothelium. Endothelial cells can be propagated in culture dishes, the most commonly applied method, on suspended microbeads (dextrane, polyacrylamide), a technique giving large yields, or on thin porous membranes, a procedure suited for the study of transport processes across the endothelial layer. Different structural, biochemical and functional properties of the luminal (apical) and abluminal (basal) cell membrane determine important polarity features of the endothelium. Endothelial cells exhibit a variety of biochemical pathways and are characterized by high metabolic activities. Of particular interest is the large content of ATP in endothelial cells of different vascular origin. The rapid intracellular degradation of adenine nucleotides to nucleosides and bases, which are constantly released, is balanced by synthesis, mainly via salvage pathways. In endothelial cells of microvascular origin uric acid predominates by far as the final purine degradative because of the presence of xanthine dehydrogenase in these cells; in the macrovascular endothelium purine breakdown proceeds only to hypoxanthine, since xanthine dehydrogenase is lacking. In this connection interrelations between nucleotide catabolism in myocardial tissue and in coronary endothelial cells are discussed, also with respect to the participation of endothelial xanthine oxidase in the formation of oxygen radicals during post-ischemic reperfusion of the heart. Vascular endothelial cells of different origin are also capable of a rapid extracellular degradation of ATP, ADP and AMP to adenosine by means of specific ecto-nucleotidases. The subsequent fate of extracellularly formed adenosine appears to be different for endothelial cells of microvascular (preferential adenosine uptake) and macrovascular origin (preferential extracellular adenosine accumulation), thus implying functional consequences for platelet aggregation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenine Nucleotides↗
PubMedDate not supplied

The coronary endothelium: a highly active metabolic barrier for adenosine.

Cultured coronary endothelial cells and the coronary endothelium of isolated perfused guinea-pig hearts are characterized by a very active adenosine and adenine nucleotide metabolism. Adenosine applied to the endothelium at low concentrations is avidly metabolized and preferentially incorporated into different nucleotide pools--only a minor amount is degraded to uric acid. Physiologically, the coronary endothelium therefore functions as an impermeable metabolic barrier for interstitially or intravascularly accumulating adenosine. Only at concentrations greater than or equal to 10(-6) M adenosine can pass the endothelial barrier. As a consequence, the vasodilatory action of adenosine formed in or administered into the coronary system cannot be induced by a direct association of the nucleoside with the putative adenosine receptor of the arteriolar smooth muscle cells, but must be mediated by the endothelium. High molecular weight derivatives of adenosine, clearly confined to the coronary system, can also induce a coronary dilation. The endothelium-mediated smooth muscle relaxation is therefore obviously due to triggering of an extracellular adenosine receptor at the luminal surface of the endothelium. Since this process is accompanied by a rapid and pronounced activation of the adenylate cyclase system, the endothelial receptor conforms to an A2-type. According to our results it is necessary to reconsider qualitative and quantitative facets of the adenosine hypothesis of metabolic regulation of coronary blood flow, which--in its original formulation--exclusively centers on the cardiomyocyte metabolism. With respect to the vasoactivity of adenosine one obviously has to distinguish between its action from the interstitial space directly via the myocyte receptors of the vessel wall, and/or its action from the intracoronary space via the newly detected endothelial A2-receptor. More information is needed to determine the extent to which both receptor populations actually participate in the metabolic regulation of coronary flow under physiological and pathophysiological conditions.

Adenine Nucleotides↗
PubMedDate not supplied

Significance of the hexose monophosphate shunt in experimentally induced cardiac hypertrophy.

1. In three models of cardiac hypertrophy in rats (aortic constriction, application of a single dose of isoproterenol and daily injections of triiodothyronine) the biosynthesis of myocardial adenine nucleotides was enhanced. 2. In hypertrophying hearts due to aortic constriction and isoproterenol application, the activity of glucose-6-phosphate dehydrogenase and the available pool of 5-phosphoribosyl-1-pyrophosphate were increased indicating a stimulation of the hexose monophosphate shunt. In triiodothyronine-treated animals only the cardiac pool of 5-phosphoribosyl-1-pyrophosphate turned out to be elevated. 3. In all three models of cardiac hypertrophy, the enhancement of myocardial adenine nucleotide biosynthesis was exaggerated by ribose. It thus appears that the 5-phosphoribosyl-1-pyrophosphate pool is the limiting factor for the increase of adenine nucleotide biosynthesis under these conditions. 4. Long-term i.v. infusion of ribose (200 mg/kg/h) in isoproterenol-treated rats prevented the decrease of the cardiac ATP concentration induced by isoproterenol. However, the isoproterenol-induced stimulation of total cardiac protein synthesis was not altered, suggesting that the ATP decline may not be the trigger for stimulating protein synthesis in this model of myocardial hypertrophy.

Adenine Nucleotides↗