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J M Walther

Publications and source records attributed to J M Walther.

4 recordsLinked to original sources
PubMed1997

Postischemic administration of succinate reverses the impairment of oxidative phosphorylation after cardiac ischemia and reperfusion injury.

BACKGROUND: Ischemia and reperfusion (IR) can lead to impaired myocardial mechanical function and inhibition of key metabolic enzyme systems after IR. In this study, we sought to identify the postischemic lesion in oxidative phosphorylation and hypothesized that selective substrate repletion would restore mitochondrial metabolic function during reperfusion. METHODS AND RESULTS: Isolated rat hearts were subjected to global ischemia (25 minutes; 37 degrees C) and reperfusion (40 minutes). Left ventricular developed pressure (LVDP) and the cytochrome a,a3 redox state (near infrared spectroscopy) were continuously monitored. Oxygen consumption was measured for the NADH (mitochondrial complex I) and FADH2 (complex II) pathways in both the resting and maximal ADP-stimulated states. Myocellular oxidative phosphorylation capacity was measured using an NADPH-linked assay specific for mitochondrial ATPase. The hearts were randomized to either succinate (200 micromol/L) or control for the first 5 minutes of reperfusion after ischemia. IR in the control group resulted in an impairment of NADH (complex I) oxidative phosphorylation capacity (1.4+/-0.4 versus control 3.9+/-0.6 nmol ATP/min/mg) and depressed LVDP (49+/-3% of baseline; P<.05). The oxidative phosphorylation capacity for the succinate-using FADH2 pathway remained intact (2.6+/-0.3 versus 2.4+/-0.4). Postischemic succinate administration enhanced LVDP recovery after IR (89+/-8% of baseline; P<.05). Diminished electron transport resulted in depletion of electrons from cytochrome a,a3 during ischemia and early reperfusion, which was reversed by providing succinate as substrate. CONCLUSIONS: Cardiac ischemia and reperfusion results in a defect at mitochondrial complex I but not complex II. Cytochrome a,a3 undergoes anomalous oxidation during ischemia. Postischemic administration of succinate infusion restores the cytochrome a,a3 redox state balance and myocardial function after IR.

Adenosine Triphosphate↗
PubMed1990

On the ability of endogenous adenosine to regulate purine nucleoside receptor binding of antagonists in smooth muscle membranes.

Adenosine, acting at A1 and A2 purine nucleoside receptors, regulates the physiology of many tissues. Myometrial smooth muscle from pregnant guinea pigs, which is contracted by the actions of adenosine, possesses an A1 receptor whose agonist affinity is regulated by guanine nucleotides. In addition to its expected effect on the affinity of the A1 receptor for agonist, the addition of guanine nucleotide also dramatically increases antagonist binding by as much as 62%. This action of guanine nucleotides on adenosine A1 receptors is common to many smooth muscle preparations and suggests the possibility that GTP-binding proteins might alter the conformation of the adenosine receptor in such a way that receptors not previously able to bind ligands are recruited by the guanine nucleotide. Such an action of guanine nucleotides would alter our general view of the interaction of antagonists with GTP-binding protein coupled receptors, as well as bear significantly on the interpretation of experimental data designed to characterize purinergic receptors. Thus, we have investigated the actions of guanosine-5'-O-[3-thiotriphosphate] on A1 adenosine receptor binding in membranes prepared from pregnant guinea pig myometrium containing 61% right-side-out vesicles. We show that guanosine-5'-O-[3-thiotriphosphate] lowers the affinity of adenosine A1 receptors for agonist in vesicles leading to increased competition of antagonist radioligand for receptor. We suggest that the endogenous adenosine we measure originates from breakdown of significant amounts of adenine nucleotides present in membranes vesicles. Furthermore, we demonstrate that opening membrane vesicles to remove trapped adenosine yields maximal antagonist radioligand binding without subsequent effects of guanosine-5'-O-[3-thiotriphosphate]. We conclude that the presence of endogenous adenosine, unavailable to the actions of adenosine deaminase, is responsible for the effect of guanine nucleotides to increase antagonist binding to adenosine A1 receptors.

Adenosine↗
PubMed1987

Barium granuloma: an unusual cause of unilateral ureteral obstruction.

A small amount of barium extravasated at the time of colonic surgery led to the development of a barium granuloma that caused unilateral ureteral obstruction. Although the barium was not detected on radiography or urography preoperatively, it was clearly visible at the time of ureteral exploration and ureterolysis.

Barium Sulfate↗