PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 3388406

Relationship between the high-energy phosphate content and various left ventricular functional parameters of the normal and hypertrophied heart after global ischemia and reperfusion.

G Fenchel·R Storf·J Michel·H E Hoffmeister
View original source ↗Export metadata ↓

Abstract

Using an isolated rat heart preparation (Langendorff perfusion, perfusion pressure 100 cm H2O) the correlation between the high-energy phosphate content and various left ventricular (lv) functional parameters of the hypertrophied heart (spontaneous hypertensive rats lv/body weight ratio 3.6 +/- 0.5 x 10(-3) was determined after normo- (30 min) and hypothermic (25 degrees C, 120 min) cardioplegic arrest and reperfusion, and compared with normal hearts (Wistar rats lv/body weight ratio 2.0 +/- 0.3 x 10(-3). St. Thomas Hospital solution was used as the cardioplegic agent. Before ischemia hypertrophied hearts had a significantly higher developed left ventricular pressure, pressure rate product and dp/dtmax, but a significantly lower ATP and total adenine nucleotide content. Irrespective of the mode and temperature of cardiac arrest there was a strong correlation both for normal and for hypertrophied hearts between the high-energy phosphate content expressed as ATP, total adenine nucleotides or the "energy charge" and the left ventricular functional parameters pressure rate product and dp/dtmax. The correlation coefficient ranged from 0.80 to 0.89 and was highest when the ATP content was plotted against pressure rate product (r = 0.89). There was a different slope for normal and hypertrophied hearts with a steeper decline of the left ventricular function in hypertrophied hearts for any given reduction of the myocardial adenine nucleotide content. Our results indicate that a similar reduction of the ATP or total adenine nucleotide content in both the normal and hypertrophied heart reduces left ventricular function to a greater degree in the hypertrophied heart.

Explore related subjects

Adenosine DiphosphateAdenosine TriphosphateAnimalsCardiomyopathy, HypertrophicCoronary CirculationEnergy MetabolismHeart Arrest, InducedMyocardial ContractionMyocardiumRatsRats, Inbred SHRJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

G Fenchel, R Storf, J Michel, H E Hoffmeister. 1988. Relationship between the high-energy phosphate content and various left ventricular functional parameters of the normal and hypertrophied heart after global ischemia and reperfusion.. https://doi.org/10.1055/s-2007-1020048

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2022

A novel DPH5-related diphthamide-deficiency syndrome causing embryonic lethality or profound neurodevelopmental disorder.

PURPOSE: Diphthamide is a post-translationally modified histidine essential for messenger RNA translation and ribosomal protein synthesis. We present evidence for DPH5 as a novel cause of embryonic lethality and profound neurodevelopmental delays (NDDs). METHODS: Molecular testing was performed using exome or genome sequencing. A targeted Dph5 knockin mouse (C57BL/6Ncrl-Dph5em1Mbp/Mmucd) was created for a DPH5 p.His260Arg homozygous variant identified in 1 family. Adenosine diphosphate-ribosylation assays in DPH5-knockout human and yeast cells and in silico modeling were performed for the identified DPH5 potential pathogenic variants. RESULTS: DPH5 variants p.His260Arg (homozygous), p.Asn110Ser and p.Arg207Ter (heterozygous), and p.Asn174LysfsTer10 (homozygous) were identified in 3 unrelated families with distinct overlapping craniofacial features, profound NDDs, multisystem abnormalities, and miscarriages. Dph5 p.His260Arg homozygous knockin was embryonically lethal with only 1 subviable mouse exhibiting impaired growth, craniofacial dysmorphology, and multisystem dysfunction recapitulating the human phenotype. Adenosine diphosphate-ribosylation assays showed absent to decreased function in DPH5-knockout human and yeast cells. In silico modeling of the variants showed altered DPH5 structure and disruption of its interaction with eEF2. CONCLUSION: We provide strong clinical, biochemical, and functional evidence for DPH5 as a novel cause of embryonic lethality or profound NDDs with multisystem involvement and expand diphthamide-deficiency syndromes and ribosomopathies.

Adenosine Diphosphate↗
PubMed2007

A mobile tryptophan is the intrinsic charge transfer donor in a flavoenzyme essential for nikkomycin antibiotic biosynthesis.

The flavoenzyme nikD is required for the biosynthesis of nikkomycin antibiotics. NikD exhibits an unusual long wavelength absorption band attributed to a charge transfer complex of FAD with an unknown charge transfer donor. NikD crystals contain an endogenous active site ligand. At least four different compounds are detected in nikD extracts, including variable amounts of two ADP derivatives that bind to the enzyme's dinucleotide binding motif in competition with FAD, picolinate (0.07 mol/mol of nikD) and an unknown picolinate-like compound. Picolinate, the product of the physiological catalytic reaction, matches the properties deduced for the active site ligand in nikD crystals. The charge transfer band is eliminated upon mixing nikD with excess picolinate but not by a reversible unfolding procedure that removes the picolinate-like compound, ruling out both compounds as the intrinsic charge transfer donor. Mutation of Trp355 to Phe eliminates the charge transfer band, accompanied by a 30-fold decrease in substrate binding affinity. The results provide definitive evidence for Trp355 as the intrinsic charge transfer donor. The indole ring of Trp355 is coplanar with or perpendicular to the flavin ring in "open" or "closed" crystalline forms of nikD, respectively. Importantly, a coplanar configuration is required for charge transfer interaction. Absorption in the long wavelength region therefore constitutes a valuable probe for monitoring conformational changes in solution that are likely to be important in nikD catalysis.

Adenosine Diphosphate↗
PubMed2007

Bioinformatic discovery of novel bioactive peptides.

Short synthetic oligopeptides based on regions of human proteins that encompass functional motifs are versatile reagents for understanding protein signaling and interactions. They can either mimic or inhibit the parent protein's activity and have been used in drug development. Peptide studies typically either derive peptides from a single identified protein or (at the other extreme) screen random combinatorial peptides, often without knowledge of the signaling pathways targeted. Our objective was to determine whether rational bioinformatic design of oligopeptides specifically targeted to potentially signaling-rich juxtamembrane regions could identify modulators of human platelet function. High-throughput in vitro platelet function assays of palmitylated cell-permeable oligopeptides corresponding to these regions identified many agonists and antagonists of platelet function. Many bioactive peptides were from adhesion molecules, including a specific CD226-derived inhibitor of inside-out platelet signaling. Systematic screens of this nature are highly efficient tools for discovering short signaling motifs in molecular signaling pathways.

Adenosine Diphosphate↗