pyrophosphate and Myocardial-Ischemia

Idiopathic infantile arterial calcification (IIAC) is a rare, but important, cause of rapidly progressive ischemic heart disease in children. In this paper, we report two recent cases of IIAC seen at tertiary referral hospitals. Both cases presented in infancy with signs of heart failure and, ultimately, died with the diagnosis of IIAC confirmed at postmortem examination. A thorough review of the literature reveals approximately 160 reported cases of IIAC. The clinical outcomes, radiographic findings and pathologic details are summarized. Proposed etiologic mechanisms are reviewed, including promising research into the role of inorganic pyrophosphate as a regulatory factor in the development of IIAC. Because of the typically fatal outcome of IIAC and the lack of proven therapies, the potential role for cardiac transplantation is discussed.

Topics: Arteries; Basement Membrane; Calcinosis; Cardiomyopathies; Coronary Vessels; Diphosphates; Disease Progression; Fatal Outcome; Female; Heart Transplantation; Humans; Infant; Myocardial Ischemia; Myocardium; Tunica Intima; Vascular Diseases

Topics: Animals; Diphosphates; Heart; Humans; Myocardial Ischemia; Myocardium; Necrosis; Radionuclide Imaging; Reperfusion Injury; Technetium Tc 99m Pyrophosphate

Deterioration of ventricular fibrillation (VF) into asystole or severe bradycardia (electrical failure) heralds a fatal outcome of cardiac arrest. The role of metabolism in the timing of electrical failure remains unknown.. To determine metabolic factors of early electrical failure in an ex-vivo canine model of cardiac arrest (VF+global ischemia).. Metabolomic screening was performed in left ventricular biopsies collected before and after 0.3, 2, 5, 10 and 20 min of VF and global ischemia. Electrical activity was monitored via plunge needle electrodes and pseudo-ECG. Four out of nine hearts exhibited electrical failure at 10.1±0.9 min (early-asys), while 5/9 hearts maintained VF for at least 19.7 min (late-asys). As compared to late-asys, early-asys hearts had more ADP, less phosphocreatine, and higher levels of lactate at some time points during VF/ischemia (all comparisons p<0.05). Pre-ischemic samples from late-asys hearts contained ∼25 times more inorganic pyrophosphate (PPi) than early-asys hearts. A mechanistic role of PPi in cardioprotection was then tested by monitoring mitochondrial membrane potential (ΔΨ) during 20 min of simulated-demand ischemia using potentiometric probe TMRM in rabbit adult ventricular myocytes incubated with PPi versus control group. Untreated myocytes experienced significant loss of ΔΨ while in the PPi-treated myocytes ΔΨ was relatively maintained throughout 20 min of simulated-demand ischemia as compared to control (p<0.05).. High tissue level of PPi may prevent ΔΨm loss and electrical failure at the early phase of ischemic stress. The link between the two protective effects may involve decreased rates of mitochondrial ATP hydrolysis and lactate accumulation.

Topics: Animals; Cardiotonic Agents; Cells, Cultured; Diphosphates; Dogs; Female; Heart Arrest; Male; Membrane Potential, Mitochondrial; Mitochondria, Heart; Myocardial Ischemia; Myocytes, Cardiac; Rabbits