Abstract P502: Abnormal Myocyte Calcium Dynamics And The Resultant Contraction Band Formation Of The Rat Heart Under Irreversible Injury By Membrane Permeabilization

Ca 2+ overload is a cardinal feature of cardiomyocyte injury, and its progression to irreversible state leads to cell death. However, unknowns are the precise spatiotemporal changes in the myocyte Ca 2+ dynamics and the relevant cell morphology of irreversibly injured hearts. On the hypothesis that myocytes exhibit high-frequency Ca 2+ waves and contraction band necrosis in saponin-permeabilized injured heart, we observed changes in the Ca 2+ dynamics and the relevant morphological changes in the subepicardial myocardium of the Fluo4-loaded rat hearts (n = 14) by rapid-scanning confocal microscopy (100 frames/s) under Langendorff perfusion with 0.3 mM Ca 2+ -Tyrode solution including 0.4 % saponin at 30°C. Also performed was confocal imaging of tetramethylrhodamine methyl ester (TMRM) fluorescence of the myocardium. Under quasi-quiescence of the heart after dissection of the SA node, individual myocytes barely exhibited spontaneous Ca 2+ waves, whereas after commencement of saponin perfusion high-frequency (118 ± 9.7 /min/cell, mean ± SEM) Ca 2+ waves (hereafter, “agonal waves”) emerged within 1 min, showing asynchronous, oscillatory contractions in the individual myocytes with a V prop of 124 ± 2.5 μm/s (n = 60). Subsequently, the waves gradually decreased in frequency with concomitant slowing of its decay time course, and eventually, disappeared in 6 min; myocytes exhibited high, static Fluo4-fluorescence intensity. Along with the progression of Ca 2+ overload by saponin, the TMRM fluorescence intensity was discretely lost in individual myocytes. The myocytes showing the agonal waves exhibited contraction bands, i.e., band-like aggregations of the actin fibers. Under mechanical arrest of the heart by 2,3-butanedione monoxime (20 mM), saponin still induced the agonal waves with a frequency of 253 ± 10.6 /cell/min and V prop of 118 ± 2.1 μm/s (n = 60); however, contraction bands were barely seen.In conclusion, irreversible myocyte injury by saponin provoked agonal Ca 2+ waves and oscillatory contractions indicating progressive Ca 2+ overload and the following mitochondrial damage, which may provide deeper insights into understanding the mechanism of contraction band necrosis.

Morphological and histopathological heart changes in autopsies of heroin abusers

Backround/Aim. Heroin is a semisynthetic opioid that may cause morphological and histopathological changes in heart: ventricular hypertrophy, myocardial fibrosis, hypertrophy of cardiomyocytes, myofibrils contraction band necrosis, loss of myocytes nuclei and cross-striation, perivascular bleeding, inflammatory cells infiltrate. The aim of the study was to show morphological and histopathological heart changes in autopsies of the long-time heroin abusers with positive toxicological analysis for 6-monoacetylmorphine (6-MAM) and morphine in blood and urine. Methods. Retrospective study was done at the Institute of Pathology and Forensic of the Medicine Military Medical Academy in Belgrade between 2010 and 2014 and included forensic autopsies of 27 examinees aged between 18 and 60. Heart ventricles thicknesses was analysed and histopathological myocard findings from processed material stained by hematoxyline-eosine (H&E) and trichrome stains (Masson) were examined. 6-MAM and morphine concentration in blood and urine using high-performance liquid chromatography coupled with photodiode (HPLC-PDA) and ultraviolet (UV) detector were analysed. Results. Heart ventricles thickness was increased in all persons (27/27; 100%) left 1.74 ? 0.17 cm and right 0.6 ? 0.09 cm. Myocardial fibrosis affected 27/27 (100%) of the examined persons including perivascular one in 24/27 (88.89%) and interstitial focal fibrosis in 3/27 (11.11%); hypertrophy of cardiomyocytes was present in 22/27 (81.48%); myofibril contraction band necrosis in 22/27 (81.48%); loss of myocytes nuclei and cross-striation in 10/27 (37.04%); fresh perivascular bleeding in 23/27 (85.19%); focal inflammatory cells infiltrate in 14/27 (51.85%). In toxicological findings, in 27/27 (100%), 6-MAM and morphine were found in urine. Both 6-MAM and morphine in blood were found in 3/27 (11.11%) and only morphine in blood in 16/27 (59.26%) persons subjected to an autopsy. Conclusion. Our results indicate both morphological (left and right ventricle hypertrophy) and histopathological heart changes (myocardial fibrosis, hypertrophy of cardiomyocytes, contraction-band necrosis, loss of myocytes nuclei and cross-striation, fresh perivascular bleeding and focal inflammatory infiltrate) in long-term heroin obusers. These changes are non-specific and could be caused either by long-term heroin abuse or by other factors. Having in mind a lack of medical histories of examined we could not exclude other factors besides long-term heroin abuse as cause of heart changes.

Diagnostic Exercise

Parenteral selenium (Se) and vitamin E (Vit E) were administered to all newborn kids at a Boer goat farm where there was previous high neonatal mortality assumed to be due to nutritional myopathy. All treated kids were affected by severe respiratory distress and died within 8 hours of Se/Vit E administration. Gross lesions included severe pulmonary edema, hydrothorax, and hydropericardium. The primary histopathologic finding was severe, acute, and monophasic myocardial contraction band necrosis. The diagnosis was accidental acute selenosis based on trace mineral analysis of the liver. This case highlights an important differential diagnosis in cases of acute myocardial contraction band necrosis and sudden death in goats and emphasizes the need for caution when administering parenteral Se/Vit E preparations.

Heart and Brain: A Case of Focal Myocytolysis in Severe Pneumococcal Meningoencephalitis with Review of the Contemporary Literature

We report electrocardiographic changes mimicking myocardial ischaemia in a 73-year-old man with fatal pneumococcal meningoencephalitis, present the autopsy-confirmed histological picture of extensive focal myocytolysis (contraction band necrosis) without myocardial infarction or myocarditis, and review the contemporary literature. Potentially reversible, probably non-ischaemic myocardial dysfunction may occur in association with acute noncardiac illnesses, such as brain injuries. Biochemical and morphological abnormalities in acutely failing hearts from head-injured organ donors point to specific pathophysiological mechanisms, which are different from heart failure from other causes. Sepsis-related factors may add to the myocardial dysfunction in patients with brain injury from meningoencephalitis.