The impact of choline deficient diet on rat myocardium: investigation of carnitine effect

Choline belongs to the B vitamin complex and its deficiency has been associated with cardiovascular morbidity. Carnitine, a chemical analogue of choline, has been widely used in the management of cardiac diseases. The present study on male Wistar Albino rats aimed to investigate the dietary choline deprivation impact on the: a) cardiac function (Langendorff method), b) heart histopathology, c) enzyme activities of AChE (cholinergic marker), Na+/K+-ΑΤΡase, and Mg2+-ΑΤΡase (spectrophotometrically in the myocardium homogenate), d) immunohistochemical expression of matrix metalloproteinases and their tissue inhibitors (MMPs and TIMPs), which regulate the normal turnover of the extracellular matrix and e) the effect of carnitine in this setting (supplemented in drinking water at a concentration of 0.15%w/v). The results showed that a) dietary choline restriction caused heart diastolic dysfunction and lymphocytic infiltration of the myocardium with cardiac interstitial edema and fibrosis along with increased serum BNP levels; all changes were attenuated by carnitine administration, b) the MMP and TIMP modulation in a choline deficiency setting appears also to promote cardiac interstitial fibrosis (there was suppression of MMP-2 and increase of TIMP-2 expression) and carnitine, although seems to suppress the fibrotic lesions, does not restore the balance of MMPs and TIMPs, c) under the combination of dietary choline deprivation and carnitine supplementation there was increase in the myocardial Na+/K+-ATPase activity along with a concomitant decrease in the activities of Mg2+-ATPase and AChE. These results suggest that carnitine, in a choline deficiency setting, modulates cholinergic myocardial neurotransmission and ATPase activity in favor of cardiac work efficiency. Conclusively, choline deficiency impairs heart performance and carnitine exerts a beneficial and cardioprotective action against these changes.Η χολίνη ανήκει στο σύμπλεγμα βιταμινών Β και η ανεπάρκειά της συνδέεται με καρδιαγγειακή νοσηρότητα. Χημικό ανάλογο της χολίνης, επικουρικό στη διαχείριση καρδιακών παθήσεων, είναι η καρνιτίνη. Στην παρούσα μελέτη διερευνήθηκε, σε αρσενικούς επίμυες τύπου Wistar Albino, η επίδραση της διαιτητικής στέρησης χολίνης στην: α) καρδιακή λειτουργία (μέθοδος Langendorff), β) ιστοπαθολογία του μυοκαρδίου, γ) δραστικότητα των ενζύμων AChE (χολινεργικός δείκτης), Na+/K+-ΑΤΡάσης, και Mg2+-ΑΤΡάσης (φασματομετρικά στο ομογενοποίημα μυοκαρδίου), δ) ανοσοϊστοχημική έκφραση των μεταλλοπρωτεϊνασών και των ανασταλτών τους (ΜΜΡs και ΤΙΜΡs), που καθορίζουν τη δομική σύσταση της εξωκυττάριας θεμέλιας ουσίας και επιπλέον μελετήθηκε η δράση της καρνιτίνης σε αυτό το υπόστρωμα (χορηγούμενη στο πόσιμο ύδωρ σε συγκέντρωση 0,15% w/v). Από τα αποτελέσματα προέκυψε ότι: α) σε έδαφος ανεπάρκειας χολίνης εγκαθίσταται καρδιακή διαστολική δυσλειτουργία και λεμφοκυτταρική διήθηση του μυοκαρδίου με διάμεσο οίδημα και ίνωση και συνοδό αύξηση των επιπέδων BNP στον ορό, που μετριάζονται με τη χορήγηση καρνιτίνης, β) οι μεταβολές στην ανοσοϊστοχημική αποτύπωση των ΜΜΡs και ΤΙΜΡs (καταστολή της έκφρασης της MMP-2 και αύξησης του TIMP-2) προάγουν επίσης τη διάμεση ίνωση, την οποία η καρνιτίνη αναχαιτίζει μερικώς χωρίς όμως να αποκαθιστά τη διαταραχθείσα ισορροπία των MMPs-TIMPs, γ) σε συνθήκες διαιτητικής στέρησης χολίνης και παράλληλης χορήγησης καρνιτίνης παρατηρείται αύξηση της δραστικότητας της Na+/Κ+-ΑΤΡάσης με ταυτόχρονη μείωση στις δραστικότητες των Mg2+-ΑΤΡάσης και AChE. Τα ευρήματα αυτά δείχνουν ότι η καρνιτίνη σε έδαφος ανεπάρκειας χολίνης επηρεάζει τη χολινεργική νευρομεταβίβαση και τη δραστικότητα των ΑΤΡασών υπέρ του αποδοτικού καρδιακού έργου. Συμπερασματικά, η ανεπάρκεια χολίνης επιδεινώνει την καρδιακή λειτουργικότητα και η καρνίτινη ασκεί καρδιοπροστατευτική επίδραση σε αυτό το υπόστρωμα

Heart dysfunction induced by choline-deficiency in adult rats: The protective role of L-carnitine

Choline is a B vitamin co-factor and its deficiency seems to impair heart function. Carnitine, a chemical analog of choline, has been used as adjunct in the management of cardiac diseases. The study investigates the effects of choline deficiency on myocardial performance in adult rats and the possible modifications after carnitine administration. Wistar Albino rats (n=24), about 3 months old, were randomized into four groups fed with: (a) standard diet (control-CA), (b) choline deficient diet (CDD), (c) standard diet and carnitine in drinking water 0.15% w/v (CARN) and (d) choline deficient diet and carnitine (CDD+CARN). After four weeks of treatment, we assessed cardiac function under isometric conditions using the Langendorff preparations [Left Ventricular Developed Pressure (LVDP-mmHg), positive and negative first derivative of LVDP were evaluated], measured serum homocysteine and brain natriuretic peptide (BNP) levels and performed histopathology analyses. In the CDD group a compromised myocardium contractility compared to control (P=0.01), as assessed by LVDP, was noted along with a significantly impaired diastolic left ventricular function, as assessed by (-) dp/dt (P=0.02) that were prevented by carnitine. Systolic force, assessed by (+) dp/dt, showed no statistical difference between groups. A significant increase in serum BNP concentration was found in the CDD group (P<0.004) which was attenuated by carnitine (P<0.05), whereas homocysteine presented contradictory results (higher in the CDD+CARN group). Heart histopathology revealed a lymphocytic infiltration of myocardium and valves in the CDD group that was reduced by carnitine. In conclusion, choline deficiency in adult rats impairs heart performance; carnitine acts against these changes. (C) 2013 Elsevier B.V. All rights reserved

Hospital Resources May Be an Important Aspect of Mortality Rate among Critically Ill Patients with COVID-19: The Paradigm of Greece

For critically ill patients with coronavirus disease 2019 (COVID-19) who require intensive care unit (ICU) admission, extremely high mortality rates (even 97%) have been reported. We hypothesized that overburdened hospital resources by the extent of the pandemic rather than the disease per se might play an important role on unfavorable prognosis. We sought to determine the outcome of such patients admitted to the general ICUs of a hospital with sufficient resources. We performed a prospective observational study of adult patients with COVID-19 consecutively admitted to COVID—designated ICUs at Evangelismos Hospital, Athens, Greece. Among 50 patients, ICU and hospital mortality was 32% (16/50). Median PaO2/FiO2 was 121 mmHg (interquartile range (IQR), 86–171 mmHg) and most patients had moderate or severe acute respiratory distress syndrome (ARDS). Hospital resources may be an important aspect of mortality rates, since severely ill COVID-19 patients with moderate and severe ARDS may have understandable mortality, provided that they are admitted to general ICUs without limitations on hospital resources