46 research outputs found
Suboptymalna kontrola poziomu glikemii a jej związek z niezależnym od czasu trwania odstępu QT zwiększonym ryzykiem wystąpienia arytmii komorowych u pacjentów z populacji dużego ryzyka
Wstęp: Mimo że choroby układu sercowo-naczyniowego są główną przyczyną śmiertelności
wśród chorych na cukrzycę wciąż niewiele wiadomo na temat wpływu kontroli poziomu glikemii
na częstość występowania częstoskurczów komorowych (VT). Celem pracy było zbadanie,
czy stężenie hemoglobiny glikowanej wpływa na częstość VT.
Metody: Przeprowadzono retrospektywne badanie obejmujące 336 osób z implantowanym
kardiowerterem-defibrylatorem serca - zarówno chorych na cukrzycę, jak i bez tego schorzenia.
Wyniki: Stężenie HbA1c w granicach 8-10% istotnie wiąże się ze zwiększoną częstością
występowania spontanicznego VT, niezależnie od czasu trwania odstępu QT lub QTc.
Wnioski: Indeks glikemiczny jest istotnym predykatorem wystąpienia spontanicznego VT,
niezależnie od czasu trwania odstępu QT. Optymalna kontrola poziomu glikemii pomaga
zredukować częstość występowania VT oraz przypadków nagłej śmierci sercowej u chorych na
cukrzycę z grupy dużego ryzyka. (Folia Cardiologica Excerpta 2006; 1: 484-491
Diet, Muscle Protein Synthesis and Autophagy Relationships in Cancer. An Attempt to Understand Where Are We Going, and Why
Protein-based structures are indispensable to maintain life,
so identification and removal of worn out structures achieved
through proteostasis, the sum of micro and macro-autophagy
(autophagy) plus ubiquitin-proteasome system, must balance
renewal by new synthesis. Many of the elements controlling
dynamically equilibria between protein synthesis and protein
degradation have been identified and modalities of activation
actively studied, still we are quite far from mastering how this
balance is ruled. Failure to maintain a positive balance
between protein synthesis and protein degradation would
result in sarcopenia, defined as the loss of skeletal muscle
mass and function, a major clinical problem frequently
accompanying chronic illnesses, but peculiarly spotted in
cancer and in elderly patients. Also, how cancer is fed, and
how nutrition in cancer patients may affect evolution and
therapy effectiveness is another field of opinions and
uncertainty. On the other hand, exercise and nutrition tailored
to provide adequate amounts of amino acids are widely
considered a necessary strategy for prevention and treatment
of protein synthetic deficits in muscles. This paper will
synthetically review how different nutritional strategies and
energy production may interconnect efficiently synthesis and
scavenging of aged and overused protein molecules by
autophagy. Finally, since energy availability rules life and
death of cells and organisms, an hypothesis predicting how
energy may control the ratios among protein synthesis and
autophagy is proposed: in normal conditions, protein syntheses
have a key role in autophagy activation by consuming large
amounts of energy when forming peptidic bonds, that is
adenosine tri-phosphate (ATP) is consumed to monophospahate (AMP), thus decreasing ATP to AMP ratios.
Conversely, both protein syntheses and autophagy may be
scarcely activated when low availability of ATP would result
also in lowest concentrations of AMP. In this peculiar setting,
reduced rates of both protein syntheses and autophagy would
be observed, resulting in worsening of protein balance and
functions
Bag-1 relocates within cardiac myocytes following ischemia/reperfusion and prevents myocyte apoptosis by interaction with Hsc70
A case of fatal ephedra intake associated with lipofuscin accumulation, caspase activation and cleavage of myofibrillary proteins
Ephedra, a herb reported to suppress appetite and stimulate the sympathetic nervous system as well as cardiac performance, has recently been related to several adverse events, including seizure, stroke, hypertension, myocardial infarction, and sudden death. Here, we describe the case of a 45‐year‐old woman who died of cardiovascular collapse while taking ephedra. Tissue analysis revealed non‐specific degenerative alterations in the myocardium (lipofuscin accumulation, basophilic degeneration and vacuolation of myocytes, as well as myofibrillary loss), associated with myocyte apoptosis, caspase activation, and extensive cleavage of miofibrillary proteins α‐actin, α‐actinin, and cardiac troponin T. Healthcare professionals are therefore urged to warn their patients about the risk of serious adverse effects, which may follow ephedra intake.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102708/1/ejhf2004-09-012.pd
Warm blood cardioplegia induces mitochondria- initiated myocyte apoptosis which is ameliorated by overexpression of endogeneous urocortin
Spasmogenic Effects of the Proteasome Inhibitor Carfilzomib on Coronary Resistance, Vascular Tone and Reactivity
Background: Carfilzomib (CFZ) is a new proteasome inhibitor used for the treatment of multiple myeloma. Besides
heart failure, angina and myocardial ischemia occurred following administration of CFZ, which is not contraindicated
in patients with recent myocardial infarction/unstable angina excluded from the safety trials.
Aimof Study: To test the effects of CFZ (10−9 to 10−7 mol/L) on vascular tone and reactivity in the isolated rabbit
heart and aorta.
Methods and Results: CFZ administered by bolus injection to the isolated heart increased coronary perfusion pressure
(CPP) at all tested concentrations and mildly raised left ventricular pressure and heart rate, only at the
highest concentration. Addition of CFZ directly into the organ bath increased the basal tone of isolated aortic
strips with contraction plateau reached after 10 min. This spasmogenic effect doubled following ablation of the
endothelium. Pretreatment with CFZ amplified the vasospastic action exerted by KCl, noradrenaline (NA) and angiotensin
II (A) on aortic strips, and impaired vasodilation following administration of nitroglycerin (NTG) and
nifedipine (NFP) on the contraction plateau induced by KCl, NA and A. Aortic strips pretreatedwith CFZ exhibited
impaired relaxation, as compared to untreated strips, following administration of acetylcholine (Ach), an endothelium-
dependent vasodilating agent, on the plateau of NA contraction (p b 0.05).
Conclusions: CFZ increased CPP, resting vasoconstricting tone and the spasmogenic effect of different agents.
Preincubation with CFZ decreased the anti-spasmogenic activity of NTG and NFP, as well as reduced by over
50% the vasodilating effect of Ach, suggesting that CFZ can impair vasodilation via an endothelium dependent
mechanism. Further studies are warranted to establish its clinical safety in patients with known CAD and prior
history of coronary spasm
Decreased expression of Klotho in cardiac atria biopsy samples from patients at higher risk of atherosclerotic cardiovascular disease
Background. Klotho proteins (α- and β) are membrane-based circulating proteins that regulate cell metabolism, as well as the lifespan modulating activity of Fibroblast Growth Factors. Recent data has shown that higher plasma circulating Klotho levels reduce cardiovascular risk, suggesting Klotho has a protective role in cardiovascular diseases. However, although so far it has been identified in various organs, it is unknown whether cardiomyocytes express Klotho and Fibroblast Growth Factors(FGFs), and whether high cardiovascular risk could affect cardiac expression of Klotho, FGFs and other molecules. Methods. We selected 20 patients with an estimated 10-year high atherosclerotic cardiovascular disease and 10 age-matched control subjects with an estimated 10-year low risk undergone cardiac surgery for reasons other than coronary artery by-pass. In myocardial biopsies, we evaluated by immuno-histochemistry whether Klotho and FGFs were expressed in cardiomyocytes, and whether higher cardiovascular risk influenced the expression of other molecules involved in endoplasmic reticulum stress, oxidative stress, inflammation and fibrosis. Results. Only cardiomyocytes of patients with a higher cardiovascular risk showed lower expression of Klotho, but higher expressions of FGFs. Furthermore, higher cardiovascular risk was associated with increased expression of oxidative and endoplasmic reticular stress, inflammation and fibrosis. Conclusions. This study showed for the first time that Klotho proteins are expressed in human cardiomyocytes and that cardiac expression of Klotho is down-regulated in higher cardiovascular risk patients, while expression of stress-related molecules were significantly increased
Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest
Abstract
Introduction
Rewarming from deep hypothermic circulatory arrest (DHCA) produces calcium desensitization by troponin I (cTnI) phosphorylation which results in myocardial dysfunction. This study investigated the acute overall hemodynamic and metabolic effects of epinephrine and levosimendan, a calcium sensitizer, on myocardial function after rewarming from DHCA.
Methods
Forty male Wistar rats (400 to 500 g) underwent cardiopulmonary bypass (CPB) through central cannulation and were cooled to a core temperature of 13°C to 15°C within 30 minutes. After DHCA (20 minutes) and CPB-assisted rewarming (60 minutes) rats were randomly assigned to 60 minute intravenous infusion with levosimendan (0.2 μg/kg/min; n = 15), epinephrine (0.1 μg/kg/min; n = 15) or saline (control; n = 10). Systolic and diastolic functions were evaluated at different preloads with a conductance catheter.
Results
The slope of left ventricular end-systolic pressure volume relationship (Ees) and preload recruitable stroke work (PRSW) recovered significantly better with levosimendan compared to epinephrine (Ees: 85 ± 9% vs 51 ± 11%, P\u3c0.003 and PRSW: 78 ± 5% vs 48 ± 8%, P\u3c0.005; baseline: 100%). Levosimendan but not epinephrine reduced left ventricular stiffness shown by the end-diastolic pressure-volume relationship and improved ventricular relaxation (Tau). Levosimendan preserved ATP myocardial content as well as energy charge and reduced plasma lactate concentrations. In normothermia experiments epinephrine in contrast to Levosimendan increased cTnI phosphorylation 3.5-fold. After rewarming from DHCA, cTnI phosphorylation increased 4.5-fold in the saline and epinephrine group compared to normothermia but remained unchanged with levosimendan.
Conclusions
Levosimendan due to prevention of calcium desensitization by cTnI phosphorylation is more effective than epinephrine for treatment of myocardial dysfunction after rewarming from DHCA
Targeting STAT1 by myricetin and delphinidin provides efficient protection of the heart from ischemia/reperfusion-induced injury
AbstractFlavonoids exhibit a variety of beneficial effects in cardiovascular diseases. Although their therapeutic properties have been attributed mainly to their antioxidant action, they have additional protective mechanisms such as inhibition of signal transducer and activator of transcription 1 (STAT1) activation. Here, we have investigated the cardioprotective mechanisms of strong antioxidant flavonoids such as quercetin, myricetin and delphinidin. Although all of them protect the heart from ischemia/reperfusion-injury, myricetin and delphinidin exert a more pronounced protective action than quercetin by their capacity to inhibit STAT1 activation. Biochemical and computer modeling analysis indicated the direct interaction between STAT1 and flavonoids with anti-STAT1 activity