R56865, a Na+- and Ca2+-Overload Inhibitor, Reduces Myocardial Ischemia-Reperfusion Injury in Blood-Perfused Rabbit Hearts

Chen, Changchun; Morishige, Noritsugu; Masuda, Mitsuharu; Lin, Wei; Wieland, Werner; Thoné, Fred; Mubagwa, Kanigula; Borgers, M.; Flameng, Willem

doi:10.1006/jmcc.1993.1161

Cited by 33 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanisms by which a cutaneous burn injury alters myocardial Na ϩ homeostasis remains unclear. However, studies using models of ischemia and reperfusion have shown that myocyte acidification early in the ischemic period is a precipitating event in both myocardial Na ϩ and Ca 2ϩ accumulation and cardiac contractile dysfunction (6,7,10,25,28). The negative inotropic effects of intracellular acidosis may be related to competition of hydrogen ions with Ca 2ϩ for binding sites on the contractile proteins, impairing actin-myosin interaction and reducing tension development (26).…”

mentioning

confidence: 99%

Time course of myocardial sodium accumulation after burn trauma: a³¹P- and²³Na-NMR study

Sikes

Zhao

Maass

et al. 2001

Journal of Applied Physiology

View full text Add to dashboard Cite

In this study, (23)Na- and (31)P- nuclear magnetic resonance (NMR) spectra were examined in perfused rat hearts harvested 1, 2, 4, and 24 h after 40% total body surface area burn trauma and lactated Ringer resuscitation, 4 ml. kg(-1). %(-1) burn. (23)Na-NMR spectroscopy monitored myocardial intracellular Na+ using the paramagnetic shift reagent thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methylenephosphonic acid). Left ventricular function, cardiac high-energy phosphates (ATP/PCr), and myocyte intracellular pH were studied by using (31)P NMR spectroscopy to examine the hypothesis that burn-mediated acidification of cardiomyocytes contributes to subsequent Na+ accumulation by this cell population. Intracellular Na+ accumulation was confirmed by sodium-binding benzofuran isophthalate loading and fluorescence spectroscopy in cardiomyocytes isolated 1, 2, 4, 8, 12, 18, and 24 h postburn. This myocyte Na+ accumulation as early as 2 h postburn occurred despite no changes in cardiac ATP/PCr and intracellular pH. Left ventricular function progressively decreased after burn trauma. Cardiomyocyte Na+ accumulation paralleled cardiac contractile dysfunction, suggesting that myocardial Na+ overload contributes, in part, to the progressive postburn decrease in ventricular performance.

show abstract

mentioning

confidence: 99%

Time course of myocardial sodium accumulation after burn trauma: a³¹P- and²³Na-NMR study

Sikes

Zhao

Maass

et al. 2001

Journal of Applied Physiology

View full text Add to dashboard Cite

show abstract

“…It can directly affect myocardial contraction by inhibiting myocardial repolarization. Aconitine can also cause calcium overload through the exchange of sodium and calcium or the opening of the sodium passage, which may also be caused by promoting the triggering activity of the myocardium, increasing parasympathetic activity, and decreasing atrioventricular conduction [ 11 ]. Consciousness deterioration may be caused by cerebral hypoperfusion due to hypotension.…”

Section: Discussionmentioning

confidence: 99%

“…2021, 10, x FOR PEER REVIEW 2 of 11 action of the voltage-gated sodium ion channels (VGSCs) [8][9][10]. The mechanisms under lying neurotoxicity are triggered by the interaction of aconitine with VGSCs, which en hances the state of open VGSCs [4,10,11]. There are several reports on cardiac toxicity caused by aconitine, but there are no studies on neurotoxicity associated with dosage and processing methods.…”

Section: Introductionmentioning

confidence: 99%

“…Cardiotoxicity and neurotoxicity are the most critical effects of aconitine, and the pathological pathway of the alkaloid molecule, a crucial secondary messenger in plants, is explained using the details of the interaction of the voltage-gated sodium ion channels (VGSCs) [ 8 , 9 , 10 ]. The mechanisms underlying neurotoxicity are triggered by the interaction of aconitine with VGSCs, which enhances the state of open VGSCs [ 4 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Aconitine Neurotoxicity According to Administration Methods

Chung

Lee

et al. 2021

JCM

View full text Add to dashboard Cite

We evaluated the toxic effects of aconitine on the human nervous system and its associated factors, and the general clinical characteristics of patients who visited the emergency room due to aconitine intoxication between 2008 and 2017. We also analyzed the differences related to aconitine processing and administration methods (oral pill, boiled in water, and alcohol-soaked), and the clinical characteristics of consciousness deterioration and neurological symptoms. Of the 41 patients who visited the hospital due to aconitine intoxication, 23 (56.1%) were female, and most were older. Aconitine was mainly used for pain control (28 patients, 68.3%) and taken as oral pills (19 patients, 46%). The patients showed a single symptom or a combination of symptoms; neurological symptoms were the most common (21 patients). All patients who took aconitine after processing with alcohol showed neurological symptoms and a higher prevalence of consciousness deterioration. Neurological symptoms occurred most frequently in patients with aconitine intoxication. Although aconitine intoxication presents with various symptoms, its prognosis may vary with the processing method and prevalence of consciousness deterioration during the early stages. Therefore, the administration method and accompanying symptoms should be comprehensively investigated in patients who have taken aconitine to facilitate prompt and effective treatment and better prognoses.

show abstract

“…In particular, perturbations of calcium homeostasis play an important role in reperfusion arrhythmias, including idioventricular rhythm, ventricular tachycardia, and ventricular fibrillation after MIRI [34]. The inhibition of intracellular Ca 2+ overload improves the recovery of heart function and prevents the heart from contracture during reperfusion [35]. Consistently, damage to the cell membrane, which causes dysregulation of Na + /Ca 2+ exchange and Na + /H + exchange, is one of the reasons for cell edema leading to myocardial stunning [36].…”

Section: Defects In Calcium Handlingmentioning

confidence: 99%

The Rationale of Neprilysin Inhibition in Prevention of Myocardial Ischemia-Reperfusion Injury during ST-Elevation Myocardial Infarction

Bellis¹,

Mauro

Barbato³

et al. 2020

Cells

View full text Add to dashboard Cite

During the last three decades, timely myocardial reperfusion using either thrombolytic therapy or primary percutaneous intervention (pPCI) has allowed amazing improvements in outcomes with a more than halving in 1-year ST-elevation myocardial infarction (STEMI) mortality. However, mortality and left ventricle (LV) remodeling remain substantial in these patients. As such, novel therapeutic interventions are required to reduce myocardial infarction size, preserve LV systolic function, and improve survival in reperfused-STEMI patients. Myocardial ischemia-reperfusion injury (MIRI) prevention represents the main goal to reach in order to reduce STEMI mortality. There is currently no effective therapy for MIRI prevention in STEMI patients. A significant reason for the weak and inconsistent results obtained in this field may be the presence of multiple, partially redundant, mechanisms of cell death during ischemia-reperfusion, whose relative importance may depend on the conditions. Therefore, it is always more recognized that it is important to consider a “multi-targeted cardioprotective therapy”, defined as an additive or synergistic cardioprotective agents or interventions directed to distinct targets with different timing of application (before, during, or after pPCI). Given that some neprilysin (NEP) substrates (natriuretic peptides, angiotensin II, bradykinin, apelins, substance P, and adrenomedullin) exert a cardioprotective effect against ischemia-reperfusion injury, it is conceivable that antagonism of proteolytic activity by this enzyme may be considered in a multi-targeted strategy for MIRI prevention. In this review, by starting from main pathophysiological mechanisms promoting MIRI, we discuss cardioprotective effects of NEP substrates and the potential benefit of NEP pharmacological inhibition in MIRI prevention.

show abstract

R56865, a Na+- and Ca2+-Overload Inhibitor, Reduces Myocardial Ischemia-Reperfusion Injury in Blood-Perfused Rabbit Hearts

Cited by 33 publications

References 0 publications

Time course of myocardial sodium accumulation after burn trauma: a³¹P- and²³Na-NMR study

Time course of myocardial sodium accumulation after burn trauma: a³¹P- and²³Na-NMR study

Aconitine Neurotoxicity According to Administration Methods

The Rationale of Neprilysin Inhibition in Prevention of Myocardial Ischemia-Reperfusion Injury during ST-Elevation Myocardial Infarction

Contact Info

Product

Resources

About

R56865, a Na+- and Ca2+-Overload Inhibitor, Reduces Myocardial Ischemia-Reperfusion Injury in Blood-Perfused Rabbit Hearts

Cited by 33 publications

References 0 publications

Time course of myocardial sodium accumulation after burn trauma: a31P- and23Na-NMR study

Time course of myocardial sodium accumulation after burn trauma: a31P- and23Na-NMR study

Aconitine Neurotoxicity According to Administration Methods

The Rationale of Neprilysin Inhibition in Prevention of Myocardial Ischemia-Reperfusion Injury during ST-Elevation Myocardial Infarction

Contact Info

Product

Resources

About

Time course of myocardial sodium accumulation after burn trauma: a³¹P- and²³Na-NMR study

Time course of myocardial sodium accumulation after burn trauma: a³¹P- and²³Na-NMR study