Decreased contractility and altered responses to inotropic agents in myocytes from tachypacing-induced heart failure canines

Gao, BaoXi; Qu, Yusheng; Sutherland, Weston; Chui, Ray W.; Hoagland, Kim; Vargas, Hugo M.

doi:10.1016/j.vascn.2018.06.001

Cited by 18 publications

(19 citation statements)

References 43 publications

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“…Apart from β-blockers, other drugs that contribute to negative inotropic effects include Ca 2+ channel blockers (e.g. verapamil or diltiazem), Na + channel blockers (such as quinidine, flecainide, or mexiletine) and myosin II ATPase inhibitors (notably, blebbistatin, N-benzyl- p -toluene sulphonamide; BTS, or 2,3 butanedione monoxime; BDM) [ 18 - 20 ]. Of note, latter compounds are the only group that blunt ventricular myocyte contractility without affecting the peak intracellular calcium concentration reached in during the calcium transient.…”

Section: Discussionmentioning

confidence: 99%

Suppression of cardiomyocyte functions by β-CTX isolated from the Thai king cobra (Ophiophagus hannah) venom via an alternative method

Lertwanakarn

Suntravat

Sánchez

et al. 2020

J. Venom. Anim. Toxins incl. Trop. Dis

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Background: Beta-cardiotoxin (β-CTX), the three-finger toxin isolated from king cobra (Ophiophagus hannah) venom, possesses β-blocker activity as indicated by its negative chronotropy and its binding property to both β-1 and β-2 adrenergic receptors and has been proposed as a novel β-blocker candidate. Previously, β-CTX was isolated and purified by FPLC. Here, we present an alternative method to purify this toxin. In addition, we tested its cytotoxicity against different mammalian muscle cell types and determined the impact on cardiac function in isolated cardiac myocyte so as to provide insights into the pharmacological action of this protein. Methods: β-CTX was isolated from the crude venom of the Thai king cobra using reverse-phased and cation exchange HPLC. In vitro cellular viability MTT assays were performed on mouse myoblast (C2C12), rat smooth muscle (A7r5), and rat cardiac myoblast (H9c2) cells. Cell shortening and calcium transient dynamics were recorded on isolated rat cardiac myocytes over a range of β-CTX concentration. Results: Purified β-CTX was recovered from crude venom (0.53% w/w). MTT assays revealed 50% cytotoxicity on A7r5 cells at 9.41 ± 1.14 µM (n = 3), but no cytotoxicity on C2C12 and H9c2 cells up to 114.09 µM. β-CTX suppressed the extend of rat cardiac cell shortening in a dose-dependent manner; the half-maximal inhibition concentration was 95.97 ± 50.10 nM (n = 3). In addition, the rates of cell shortening and re-lengthening were decreased in β-CTX treated myocytes concomitant with a prolongation of the intracellular calcium transient decay, indicating depression of cardiac contractility secondary to altered cardiac calcium homeostasis.

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Section: Discussionmentioning

confidence: 99%

Suppression of cardiomyocyte functions by β-CTX isolated from the Thai king cobra (Ophiophagus hannah) venom via an alternative method

Lertwanakarn

Suntravat

Sánchez

et al. 2020

J. Venom. Anim. Toxins incl. Trop. Dis

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“…However, multiple complications (including MI, myocardial ischemia, arrhythmia, stroke, and kidney failure) are common postoperative syndromes after CABG [ 7 , 17 , 19 , 20 , 79 ]. Surgery, combined with medication pre- and/or postoperatively, such as inotropic agents, which can increase myocardial contractility that results, in most cases, in increasing intracellular cAMP levels, can effectively avoid or ameliorate these unwanted outcomes [ 80 – 82 ]. Increased cAMP subsequently stimulates adenylate cyclase and inhibits PDE III simultaneously [ 83 ].…”

Section: Discussionmentioning

confidence: 99%

The effect of milrinone on mortality in adult patients who underwent CABG surgery: a systematic review of randomized clinical trials with a meta-analysis and trial sequential analysis

Ren

Peng

et al. 2020

BMC Cardiovasc Disord

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Background: As an inodilator, milrinone is commonly used for patients who undergo coronary artery bypass graft (CABG) surgery because of its effectiveness in decreasing the cardiac index and mitral regurgitation. The aim of this study was to perform a systematic review and meta-analysis of existing studies from the past 20 years to evaluate the impact of milrinone on mortality in patients who undergo CABG surgery. Methods: We performed a systematic literature search on the application of milrinone in patients who underwent CABG surgery in studies published between 1997 and 2017 in BioMed Central, PubMed, EMBASE, and the Cochrane Central Register. The included studies evaluated milrinone groups compared to groups receiving either placebo or standard treatment and further compared the systemic administration. Results: The network meta-analysis included 723 patients from 16 randomized clinical trials. Overall, there was no significant difference in mortality between the milrinone group and the placebo/standard care group when patients underwent CABG surgery. In addition, 9 trials (with 440 randomized patients), 4 trials (with 212 randomized patients), and 10 trials (with 470 randomized patients) reported that the occurrence of myocardial infarction (MI), myocardial ischemia, and arrhythmia was lower in the milrinone group than in the placebo/standard care group. Between the milrinone treatment and placebo/standard care groups, the occurrence of myocardial infarction, myocardial ischemia, and arrhythmia was significantly different. However, the occurrence of stroke and renal failure, the duration of inotropic support (h), the need for an intra-aortic balloon pump (IABP), and mechanical ventilation (h) between these two groups showed no differences.

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“…8,18,20,21,78 Surgery, combined with medication pre-and/or postoperatively, such as inotropic agents, which can increase myocardial contractility that results, in most cases, in increasing intracellular cAMP levels, can effectively avoid or ameliorate these unwanted outcomes. [79][80][81] Increased cAMP subsequently stimulates adenylate cyclase and inhibits PDE III simultaneously. 82 Despite (or because of) their effectiveness, inotropic agents face various substantial limitations, such as acute myocardial β-adrenergic receptor desensitization, limiting the function for post-bypass cardiac failure; 83 additional observational data suggest that inotropic agents contribute to worse clinical outcomes due to the high incidence of renal dysfunction and death ratio.…”

Section: Discussionmentioning

confidence: 99%

The effect of milrinone on mortality in adult patients who underwent CABG surgery: A systematic review of randomized clinical trials with a meta-analysis and trial sequential analysis

Ren¹,

Li²,

Peng³

et al. 2020

Preprint

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Background: As an inodilator, milrinone is commonly used for patients who undergo coronary artery bypass graft (CABG) surgery because of its effectiveness in decreasing the cardiac index and mitral regurgitation. The aim of this study was to perform a systematic meta-analysis of existing studies from the past 20 years to evaluate the impact of milrinone on mortality in patients who undergo CABG surgery.Methods: We performed a systematic literature search on the application of milrinone in patients who underwent CABG surgery in studies published between 1997 and 2017 in BioMed Central, PubMed, EMBASE, and the Cochrane Central Register. The included studies evaluated milrinone groups compared to groups receiving either placebo or standard treatment and further compared the systemic administration.Results: The network meta-analysis included 723 patients from 16 randomized clinical trials. Overall, there was no significant difference in mortality between the milrinone group and the placebo/standard care group when patients underwent CABG surgery. In addition, 9 trials (with 440 randomized patients), 4 trials (with 212 randomized patients), and 10 trials (with 470 randomized patients) reported that the occurrence of myocardial infarction (MI), myocardial ischemia, and arrhythmia was lower in the milrinone group than in the placebo/standard care group. Between the milrinone treatment and placebo/standard care groups, the occurrence of myocardial infarction, myocardial ischemia, and arrhythmia was significantly different. However, the occurrence of stroke and renal failure, the duration of inotropic support (h), the need for an intra-aortic balloon pump (IABP), and mechanical ventilation (h) between these two groups showed no differences.Conclusions: Based on the current results, compared with placebo, milrinone might be unable to decrease mortality in adult CABG surgical patients but can significantly ameliorate the occurrence of MI, myocardial ischemia, and arrhythmia. These results provide evidence for the further clinical application of milrinone and of therapeutic strategies for CABG surgery. However, along with milrinone application in clinical use, sufficient data from randomized clinical trials need to be collected, and the potential benefits and adverse effects should be analyzed and reevaluated.

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Decreased contractility and altered responses to inotropic agents in myocytes from tachypacing-induced heart failure canines

Cited by 18 publications

References 43 publications

Suppression of cardiomyocyte functions by β-CTX isolated from the Thai king cobra (Ophiophagus hannah) venom via an alternative method

Suppression of cardiomyocyte functions by β-CTX isolated from the Thai king cobra (Ophiophagus hannah) venom via an alternative method

The effect of milrinone on mortality in adult patients who underwent CABG surgery: a systematic review of randomized clinical trials with a meta-analysis and trial sequential analysis

The effect of milrinone on mortality in adult patients who underwent CABG surgery: A systematic review of randomized clinical trials with a meta-analysis and trial sequential analysis

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