Milrinone Administered Before Ischemia or Just After Reperfusion, Attenuates Myocardial Stunning in Anesthetized Swine

Use, Tadasuke; Makita, Tetsuji; Ureshino, Hiroyuki; Cho, Sungsam; Akiyama, Daiji; Oshibuchi, Motoko; Hara, Tetsuya; Sumikawa, Koji

doi:10.1007/s10557-006-0166-7

Cited by 6 publications

(4 citation statements)

References 36 publications

(38 reference statements)

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“…This ischemia/reperfusion injury could occur after cardiac surgery, cardiopulmonary resuscitation or percutaneous transluminal coronary angioplasty. Some perioperative agents such as sevoflurane [20] or milrinone [21] have been suggested to serve as a protectant against myocardial ischemic-reperfusion injury. However, their clinical effectiveness has not yet been established.…”

Section: Discussionmentioning

confidence: 99%

Postischemic infusion of sivelestat sodium hydrate, a selective neutrophil elastase inhibitor, protects against myocardial stunning in swine

et al. 2010

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Purpose. It seems controversial whether or not neutrophil elastase inhibitors are effective in attenuating the myocardial ischemia/reperfusion injury. We thus investigated possible protective effects of sivelestat, a neutrophil elastase inhibitor, against myocardial stunning-i.e., prolonged myocardial dysfunction following a brief episode of ischemia.Methods. Swine were divided into control group (group C), low-dose sivelestat group (group L), and high-dose sivelestat group (group H) (n=7 for each group). All the swine were subjected to myocardial ischemia through ligation of the left anterior descending coronary artery (LAD) for 12-min, followed by 90-min reperfusion. Sivelestat was infused intracoronally at concentrations of 6 and 60 mg/ml throughout the reperfusion period in the group L and H, respectively, while saline in the group C. Heart rate (HR), left ventricular developed pressure (LVdP), maximum rate of LVdP (LVdP/dtmax), LV end-diastolic pressure (LVEDP), percentage of segment shortening (%SS, an index of regional myocardial contractility), and coronary venous interleukin-6 concentration in LAD perfusion area were measured before ischemic induction and during reperfusion. Results. The ischemia-reperfusion insult did not cause any significant changes in the HR, LVdP, LVdP/dtmax, and LVEDP in all groups. However, it significantly decreased %SS in the LAD perfusion area, while increased the interleukin-6 concentration in the group C. Those changes in %SS and the interleukin-6 concentration were both greatly attenuated, but not prevented, in the group L and group H. Conclusion.Sivelestat presumably attenuates myocardial contractile dysfunction due to myocardial stunning by inhibiting neutrophil-derived elastase and thereby suppressing the production of interleukin-6 in activated neutrophils.(250 words) 4

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Section: Discussionmentioning

confidence: 99%

Postischemic infusion of sivelestat sodium hydrate, a selective neutrophil elastase inhibitor, protects against myocardial stunning in swine

et al. 2010

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“…It has been reported that the administration of olprinone before ischemia could lead to a reduction in myocardial infarct size in dogs 11 and rats 12,16 . Use et al 17 showed that milrinone, a PDE3-I, administered before ischemia or just after reperfusion, attenuates myocardial stunning in swine. The present results show that a bolus application of the clinical loading dose, 10 μg/kg of olprinone just prior to reperfusion, has a significant effect on reducing myocardial infarct size.…”

Section: Discussionmentioning

confidence: 99%

Roles of Cyclooxygenase 2 in Sevoflurane- and Olprinone-Induced Early Phase of Preconditioning and Postconditioning Against Myocardial Infarction in Rat Hearts

Tosaka

Matsumoto

et al. 2010

J Cardiovasc Pharmacol Ther

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Implications statement: A selective COX-2 inhibitor prevents the cardioprotective effect of sevoflurane but not olprinone in rat hearts. (16 words) 2 AbstractPurpose: It is known that selective cyclooxygenase (COX)-2 inhibitors increase mortality in patients with previous myocardial infarction, and it has been suggested that COX-2 plays an important role in cardioprotection against ischemia. The present study was carried out to determine whether COX-2 is involved in the mechanisms of sevoflurane-and olprinone-induced early-phase preconditioning (E-PreC) and postconditioning (PostC) in rat hearts.Methods: Male SD rats were anesthetized with sodium pentobarbital. After opening the chest, all rats underwent 30-min left anterior descending coronary artery occlusion followed by 2-h reperfusion, and the infarct size was measured after the reperfusion. The rats were randomly assigned to groups with pre-and post-ischemic exposure to sevoflurane and administration of olprinone with or without a selective COX-2 inhibitor, NS-398.Results: The infarct size in the control group was 42 ± 6% of the area at risk. Infarct size was significantly reduced by pre-and post-ischemic administration of sevoflurane (16 ± 7% and 17 ± 6%, respectively), as well as by olprinone (14 ± 4% and 15 ± 10%, respectively). NS-398 prevented the protective effects of both pre and post-ischemic exposure to sevoflurane (35 ± 8% and 42 ± 10%, respectively), whereas the protective effect of both pre-and post-ischemic administration of olprinone was not influenced by NS-398 (12 ± 5% and 19 ± 7%, respectively).Conclusions: COX-2 could be a critical mediator of sevoflurane-induced but not olprinone-induced E-PreC or PostC in rat hearts. (236 words) 3

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“…The authors proposed that the end-effectors of p38-MAPK may include opening of the mitochondrial ATP-sensitive potassium channel (mitoKATP) channel or translocation of Hsp27 to the Z-disc to stabilize the myofibril and cytoskeleton. Milrinone, administered before ischemia or at the onset of reperfusion, has recently been shown to attenuate myocardial stunning in pigs [95] . However, milrinone did not reduce the incidence of arrhythmias due to IR injury in dogs [96] .…”

Section: Phosphodiesterasementioning

confidence: 99%

Pivotal effects of phosphodiesterase inhibitors on myocyte contractility and viability in normal and ischemic hearts

Rao

2008

Acta Pharmacol Sin

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Phosphodiesterases (PDEs) are enzymes that degrade cellular cAMP and cGMP and are thus essential for regulating the cyclic nucleotides. At least 11 families of PDEs have been identified, each with a distinctive structure, activity, expression, and tissue distribution. The PDE type-3, -4, and -5 (PDE3, PDE4, PDE5) are localized to specific regions of the cardiomyocyte, such as the sarcoplasmic reticulum and Z-disc, where they are likely to influence cAMP/cGMP signaling to the end effectors of contractility. Several PDE inhibitors exhibit remarkable hemodynamic and inotropic properties that may be valuable to clinical practice. In particular, PDE3 inhibitors have potent cardiotonic effects that can be used for short-term inotropic support, especially in situations where adrenergic stimulation is insufficient. Most relevant to this review, PDE inhibitors have also been found to have cytoprotective effects in the heart. For example, PDE3 inhibitors have been shown to be cardioprotective when given before ischemic attack, whereas PDE5 inhibitors, which include three widely used erectile dysfunction drugs (sildenafil, vardenafil and tadalafil), can induce remarkable cardioprotection when administered either prior to ischemia or upon reperfusion. This article provides an overview of the current laboratory and clinical evidence, as well as the cellular mechanisms by which the inhibitors of PDE3, PDE4 and PDE5 exert their beneficial effects on normal and ischemic hearts. It seems that PDE inhibitors hold great promise as clinically applicable agents that can improve cardiac performance and cell survival under critical situations, such as ischemic heart attack, cardiopulmonary bypass surgery, and heart failure.

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Milrinone Administered Before Ischemia or Just After Reperfusion, Attenuates Myocardial Stunning in Anesthetized Swine

Abstract: We conclude that milrinone administered before ischemia or just after reperfusion attenuates myocardial stunning.

Cited by 6 publications

References 36 publications

Postischemic infusion of sivelestat sodium hydrate, a selective neutrophil elastase inhibitor, protects against myocardial stunning in swine

Postischemic infusion of sivelestat sodium hydrate, a selective neutrophil elastase inhibitor, protects against myocardial stunning in swine

Roles of Cyclooxygenase 2 in Sevoflurane- and Olprinone-Induced Early Phase of Preconditioning and Postconditioning Against Myocardial Infarction in Rat Hearts

Pivotal effects of phosphodiesterase inhibitors on myocyte contractility and viability in normal and ischemic hearts

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