A Double-Blind Placebo-Controlled Study of the Effects of Olprinone, a Specific Phosphodiesterase III Inhibitor, for Preventing Postoperative Atrial Fibrillation in Patients Undergoing Pulmonary Resection for Lung Cancer

Nojiri, Takashi; Yamamoto, Keiji; Maeda, Hitoshi; Takeuchi, Yukiyasu; Ose, Naoko; Susaki, Yoshiyuki; Inoue, Masayoshi; Okumura, Meinoshin

doi:10.1378/chest.15-0852

Cited by 16 publications

(8 citation statements)

References 36 publications

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“…The use of a PDE inhibitor is one of the major approaches to increase cGMP levels indirectly 12 . We previously reported that cGMP has an inhibitory effect on the CSC properties in PDAC 14 and a clinical study showed PDE3 inhibitors to be safe in patients with cancer and are beneficial for the prevention of atrial fibrillation 28 . These findings suggest that PDE3 inhibition could be potentential target candidate for PDAC and thus, we first assessed the expression levels of PDE3 in PDAC patient tissues.…”

Section: Resultsmentioning

confidence: 99%

“…Further, our results showed that PDE3s are expressed in Panc-1 cells (Supplementary Figure 1b). Our previous clinical study based on 40 patients showed that the PDE3 inhibitor was safe even among patients with heart diseases who presented elevated preoperative BNP levels (≥30 pg/mL) 28 while few clinical studies have provided information on the safety of the other PDE inhibitors administration for patients with cancer.…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, a PDE3 inhibitor was widely used as treatment of acute heart failure and cardiogenic shock 24 , as well as in patients with lung cancer for the prevention of postoperative atrial fibrillation 28 . Polyphenon E™ is a botanical drug containing 60% EGCG that has been approved for the treatment of external genital and perianal warts by the US FDA 30 .…”

Section: Discussionmentioning

confidence: 99%

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PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma

Kumazoe

Takai

Hiroi

et al. 2017

Sci Rep

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Recurrence following chemotherapy is observed in the majority of patients with pancreatic ductal adenocarcinoma (PDAC). Recent studies suggest that cancer stem cells (CSCs) may be involved in PDAC recurrence and metastasis. However, an efficient approach to targeting pancreatic CSCs remains to be established. Here we show that in cancer cells overexpressing the 67-kDa laminin receptor (67LR)-dependent cyclic GMP (cGMP) inducer, epigallocatechin-3-O-gallate (EGCG) and a phosphodiesterase 3 (PDE3) inhibitor in combination significantly suppressed the Forkhead box O3 and CD44 axis, which is indispensable for the CSC properties of PDAC. We confirmed that the EGCG and PDE3 inhibitor in combination strongly suppressed tumour formation and liver metastasis in vivo. We also found that a synthesized EGCG analog capable of inducing strong cGMP production drastically suppressed the CSC properties of PDAC and extended the survival period in vivo. In conclusion, the combination treatment of EGCG and a PDE3 inhibitor as a strong cGMP inducer could be a potential treatment candidate for the eradication of CSCs of PDAC.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma

Kumazoe

Takai

Hiroi

et al. 2017

Sci Rep

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“…A recent study highlighted the role of olprinone, a specific phosphodiesterase III inhibitor, in PAF prevention [110]. In particular, continuous infusion of olprinone during lung surgery was safe and reduced the rate of PAF following lung resection in patients with increased pre-operative BNP concentrations.…”

Section: Atrial Fibrillation Prophylaxismentioning

confidence: 99%

Incidence, Management, Prevention and Outcome of Post-Operative Atrial Fibrillation in Thoracic Surgical Oncology

Fabiani

Colombo

Bacchiani

et al. 2019

JCM

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Atrial fibrillation (AF) is a common supraventricular arrhythmia, a recognized risk factor for ischemic stroke, as a potential driver for heart failure (HF). Cancer patients have an increased risk for AF, even not including any cancer-specific treatment, as surgery or chemotherapy. The mechanism is multifactorial, with inflammation and changes in autonomic tone as critical actors. Commonly, AF is a recurrent complication of the post-operative period in cancer surgery (especially thoracic). Recent papers confirmed a significant incidence of post-operative (non-cardiac surgery) AF (PAF), partially mitigated by the use of prophylactic (rate o rhythm control) treatments. A relevant difference, in terms of mean hospitalization time, emerges between patients developing PAF and those who do not, while long term impact remains a matter of debate, due to several potential confounding factors. Besides clinical predictors, structural (i.e., echocardiographic) and bio-humoral findings may help in risk prediction tasks. In this respect, pre-operative natriuretic peptides (NPs) concentrations are nowadays recognized as significant independent predictors of perioperative cardiovascular complications (including PAF), while elevated post-operative levels may further enhance risk stratification. The aim of the present paper is to trace the state of the art in terms of incidence, management, prevention, and outcome of PAF in the field of thoracic surgical oncology.

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“…CABG surgery is a surgical procedure in which vascular access between the root of the ascending aorta and the distal end of the lesion site is established to make blood bypass the coronary artery lesion site, flow to the distal end of the coronary artery stenosis or obstruction, and reach the ischemic myocardium, thus improving coronary perfusion and increasing myocardial oxygen supply [10][11][12]. Although CABG surgery has been reported to be associated with low costs, superior outcomes, and particularly short-term mortality [13][14][15][16], multiple complications, such as MI, myocardial ischemia, arrhythmia, stroke, and acute renal failure (ARF), are impossible to ignore and are still concerning to researchers and clinical doctors [7,[17][18][19][20], To minimize the occurrence of postoperative complications, pre-and/or postoperative medicinal applications, such as phosphodiesterase (PDE) III inhibitors, have been the primary strategies to date [21][22][23].…”

Section: Introductionmentioning

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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A Double-Blind Placebo-Controlled Study of the Effects of Olprinone, a Specific Phosphodiesterase III Inhibitor, for Preventing Postoperative Atrial Fibrillation in Patients Undergoing Pulmonary Resection for Lung Cancer

Cited by 16 publications

References 36 publications

PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma

PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma

Incidence, Management, Prevention and Outcome of Post-Operative Atrial Fibrillation in Thoracic Surgical Oncology

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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