Effects of CP‐060S, a novel cardioprotective drug, in the methacholine‐induced ECG change model in rats

Fukazawa, Motoharu; Adachi, Yuichiro; Akima, Michitaka; Imagawa, Jun-ichi; Suzuki, Yoshiyuki; Kuromaru, Osamu; Tamura, Kazuhiko

doi:10.1046/j.1472-8206.2001.00014.x

Cited by 3 publications

(3 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In all rats of both groups, ischemia led to significant and equivalent ST-segment elevation prior to treatment. In rats destined to receive STAZN, the ST-segment (identified as per the method of Fukazawa et al [15]) was elevated from -0 244 mV to -0.168 mV (P<0.05); and in animals that subsequently received vehicle, the ST-segment was elevated from -0.254 mV to -0.134 mV (P<0.01; NS for differences between treatment groups).…”

Section: Stazn Reduces Electrocardiographic Changes After Reperfusionmentioning

confidence: 95%

Neuroprotective antioxidant STAZN protects against myocardial ischemia/reperfusion injury

Ley

Prado

Wei

et al. 2008

Biochemical Pharmacology

View full text Add to dashboard Cite

Background-Protecting the myocardium from ischemia-reperfusion injury has significant potential to reduce the complications of myocardial infarction and interventional revascularization procedures. Reperfusion damage is thought to result, in part, from oxidative stress. Here we use a novel method of percutaneous coronary occlusion to show that the potent antioxidant and neuroprotective free-radical scavenger, stilbazulenyl nitrone (STAZN), confers marked cardioprotection when given immediately prior to reperfusion.Methods and Results-Physiologically controlled male Sprague-Dawley rats were anesthetized with isoflurane, paralyzed with pancuronium and mechanically ventilated. A guide wire was introduced via the femoral artery and advanced retrogradely via the aorta into the left coronary artery under fluoroscopic guidance. Rats with established coronary ischemia (85 min after occlusion) were given STAZN 3.5 mg/kg or its vehicle 5 minutes before and 2 hours after reperfusion, and were subjected to functional and histopathologic studies at 3 days. Ischemia-associated Q wave amplitude was reduced by 73% in STAZN-treated rats (P=0.01), while infarct-related ejection fraction, fractional shortening and severe regional wall-motion impairments were reduced by 48%, 54% and 37%, respectively, relative to vehicle-treated controls (P=0.05). Total myocardial infarct volume in STAZN-treated rats was correspondingly reduced by 43% (P<0.05), representing a sparing of 14% of the total left ventricular myocardium.Conclusions-STAZN, a second-generation azulenyl nitrone with potent neuroprotective efficacy in brain ischemia, is also a rapidly acting and highly effective cardioprotective agent in acute coronary ischemia. Our results suggest the potential for clinical benefit in the setting of acute coronary syndromes.

show abstract

Section: Stazn Reduces Electrocardiographic Changes After Reperfusionmentioning

confidence: 95%

Neuroprotective antioxidant STAZN protects against myocardial ischemia/reperfusion injury

Ley

Prado

Wei

et al. 2008

Biochemical Pharmacology

View full text Add to dashboard Cite

show abstract

“…Arotinolol can also be used to treat essential tremor, and the results of a randomized crossover trial showed that taking arotinolol 20 mg twice a day is more effective than taking propranolol 80 mg twice a day in treating essential tremor ( 23 ). In addition, a study showed that ( 24 ) patients with CHF are often associated with increased sympathetic excitability and elevated levels of catecholamines, renin, and angiotensin in their circulating blood. Arotinolol reduces coronary artery resistance and dilates coronary arteries through α receptor blocking effects.…”

Section: Introductionmentioning

confidence: 99%

Effect of arotinolol on chronic heart failure: A systematic review and meta-analysis of randomized controlled trials

Huang

Song

Wang

et al. 2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

BackgroundHeart failure is the end stage of all cardiovascular diseases, which brings a heavy burden to the global health network. Arotinolol, as a new type of β Receptor blocker, has a good antihypertensive effect. Many clinical trials have observed the clinical efficacy of arotinolol in the treatment of essential hypertension. However, so far, there has been no systematic evaluation on the efficacy and safety of arotinolol in the treatment of chronic heart failure.ObjectiveThe purpose of this review was to systematically evaluate the clinical efficacy of arotinolol in patients with chronic heart failure.MethodsRandomized controlled trials (RCTs) of arotinolol in the treatment of chronic heart failure were retrieved from seven databases according to the Cochrane manual, including CNKI (China National Knowledge Infrastructure), Wan fang database, VIP database, PubMed, Sinomed, EMBASE, and the Cochrane Library databases. The main outcomes were the effective rate, left ventricular ejection fraction (LVEF), blood pressure, heart rate, cardiac index, stroke volume (SV), brain natriuretic peptide (BNP), hypersensitive C-reactive protein (Hs-CRP), left ventricular end diastolic volume (LVEDV), left ventricular end diastolic diameter (LVEDD), and adverse events (AEs).ResultsA total of 17 trials met the qualification criteria, which included 1,717 patients with heart failure. Most trials had uncertain risks in terms of random sequence generation, allocation hiding, patient loss, and result evaluation. Meta analysis showed that arotinolol significantly improved the treatment efficiency of patients with heart failure (standardized mean difference (SMD) = 4.07, 95% confidence interval (CI) [2.89, 5.72], p = 0.00, I2 = 0), LVEF (SMD = 1.59, 95% CI [0.99, 2.19], p = 0.000 0, I2 = 95.8%), cardiac index (SMD = 0.32, 95% CI [0.11, 0.53], p = 0.03), I2 = 0), SV (SMD = 2.00, 95% CI [1.57, 2.34], p = 0.000, I2 = 64.2%), lower BNP (SMD = −0.804, 95% CI [−0.97, −0.64], p = 0.000, I2 = 94.4%), and LVEDV (SMD = −0.25, 95% CI [−0.45, −0.05], p = 0.015, I2 = 0). There was no statistical significance for blood pressure (SMDsystolic pressure = −0.09, 95% CI [−0.69, 0.51], p = 0.775, I2systolic pressure = 90.2%; SMDdiastolic pressure = −0.16, 95% CI [−0.79, 0.48], P = 0.632, I2diastolic pressure = 91.2%), heart rate (SMD = −0.12, 95% CI [−1.00, 0.75], P = 0.787, I2 = 96.1%), Hs-CRP (SMD = −1.52, 95% CI [−3.43, 0.40], P = 0.121, I2 = 98.3%), and LVEDD (SMD = −0.07, 95% CI [−0.90, 0.76], P = 0.870, I2 = 96.5%).ConclusionArotinolol can safely and effectively improve the effective rate of patients with chronic heart failure, increase LVEF, increase CI and SV, and reduce BNP and LVEDV. However, because of the low overall quality of the included randomized controlled trials, these findings need to be considered carefully. More high-quality randomized controlled trials are needed for further verification, to provide a more scientific basis for the safety and effectiveness of arotinolol in the clinical treatment of heart failure.Systematic review registration[https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=371214], identifier [CRD:420223371214].

show abstract

“…Moreover, in a model of myocardial pacinginduced ischaemia, which simulates stable eOE ort angina, CP-060S also suppresses the pacing-induced ST-segment elevation in dogs by this dual action (Adachi et al 1999). On the other hand, as a result of its Ca 2 + -channel blockade, CP-060S decreases myocardial oxygen consumption in dogs and suppresses the ST-segment changes in a rat model of methacholineinduced vasospastic angina, which simulates variant angina (Fukazawa et al 2001). However, the eOE ects of orally administered CP-060S in models of experimental angina remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

The long-lasting anti-anginal effects of CP-0605 in a rat model of arginine vasopressin-induced myocardial ischaemia

Adachi¹,

Suzuki²,

Hatanaka³

et al. 2002

Journal of Pharmacy and Pharmacology

Self Cite

View full text Add to dashboard Cite

The anti-anginal effect of CP-060S, a new cardioprotective agent that prevents myocardial Na+-, Ca2+-overload and has Ca2+-channel blocking activity, was evaluated in a rat model of arginine8-vasopressin (AVP)-induced cardiac ischaemia. Infusion of AVP (0.2 IU kg(-1)) depressed the electrocardiogram (ECG) ST segment, an index of myocardial ischaemia. Vehicle, CP-060S and diltiazem were given orally 1, 2, 4, 8, 12 and 24 h before the administration of AVP. CP-060S, at 3 mg kg(-1) and 10 mg kg(-1), suppressed AVP-induced ST-segment depression for 2 h and 12 h, respectively. In contrast, diltiazem, at 10 and 30 mg kg(-1), suppressed AVP-induced ST-segment depression for only 1 h. The persistent suppression of the AVP-induced ST-segment depression by CP-060S correlated with the time course of changes in its plasma concentration. The minimum effective concentration of CP-060S was estimated to be 30 ng mL(-1) (approximately 50 nM), consistent with its vasorelaxant potency in rat isolated aortic strips (concentration producing 50% relaxation of KCl contraction, IC50 = 32.6+/-8.3 nM). Intravenously administered CP-060S, at 300 microg kg(-1) and diltiazem at 500 microg kg(-1) showed similar haemodynamic changes, whereas CP-060S, at 300 microg kg(-1), significantly suppressed AVP-induced ST-segment depression and diltiazem, at 500 microg kg(-1), had no effect on AVP-induced ST-segment depression. In summary, orally administered CP-060S exerted a long-lasting anti-anginal effect proportionate to the time course of changes in its plasma concentration in a rat model of AVP-induced ischaemia.

show abstract

Effects of CP‐060S, a novel cardioprotective drug, in the methacholine‐induced ECG change model in rats

Cited by 3 publications

References 26 publications

Neuroprotective antioxidant STAZN protects against myocardial ischemia/reperfusion injury

Neuroprotective antioxidant STAZN protects against myocardial ischemia/reperfusion injury

Effect of arotinolol on chronic heart failure: A systematic review and meta-analysis of randomized controlled trials

The long-lasting anti-anginal effects of CP-0605 in a rat model of arginine vasopressin-induced myocardial ischaemia

Contact Info

Product

Resources

About