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In experiments on Wistar rats, the effect of a new selective JNK inhibitor tryptanthrin oxime (TR-Ox) on parameters of systemic hemodynamics, cardiohemodynamics, and post-infarction fibrosis was studied 4 months after acute myocardial ischemia (1 h) followed by reperfusion. TR-Ox was administered intraperitoneally at a dose of 12 mg/kg 20 min before reperfusion, and then once a day for the next 4 days. Administration of TR-Ox to animals in the acute phase of myocardial infarction contributed to more complete preservation of myocardial viability in the delayed period: a relative increase of muscle elements proportion in the scar, a decrease in the formation of connective tissue areas with complete and >50% replacement of the myocardium, and deceleration of fibrotic scarring in myocardium areas distant from the focus of injury, resulting in improved systolic and diastolic myocardial function.
View Article and Find Full Text PDFIn vivo cardiovascular profile of ryanodine receptor 2 inhibitor M201-A: Utility as an anti-atrial fibrillatory drug for patients suffering from heart failure with preserved ejection fraction.
J Pharmacol Sci
November 2024
Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan; Kazuya Yokoyama Cancer Research Institute, 1-4-8 Ueno, Taito-ku, Tokyo, 110-0005, Japan. Electronic address:
Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) often coexist; however, clinically available anti-AF drugs can exacerbate symptoms of HFpEF. M201-A suppressed ryanodine receptor-mediated diastolic Ca leakage, possibly inhibiting common pathological processes toward AF and HFpEF. To bridge the basic information to clinical practice, we assessed its cardiohemodynamic, anti-AF and ventricular proarrhythmic profile using halothane-anesthetized dogs (n = 4).
View Article and Find Full Text PDFAnalysis of cardiohemodynamic and electrophysiological effects of morphine along with its toxicokinetic profile using the halothane-anesthetized dogs.
J Toxicol Sci
June 2024
Department of Pharmacology, Faculty of Medicine, Toho University.
Although morphine has been used for treatment-resistant dyspnea in end-stage heart failure patients, information on its cardiovascular safety profile remains limited. Morphine was intravenously administered to halothane-anesthetized dogs (n=4) in doses of 0.1, 1 and 10 mg/kg/10 min with 20 min of observation period.
View Article and Find Full Text PDFPathophysiology of Hepatorenal Syndrome.
Adv Kidney Dis Health
March 2024
Division of Nephrology, Rush University School of Medicine, Chicago, IL.
Hepatorenal syndrome type 1 (HRS-1) is a unique form of acute kidney injury that affects individuals with decompensated cirrhosis with ascites. The primary mechanism leading to reduction of kidney function in HRS-1 is hemodynamic in nature. Cumulative evidence points to a cascade of events that led to a profound reduction in kidney perfusion.
View Article and Find Full Text PDFIn vivo analysis of acute eletropharmacological effects of proton pump inhibitors using halothane-anesthetized dogs: a translational study of cardiovascular adverse events.
J Toxicol Sci
July 2023
Department of Pharmacology, Faculty of Medicine, Toho University.
Long-term use of proton pump inhibitors (PPIs) is known to clinically induce hypomagnesemia, increasing the risk toward QT-interval prolongation and lethal ventricular arrhythmias, whereas PPIs can directly modulate cardiac ionic currents in the in vitro experiments. In order to fill the gap between those information, we assessed acute cardiohemodynamic and electrophysiological effects of sub- to supra-therapeutic doses (0.05, 0.
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