• Archives of Pharmacal Research
• /
• v.14 no.3
• /
• pp.242-248
• /
• 1991

Antihypertensive effect of YH 334 was examined in various experimental hypertension rat models and the systemic and regional hymohynamic profiles of the compound were investigated in conscious spontaneously hypertensive rats (SHR). The antiypertensive potensive potency of YH 334 is found to be more than 10 times stronger than that of nitrendipine in the all hypertensive models. The effective doses to lower the initial blood pressure by 20% $(ED_{20})$ of YH334 were 1.4 mg/kg in normotensive rats (NR), 0.7 mglkg in SHR. 0.1 mg/kg in DOCA salt hypertensive rats (DHR) and 0.4 mg/kg in renal hypertensive rats (RHR), and the $ED_{20}$ values of nitrendipine were 15.8 mg/kg in NR, 7.1 mg/kg in SHR, 1.7 mg/kg in DHR and 4.8 mg/kg in RHR. The primary hemodynamic effect hemodynamic profile is similar to that of nitrendipine. Both compounds seem to produce potent antihypertensive effects by lowering peripheral resistance in the skeletal muscles. In the organ bath study using isolated rabbit aorta, YH 334 was found to be a potent voltage dependent calcium channel blocker without significant inhibitory effect on the receptor operated calcium channels like the most of other dihydropyridine type calcium antagonists. Furthermore, YH334 showed acute diuretic and natriuretic effects in conscious SHR, which may render the unnecessary restriction of sodium in the diet of those patients on long term hypertension therapy. This effect would provide an additional benefit to its potent antihypertensive activity.

• Korean Journal of Radiology
• /
• v.24 no.7
• /
• pp.647-659
• /
• 2023

Objective: The study was conducted to investigate the effect of correct occlusion of the left atrial appendage (LAA) on intracardiac blood flow and thrombus formation in patients with atrial fibrillation (AF) using four-dimensional (4D) flow magnetic resonance imaging (MRI) and three-dimensional (3D)-printed phantoms. Materials and Methods: Three life-sized 3D-printed left atrium (LA) phantoms, including a pre-occlusion (i.e., before the occlusion procedure) model and correctly and incorrectly occluded post-procedural models, were constructed based on cardiac computed tomography images from an 86-year-old male with long-standing persistent AF. A custom-made closed-loop flow circuit was set up, and pulsatile simulated pulmonary venous flow was delivered by a pump. 4D flow MRI was performed using a 3T scanner, and the images were analyzed using MATLAB-based software (R2020b; Mathworks). Flow metrics associated with blood stasis and thrombogenicity, such as the volume of stasis defined by the velocity threshold ($\left|\vec{V}\right|$ < 3 cm/s), surface-and-time-averaged wall shear stress (WSS), and endothelial cell activation potential (ECAP), were analyzed and compared among the three LA phantom models. Results: Different spatial distributions, orientations, and magnitudes of LA flow were directly visualized within the three LA phantoms using 4D flow MRI. The time-averaged volume and its ratio to the corresponding entire volume of LA flow stasis were consistently reduced in the correctly occluded model (70.82 mL and 39.0%, respectively), followed by the incorrectly occluded (73.17 mL and 39.0%, respectively) and pre-occlusion (79.11 mL and 39.7%, respectively) models. The surfaceand-time-averaged WSS and ECAP were also lowest in the correctly occluded model (0.048 Pa and 4.004 Pa^-1, respectively), followed by the incorrectly occluded (0.059 Pa and 4.792 Pa^-1, respectively) and pre-occlusion (0.072 Pa and 5.861 Pa^-1, respectively) models. Conclusion: These findings suggest that a correctly occluded LAA leads to the greatest reduction in LA flow stasis and thrombogenicity, presenting a tentative procedural goal to maximize clinical benefits in patients with AF.