Vagal nerve stimulation preserves right ventricular function in a rat model of right ventricular pressure overload

Abstract Vagal nerve stimulation (VNS) ameliorates pulmonary vascular remodeling and improves survival in a rat model of pulmonary hypertension (PH). However, the direct impact of VNS on right ventricular (RV) function, which is the key predictor of PH patients, remains unknown. We evaluated the effect of VNS among the three groups: pulmonary artery banding (PAB) with sham stimulation (SS), PAB with VNS, and control (no PAB). We stimulated the right cervical vagal nerve with an implantable pulse generator, initiated VNS 2 weeks after PAB, and stimulated for 2 weeks. Compared to SS, VNS increased cardiac index (VNS: 130 ± 10 vs. SS: 93 ± 7 ml/min/kg; p < 0.05) and end‐systolic elastance assessed by RV pressure–volume analysis (VNS: 1.1 ± 0.1 vs. SS: 0.7 ± 0.1 mmHg/μl; p < 0.01), but decreased RV end‐diastolic pressure (VNS: 4.5 ± 0.7 vs. SS: 7.7 ± 1.0 mmHg; p < 0.05). Furthermore, VNS significantly attenuated RV fibrosis and CD68‐positive cell migration. In PAB rats, VNS improved RV function, and attenuated fibrosis, and migration of inflammatory cells. These results provide a rationale for VNS therapy as a novel approach for RV dysfunction in PH patients

Beneficial Effects of Pulmonary Vasodilators on Pre-Capillary Pulmonary Hypertension in Patients with Chronic Kidney Disease on Hemodialysis

Background: In patients with chronic kidney disease (CKD) on hemodialysis, comorbid pulmonary hypertension (PH) aggravates exercise tolerance and eventually worsens the prognosis. The treatment strategy for pre-capillary PH, including combined pre- and post-capillary PH (Cpc-PH), has not been established. Objectives: This study aimed to evaluate the impact of pulmonary vasodilators on exercise tolerance and pulmonary hemodynamics in patients with CKD on hemodialysis. Methods and Results: The medical records of 393 patients with suspected PH who underwent right heart catheterization were reviewed. Of these, seven patients had isolated pre-capillary PH and end-stage CKD on hemodialysis. Pulmonary vasodilators decreased pulmonary vascular resistance from 5.9 Wood units (interquartile range (IQR), 5.5&ndash;7.6) at baseline to 3.1 Wood units (IQR, 2.6&ndash;3.3) post-treatment (p = 0.02) as well as increased pulmonary capillary wedge pressure from 10 mmHg (IQR, 7&ndash;11) to 11 mmHg (IQR, 8&ndash;16) (p = 0.04). Pulmonary vasodilators increased the World Health Organization functional class I or II from 0% to 100% (p = 0.0002) and the 6 min walk distance from 273 m (IQR, 185&ndash;365) to 490 m (IQR, 470&ndash;550) (p = 0.03). Conclusions: Pulmonary vasodilators for PH in patients with CKD on hemodialysis decrease pulmonary vascular resistance and eventually improve exercise tolerance. Pulmonary vasodilators may help hemodialysis patients with pre-capillary PH, although careful management considering the risk of pulmonary edema is required

Ferrocene-Containing Pseudorotaxanes in Crystals: Aromatic Interactions with Hammett Correlation

Single crystals of pseudorotaxanes, [(FcCH2NH2CH2Ar)(DB24C8)][PF6] (DB24C8 = dibenzo[24]crown-8, Fc = Fe(C5H4)(C5H5), Ar = -C6H3-3,4-Cl2, -C6H3-3,4-F2, -C6H4-4-F, -C6H4-4-Cl, -C6H4-4-Br, -C6H3-3-F-4-Me, -C6H4-4-I) and [(FcCH2NH2CH2C6H4-4-Me)(DB24C8)][Ni(dmit)2] (dmit = 1,3-dithiole-2,4,5-dithiolate), were obtained from solutions containing DB24C8 and ferrocenylmethyl(arylmethyl)ammonium. X-ray crystallographic analyses of the pseudorotaxanes revealed that the aryl ring of the axle moiety and the catechol ring of the macrocyclic component were at close centroid distances and parallel or tilted orientation. The structures with parallel aromatic rings showed correlation of the distances between the centroids to Hammett substituent constants of the aryl groups

S1P4 receptor mediates S1P-induced vasoconstriction in normotensive and hypertensive rat lungs

This study aimed to identify receptors mediating sphingosine-1-phosphate (S1P)-induced vasoconstriction in the normotensive and chronic hypoxia-induced hypertensive rat pulmonary circulation. In isolated perfused lungs from normoxic rats, infusion of S1P caused a sustained vasoconstriction, which was not reduced by combinational pretreatment with the dual S1P1 and 3 receptor antagonist VPC23019 and the S1P2 receptor antagonist JTE013. The S1P4 receptor agonists phytosphingosine-1-phospate and VPC23153, but not the dual S1P1 and 3 receptor agonist VPC24191, caused dose-dependent vasoconstrictions. In hypertensive lungs from chronically hypoxic rats, the vasoconstrictor responses to S1P and VPC23153 were markedly enhanced. The S1P4 receptor agonist VPC 23153 caused contraction of isolated pulmonary but not of renal or mesenteric arteries from chronically hypoxic rats. S1P4 receptor protein as well as mRNA were detected in both normotensive and hypertensive pulmonary arteries. In contrast to what has been reported in the systemic circulation and mouse lung, our findings raise the possibility that S1P4 receptor plays a significant role in S1P-induced vasoconstriction in the normotensive and hypertensive rat pulmonary circulation