Effect of nicardipine on pulmonary hypertension after repair of congenital heart defects in early postoperative period

Maruyama, Kazuo; Maruyama, Junko; Utsunomiya, Hirofumi; Furuhashi, Kazuhisa; Kurobuchi, Motoyuki; Katayama, Yoshihiko; Yada, Isao; Muneyuki, Mannosuke

doi:10.1007/s0054030070095

Cited by 5 publications

(4 citation statements)

References 14 publications

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“…The increase in mPAP was significantly attenuated in the HV/TM group compared with the HV/SAL group at 1 and 1.5 h. There were no differences in the mPAP between the HV/TM and LV groups (Figure 3 A), suggesting that TM treatment prevented the increase in mPAP caused by high tidal volume ventilation. Similar results were obtained for Pp/Ps, an index of pulmonary hypertension [ 25 ]. Pp/Ps was significantly higher in HV/SAL rats than LV/SAL rats at 1.5 and 2 h after the start of mechanical ventilation.…”

Section: Resultssupporting

confidence: 86%

Thrombomodulin protects against lung damage created by high level of oxygen with large tidal volume mechanical ventilation in rats

et al. 2014

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BackgroundVentilator-induced lung injury (VILI) is associated with inflammatory responses in the lung. Thrombomodulin (TM), a component of the coagulation system, has anticoagulant and anti-inflammatory effects. We hypothesized that the administration of recombinant human soluble TM (rhsTM) would block the development of lung injury.MethodsLung injury was induced by high tidal volume ventilation for 2 h with 100% oxygen in rats. Rats were ventilated with a tidal volume of 35 ml/kg with pretreatment via a subcutaneous injection of 3 mg/kg rhsTM (HV (high tidal volume)/TM) or saline (HV/SAL) 12 h before mechanical ventilation. Rats ventilated with a tidal volume of 6 ml/kg under 100% oxygen with rhsTM (LV (low tidal volume)/TM) or saline (LV/SAL) were used as controls. Lung protein permeability was determined by Evans blue dye (EBD) extravasation.ResultsLung injury was successfully induced in the HV/SAL group compared with the LV/SAL group, as shown by the significant decrease in arterial oxygen pressure (PaO2), increased protein permeability, and increase in mean pulmonary artery pressure (mPAP) and ratio of mean pulmonary artery pressure to mean artery pressure (Pp/Ps). Treatment of rats with lung injury with rhsTM (HV/TM) significantly attenuated the decrease in PaO2 and the increase in both mPAP and Pp/Ps, which was associated with a decrease in the lung protein permeability. Lung tissue mRNA expressions of interleukin (IL)-1α, IL-1β, IL-6, tumor necrosis factor-α, and macrophage inflammatory protein (MIP)-2 were significantly higher in HV than in LV rats. Rats with VILI treated with rhsTM (HV/TM) had significantly lower mRNA expressions of IL-1α, IL-1β, IL-6, and MIP-2 than those expressions in HV/SAL rats.ConclusionsAdministration of rhsTM may prevent the development of lung injury created by high level of oxygen with large tidal volume mechanical ventilation, which has concomitant decrease in proinflammatory cytokine and chemokine expression in the lung.

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Section: Resultssupporting

confidence: 86%

Thrombomodulin protects against lung damage created by high level of oxygen with large tidal volume mechanical ventilation in rats

et al. 2014

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“…Under intraperitoneal pentobarbital sodium (45 mg/kg) anesthesia, a right internal carotid and a pulmonary artery catheter (Silastic tubing, 0.31 mm inner diameter and 0.64 mm outer diameter) were inserted by using the closed-chest technique, as described previously [ 11 , 23 , 30 , 33 ]. Mean pulmonary arterial pressure (mPAP), and peak inspiratory airway pressure (PIP) at the tracheostomy cannula (SP-110; Natsume, Tokyo, Japan) were recorded with a physiological transducer and amplifier system (AP 620; Nihon Kohden, Tokyo, Japan) [ 11 , 13 , 24 , 25 , 30 , 33 ].…”

Section: Methodsmentioning

confidence: 99%

Lung damage created by high tidal volume ventilation in rats with monocrotaline-induced pulmonary hypertension

et al. 2022

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Background Rats with chronic hypoxia-induced non-inflammatory pulmonary hypertension (PH) are resistant to ventilator-induced lung injury. We investigated the effect of high tidal volume ventilation in another model of PH, monocrotaline (MCT)-induced PH, which is a type of inflammatory PH. Methods PH was induced in rats by subcutaneous injection with 60 mg/kg MCT. Normal control rats, rats at 2 weeks after MCT injection (MCT2), and rats at 3 weeks after MCT injection (MCT3) were ventilated with low tidal volume (LV, 6 mL/kg) or high tidal volume (HV, 35 mL/kg) for 2 h with room air without positive end-expiratory pressure. Arterial oxygen pressure (PaO2) and Evans blue dye (EBD) extravasation were measured. Hypertensive pulmonary vascular remodeling was assessed morphometrically by the percentage of muscularized peripheral pulmonary arteries (%Muscularization) and the media wall thickness to external diameter ratio, namely percentage medial wall thickness (%MWT). To assess inflammation, lung IκB protein and cytokine mRNA expression levels were assessed. Results Baseline mean pulmonary arterial pressure was significantly higher in MCT rats (normal, 15.4 ± 0.5 mmHg; MCT2, 23.7 ± 0.9; and MCT3, 34.5 ± 1.5). After 2-h ventilation, PaO2 was significantly lower in the HV groups compared with the LV groups in normal and MCT2 rats, but not in MCT3 rats. Impairment of oxygenation with HV was less in MCT3 rats compared with normal and MCT2 rats. Among the HV groups, MCT3 rats showed significantly lower levels of EBD extravasation than normal and MCT2 rats. HV significantly downregulated IκB protein expression in normal and MCT3 rats and increased IL-6, MCP-1, CXCL-1 (MIP-1), and IL-10 mRNA levels in MCT3 rats. %Muscularization, %MWT, and the expression of lung elastin were significantly higher in MCT3 rats than in normal and MCT2 rats. Conclusion We found that HV-associated damage might be reduced in MCT-induced PH rats compared with normal rats. The results of this and earlier studies suggest that hypertensive pulmonary vascular structural changes might be protective against the occurrence of ventilator-induced lung injury, irrespective of the etiology of PH.

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“…In all conditions causing PH in humans [ 3 – 5 ] and experimental models [ 6 – 20 ], vascular changes include new muscularization of normally nonmuscular peripheral pulmonary arteries and medial hypertrophy of muscular arteries. PH may be encountered in the intensive care unit in patients with acute respiratory distress syndrome (ARDS) [ 21 – 23 ], congenital heart disease with left-to-right shunt [ 3 , 24 , 25 ], mitral valve disease [ 26 ], and interstitial pulmonary fibrosis [ 27 ], as well as after cardiothoracic surgery [ 28 , 29 ]. Nitric oxide (NO) is a vasodilator and suppressor of smooth muscle cell proliferation [ 1 , 2 ], and the bioavailability of NO is reduced in patients with PH and in experimental PH models [ 30 – 32 ].…”

Section: Introductionmentioning

confidence: 99%

Model difference in the effect of cilostazol on the development of experimental pulmonary hypertension in rats

et al. 2021

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Background Preventing pulmonary vascular remodeling is a key strategy for pulmonary hypertension (PH). Causes of PH include pulmonary vasoconstriction and inflammation. This study aimed to determine whether cilostazol (CLZ), a phosphodiesterase-3 inhibitor, prevents monocrotaline (MCT)- and chronic hypoxia (CH)-induced PH development in rats. Methods Fifty-one male Sprague–Dawley rats were fed rat chow with (0.3% CLZ) or without CLZ for 21 days after a single injection of MCT (60 mg/kg) or saline. Forty-eight rats were fed rat chow with and without CLZ for 14 days under ambient or hypobaric (air at 380 mmHg) CH exposure. The mean pulmonary artery pressure (mPAP), the right ventricle weight-to-left ventricle + septum weight ratio (RV/LV + S), percentages of muscularized peripheral pulmonary arteries (%Muscularization) and medial wall thickness of small muscular arteries (%MWT) were assessed. Levels of the endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (peNOS), AKT, pAKT and IκB proteins in lung tissue were measured using Western blotting. Monocyte chemotactic protein (MCP)-1 mRNA in lung tissue was also assessed. Results mPAP [35.1 ± 1.7 mmHg (MCT) (n = 9) vs. 16.6 ± 0.7 (control) (n = 9) (P < 0.05); 29.1 ± 1.5 mmHg (CH) (n = 10) vs. 17.5 ± 0.5 (control) (n = 10) (P < 0.05)], RV/LV + S [0.40 ± 0.01 (MCT) (n = 18) vs. 0.24 ± 0.01 (control) (n = 10) (P < 0.05); 0.41 ± 0.03 (CH) (n = 13) vs. 0.27 ± 0.06 (control) (n = 10) (P < 0.05)], and %Muscularization and %MWT were increased by MCT injection and CH exposure. CLZ significantly attenuated these changes in the MCT model [mPAP 25.1 ± 1.1 mmHg (n = 11) (P < 0.05), RV/LV + S 0.30 ± 0.01 (n = 14) (P < 0.05)]. In contrast, these CLZ effects were not observed in the CH model. Lung eNOS protein expression was unchanged in the MCT model and increased in the CH model. Lung protein expression of AKT, phosphorylated AKT, and IκB was downregulated by MCT, which was attenuated by CLZ; the CH model did not change these proteins. Lung MCP-1 mRNA levels were increased in MCT rats but not CH rats. Conclusions We found model differences in the effect of CLZ on PH development. CLZ might exert a preventive effect on PH development in an inflammatory PH model but not in a vascular structural change model of PH preceded by vasoconstriction. Thus, the preventive effect of CLZ on PH development might depend on the PH etiology.

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Effect of nicardipine on pulmonary hypertension after repair of congenital heart defects in early postoperative period

Cited by 5 publications

References 14 publications

Thrombomodulin protects against lung damage created by high level of oxygen with large tidal volume mechanical ventilation in rats

Thrombomodulin protects against lung damage created by high level of oxygen with large tidal volume mechanical ventilation in rats

Lung damage created by high tidal volume ventilation in rats with monocrotaline-induced pulmonary hypertension

Model difference in the effect of cilostazol on the development of experimental pulmonary hypertension in rats

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