Pulmonary Hypertension

Oishi, Peter; Fineman, Jeffrey R.

doi:10.1097/pcc.0000000000000754

Cited by 23 publications

(12 citation statements)

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“…A patient with a pulmonary hypertensive crisis will have a constellation of symptoms as described above—with varying degrees of cyanosis versus systemic hypotension depending on the presence of an intracardiac shunt. Invasive monitoring, including central venous pressure monitoring, and, rarely, a pulmonary artery catheter, may assist in the diagnosis [ 5 , 10 ]. One would expect the central venous pressure to be elevated in a patient with normal cardiac anatomy who is suffering a pulmonary hypertensive crisis.…”

Section: Discussionmentioning

confidence: 99%

“…Perhaps the most useful non-invasive imaging tool is an echocardiogram—looking specifically at right and left ventricular size and function, ventricular septal shift, valve function and estimated pulmonary arterial pressure via estimated right ventricular systolic pressures (RVSP). Additionally, if the patient has an intracardiac shunt (e.g., atrial septal defect), the direction of flow and size of the shunt can be assessed [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

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Pediatric Perioperative Pulmonary Arterial Hypertension: A Case-Based Primer

Shah

Szmuszkovicz

2017

Children

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pediatric Perioperative Pulmonary Arterial Hypertension: A Case-Based Primer

Shah

Szmuszkovicz

2017

Children

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“…(3) comprehensively to characterize in vitro aerosol performance using Food and Drug Administration (FDA)-approved human DPI devices with different shear stress device properties; (4) to examine biocompatibility, cell viability, and transepithelial electrical resistance (TEER) in vitro on human pulmonary cell two-dimensional (2D) and threedimensional (3D) models including primary pulmonary cells at the air-liquid interface as a function of simvastatin dose; and (5) to demonstrate the safety and efficacy of inhaled simvastatin aerosols in two different in vivo animal models including a healthy rodent model (rat) and a higher animal model in a validated lamb model of PH disease. To the authors' knowledge, this is the first study to report such findings using this approach and these conditions.…”

Section: Introductionmentioning

confidence: 99%

Advanced therapeutic inhalation aerosols of a Nrf2 activator and RhoA/Rho kinase (ROCK) inhibitor for targeted pulmonary drug delivery in pulmonary hypertension: design, characterization, aerosolization, in vitro 2D/3D human lung cell cultures, and in vivo efficacy

Acosta

Muralidharan

Grijalva

et al. 2021

Ther Adv Respir Dis

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Inhalable nanostructured microparticles of simvastatin, a Nrf2 activator and RhoA/Rho kinase (ROCK) inhibitor, were rationally designed for targeted pulmonary delivery as dry powder inhalers (DPIs) for the treatment of pulmonary hypertension (PH). Advanced particle engineering design technology was employed to develop inhalable dry powders using different dilute feed concentrations and spray drying pump rates. Several analytical techniques were used comprehensively to characterize the physicochemical properties of the resulting powders. Scanning electron microscopy (SEM) was used to visualize particle morphology (shape), surface structure, size, and size distribution. Karl Fischer titration (KFT) was employed to quantify the residual water content in the powders. X-ray powder diffraction (XRPD) was used to determine crystallinity. Hot-stage microscopy (HSM) under cross-polarizing lens was used to observe the presence or absence of birefringence characteristic of crystallinity. Differential scanning calorimetry (DSC) was employed to quantify thermotropic phase behavior. Attenuated total reflectance (ATR)-Fourier-transform infrared (FTIR) spectroscopy and Raman spectroscopy were used to determine the molecular fingerprint of simvastatin powders before and after particle engineering design. In vitro aerosol dispersion performance was performed with three different Food and Drug Administration (FDA)-approved human DPI devices. Cell viability and transepithelial electrical resistance (TEER) were demonstrated using different in vitro human pulmonary cell two and three-dimensional models at the air–liquid interface, and in vivo safety in healthy rats by inhalation. Efficacy was demonstrated in the in vivo lamb model of PH. Four different inhalable powders of simvastatin were successfully produced. They possessed nanostructured surfaces and were in the inhalable size range. Simvastatin retained its crystallinity following particle engineering design. The more dilute feed concentration spray dried at the lower pump rate produced the smallest particles. All powders successfully aerosolized with all three DPI human devices. Inhaled simvastatin as an aerosol restored the endothelial function in the shunt lamb model of PH, as demonstrated by the reduction of pulmonary vascular resistance (PVR) in response to the endothelium-dependent vasodilator acetylcholine. The reviews of this paper are available via the supplemental material section.

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“…Since mitochondrial glucose oxidation is inhibited in patients with pulmonary hypertension (PH) and glucose levels are increased in endothelial and smooth muscle cells, metformin has been reported to have positive effects in the treatment of PH ( 2 ). Pulmonary hypertension affects adult and children ( 3 ). It is important to note that PH ( 4 ) is known to exist concomitantly with other pulmonary diseases including cystic fibrosis (CF) ( 5 – 7 ), IPF ( 8 , 9 ), and chronic obstructive pulmonary disease (COPD) ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

Inhalable Nanoparticles/Microparticles of an AMPK and Nrf2 Activator for Targeted Pulmonary Drug Delivery as Dry Powder Inhalers

Acosta

Abrahamson

Encinas-Basurto

et al. 2020

AAPS J

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Metformin is an activator of the AMPK and Nrf2 pathways which are important in the pathology of several complex pulmonary diseases with unmet medical needs. Organic solution advanced spray drying in the absence of water in closed-mode was used to design and develop respirable dry powders. Following comprehensive characterization, the influence of physicochemical properties was correlated with performance as aerosols using inertial impaction and three different human dry powder inhaler (DPI) devices varying in device properties. In vitro cell assays were conducted to test safety in 2D human pulmonary cell lines and in 3D small airway epithelia comprising primary cells at the air-liquid interface (ALI). In addition, in vitro transepithelial electrical resistance (TEER) was carried out. Metformin remained crystalline following advanced spray drying under these conditions. All SD powders consisted of nanoparticles/microparticles in the solid state. In vitro aerosol dispersion performance showed high aerosolization for all SD metformin powders with all DPI devices tested. High emitted dose for all powders with all three DPI devices was measured. Differences in other aerosol performance parameters and the interplay between the properties of different formulations produced at specific pump rates and the three different DPI devices were correlated with spray drying pump rate and device properties. Safety over a wide metformin dose range was also demonstrated in vitro. Aerosol delivery of metformin nanoparticles/microparticles has the potential to be a new “first-in-class” therapeutic for the treatment of a number of pulmonary diseases including pulmonary vascular diseases such as pulmonary hypertension.

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Pulmonary Hypertension

Cited by 23 publications

References 54 publications

Pediatric Perioperative Pulmonary Arterial Hypertension: A Case-Based Primer

Pediatric Perioperative Pulmonary Arterial Hypertension: A Case-Based Primer

Advanced therapeutic inhalation aerosols of a Nrf2 activator and RhoA/Rho kinase (ROCK) inhibitor for targeted pulmonary drug delivery in pulmonary hypertension: design, characterization, aerosolization, in vitro 2D/3D human lung cell cultures, and in vivo efficacy

Inhalable Nanoparticles/Microparticles of an AMPK and Nrf2 Activator for Targeted Pulmonary Drug Delivery as Dry Powder Inhalers

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