Persistent Pulmonary Hypertension of the Newborn - Mattel ...

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Regulation of Pulmonary Vascular Tone, 3MILRINONE, 3
PDE-3 3 Inhibitor - Milrinone• Primary physiological disturbance in PPHN →↑RV afterload• Traditionally, physicians reluctant to treat PPHNwith afterload-reducing reducing agents because ofconcerns of systemic hypotension & desire tomaintain supranormal systemic BP• very high-dose vasopressors• dopamine or epinephrine may exacerbate PPHN• tachycardia, ↑ increasing myocardial O2 demand,McNamara, 2006, J Crit Care
Page 7 and 8: It is 4 AM in the morning -------Yo
Page 9 and 10: Off Label Drug Use• FDA regulates
Page 11 and 12: Off Label Drug Use• New uses, dos
Page 13 and 14: Post-INO Era• Questionnaire to220
Page 16 and 17: Regulation of Pulmonary Vascular To
Page 18: Regulation of Pulmonary Vascular To
Page 21 and 22: PO Sildenafil• 1 st dose - 1 mg/0
Page 23 and 24: PDE-5 5 Inhibitor - Sildenafil• R
Page 25: PDE-5 5 Inhibitor - Sildenafil• P
Page 29 and 30: Milrinone Improves Oxygenationin Ne
Page 31 and 32: Regulation of Pulmonary Vascular To
Page 35: Regulation of Pulmonary Vascular To
Page 38 and 39: In utero exposure to PGSynthetase i
Page 40 and 41: Non-selective action:• Systemic &
Page 42 and 43: PGE 1 - Metabolism70-95%PGE 115-OH
Page 44 and 45: Studies of Inhaled Prostaglandins i
Page 46 and 47: Studies of Inhaled Prostaglandins i
Page 48 and 49: Phase I Clinical Trial of IPGE 1 in
Page 50 and 51: Phase I Trial: Dose ResponseDoseng/
Page 52 and 53: Phase I Trial: Adverse Effects:No e
Page 54 and 55: Effect on Ductus Arteriosus• Echo
Page 56 and 57: Stability and Emitted DoseModified
Page 58 and 59: ResultsLC-MS Chromatograms Followin
Page 60 and 61: Aerosol Particle Size DistributionA
Page 62 and 63: Pharmacokinetics of IPGE 1 ?
Page 64 and 65: Nominal DoseAerosolizedRemain in de
Page 66 and 67: Aerosol Delivery Assessed by MRIExp
Page 68 and 69: Aerosol Delivery Assessed by MRI450
Page 70 and 71: Aerosol Delivery During HFOVSood et
Page 72 and 73: Preliminary Data - Conclusions• P
Page 74 and 75: Specific AimsPrimary Aims:‣ Evalu
Page 76:
Challenges: RCTs in PPHN• Small n
Page 79 and 80:
Thank YouDiscussion
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