Research InterestsEffect of left ventricular afterload in the setting of: 1. Patent Ductus Arteriosus 2. Pulmonary Hypertension 3. Acute Hypoxemia
Detailed Description: My training in echocardiography methods has allowed me to perform physiology based cardiovascular research both in human neonates and animal experimental models. The cornerstone of my research is to improve our understanding of the neonatal heart and how acute cardiovascular physiologic change is influenced by disease processes and therapeutic interventions.
1. Physiology of the Ductus Arteriosus; Over the past 5 years our work has focused on the physiologic effects of PDA ligation. We were the first to describe the Post-Ligation Cardiac Syndrome (PLCS) characterized by oxygenation failure and hemodynamic instability, 8-12 hours after surgical intervention [Teixeira et al, J Perinat 2008]. We subsequently demonstrated that the nature of left ventricular (LV) dysfunction relates to altered loading conditions [McNamara et al, J Thoracic & Cardiovasc Surg 2010]. Recently we have developed a predictive model, based on echo-derived estimation of left ventricular output, and demonstrated that commencement of prophylactic afterload reducing treatment with intravenous milrinone leads to improvement in neonatal outcomes. Current studies are investigating the value of plasma troponin and adrenal gland performance testing in the perioperative period.
2. Adjunctive Pulmonary Vasodilator Therapy in Persistent Pulmonary Hypertension of the Newborn. We were the first to report improvement in oxygenation in neonates with resistant PPHN with intravenous Milrinone (PDE 3 inhibitor) [McNamara et al, J of Critical Care 2006; Bassler et al. Biol Neonate 2005]. We have recently completed a pharmacological study of the effects of milrinone in PPHN; the manuscript is currently under review. Recently, we have completed a similar study that demonstrates the efficacy of Vasopressin in iNO responsive patients.
3. Echocardiography and Animal Experimental studies: High frequency ultrasound (13-15 MHz) using a small iL13 probe has allowed us to image small animal models. We are the first group to conduct dynamic evaluations of neonatal rodent myocardial function and have performed more than 1000 animal evaluations to date. My expertise in animal echocardiography has allowed me to establish many collaborations. We have successfully used echocardiography in both rodent and neonatal porcine models to investigate the effect of resuscitation gas mixtures, ventilation and drugs on myocardial performance (McCaul et al, Resuscitation 2006; 68:267-75, McCaul et al, Anaesthesia & Analgesia 2006; 102(2):542-8). We have also pioneered the assessment of myocardial performance and pulmonary hemodynamics in a neonatal rodent (< 20 grams) model of hypoxia using high frequency echocardiography and contributed to several publications using these techniques.
Within the Department of Physiology
Outside the Department of Physiology:
Ron Clyman University of San Francisco
Jeff Reese Vanderbilt university, Nashville
Publications and Awards
1. Teixeira LS, Shivananda S, Van Arsdell G, James A, McNamara PJ: PDA ligation is associated with an increased risk of postoperative cardiorespiratory failure in VLBW infants. J Perinatol. 2008 Dec; 28(12):803-10. Epub 2008 Jul 10. SRA [Original Research]
2. McNamara PJ, Teixeira LS, Stephens D, Shivananda S. Patent Ductus Arteriosus Ligation is associated with impaired left ventricular systolic performance in premature infants < 1000 grams. J Thorac Cardiovasc Surg. 2010 Jul; 140(1):150-7. Epub 2010 Apr 3 PA [Original Research]
3. Jain A, Sahni M, El-Khuffash A, Khadawardi E, Sehgal A, McNamara PJ. Use of Targeted Neonatal Echocardiography (TnECHO) to Prevent Postoperative Cardiorespiratory Instability After Patent Ductus Arteriosus Ligation. J Pediatr. 2012 Apr; 160(4):584-589.e1. Epub 2011 Nov 3.
4. McNamara PJ, Shivananda SP, Sahni M, Freeman D, Taddio A. Pharmacology of Milrinone in Persistent Pulmonary Hypertension of the Newborn. Pediatr Crit Care Med. 2013 Jan; 14(1):74-84. doi: 10.1097/PCC.0b013e31824ea2cd
5. El-Khuffash AF, Jain A, Weisz D, Mertens L, McNamara PJ. Assessment and Treatment of Post Patent Ductus Arteriosus Ligation Syndrome. J Pediatr 2014 Jul; 165(1): pp 46-52.e1
6. McNamara PJ, Engelberts D, Finelli M, Sahni M, Adeli K, Kavanagh BP. Vasopressin improves survival rates in neonatal porcine model of asphyxial cardiac arrest. Pediatr Res. 2014 Jun; 75(6):738-48. doi: 10.1038/pr.2014.38. Epub 2014 Mar 10
- El-Khuffash A, McNamara PJ. Neonatologist performed functional echocardiography in the neonatal intensive care unit. Semen Fetal Neonatal Med. 2011 Feb; 16(1):50-60. doi:
- Sehgal A, McNamara PJ. The Ductus Arteriosus. A Refined Approach? Semin Perinatol. 2012 Apr; 36(2):105-13
- Ligation of a Patent Ductus Arteriosus in Preterm Infants: Understanding the Physiology. J Pediatr. 2013 Feb 11. doi:pii: S0022-3476(13)00006-1. 10.1016/j.jpeds.2012.12.094. [Epub ahead of print]