Summary of Research Career in NIH Format

My earliest laboratory and clinical studies focused on the development of an improved right ventricle to pulmonary artery conduit suitable for reconstructive procedures in the neonate and infant. In the early 1980s rigid Dacron tube grafts were being used for this purpose. My studies addressed preparation and storage of allograft valved conduits as well as examining methods for sealing softer knitted Dacron including what was to become known as the Hemashield graft.

1. Jonas RA, Schoen FJ, Ziemer G, Britton L, Castaneda AR. Biological sealants and knitted Dacron conduits: Comparison of collagen and fibrin glue pretreatments in circulatory models. Ann Thorac Surg 1987; 44:283-290.
2. Jonas RA, Schoen FJ, Ziemer G, Britton L, Castaneda AR. A new sealant for knitted Dacron prostheses: minimally cross-linked gelatin. J Vasc Surg 1988;7:414-419.
3. Jonas RA, Ziemer G, Britton L, Armiger LC. Cryopreserved and fresh antibiotic-sterilized valved aortic homograft conduits in a long-term sheep model. J Thorac Cardiovasc Surg 1988;96:746-755.
4. Kadoba K, Armiger L, Sawatari K, Jonas RA. The influence of time from donor death to graft harvest on conduit function of cryopreserved aortic allografts in lambs. Circulation 1991; 84 (suppl III) III-100-III-111.
5. Kadoba K, Schoen FJ, Jonas RA. Experimental comparison of albumin and gelatin sealed knitted Dacron conduits. J Thorac Cardiovasc Surg 1992; 103:1059-1067.

In the late 1980s I began working with Dale Corbett PhD in the psychology department at Harvard developing rodent models of ischemic brain injury. This led to a career long interest in maximizing neurological and developmental outcomes after cardiac surgery. Early laboratory studies were conducted in the National Magnet Laboratory at MIT and undertaking magnetic resonance spectroscopy studies using piglets exposed to cardiopulmonary bypass and circulatory arrest. These studies suggested that the technique of bypass being used at the time in the late 1980s was suboptimal including rapid cooling with severe hemodilution and alkalosis.

1. Corbett D, Evans S, Thomas R, Wang D, Jonas RA. MK-801 reduces cerebral ischemic injury by inducing hypothermia. Brain Research 1990;514:300-304.
2. Aoki M, Nomura F, Stromski ME, Tsuji MK, Fackler JC, Hickey PR, Holtzman D, Jonas RA. Effects of MK-801 and NBQX on acute recovery of piglet cerebral metabolism after hypothermic circulatory arrest. J Cereb Blood Flow & Metab 1994; 14:156-165.
3. Hiramatsu T, Miura T, Forbess JM, Du Plessis A, Cioffi MA, Aoki M, Nomura F, Holtzman D, Jonas RA. pH strategy and cerebral energetics before and after circulatory arrest. J Thorac Cardiovasc Surg, 1995; 109:948-958.
4. Hiramatsu T, Jonas RA, Miura T, du Plessis A, Tanji M, Forbess JM, Holtzman D. Cerebral metabolic recovery from deep hypothermic circulatory arrest after treatment with arginine and nitro-arginine-methylester. J Thorac Cardiovasc Surg, 1996; 112:698-707.
5. Shin’oka T, Shum-Tim D, Laussen PC, Zinkovsky SM, Lidov HGW, du Plessis A, Jonas RA. Effects of oncotic pressure and hematocrit on outcome after hypothermic circulatory arrest. Ann Thorac Surg 1998; 65:155-164.
6. Sakamoto T, Hatsuoka S, Stock UA, Duebener LF, Lidov HG, Holmes GL, Sperling JS, Munakata M, Laussen PC, Jonas RA. Prediction of safe duration of hypothermic circulatory arrest by near infrared spectroscopy. J Thorac Cardiovasc Surg 2001; 122:39-350.
7. Sakamoto T, Jonas RA, Stock UA, Hatsuoka S, Cope M, Springett RJ, Nollert G. Utility and limitations of near infrared spectroscopy during cardiopulmonary bypass in a piglet model. Pediatr Res 2001; 49:770-776.
8. Duebener LF, Sakamoto T, Hatsuoka S, Stamm C, Zurakowski D, Vollmar B, Menger MD, Schafers HJ, Jonas RA. Effects of hematocrit on cerebral microcirculation and tissue oxygenation during deep hypothermic bypass. Circulation 2001; 104 [suppl I] I260-I264.

An epidemic of choreoathetosis in the late 1980s at Boston Children’s led to retrospective studies and subsequently prospective trials to determine if the suspicions raised by our laboratory studies were contributing to the disturbing recurrence of this devastating neurological complication that had not been seen since the early years of cardiac surgery. Working in conjunction with Dr. Jane Newburger from the Boston Cardiology group as well as the renowned developmental psychologist David Bellinger, I began to study in a systematic fashion the various factors suggested by our laboratory work. Several prospective randomized clinical trials revealed that the motor skills of infants were a sensitive endpoint for such studies. A study of hemodilution was terminated early by the NIH when it was found that the current recommended and widely followed practice of hemodiluting to a hematocrit of 20% was associated with important motor deficits. This clinical trial led to a worldwide shift in the technique of cardiopulmonary bypass for neonates and infants.

1. Jonas RA, Bellinger DC, Rappaport LA, Wernovsky G, Hickey PR, Farrell DM, Newburger JW. pH strategy and developmental outcome after hypothermic circulatory arrest. J Thorac Cardiovasc Surg 1993; 106:362-368.
2. du Plessis AJ, Jonas RA, Wypij D, Hickey PR, Riviello J, Wessel DL, Roth SJ, Burrows F, Farrell DM, Walsh AZ, Plumb CA, del Nido P, Burke RP, Castaneda AR, Mayer JE, Newburger JW. Perioperative effects of alpha stat versus pH stat strategies for deep hypothermic cardiopulmonary bypass in infants. J Thorac Cardiovasc Surg 1997; 114:991-1001.
3. Kinney HC, Panigrahy A, Newburger JW, Jonas RA, Sleeper LA. Hypoxic-ischemic brain injury in infants with congenital heart disease dying after cardiac surgery. Acta Neuropathol 2005; 22.
4. Newburger JW, Jonas RA, Soul J, Kussman BD, Bellinger DC, Laussen PC, Robertson R, Mayer JE, del Nido PJ, Bacha EA, Forbess JM, Pigula F, Roth SJ, Visconti KJ, du Plessis AJ, Farrell DM, McGrath E, Rappaport LA, Wypij D. Randomized trial of hematocrit 25% vs. 35% during hypothermic cardiopulmonary bypass in infant heart surgery. J Thorac Cardiovasc Surg 2008; 135:347-354.
5. Wypij D, Jonas RA, Bellinger DC, del Nido PJ, Mayer JE, Bacha EA, Forbess JM, Pigula F, Laussen PC, Newburger JW. The effect of hematocrit during hypothermic cardiopulmonary bypass in infant heart surgery: Results from the combined Boston hematocrit trials. J Thorac Cardiovasc Surg 2008; 135:355-360.