HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Beverley J. Hunt Kenneth M. Taylor Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ohri, S. K. Articles by Taylor, K. M. Search for Related Content PubMed PubMed Citation Articles by Ohri, S. K. Articles by Taylor, K. M.

Ann Thorac Surg 1996;61:1223-1230
© 1996 The Society of Thoracic Surgeons

---

Original Article: Cardiovascular

Genetically Engineered Serine Protease Inhibitor for Hemostasis After Cardiac Operations

Cardiothoracic Unit, Department of Surgery, Royal Postgraduate Medical School, Hammersmith Hospital, London, and Research Haematology, Harefield Hospital, Middlesex, England

Accepted for publication December 28, 1995.

Background. The serine protease inhibitor aprotinin has been widely reported for its beneficial action in limiting blood loss after cardiopulmonary bypass (CPB). A potent human serine protease inhibitor known as protease nexin II or amyloid precursor protein has been recently isolated. A recombinant protein known as recombinant Kunitz protease inhibitor (rKPI; Scios Nova, Mountain View, CA) with sequence homology to the protease nexin II–amyloid precursor protein molecule has been manufactured.

Methods. Recombinant Kunitz protease inhibitor was assessed in an ovine model of CPB as a hemostatic agent after CPB. Sheep (n = 22) underwent CPB for 90 minutes. Two thoracic drains were sited and drain losses collected for a period of 3 hours after CPB. Wounds were subjectively assessed before closure for ``dryness'' using a visual analogue scale. Sheep were randomized to control (n = 8), aprotinin (n = 8), and rKPI (n = 6) groups.

Results. Control animals had a drain loss of 409.4 ± 39.4 mL/3 h, compared with 131.3 ± 20.3 mL/3 h for the aprotinin group and 163.7 ± 34.3 mL/3 h for the rKPI group (p= 0.16). Hemoglobin loss was 11.6 ± 3.6, 6.02 ± 2.1, and 4.6 ± 1.2 g/3 h for the control, rKPI, and aprotinin groups respectively (p = 0.25). The subjective analysis of the wounds at the end of CPB found aprotinin (1.25 ± 0.16; p < 0.05) and rKPI (1.17 ± 0.17; p < 0.05) animals to score significantly lower than control animals (2.63 ± 0.42).

Conclusions. On the basis of these in vivo findings, genetic modification may yield a more efficacious serine protease inhibitor with the inherent advantages of using a human-based protein.

This article has been cited by other articles:

				S. K Ohri, R. Parratt, T. White, J. Becket, J. J Brannan, B. J Hunt, and K. M Taylor A genetically engineered human Kunitz protease inhibitor with increased kallikrein inhibition in an ovine model of cardiopulmonary bypass Perfusion, May 1, 2001; 16(3): 199 - 206. [Abstract] [PDF]

				I. Nagahiro, T. White, M. Yano, C. H.R. Boasquevisque, M. Hiratsuka, J. D. Cooper, and G. A. Patterson Recombinant kunitz protease inhibitor ameliorates reperfusion injury in rat lung transplantation Ann. Thorac. Surg., August 1, 1998; 66(2): 351 - 355. [Abstract] [Full Text] [PDF]