Reduction of platelet thrombi and emboli by L-arginine during cardiopulmonary bypass in a pig model

Mrinal K. Dewanjee, Shu Ming Wu, Mansoor Kapadvanjwala, Dibyendu De, Sumit Dewanjee, Stana Novak, Li Chien Hsu, Richard A. Perryman, Aldo N Serafini, George N Sfakianakis, Robert C. Duncan, W. Dalton Dietrich, Allan F. Horton

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

We wanted to test the hypothesis that NO generation by L-arginine (LA) infusion will be beneficial in increasing blood flow to all organs to counteract the process of global ischemia during cardiopulmonary bypass (CPB) and to reduce platelet emboli by platelet inhibition. The effect of LA infusion on NO formation, vasodilation, and reduction of thromboembolic burden in organs and tissues after CPB was quantified with In-111-labeled autologous platelets in two major groups: 180 minutes CPB (CPB) and 90 minutes CPB plus 90 minutes reperfusion (RP). Platelets labeled with In-111 tropolone (650-780 μCi) were administered 24 hours before CPB and LA infusion (bolus, 10 mg/kg and infusion at 2 mg/kg/min, 21 pigs for 180 minutes CPB) in 8 groups of 30 Yorkshire pigs (30-35 kg, 6 pigs; LA 2 mg/kg/min, 3 pigs; sham-thoracotomy control, 6 pigs; unoperated control, 6 pigs). Two groups of 9 pigs (control CPB, 6 pigs; LA 2 mg/kg/min, 3 pigs) underwent 90 minutes of CPB and 90 minutes of reperfusion. All pigs were heparinized (ACT > 400 seconds); CPB was instituted with a roller pump, an oxygenator (OX: Bentley Univox, 1.8 m2), and an arterial filter (AF: 0.25 m2, Bentley) at a blood flow of 2.5-3.5 l/min. Radioactive thrombi in OX and AF and emboli in viscera, brain, and connective tissues were imaged with a gamma camera and were finally measured with an ion chamber and a gamma counter. The percent of injected platelets (mean ± SD) in the organs and tissues of all pigs was calculated. Cerebral emboli were mapped in 25 regions of both hemispheres of pig brain. Flow cytometry with antibodies to CD61 (GPIIIa) and CD62P (GMP-140:control) of porcine platelets was carried out with blood samples taken before, during, and after CPB. Coronary bypass with LA infusion decreased the amount of adherent thrombi in OX and AF (p < 0.07). The embolic burden in brain and lung also decreased. Regional cerebral mapping of In-111 platelets showed reduced emboli in almost all regions, including the medulla, hippocampus, and posterior cerebral cortex in both LA-treated groups. Flow cytometry of blood samples demonstrated the shift of equilibria from single platelet to platelet-aggregate-microparticle during CPB and steady-state level after the first 5-10 minutes of initiation of CPB. The L-arginine infusion reduced thrombi and emboli during CPB in the pig model.

Original languageEnglish
Pages (from-to)343-360
Number of pages18
JournalJournal of Thrombosis and Thrombolysis
Volume3
Issue number4
StatePublished - Sep 17 1996

Fingerprint

Embolism
Cardiopulmonary Bypass
Arginine
Thrombosis
Swine
Blood Platelets
Reperfusion
Flow Cytometry
Brain
Tropolone
Integrin beta3
Oxygenators
Intracranial Embolism
Gamma Cameras
P-Selectin
Viscera
Thoracotomy
Vasodilation
Cerebral Cortex
Connective Tissue

Keywords

  • Cardiopulmonary bypass
  • Emboli
  • Flow-cytometry
  • Indium-111 label
  • L-arginine
  • NOS gene
  • Platelets
  • Thrombi
  • Trapped platelet-emboli
  • Yorkshire pigs

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine

Cite this

Dewanjee, M. K., Wu, S. M., Kapadvanjwala, M., De, D., Dewanjee, S., Novak, S., ... Horton, A. F. (1996). Reduction of platelet thrombi and emboli by L-arginine during cardiopulmonary bypass in a pig model. Journal of Thrombosis and Thrombolysis, 3(4), 343-360.

Reduction of platelet thrombi and emboli by L-arginine during cardiopulmonary bypass in a pig model. / Dewanjee, Mrinal K.; Wu, Shu Ming; Kapadvanjwala, Mansoor; De, Dibyendu; Dewanjee, Sumit; Novak, Stana; Hsu, Li Chien; Perryman, Richard A.; Serafini, Aldo N; Sfakianakis, George N; Duncan, Robert C.; Dalton Dietrich, W.; Horton, Allan F.

In: Journal of Thrombosis and Thrombolysis, Vol. 3, No. 4, 17.09.1996, p. 343-360.

Research output: Contribution to journalArticle

Dewanjee, MK, Wu, SM, Kapadvanjwala, M, De, D, Dewanjee, S, Novak, S, Hsu, LC, Perryman, RA, Serafini, AN, Sfakianakis, GN, Duncan, RC, Dalton Dietrich, W & Horton, AF 1996, 'Reduction of platelet thrombi and emboli by L-arginine during cardiopulmonary bypass in a pig model', Journal of Thrombosis and Thrombolysis, vol. 3, no. 4, pp. 343-360.
Dewanjee MK, Wu SM, Kapadvanjwala M, De D, Dewanjee S, Novak S et al. Reduction of platelet thrombi and emboli by L-arginine during cardiopulmonary bypass in a pig model. Journal of Thrombosis and Thrombolysis. 1996 Sep 17;3(4):343-360.
Dewanjee, Mrinal K. ; Wu, Shu Ming ; Kapadvanjwala, Mansoor ; De, Dibyendu ; Dewanjee, Sumit ; Novak, Stana ; Hsu, Li Chien ; Perryman, Richard A. ; Serafini, Aldo N ; Sfakianakis, George N ; Duncan, Robert C. ; Dalton Dietrich, W. ; Horton, Allan F. / Reduction of platelet thrombi and emboli by L-arginine during cardiopulmonary bypass in a pig model. In: Journal of Thrombosis and Thrombolysis. 1996 ; Vol. 3, No. 4. pp. 343-360.
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AU - Dewanjee, Mrinal K.

AU - Wu, Shu Ming

AU - Kapadvanjwala, Mansoor

AU - De, Dibyendu

AU - Dewanjee, Sumit

AU - Novak, Stana

AU - Hsu, Li Chien

AU - Perryman, Richard A.

AU - Serafini, Aldo N

AU - Sfakianakis, George N

AU - Duncan, Robert C.

AU - Dalton Dietrich, W.

AU - Horton, Allan F.

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N2 - We wanted to test the hypothesis that NO generation by L-arginine (LA) infusion will be beneficial in increasing blood flow to all organs to counteract the process of global ischemia during cardiopulmonary bypass (CPB) and to reduce platelet emboli by platelet inhibition. The effect of LA infusion on NO formation, vasodilation, and reduction of thromboembolic burden in organs and tissues after CPB was quantified with In-111-labeled autologous platelets in two major groups: 180 minutes CPB (CPB) and 90 minutes CPB plus 90 minutes reperfusion (RP). Platelets labeled with In-111 tropolone (650-780 μCi) were administered 24 hours before CPB and LA infusion (bolus, 10 mg/kg and infusion at 2 mg/kg/min, 21 pigs for 180 minutes CPB) in 8 groups of 30 Yorkshire pigs (30-35 kg, 6 pigs; LA 2 mg/kg/min, 3 pigs; sham-thoracotomy control, 6 pigs; unoperated control, 6 pigs). Two groups of 9 pigs (control CPB, 6 pigs; LA 2 mg/kg/min, 3 pigs) underwent 90 minutes of CPB and 90 minutes of reperfusion. All pigs were heparinized (ACT > 400 seconds); CPB was instituted with a roller pump, an oxygenator (OX: Bentley Univox, 1.8 m2), and an arterial filter (AF: 0.25 m2, Bentley) at a blood flow of 2.5-3.5 l/min. Radioactive thrombi in OX and AF and emboli in viscera, brain, and connective tissues were imaged with a gamma camera and were finally measured with an ion chamber and a gamma counter. The percent of injected platelets (mean ± SD) in the organs and tissues of all pigs was calculated. Cerebral emboli were mapped in 25 regions of both hemispheres of pig brain. Flow cytometry with antibodies to CD61 (GPIIIa) and CD62P (GMP-140:control) of porcine platelets was carried out with blood samples taken before, during, and after CPB. Coronary bypass with LA infusion decreased the amount of adherent thrombi in OX and AF (p < 0.07). The embolic burden in brain and lung also decreased. Regional cerebral mapping of In-111 platelets showed reduced emboli in almost all regions, including the medulla, hippocampus, and posterior cerebral cortex in both LA-treated groups. Flow cytometry of blood samples demonstrated the shift of equilibria from single platelet to platelet-aggregate-microparticle during CPB and steady-state level after the first 5-10 minutes of initiation of CPB. The L-arginine infusion reduced thrombi and emboli during CPB in the pig model.

AB - We wanted to test the hypothesis that NO generation by L-arginine (LA) infusion will be beneficial in increasing blood flow to all organs to counteract the process of global ischemia during cardiopulmonary bypass (CPB) and to reduce platelet emboli by platelet inhibition. The effect of LA infusion on NO formation, vasodilation, and reduction of thromboembolic burden in organs and tissues after CPB was quantified with In-111-labeled autologous platelets in two major groups: 180 minutes CPB (CPB) and 90 minutes CPB plus 90 minutes reperfusion (RP). Platelets labeled with In-111 tropolone (650-780 μCi) were administered 24 hours before CPB and LA infusion (bolus, 10 mg/kg and infusion at 2 mg/kg/min, 21 pigs for 180 minutes CPB) in 8 groups of 30 Yorkshire pigs (30-35 kg, 6 pigs; LA 2 mg/kg/min, 3 pigs; sham-thoracotomy control, 6 pigs; unoperated control, 6 pigs). Two groups of 9 pigs (control CPB, 6 pigs; LA 2 mg/kg/min, 3 pigs) underwent 90 minutes of CPB and 90 minutes of reperfusion. All pigs were heparinized (ACT > 400 seconds); CPB was instituted with a roller pump, an oxygenator (OX: Bentley Univox, 1.8 m2), and an arterial filter (AF: 0.25 m2, Bentley) at a blood flow of 2.5-3.5 l/min. Radioactive thrombi in OX and AF and emboli in viscera, brain, and connective tissues were imaged with a gamma camera and were finally measured with an ion chamber and a gamma counter. The percent of injected platelets (mean ± SD) in the organs and tissues of all pigs was calculated. Cerebral emboli were mapped in 25 regions of both hemispheres of pig brain. Flow cytometry with antibodies to CD61 (GPIIIa) and CD62P (GMP-140:control) of porcine platelets was carried out with blood samples taken before, during, and after CPB. Coronary bypass with LA infusion decreased the amount of adherent thrombi in OX and AF (p < 0.07). The embolic burden in brain and lung also decreased. Regional cerebral mapping of In-111 platelets showed reduced emboli in almost all regions, including the medulla, hippocampus, and posterior cerebral cortex in both LA-treated groups. Flow cytometry of blood samples demonstrated the shift of equilibria from single platelet to platelet-aggregate-microparticle during CPB and steady-state level after the first 5-10 minutes of initiation of CPB. The L-arginine infusion reduced thrombi and emboli during CPB in the pig model.

KW - Cardiopulmonary bypass

KW - Emboli

KW - Flow-cytometry

KW - Indium-111 label

KW - L-arginine

KW - NOS gene

KW - Platelets

KW - Thrombi

KW - Trapped platelet-emboli

KW - Yorkshire pigs

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