PMID- 7832299
OWN - NLM
STAT- MEDLINE
DCOM- 19950217
LR  - 20190628
IS  - 0003-3022 (Print)
IS  - 0003-3022 (Linking)
VI  - 82
IP  - 1
DP  - 1995 Jan
TI  - Platelet factor 4 injection produces acute pulmonary hypertension in the awake 
      lamb.
PG  - 183-7; discussion 31A
AB  - BACKGROUND: Reversal of heparin anticoagulation by intravenous protamine sulfate 
      consistently produces acute pulmonary vasoconstriction mediated by the release of 
      thromboxane in the awake lamb. Recently, recombinant platelet factor 4 (rPF4) has 
      been cloned, expressed in Escherichia coli, and infused to reverse heparin 
      anticoagulation in the rat, without producing adverse hemodynamic or pulmonary 
      morphologic effects. The authors sought to learn whether intravenous 
      administration of PF4 is devoid of side effects in the pulmonary circulation of 
      lambs. METHODS: The authors evaluated the hemodynamic response and plasma release 
      rates of thromboxane during intravenous challenges with heparin-rPF4 (n = 2), 
      rPF-free carrier (n = 5), rPF4 (n = 5), rPF4 after indomethacin (n = 5), 
      protamine (n = 5) and heparin-protamine (n = 5) in 17 awake, hemodynamically 
      monitored lambs. Each lamb underwent up to three random challenges with a 2-h 
      recovery period between each challenge. RESULTS: In two lambs, systemic 
      anticoagulation with heparin followed by reversal of anticoagulation with an 
      intravenous bolus of rPF4 (4 mg/kg) led to acute pulmonary vasoconstriction and 
      hypertension with the release of thromboxane (peak pulmonary artery pressure 
      [Ppa] 40 and 33 mmHg and peak plasma thromboxane B2 50 and 30 ng/ml, 
      respectively). Intravenous administration of rPF4 (1.5 mg/kg) alone increased the 
      Ppa from 17.2 +/- 0.7 mmHg (mean +/- SEM) at baseline to 31.2 +/- 2 mmHg at 1 min 
      (n = 5, P < 0.05). This was associated with an increase of plasma thromboxane B2 
      from 0.06 +/- 0.02 to 3.96 +/- 1.21 ng/ml. Acute pulmonary vasoconstriction 
      lasted approximately 5 min and was completely prevented by pre-treatment with 
      oral indomethacin (10 mg/kg). Intravenous bolus administration of rPF4 carrier (n 
      = 5) or protamine (2 mg/kg) alone (n = 5) did not induce pulmonary hypertension 
      or the release of thromboxane. In five lambs, intravenous heparin (200 U/kg) 
      followed by protamine (2 mg/kg) consistently produced acute pulmonary 
      vasoconstriction and hypertension. CONCLUSIONS: Intravenous injection of human 
      rPF4 into the awake lamb produces acute pulmonary vasoconstriction and 
      hypertension associated with thromboxane release into circulating blood. The 
      effects of rPF4 on the pulmonary vasculature should be evaluated in primates 
      before rPF4 is substituted for protamine in reversing heparin anticoagulation in 
      humans.
FAU - Kurrek, M M
AU  - Kurrek MM
AD  - Department of Anesthesia, Harvard Medical School, Beth Israel Hospital, Boston, 
      Massachusetts.
FAU - Winkler, M
AU  - Winkler M
FAU - Robinson, D R
AU  - Robinson DR
FAU - Zapol, W M
AU  - Zapol WM
LA  - eng
GR  - HL42397/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Anesthesiology
JT  - Anesthesiology
JID - 1300217
RN  - 0 (Heparin Antagonists)
RN  - 0 (Protamines)
RN  - 37270-94-3 (Platelet Factor 4)
RN  - 54397-85-2 (Thromboxane B2)
SB  - IM
CIN - Anesthesiology. 1995 Sep;83(3):644-5. PMID: 7661374
CIN - Acta Obstet Gynecol Scand. 2016 Jun;95(6):652-63. PMID: 26918772
MH  - Animals
MH  - Hemodynamics/drug effects
MH  - Heparin Antagonists/pharmacology
MH  - Hypertension, Pulmonary/*chemically induced
MH  - Injections, Intravenous
MH  - Platelet Factor 4/administration & dosage/*toxicity
MH  - Protamines/pharmacology
MH  - Sheep
MH  - Thromboxane B2/blood
EDAT- 1995/01/01 00:00
MHDA- 1995/01/01 00:01
CRDT- 1995/01/01 00:00
PHST- 1995/01/01 00:00 [pubmed]
PHST- 1995/01/01 00:01 [medline]
PHST- 1995/01/01 00:00 [entrez]
AID - 10.1097/00000542-199501000-00023 [doi]
PST - ppublish
SO  - Anesthesiology. 1995 Jan;82(1):183-7; discussion 31A. doi: 
      10.1097/00000542-199501000-00023.