Abstract
Severe endotoxemia, a condition where microembolization and intravascular coagulation are thought to play important roles, was treated experimentally with prostacyclin (PGI2). In a study of 24 dogs, 8 control animals injected with 1.75 mg·kg−1 of endotoxin died within 24 h. Six animals given intravenous aspirin 100 mg/kg, 30 min after endotoxin died. 9 of 10 dogs infused with 100 ng PGI2·kg−1·min−1 for 3 h, given 30 min after the injection of endotoxin survived 24 h (P < 0.025). Injection of endotoxin resulted in a: (a) maximal 62% fall in mean arterial pressure (P < 0.001); (b) transient doubling of mean pulmonary arterial pressure (P < 0.001); (c) initial 70% drop in cardiac index (P < 0.001); (d) decline in blood platelets from 213,700 to 13,700/mm3 (P < 0.001), and leukocytes from 7,719 to < 750/mm3 (P < 0.001); (e) depressed urine output (P < 0.001); (f) 34% decrease in blood fibrinogen (P < 0.01) and an increase in fibrin degradation products > 50 μg/ml (P < 0.001); (g) fivefold increase in circulating cathepsin D titer (P < 0.005) and (h) increase in blood norepinephrine (P < 0.005), dopamine (P < 0.005), and epinephrine (P < 0.001). Aspirin treatment led to an increase in mean arterial pressure (P < 0.001) and mean pulmonary arterial pressure (P < 0.005), but cardiac index, urine flow, platelets, leukocytes, fibrin degradation products, and cathepsin D levels remained similar to untreated controls. After infusion of PGI2 there was a: (a) prompt increase of cardiac index to base-line levels; (b) late increase in mean arterial pressure (P < 0.005) after the discontinuation of PGI2 treatment (c) restoration of urine output; (d) increase in circulating platelets to levels still below base line but above untreated control animals (P < 0.05); (e) no effect on circulating leukocyte levels; (f) fall in fibrin degradation products to 11.2 μg/ml (P < 0.05); (g) decline in cathepsin D levels to values 60% lower than the untreated controls (P < 0.025); and (h) reduction in plasma norepinephrine levels to base line at 4 h (P < 0.005). Although the mode of PGI2 action is not clear, it is effective in the treatment of experimental endotoxemia.
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- Best L. C., Martin T. J., Russell R. G., Preston F. E. Prostacyclin increases cyclic AMP levels and adenylate cyclase activity in platelets. Nature. 1977 Jun 30;267(5614):850–852. doi: 10.1038/267850a0. [DOI] [PubMed] [Google Scholar]
- Bredenberg C. E., Taylor G. A., Wax S., Webb W. R. Thrombocytopenia altering the pulmonary hemodynamic response to intravenous endotoxin. Surg Forum. 1977;28:186–189. [PubMed] [Google Scholar]
- Coalson J. J., Benjamin B., Archer L. T., Beller B., Gilliam C. L., Taylor F. B., Hinshaw L. B. Prolonged shock in the baboon subjected to infusion of E. coli endotoxin. Circ Shock. 1978;5(4):423–437. [PubMed] [Google Scholar]
- Cook J. A., Wise W. C., Halushka P. V. Elevated thromboxane levels in the rat during endotoxic shock: protective effects of imidazole, 13-azaprostanoic acid, or essential fatty acid deficiency. J Clin Invest. 1980 Jan;65(1):227–230. doi: 10.1172/JCI109655. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DAVIS R. B., MEEKER W. R., McQUARRIE D. G. Immediate effects of intravenous endotoxin on serotonin concentrations and blood platelets. Circ Res. 1960 Jan;8:234–239. doi: 10.1161/01.res.8.1.234. [DOI] [PubMed] [Google Scholar]
- Fletcher J. R., Ramwell P. W. Lidocaine or indomethacin improves survival in baboon endotoxin shock. J Surg Res. 1978 Mar;24(3):154–160. doi: 10.1016/0022-4804(78)90168-3. [DOI] [PubMed] [Google Scholar]
- Harrison L. H., Jr, Hinshaw L. B., Coalson J. J., Greenfield L. J. Effects of E. coli septic shock on pulmonary hemodynamics and capillary permeability. J Thorac Cardiovasc Surg. 1971 May;61(5):795–803. [PubMed] [Google Scholar]
- Hechtman H. B., Lonergan E. A., Shepro D. Platelet and leukocyte lung interactions in patients with respiratory failure. Surgery. 1978 Feb;83(2):155–163. [PubMed] [Google Scholar]
- Hechtman H. B., Lonergan E. A., Staunton H. P., Dennis R. C., Shepro D. Pulmonary entrapment of platelets during acute respiratory failure. Surgery. 1978 Mar;83(3):277–283. [PubMed] [Google Scholar]
- Karmazyn M., Dhalla N. S. Thromboxane B2: a cardiodepressant of isolated rat hearts and inhibitor of sarcolemma Na+ - K+ stimulated ATPase activity. Prostaglandins Med. 1979 Aug;3(2):81–93. doi: 10.1016/0161-4630(79)90075-2. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Leavelle D. E., Mertens B. F., Bowie E. J., Owen C. A., Jr Staphylococcal clumping on microtiter plates: a rapid, simple method for measuring fibrinogen split products. Am J Clin Pathol. 1971 Apr;55(4):452–457. doi: 10.1093/ajcp/55.4.452. [DOI] [PubMed] [Google Scholar]
- Lefer A. M. Mechanisms of cardiodepression in endotoxin shock. Circ Shock Suppl. 1979;1:1–8. [PubMed] [Google Scholar]
- Lefer A. M., Ogletree M. L., Smith J. B., Silver M. J., Nicolaou K. C., Barnette W. E., Gasic G. P. Prostacyclin: a potentially valuable agent for preserving myocardial tissue in acute myocardial ischemia. Science. 1978 Apr 7;200(4337):52–54. doi: 10.1126/science.345441. [DOI] [PubMed] [Google Scholar]
- Nordstoga K., Aasen A. O. Hepatic changes in late canine endotoxin shock. A light and electron microscopic investigation. Acta Pathol Microbiol Scand A. 1979 Sep;87A(5):335–346. doi: 10.1111/j.1699-0463.1979.tb00060.x. [DOI] [PubMed] [Google Scholar]
- Pennington D. G., Hyman A. L., Jaques W. E. Pulmonary vascular response to endotoxin in intact dogs. Surgery. 1973 Feb;73(2):246–255. [PubMed] [Google Scholar]
- Petrucco O., Rao P. S., Cavanagh D. Endotoxin shock in the dog. Alterations in hemodynamic and hematologic parameters during bolus and infusion studies. Am J Obstet Gynecol. 1972 Dec 15;114(8):1060–1065. [PubMed] [Google Scholar]
- Robb H. J., Margulis R. R., Jabs C. M. Role of pulmonary microembolism in the hemodynamics of endotoxin shock. Surg Gynecol Obstet. 1972 Nov;135(5):777–783. [PubMed] [Google Scholar]
- Sacks T., Moldow C. F., Craddock P. R., Bowers T. K., Jacob H. S. Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes. An in vitro model of immune vascular damage. J Clin Invest. 1978 May;61(5):1161–1167. doi: 10.1172/JCI109031. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith E. F., 3rd, Tabas J. H., Lefer A. M. Beneficial actions of imidazole in endotoxin shock. Prostaglandins Med. 1980 Apr;4(4):215–225. doi: 10.1016/0161-4630(80)90016-6. [DOI] [PubMed] [Google Scholar]
- Smith G. J., Pearce P. H., Oliver I. T. A lysosomal factor that interconverts multiple forms of rat liver tyrosine aminotransferase. Life Sci. 1976 Dec 1;19(11):1763–1775. doi: 10.1016/0024-3205(76)90085-0. [DOI] [PubMed] [Google Scholar]
- Snyderman R., Shin H. S., Phillips J. K., Gewurz H., Mergenhagen S. E. A neutrophil chemotatic factor derived from C'5 upon interaction of guinea pig serum with endotoxin. J Immunol. 1969 Sep;103(3):413–422. [PubMed] [Google Scholar]
- Sole M. J., Drobac M., Schwartz L., Hussain M. N., Vaughan-Neil E. F. The extraction of circulating catecholamines by the lungs in normal man and in patients with pulmonary hypertension. Circulation. 1979 Jul;60(1):160–163. doi: 10.1161/01.cir.60.1.160. [DOI] [PubMed] [Google Scholar]
- Swaim W. R., Feders M. B. Fibrinogen assay. Clin Chem. 1967 Nov;13(11):1026–1028. [PubMed] [Google Scholar]
- Utsunomiya T., Krausz M. M., Valeri C. R., Shepro D., Hechtman H. B. Treatment of pulmonary embolism with prostacyclin. Surgery. 1980 Jul;88(1):25–30. [PubMed] [Google Scholar]
- Weissmann G., Smolen J. E., Korchak H. M. Release of inflammatory mediators from stimulated neutrophils. N Engl J Med. 1980 Jul 3;303(1):27–34. doi: 10.1056/NEJM198007033030109. [DOI] [PubMed] [Google Scholar]
- Weitzell R., Steppeler A., Starke K. Effects of prostaglandin E2, prostaglandin I2 and 6-keto-prostaglandin F1 alpha on adrenergic neurotransmission in the pulmonary artery of the rabbit. Eur J Pharmacol. 1978 Nov 1;52(1):137–141. doi: 10.1016/0014-2999(78)90033-x. [DOI] [PubMed] [Google Scholar]
- Wise W. C., Cook J. A., Eller T., Halushka P. V. Ibuprofen improves survival from endotoxic shock in the rat. J Pharmacol Exp Ther. 1980 Oct;215(1):160–164. [PubMed] [Google Scholar]
- Wise W. C., Cook J. A., Halushka P. V., Knapp D. R. Protective effects of thromboxane synthetase inhibitors in rats in endotoxic shock. Circ Res. 1980 Jun;46(6):854–859. doi: 10.1161/01.res.46.6.854. [DOI] [PubMed] [Google Scholar]