Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1968 Oct;47(10):2193–2205. doi: 10.1172/JCI105905

Hemodynamic effects of isoproterenol in canine endotoxin shock

Boleslaw Starzecki 1, Wesley W Spink 1
PMCID: PMC297384  PMID: 5676517

Abstract

Myocardial function and peripheral hemodynamic alterations were measured through the late stages of canine endotoxin shock. 60 min postendotoxin paired animals were given infusions of either 5 ml/kg per hr of 5% dextrose or dextrose plus isoproterenol (0.25 μg/kg per min). Comparable blood lactic and pyruvic acid levels were determined, the excess lactic acid calculated, and pH values were obtained. During the initial stages the classic pattern of hemodynamic alterations was observed; an excess of lactic acid appeared and the pH decreased. Outstanding was evidence of markedly reduced myocardial function in the late stages of shock with progressive rise in left ventricular end diastolic pressure (LVEDP), low cardiac index, rise of central venous pressure, increased central blood volume, tachycardia, and declining arterial pressure. Analyses of left ventricular function curves also indicated myocardial failure.

Infusion of dextrose alone failed to decrease mortality rate (10 of 18 dying), whereas the rate was significantly decreased with isoproterenol (2 of 18). Dextrose infusion did not benefit myocardial function. Isoproterenol resulted in a marked improvement in myocardial action with a significant increase in heart work associated with, yet very minor, increments of LVEDP. In addition, tachycardia subsided, peripheral resistance decreased, and the blood pressure stabilized. The prognostic value of excess lactic acid was doubtful but a progressive fall in later stages was associated with survival.

Full text

PDF
2193

Images in this article

2202Image
on p.2202

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ALICAN F., DALTON M. L., Jr, HARDY J. D. Experimental endotoxin shock. Circulatory changes with emphasis upon cardiac function. Am J Surg. 1962 Jun;103:702–708. doi: 10.1016/0002-9610(62)90249-0. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. DUFF J. H., MALAVE G., PERETZ D. I., SCOTT H. M., MACLEAN L. D. THE HEMODYNAMICS OF SEPTIC SHOCK IN MAN AND IN THE DOG. Surgery. 1965 Jul;58:174–184. [PubMed] [Google Scholar]
  4. Elliott W. C., Gorlin R. Isoproterenol in treatment of heart disease. Hemodynamic effects in circulatory failure. JAMA. 1966 Aug 1;197(5):315–320. [PubMed] [Google Scholar]
  5. GILBERT R. P. Mechanisms of the hemodynamic effects of endotoxin. Physiol Rev. 1960 Apr;40:245–279. doi: 10.1152/physrev.1960.40.2.245. [DOI] [PubMed] [Google Scholar]
  6. GOLDBERG E. B., NITOWSKY H. M., COLOWICK S. P. THE ROLE OF GLYCOLYSIS IN THE GROWTH OF TUMOR CELLS. IV. THE BASIS OF GLUCOSE TOXICITY IN OXAMATE-TREATED, CULTURED CELLS. J Biol Chem. 1965 Jul;240:2791–2796. [PubMed] [Google Scholar]
  7. GUYTON A. C., SATTERFIELD J. H., HARRIS J. W. Dynamics of central venous resistance with observations on static blood pressure. Am J Physiol. 1952 Jun;169(3):691–699. doi: 10.1152/ajplegacy.1952.169.3.691. [DOI] [PubMed] [Google Scholar]
  8. HALBERG F., SPINK W. W. The influence of Brucella somatic antigen (endotoxin) upon the temperature rhythm of intact mice. Lab Invest. 1956 May-Jun;5(3):283–294. [PubMed] [Google Scholar]
  9. HARRIS P., BATEMAN M., GLOSTER J. Relations between the cardio-respiratory effects of exercise and the arterial concentration of lactate and pyruvate in patients with rheumatic heart disease. Clin Sci. 1962 Dec;23:531–543. [PubMed] [Google Scholar]
  10. HINSHAW L. B., GILBERT R. P., KUIDA H., VISSCHER M. B. Peripheral resistance changes and blood pooling after endotoxin in eviscerated dogs. Am J Physiol. 1958 Dec;195(3):631–634. doi: 10.1152/ajplegacy.1958.195.3.631. [DOI] [PubMed] [Google Scholar]
  11. HINSHAW L. B., SPINK W. W., VICK J. A., MALLET E., FINSTAD J. Effect of endotoxin on kidney function and renal hemodynamics in the dog. Am J Physiol. 1961 Jul;201:144–148. doi: 10.1152/ajplegacy.1961.201.1.144. [DOI] [PubMed] [Google Scholar]
  12. HINSHAW L. B., VICK J. A., JORDAN M. M., WITTMERS L. E. Vascular changes associated with development of irreversible endotoxin shock. Am J Physiol. 1962 Jan;202:103–110. doi: 10.1152/ajplegacy.1962.202.1.103. [DOI] [PubMed] [Google Scholar]
  13. HUCKABEE W. E. Abnormal resting blood lactate. I. The significance of hyperlactatemia in hospitalized patients. Am J Med. 1961 Jun;30:840–848. doi: 10.1016/0002-9343(61)90172-3. [DOI] [PubMed] [Google Scholar]
  14. HUCKABEE W. E. Relationships of pyruvate and lactate during anaerobic metabolism. I. Effects of infusion of pyruvate or glucose and of hyperventilation. J Clin Invest. 1958 Feb;37(2):244–254. doi: 10.1172/JCI103603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. HUCKABEE W. E. Relationships of pyruvate and lactate during anaerobic metabolism. II. Exercise and formation of O-debt. J Clin Invest. 1958 Feb;37(2):255–263. doi: 10.1172/JCI103604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. HUCKABEE W. E. Relationships of pyruvate and lactate during anaerobic metabolism. III. Effect of breathing low-oxygen gases. J Clin Invest. 1958 Feb;37(2):264–271. doi: 10.1172/JCI103605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. KAISER G. A., ROSS J., Jr, BRAUNWALD E. ALPHA AND BETA ADRENERGIC RECEPTOR MECHANISMS IN THE SYSTEMIC VENOUS BED. J Pharmacol Exp Ther. 1964 May;144:156–162. [PubMed] [Google Scholar]
  18. KNUTTGEN H. G. Oxygen debt, lactate, pyruvate, and excess lactate after muscular work. J Appl Physiol. 1962 Jul;17:639–644. doi: 10.1152/jappl.1962.17.4.639. [DOI] [PubMed] [Google Scholar]
  19. KOBOLD E. E., LOVELL R., KATZ W., THAL A. P. CHEMICAL MEDIATORS RELEASED BY ENDOTOXIN. Surg Gynecol Obstet. 1964 Apr;118:807–813. [PubMed] [Google Scholar]
  20. KRASNOW N., ROLETT E. L., YURCHAK P. M., HOOD W. B., Jr, GORLIN R. ISOPROTERENOL AND CARDIOVASCULAR PERFORMANCE. Am J Med. 1964 Oct;37:514–525. doi: 10.1016/0002-9343(64)90065-8. [DOI] [PubMed] [Google Scholar]
  21. LILIENFIELD L. S., KOVACH R. D. Simplified method for calculating flow, mean circulation time and downslope from indicator-dilution curves. Proc Soc Exp Biol Med. 1956 Apr;91(4):595–598. doi: 10.3181/00379727-91-22341. [DOI] [PubMed] [Google Scholar]
  22. LILLEHEI R. C., LONGERBEAM J. K., BLOCH J. H., MANAX W. G. THE NATURE OF IRREVERSIBLE SHOCK: EXPERIMENTAL AND CLINICAL OBSERVATIONS. Ann Surg. 1964 Oct;160:682–710. doi: 10.1097/00000658-196410000-00012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. MACLEAN L. D., SPINK W. W., VISSCHER M. B., WEIL M. H. Studies on the circulatory changes in the dog produced by endotoxin from gram-negative microorganisms. J Clin Invest. 1956 Nov;35(11):1191–1198. doi: 10.1172/JCI103373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. MELBY J. C., BOSSENMAIER I. C., EGDAHL R. H., SPINK W. W. Suppression by cortisol of increased serum-transaminase induced by endotoxin. Lancet. 1959 Feb 28;1(7070):441–444. doi: 10.1016/s0140-6736(59)92260-3. [DOI] [PubMed] [Google Scholar]
  25. NICHOLSON J. W., 3rd, WOOD E. H. Estimation of cardiac output and Evans blue space in man, using an oximeter. J Lab Clin Med. 1951 Oct;38(4):588–603. [PubMed] [Google Scholar]
  26. OLSON R. E. "EXCESS LACTATE" AND ANAEROBIOSIS. Ann Intern Med. 1963 Dec;59:960–963. doi: 10.7326/0003-4819-59-6-960. [DOI] [PubMed] [Google Scholar]
  27. RASKOVA H., VANECEK J. PHARMACOLOGY OF BACTERIAL TOXINS. Pharmacol Rev. 1964 Mar;16:1–45. [PubMed] [Google Scholar]
  28. Rosenberg J. C., Rush B. F. Basic biochemical difference in endotoxin and hemorrhagic shock. Surg Forum. 1965;16:23–25. [PubMed] [Google Scholar]
  29. Rosenberg J. C., Rush B. F. Lethal endotoxin shock. Oxygen deficit, lactic acid levels, and other metabolic changes. JAMA. 1966 May 30;196(9):767–769. doi: 10.1001/jama.196.9.767. [DOI] [PubMed] [Google Scholar]
  30. SANDLER H., DODGE H. T., MURDAUGH H. V., Jr Effects of isoproterenol on cardiac output and renal function in congestive heart failure. Am Heart J. 1961 Nov;62:643–651. doi: 10.1016/0002-8703(61)90372-6. [DOI] [PubMed] [Google Scholar]
  31. SARNOFF S. J. Myocardial contractility as described by ventricular function curves; observations on Starling's law of the heart. Physiol Rev. 1955 Jan;35(1):107–122. doi: 10.1152/physrev.1955.35.1.107. [DOI] [PubMed] [Google Scholar]
  32. SPINK W. W., DAVIS R. B., POTTER R., CHARTRAND S. THE INITIAL STAGE OF CANINE ENDOTOXIN SHOCK AS AN EXPRESSION OF ANAPHYLACTIC SHOCK: STUDIES ON COMPLEMENT TITERS AND PLASMA HISTAMINE CONCENTRATIONS. J Clin Invest. 1964 Apr;43:696–704. doi: 10.1172/JCI104954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. SPINK W. W. Endotoxin shock. Ann Intern Med. 1962 Oct;57:538–552. doi: 10.7326/0003-4819-57-4-538. [DOI] [PubMed] [Google Scholar]
  34. Shaffer A. B., Katz L. N. Hemodynamic alterations in congestive heart failure. N Engl J Med. 1967 Apr 13;276(15):853–857. doi: 10.1056/NEJM196704132761509. [DOI] [PubMed] [Google Scholar]
  35. Siegel J. H., Fabian M. Therapeutic advantages of an inotropic vasodilator in endotoxin shock. JAMA. 1967 May 22;200(8):696–704. [PubMed] [Google Scholar]
  36. Siegel J. H., Greenspan M., Del Guercio L. R. Abnormal vascular tone, defective oxygen transport and myocardial failure in human septic shock. Ann Surg. 1967 Apr;165(4):504–517. doi: 10.1097/00000658-196704000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Sleeman H. K., Jennings P. B., Hardaway R. M. Evaluation of biochemical changes associated with experimental endotoxemia. I. Transaminase activity. Surgery. 1967 Jun;61(6):945–950. [PubMed] [Google Scholar]
  38. Spink W. W., Reddin J., Zak S. J., Peterson M., Starzecki B., Seljeskog E. Correlation of plasma catecholamine levels with hemodynamic changes in canine endotoxin shock. J Clin Invest. 1966 Jan;45(1):78–85. doi: 10.1172/JCI105325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Starzecki B., Reddin J. L., Spink W. W. Effect of isoproterenol on survival in canine endotoxin shock. Ann Surg. 1968 Jan;167(1):35–40. doi: 10.1097/00000658-196801000-00005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Vick J. A., Ciuchta H. P., Manthei J. H. Use of isoproterenol and phenoxybenzamine in treatment of endotoxin shock. J Pharmacol Exp Ther. 1965 Dec;150(3):382–388. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES