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Effects of Isoproterenol and Levarterenol on Blood Flow and Oxygen Use in Hemorrhagic Shock

Effects of Isoproterenol and Levarterenol on Blood Flow and Oxygen Use in Hemorrhagic Shock Abstract THE IMPROVEMENT of vital-organ perfusion is an accepted aim in shock therapy. The most effective approach to this aim is controversial. Adequate blood volume repletion does not necessarily result in an optimal regional distribution of blood flow. The present study was designed to compare the effects of two drugs, levarterenol and isoproterenol, on cardiac output and blood flow to the superior mesenteric and renal vascular beds. Though chemically related, these drugs have divergent effects upon the resistance vessels, levarterenol being a vasoconstrictor and isoproterenol a vasodilator. Levarterenol was an obvious choice for a vasopressor drug because of its wide clinical usage, its role as an endogenous sympathetic mediator,1 and because of the inconsistency of reported results following its application in experimental and clinical shock. The use of levarterenol to elevate pressure has produced both positive and negative experimental results in terms of survival and measured blood flow data. Reports References 1. Carolina Medical Electronics, Inc. models 201 and 301. 2. Series EMP-500-I, EMP-400-I, and EMP-100-I, Electromagnetic Probe Co. 3. Von Euler, U.S.: A Specific Sympathomimetic Ergone in Adrenergic Nerve Fibers and Its Relation to Adrenaline and Noradrenaline , Acta Physiol Scandinav 12:73, 1946.Crossref 4. Griffin, J.C., Jr., et al: The Effect of Norepinephrine (Levophed) on Survival in Standard Oligemic Shock , Surg Forum 9:4, 1958. 5. Lansing, A.M., and Stevenson, J.A.F.: Mechanism of Action of Norepinephrine in Hemorrhagic Shock , Amer J Physiol 193:289, 1958. 6. Remington, J.W., et al: Role of Vasoconstriction in the Response of the Dog to Hemorrhage , Amer J Physiol 161:116, 1950. 7. Close, S.A., et al: The Effect of Norepinephrine on Survival in Experimental Acute Hemorrhagic Hypotension , Surg Forum 8:22, 1957. 8. Drucker, W.R.; Kingsbury, B.; and Graham, L.: Metabolic Effect of Vasopressors in Hemorrhagic Shock , Surg Forum 13:16, 1962. 9. Lillehei, R.C.; Longerbeam, J.K.; and Manax, W.G.: The Modern Treatment of Shock Based on Physiologic Principles , Clin Pharmacol Ther 5:63, 1954. 10. Foster, J.H.; Collins, H.A.; and Scott, H.W., Jr.: The Effect of Levarterenol on Renal Blood Flow in Dogs Subjected to Hemorrhagic Shock , Surg Forum 5:781, 1954. 11. Morris, G.C., Jr.; Moyer, J.H.; and Beasley, H.L.: Renal Function Response to Vasopressor Agents in Shock , Surg Forum 5:798, 1954. 12. Moyer, J.H.; Morris, G.; and Beazley, H.L.: Renal Hemodynamic Response to Vasopressor Agents in the Treatment of Shock , Circulation 12:96, 1955.Crossref 13. Mills, L.C., and Steppacher, R.: Hemodynamic Effects of Vasopressor Agents in Hemorrhagic Shock , Amer J Cardiol 12:614, 1963.Crossref 14. Teramoto, S., and Shumacker, H.B., Jr.: Influence of 1-Norepinephrine Upon Hepatic Blood Flow , Surg Gynec Obstet 116:443, 1963. 15. Corday, E., and Williams, J.H., Jr.: Effect of Shock and Vasopressor Drugs on the Regional Circulation of the Brain, Heart, Kidney, and Liver , Amer J Med 29:228, 1960.Crossref 16. Gilmore, J.P.; Smythe, C.M.; and Hanford, S.W.: The Effect of 1-Norepinephrine on Cardiac Output in the Anesthetized Dog During Graded Hemorrhage , J Clin Invest 33:884, 1954.Crossref 17. Levy, M.N., and Brind, S.H.: Influence of 1-Norepinephrine Upon Cardiac Output in Anesthetized Dogs , Circ Res 5:85, 1927.Crossref 18. Churchill-Davidson, H.C., et al: The Effects of Adrenaline, Noradrenaline, and Methedrine on the Renal Circulation During Anesthesia , Lancet 2:803, 1951.Crossref 19. Frank, E.D., et al: Effect of Norepinephrine on Circulation of Dogs in Hemorrhagic Shock , Amer J Physiol 186:74, 1956. 20. Nelson, R.M.; Henry, J.W.; and Lyman, J.H.: Influence of 1-Norepinephrine on Renal Blood Flow, Renal Vascular Resistance, and Urine Flow in Hemorrhagic Shock , Surgery 50:115, 1961. 21. Rushmer, R.F., et al: Changes in Peripheral Blood Flow Distribution in Healthy Dogs , Circ Res 9:675, 1961.Crossref 22. King, B.D.; Sokolof, L.; and Wechsler, R.L.: The Effects of 1-Epinephrine and 1-Norepinephrine Upon Cerebral Circulation and Metabolism in Man , J Clin Invest 31:273, 1952.Crossref 23. Collier, H.D.; Meyers, F.H.; and Schmitt, G.H.: Hemodynamic Effects of Infusions of Epinephrine and Arterenol in Normal and Shocked Dogs , Amer J Physiol 189:224, 1957. 24. Nickerson, M., and Gourzis, J.T.: Blockade of Sympathetic Vasoconstriction in the Treatment of Shock , J Trauma 2:399, 1962.Crossref 25. Ahlquist, R.P.: A Study of the Adrenotropic Receptors , Amer J Physiol 153:586, 1948. 26. Moran, N.C.: Adrenergic Receptors Within the Cardiovascular System , Circulation 28:987, 1963.Crossref 27. Lands, A.M., and Howard, J.W.: A Comparative Study of the Effects of 1-Arterenol, Epinephrine and Isopropylarternol on the Heart , J Pharmacol Exp Ther 106:65, 1952. 28. Eckstein, J.W., and Hamilton, W.K.: Effects of Isoproterenol on Peripheral Venous Tone and Transmural Right Atrial Pressure in Man , J Clin Invest 38:342, 1959.Crossref 29. Kaiser, G.A.; Ross, J., Jr.; and Braunwald, E.: Alpha and Beta Adrenergic Receptor Mechanisms in the Systemic Venous Bed , J Pharmacol Exp Ther 144:156, 1964. 30. Aviado, D.M., Jr., and Schmidt, C.F.: Effects of Sympathomimetic Drugs on Pulmonary Circulation With Special Reference to a New Pulmonary Vasodilator , J Pharmacol Exp Ther 120:512, 1957. 31. Castro de la Mata, R.; Penna, M.; and Aviado, D.M., Jr.: Reversal of Sympathomimetic Bronchodilation by Dichloroisoproterenol , J Pharmacol Exp Ther 135:197, 1962. 32. Cobbold, A.F.; Ginsburg, J.; and Paton, A.: Circulatory, Respiratory and Metabolic Response to Isopropylnoradrenaline in Man , J Physiol 151:539, 1960. 33. Johnson, D.G., and Parkins, W.M.: Effects of 1-Norepinephrine and Isoproterenol Upon Blood Pressure, Cardiac Output, Mesenteric, and Renal Blood Flows in Hemorrhagic Shock , Fed Proc 23:416, 1964. 34. Peters, J.P., and Van Slyke, D.D.: " Gasometric Methods for Analyses of Blood and Other Solutions " in Quantitative Clinical Chemistry , Baltimore: Williams and Wilkins Co., 1932, vol 2, pp 229-377. 35. Darby, T.D., et al: Effects of Metabolic Acidosis on Ventricular Isometric Systolic Tension and the Response to Epinephrine and Levarterenol , Circ Res 8:1242, 1960.Crossref 36. Burget, G.E., and Visscher, M.B.: Variations of the pH of the Blood and the Response of the Vascular System to Adrenalin , Amer J Physiol 8:113, 1927. 37. Watts, D.T.: Vasodilator Agents in Management of Wound Shock: A Critical Review , Washington, DC: National Academy of Sciences, National Research Council, 1963, pp 50-53. 38. Lansing, A.M.; Stevenson, J.A.F.; and McLachlin, A.D.: The Use of Vasopressor Agents in the Treatment of Shock , J Trauma 2:387, 1962.Crossref 39. Dodge, H.T.; Lord, J.D.; and Sandier, H.: Cardiovascular Effects of Isoproterenol in Normal Subjects and Subjects With Congestive Heart Failure , Amer Heart J 60:94, 1960.Crossref 40. Von Euler, U.S.: Noradrenaline , Springfield, Ill: Charles C Thomas, Publisher, 1956, pp 211-214. 41. Ribeilima, J., et al: The Effects of Norepinephrine on the Hemodynamics and Myocardial Metabolism of Normal Human Subjects , Amer Heart J 67:672, 1964.Crossref 42. Winterscheid, L.C., et al: Effects of Isoproterenol on Carbohydrate Metabolism of Isolated Canine Heart , Circ Res 12:76, 1963.Crossref 43. Mayer, S.E., and Moran, N.C.: Relation Between Pharmacologic Augmentation of Cardiac Contractile Force and the Activation of Myocardial Glycogen Phosphorylase , J Pharmacol Exp Ther 129:271, 1960. 44. Chappel, C.I., et al: Comparison of Cardiotoxic Actions of Certain Sympathomimetic Amines , Canad J Biochem Physiol 37:35, 1959.Crossref 45. Peretz, D., et al: The Significance of Lactic-Acidosis in Shock , Fed Proc 23:415, 1964. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Surgery American Medical Association

Effects of Isoproterenol and Levarterenol on Blood Flow and Oxygen Use in Hemorrhagic Shock

Archives of Surgery , Volume 92 (2) – Feb 1, 1966

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American Medical Association
Copyright
Copyright © 1966 American Medical Association. All Rights Reserved.
ISSN
0004-0010
eISSN
1538-3644
DOI
10.1001/archsurg.1966.01320200117019
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Abstract

Abstract THE IMPROVEMENT of vital-organ perfusion is an accepted aim in shock therapy. The most effective approach to this aim is controversial. Adequate blood volume repletion does not necessarily result in an optimal regional distribution of blood flow. The present study was designed to compare the effects of two drugs, levarterenol and isoproterenol, on cardiac output and blood flow to the superior mesenteric and renal vascular beds. Though chemically related, these drugs have divergent effects upon the resistance vessels, levarterenol being a vasoconstrictor and isoproterenol a vasodilator. Levarterenol was an obvious choice for a vasopressor drug because of its wide clinical usage, its role as an endogenous sympathetic mediator,1 and because of the inconsistency of reported results following its application in experimental and clinical shock. The use of levarterenol to elevate pressure has produced both positive and negative experimental results in terms of survival and measured blood flow data. Reports References 1. Carolina Medical Electronics, Inc. models 201 and 301. 2. Series EMP-500-I, EMP-400-I, and EMP-100-I, Electromagnetic Probe Co. 3. Von Euler, U.S.: A Specific Sympathomimetic Ergone in Adrenergic Nerve Fibers and Its Relation to Adrenaline and Noradrenaline , Acta Physiol Scandinav 12:73, 1946.Crossref 4. Griffin, J.C., Jr., et al: The Effect of Norepinephrine (Levophed) on Survival in Standard Oligemic Shock , Surg Forum 9:4, 1958. 5. Lansing, A.M., and Stevenson, J.A.F.: Mechanism of Action of Norepinephrine in Hemorrhagic Shock , Amer J Physiol 193:289, 1958. 6. Remington, J.W., et al: Role of Vasoconstriction in the Response of the Dog to Hemorrhage , Amer J Physiol 161:116, 1950. 7. Close, S.A., et al: The Effect of Norepinephrine on Survival in Experimental Acute Hemorrhagic Hypotension , Surg Forum 8:22, 1957. 8. Drucker, W.R.; Kingsbury, B.; and Graham, L.: Metabolic Effect of Vasopressors in Hemorrhagic Shock , Surg Forum 13:16, 1962. 9. Lillehei, R.C.; Longerbeam, J.K.; and Manax, W.G.: The Modern Treatment of Shock Based on Physiologic Principles , Clin Pharmacol Ther 5:63, 1954. 10. Foster, J.H.; Collins, H.A.; and Scott, H.W., Jr.: The Effect of Levarterenol on Renal Blood Flow in Dogs Subjected to Hemorrhagic Shock , Surg Forum 5:781, 1954. 11. Morris, G.C., Jr.; Moyer, J.H.; and Beasley, H.L.: Renal Function Response to Vasopressor Agents in Shock , Surg Forum 5:798, 1954. 12. Moyer, J.H.; Morris, G.; and Beazley, H.L.: Renal Hemodynamic Response to Vasopressor Agents in the Treatment of Shock , Circulation 12:96, 1955.Crossref 13. Mills, L.C., and Steppacher, R.: Hemodynamic Effects of Vasopressor Agents in Hemorrhagic Shock , Amer J Cardiol 12:614, 1963.Crossref 14. Teramoto, S., and Shumacker, H.B., Jr.: Influence of 1-Norepinephrine Upon Hepatic Blood Flow , Surg Gynec Obstet 116:443, 1963. 15. Corday, E., and Williams, J.H., Jr.: Effect of Shock and Vasopressor Drugs on the Regional Circulation of the Brain, Heart, Kidney, and Liver , Amer J Med 29:228, 1960.Crossref 16. Gilmore, J.P.; Smythe, C.M.; and Hanford, S.W.: The Effect of 1-Norepinephrine on Cardiac Output in the Anesthetized Dog During Graded Hemorrhage , J Clin Invest 33:884, 1954.Crossref 17. Levy, M.N., and Brind, S.H.: Influence of 1-Norepinephrine Upon Cardiac Output in Anesthetized Dogs , Circ Res 5:85, 1927.Crossref 18. Churchill-Davidson, H.C., et al: The Effects of Adrenaline, Noradrenaline, and Methedrine on the Renal Circulation During Anesthesia , Lancet 2:803, 1951.Crossref 19. Frank, E.D., et al: Effect of Norepinephrine on Circulation of Dogs in Hemorrhagic Shock , Amer J Physiol 186:74, 1956. 20. Nelson, R.M.; Henry, J.W.; and Lyman, J.H.: Influence of 1-Norepinephrine on Renal Blood Flow, Renal Vascular Resistance, and Urine Flow in Hemorrhagic Shock , Surgery 50:115, 1961. 21. Rushmer, R.F., et al: Changes in Peripheral Blood Flow Distribution in Healthy Dogs , Circ Res 9:675, 1961.Crossref 22. King, B.D.; Sokolof, L.; and Wechsler, R.L.: The Effects of 1-Epinephrine and 1-Norepinephrine Upon Cerebral Circulation and Metabolism in Man , J Clin Invest 31:273, 1952.Crossref 23. Collier, H.D.; Meyers, F.H.; and Schmitt, G.H.: Hemodynamic Effects of Infusions of Epinephrine and Arterenol in Normal and Shocked Dogs , Amer J Physiol 189:224, 1957. 24. Nickerson, M., and Gourzis, J.T.: Blockade of Sympathetic Vasoconstriction in the Treatment of Shock , J Trauma 2:399, 1962.Crossref 25. Ahlquist, R.P.: A Study of the Adrenotropic Receptors , Amer J Physiol 153:586, 1948. 26. Moran, N.C.: Adrenergic Receptors Within the Cardiovascular System , Circulation 28:987, 1963.Crossref 27. Lands, A.M., and Howard, J.W.: A Comparative Study of the Effects of 1-Arterenol, Epinephrine and Isopropylarternol on the Heart , J Pharmacol Exp Ther 106:65, 1952. 28. Eckstein, J.W., and Hamilton, W.K.: Effects of Isoproterenol on Peripheral Venous Tone and Transmural Right Atrial Pressure in Man , J Clin Invest 38:342, 1959.Crossref 29. Kaiser, G.A.; Ross, J., Jr.; and Braunwald, E.: Alpha and Beta Adrenergic Receptor Mechanisms in the Systemic Venous Bed , J Pharmacol Exp Ther 144:156, 1964. 30. Aviado, D.M., Jr., and Schmidt, C.F.: Effects of Sympathomimetic Drugs on Pulmonary Circulation With Special Reference to a New Pulmonary Vasodilator , J Pharmacol Exp Ther 120:512, 1957. 31. Castro de la Mata, R.; Penna, M.; and Aviado, D.M., Jr.: Reversal of Sympathomimetic Bronchodilation by Dichloroisoproterenol , J Pharmacol Exp Ther 135:197, 1962. 32. Cobbold, A.F.; Ginsburg, J.; and Paton, A.: Circulatory, Respiratory and Metabolic Response to Isopropylnoradrenaline in Man , J Physiol 151:539, 1960. 33. Johnson, D.G., and Parkins, W.M.: Effects of 1-Norepinephrine and Isoproterenol Upon Blood Pressure, Cardiac Output, Mesenteric, and Renal Blood Flows in Hemorrhagic Shock , Fed Proc 23:416, 1964. 34. Peters, J.P., and Van Slyke, D.D.: " Gasometric Methods for Analyses of Blood and Other Solutions " in Quantitative Clinical Chemistry , Baltimore: Williams and Wilkins Co., 1932, vol 2, pp 229-377. 35. Darby, T.D., et al: Effects of Metabolic Acidosis on Ventricular Isometric Systolic Tension and the Response to Epinephrine and Levarterenol , Circ Res 8:1242, 1960.Crossref 36. Burget, G.E., and Visscher, M.B.: Variations of the pH of the Blood and the Response of the Vascular System to Adrenalin , Amer J Physiol 8:113, 1927. 37. Watts, D.T.: Vasodilator Agents in Management of Wound Shock: A Critical Review , Washington, DC: National Academy of Sciences, National Research Council, 1963, pp 50-53. 38. Lansing, A.M.; Stevenson, J.A.F.; and McLachlin, A.D.: The Use of Vasopressor Agents in the Treatment of Shock , J Trauma 2:387, 1962.Crossref 39. Dodge, H.T.; Lord, J.D.; and Sandier, H.: Cardiovascular Effects of Isoproterenol in Normal Subjects and Subjects With Congestive Heart Failure , Amer Heart J 60:94, 1960.Crossref 40. Von Euler, U.S.: Noradrenaline , Springfield, Ill: Charles C Thomas, Publisher, 1956, pp 211-214. 41. Ribeilima, J., et al: The Effects of Norepinephrine on the Hemodynamics and Myocardial Metabolism of Normal Human Subjects , Amer Heart J 67:672, 1964.Crossref 42. Winterscheid, L.C., et al: Effects of Isoproterenol on Carbohydrate Metabolism of Isolated Canine Heart , Circ Res 12:76, 1963.Crossref 43. Mayer, S.E., and Moran, N.C.: Relation Between Pharmacologic Augmentation of Cardiac Contractile Force and the Activation of Myocardial Glycogen Phosphorylase , J Pharmacol Exp Ther 129:271, 1960. 44. Chappel, C.I., et al: Comparison of Cardiotoxic Actions of Certain Sympathomimetic Amines , Canad J Biochem Physiol 37:35, 1959.Crossref 45. Peretz, D., et al: The Significance of Lactic-Acidosis in Shock , Fed Proc 23:415, 1964.

Journal

Archives of SurgeryAmerican Medical Association

Published: Feb 1, 1966

References