Effect of chemical sympathectomy on coronary flow and cardiovascular adjustment to exercise in dogs
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The exercise capacity and the increase of coronary and systemic hemodynamics under treadmill exercise were studied in 5 dogs, chemically sympathectomized with 6-hydroxy-dopamine.
Completeness of adrenergic denervation was verified by stimulation of the right stellate ganglion, by intravenous administration of tyramine, and by demonstration of supersensitivity to exogenous norepinephrine.
These dogs demonstrated a retarded adaptation of hemodynamics to a sudden start of exercise. A fall in mean arterial pressure below 45 mmHg within 10 to 15 sec lead to collapse. After a recovery period of 60–90 sec, moderate treadmill exercise could be continued; steady state attainment of hemodynamic parameters was considerably delayed.
A steady state of exercise with an O2-consumption (vO2) of 29.6±2.6 ml/min · kg and a cardiac outupt (CO) of 307±16 ml/min · kg was tolerated for at least 20 min.
An increase of vO2 up to 42.0±1.7 ml/min · kg and of CO up to 357±13 ml/min · kg under exercise was tolerated for 5 min with steady state, maximal heart rate being 160±4 min−1 at this level of exercise.
Mean arterial pressure and total peripheral resistance were significantly reduced at rest and during steady state of exercise as compared to controls prior to sympathectomy identical vO2, whereas CO remained unchanged.
The significant fall in left circumflex coronary flow was proportional to the decline in external heart work due to sympathectomy both at rest and under exercise.
Key words6-Hydroxydopamine Treadmill Exercise Sympatho-Adrenal system Exercise Capacity
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- 1.Ashkar, E., Hamilton, W. F.: Cardiovascular response to graded exercise in the sympathectomized-vagotomized dog. Amer. J. Physiol.204, 291–296 (1963).Google Scholar
- 2.Ashkar, E., Stevens, J. J., Houssay, B. A.: Role of the sympathicoadrenal system in the hemodynamic response to exercise in dogs. Amer. J. Physiol.214, 22–27 (1968).Google Scholar
- 3.Bassenge, E., Kucharczyk, M., Holtz, J., Stoian, D.: Treadmill exercise in dogs under β-adrenergic blockade: adaptation of coronary and systemic hemodynamics. Pflügers Arch.332, 40–55 (1972).Google Scholar
- 4.Boniface, K. J., Brodie, O. J., Walton, R. P.: Resistance strain gauge arches for direct measurement of heart contractile force in animals. Proc. Soc. exp. Biol. (N.Y.)84, 263–266 (1953).Google Scholar
- 5.Brouha, L., Cannon, W. B., Dill, D. B.: The heart rate of the sympathectomized dog in rest and exercise. J. Physiol. (Lond.)87, 345–359 (1936).Google Scholar
- 6.Brouha, L., Nowak, S. J. G., Dill, D. B.: The role of the vagus in the cardioaccelerator action of muscular exercise and emotion in sympathectomized dogs. J. Physiol. (Lond.)95, 454–463 (1939).Google Scholar
- 7.Cannon, W. B., Newton, H. F., Bright, E. M., Menkin, V., Moore, R. M.: Some aspects of the physiology of animals surviving complete exclusion of sympathetic nerve impulses. Amer. J. Physiol.89, 84–107 (1929).Google Scholar
- 8.Donald, D. E., Rowlands, D. J., Ferguson, D. A.: Similarity of blood flow in the normal and the sympathectomized dog hind limb during graded exercise. Circulat. Res.26, 185–199 (1970).Google Scholar
- 9.Donald, D. E., Shepherd, J. T.: Response to exercise in dogs with cardiac denervation. Amer. J. Physiol.205, 393–400 (1963).Google Scholar
- 10.Donald, D. E., Shepherd, J. T.: Initial cardiovascular adjustment to exercise in dogs with chronic cardiac denervation. Amer. J. Physiol.207, 1325–1329 (1964).Google Scholar
- 11.Donald, D. E., Shepherd, J. T.: Supersensitivity to l-norepinephrine of the denervated sinoatrial node. Amer. J. Physiol.208, 255–259 (1965).Google Scholar
- 12.Finch, L., Haeusler, G., Kuhn, H., Thoenen, H.: The recovery of vascular adrenergic nerve function in the rat after chemical sympathectomy with 6-hydroxydopamine. Brit. J. Pharmacol.44, 357 P (1972).Google Scholar
- 13.Gauthier, P., Nadeau, R., Champlain, J. de: Acute and chronic cardiovascular effects of 6-hydroxydopamine in dogs. Circulat. Res.31, 207–217 (1972).Google Scholar
- 14.Goldstone, B. W., Silberstein, M. J., Wyndham, C. H.: The role of the vagus nerve in cardiac adaptation to exercise. Pflügers Arch.325, 113–124 (1971).Google Scholar
- 15.Goldstone, B. W., Wyndham, C. H.: Cardiac adaptation to exercise. Pflügers Arch. ges. Physiol.295, 15–29 (1967).Google Scholar
- 16.Gregg, D. E., Khouri, E. M., Donald, D. E., Lowensohn, H. S., Pasyk, S.: Coronary circulation in the conscious dog with cardiac neural ablation. Circulat. Res.31, 129–144 (1972).Google Scholar
- 17.Haeusler, G., Haefely, W., Thoenen, H.: Chemical sympathectomy of the cat with 6-hydroxydopamine. J. Pharmacol. exp. Ther.170, 50–61 (1969).Google Scholar
- 18.Higgins, C. B., Vatner, St. F., Franklin, D., Braunwald, E.: Effects of experimentally produced heart failure on the peripheral vascular response to severe exercise in conscious dogs. Circulat. Res.31, 186–194 (1972).Google Scholar
- 19.Holtz, J., Bassenge, E., Restorff, W. v., Oversohl, K.: Hemodynamic effects of chemical sympathectomy with 6-hydroxydopamine in conscious dogs. Naunyn-Schmiedeberg's Arch. Pharmacol.277, R 33 (1973).Google Scholar
- 20.Jonsson, G., Sachs, Ch.: Neurochemical properties of adrenergic nerves regenerated after 6-hydroxydopamine. J. Neurochem.19, 2577–2585 (1972).Google Scholar
- 21.Khouri, E. M., Gregg, D. E.: An inflatable cuff for zero determination in blood flow studies. J. appl. Physiol.23, 395–397 (1967).Google Scholar
- 22.Laverty, R., Sharman, D. F., Vogt, M.: Action of 2,4,5-trihydroxyphenylethylamine on the storage and release of noradrenaline. Brit. J. Pharmacol.24, 549–560 (1965).Google Scholar
- 23.Malmfors, T., Sachs, Ch.: Degeneration of adrenergic nerves produced by 6-hydroxydopamine. Europ. J. Pharmacol.3, 89–92 (1968).Google Scholar
- 24.Müller, R. A., Thoenen, H., Axelrod, J.: Adrenal tyrosine hydroxylase: Compensatory increase in activity after chemical sympathectomy. Science163, 468–469 (1969).Google Scholar
- 25.Pinkston, J. O., Partington, P. F., Rosenblueth, A.: A further study of reflex changes of blood pressure in completely sympathectomized animals. Amer. J. Physiol.115, 711–719 (1936).Google Scholar
- 26.Thoenen, H., Müller, R, A., Axelrod, J.: Trans-synaptic induction of adrenal tyrosine hydroxylase. J. Pharmacol. exp. Ther.169, 249–254 (1969).Google Scholar
- 27.Thoenen, H., Tranzer, J. P.: Chemical sympathectomy by selective destruction of adrenergic nerve endings with 6-hydroxydopamine. Naunyn-Schmiedeberg's Arch. Pharmak. exp. Path.261, 271–288 (1968).Google Scholar
- 28.Tranzer, J. P., Thoenen, H.: An electron microscopic study of selective, acute degeneration of sympathetic nerve terminals after administration of 6-hydroxydopamine. Experientia (Basel)24, 155–156 (1968).Google Scholar
- 29.Trendelenburg, U.: Mechanisms of supersensitivity and subsensitivity to sympathomimetic amines. Pharmacol. Rev.18, 629–640 (1966).Google Scholar
- 30.Van Citters, R. L., Franklin, D. L.: Cardiovascular performance of Alaska sled dogs during exercise. Circulat. Res.24, 33–42 (1969).Google Scholar
- 31.Vatner, S. F., Franklin, D., van Citters, R. L., Braunwald, E.: Effects of carotid sinus nerve stimulation on blood-flow distribution in conscious dogs at rest and during exercise. Circulat. Res.27, 495–503 (1970).Google Scholar