Skip to main content
Log in

Effects of pentobarbital on inotropic state of isolated canine left ventricle

  • Originals
  • Published:
Heart and Vessels Aims and scope Submit manuscript

Summary

Although pentobarbital has been found to depress myocardial function, the magnitude of its direct effects on ventricular contraction at anesthetic concentrations has not been well quantified. The direct effects of pentobarbital on left ventricular function were measured by employing an isolated canine heart preparation with a blood oxygenator. Seven hearts were perfused with blood, dextran, and perfluorochemical artificial blood. Ventricular function was evaluated using the slope of the end-systolic pressure-volume relationship (Ees) and the maximal rate of pressure development (dP/dtmax) in ventricles contracting isovolumically in control, after a low dose (13 µg/ml), and after a high dose (48 µg/ml) of pentobarbital. These concentrations represent one-half and two times the typical value (25 µg/ml) found to produce anesthesia in canines (assessed by tail clamp or blink reflex). The low dose of pentobarbital did not produce clear-cut depression in contractile function. The high dose of pentobarbital produced significant reductions of Ees, and dP/dtmax:Ees decreased 29%, from a control of 4.30 ± 0.84 to 3.05 ± 0.49 mmHg/ml and dP/dtmax decreased 24%, from a control of 909 ± 148 to 695 ± 173 mmHg/s. Thus, the threshold for the direct depressant effect of pentobarbital on ventricular function falls within the range of half to double the typically-reported anesthetic concentrations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Davies AO, McCans JL (1979) Effects of barbiturate anesthetics and ketamine on the force-frequency relation of cardiac muscle. Eur J Pharmacol 59:65–73

    Google Scholar 

  2. Frankl WS, Poole-Wilson PA (1981) Effects of thiopental on tension development, action potential, and exchange of calcium and potassium in rabbit ventricular myocardium. J Cardiovasc Pharmacol 3:554–565

    Google Scholar 

  3. Unruh HW, Wang R, Bose D, Mink SN (1991) Does pentobarbital anesthesia depress left ventricular contractility in dogs? Am J Physiol 261:H700-H706

    Google Scholar 

  4. Manders WT, Vatner SF (1976) Effects of sodium pentobarbital anesthesia on left ventricular function and distribution of cardiac output in dogs, with particular reference to the mechanism for tachycardia. Circ Res 39:512–517

    Google Scholar 

  5. Nash CB, Davis F, Woodbury RD (1956) Cardiovascular effects of anesthetic doses of pentobarbital sodium. Am J Physiol 185:107–112

    Google Scholar 

  6. Priano LL, Traber DL, Wilson RD (1969) Barbiturate anesthesia: An abnormal physiologic situation. J Pharmacol Exp Ther 165:126–135

    Google Scholar 

  7. Piatt JH, Schiff SJ (1984) High dose barbiturate therapy in neurosurgery and intensive care. Neurosurgery 15:427–444

    Google Scholar 

  8. Traeger SM, Henning RJ, Dobkin W, Gianotta S, Weil H, Weiss M (1983) Hemodynamic effects of pentobarbital therapy for intracranial hypertension. Crit Care Med 11:697–701

    Google Scholar 

  9. Peiss CN, Manning JW (1964) Effects of sodium pentobarbital on electrical and reflex activation of the cardiovascular system. Circ Res 14:228–235

    Google Scholar 

  10. Vatner SF, Braunwald E (1975) Cardiovascular control mechanisms in the conscious state. New Engl J Med 293:970–976

    Google Scholar 

  11. Hosomi H, Sagawa K (1979) Effect of pentobarbital anesthesia on hypotension after 10% hemorrhage in the dog. Am J Physiol 236:H607-H612

    Google Scholar 

  12. Zimpfer M, Manders WT, Barger AC, Vatner SF (1982) Pentobarbital alters compensatory neural and humoral mechanisms in response to hemorrhage. Am J Physiol 243:H713-H721

    Google Scholar 

  13. Zimpfer M, Sit SP, Vatner SF (1981) Effects of anesthesia on the canine carotid chemoreceptor reflex. Circ Res 48:400–406

    Google Scholar 

  14. Gilmore JP (1965) Pentobarbital sodium anesthesia in the dog. Am J Physiol 209:404–408

    Google Scholar 

  15. Steiner SH, Calvin HR (1967) The effects of anesthesia with pentobarbital on hemodynamics and arterial blood gases in splenectomized dogs. J Thorac Cardiovas Surg 54:592–598

    Google Scholar 

  16. Suga H, Sagawa K (1974) Instantaneous pressure-volume relationships and their ratio in the excised, supported canine left ventricle. Circ Res 35:117–126

    Google Scholar 

  17. Suga H, Sagawa K (1977) End-diastolic and end-systolic ventricular volume clamper for isolated canine heart. Am J Physiol 233:H718-H722

    Google Scholar 

  18. Janicki JS, Reeves RC, Weber KT, Donald TC, Walker AA (1974) Application of a pressure servo system developed to study ventricular dynamics. J Appl Physiol 37:736–741

    Google Scholar 

  19. Mason DT (1969) Usefulness and limitations of the rate of rise of intraventricular pressure (dp/dt) in the evaluation of myocardial contractility in man. Am J Cardiol 23:516–527

    Google Scholar 

  20. Frederiksen MC, Henthorn TK, Ruo TI, Atkinson AJ Jr (1983) Pharmacokinetics of pentobarbital in the dog. J Pharmacol Exp Ther 225:355–360

    Google Scholar 

  21. Nattel S, Wang Z, Matthews C (1990) Direct electro-physiological actions of pentobarbital at concentrations achieved during general anesthesia. Am J Physiol 259:H1743-H1751

    Google Scholar 

  22. Nayler WG, Szeto J (1972) Effect of sodium pentobarbital on calcium in mammalian heart muscle. Am J Physiol 222:339–344

    Google Scholar 

  23. Urthaler F, Krames BL, James TN (1974) Selective effects of pentobarbital on automaticity and conduction in the intact canine heart. Cardiovasc Res 8:46–57

    Google Scholar 

  24. Amlie JP, Owren T (1979) The effect of prolonged pentobarbital anesthesia on cardiac electrophysiology and inotropy of the dog heart in situ. Acta Pharmacol Toxicol 44:264–271

    Google Scholar 

  25. Baum D, Halter JB, Taborsky GJ Jr, Porte DP Jr (1985) Pentobarbital effects on plasma catecholamines: Temperature, heart rate, and blood pressure. Am J Physiol 248:E95-E100

    Google Scholar 

  26. Cox RH, Bagshaw RJ (1979) Influence of anesthesia on the response to carotid hypotension in dogs. Am J Physiol 237:H424-H432

    Google Scholar 

  27. Vatner SF, Franklin D, Braunwald E (1971) Effects of anesthesia and sleep on circulatory response to carotid sinus nerve stimulation. Am J Physiol 220:1249–1255

    Google Scholar 

  28. Exley KA (1954) Depression of autonomic ganglia by barbiturates. Br J Pharmacol 9:170–181

    Google Scholar 

  29. Cox RH (1972) Influence of pentobarbital anesthesia on cardiovascular function in trained dogs. Am J Physiol 223:651–659

    Google Scholar 

  30. Van Citters RL, Franklin DL, Rushmer RF (1964) Left ventricular dynamics in dogs during anesthesia with alpha-chloralose and sodium pentobarbital. Am J Cardiol 13:349–354

    Google Scholar 

  31. Barlow G, Knott DH (1964) Hemodynamic alterations after 30 minutes of pentobarbital sodium anesthesia in dogs. Am J Physiol 207:764–766

    Google Scholar 

  32. Shabetai R, Fowler NO, Hurlburt O (1963) Hemodynamic studies of dogs under pentobarbital and morphine chloralose anesthesia. J Surg Res 3:263–267

    Google Scholar 

  33. Howell CD, Horvath SM (1959) Reproducibility of cardiac output measurements in the dog. J Appl Physiol 14:421–423

    Google Scholar 

  34. Kass DA, Maughan WL (1988) From “Emax” to pressure-volume relations: A broader view. Circulation 77:1203–1212

    Google Scholar 

  35. Burkhoff D, Yue DT, Franz MR, Hunter WC, Sagawa K (1984) Mechanical restitution of isolated perfused canine left ventricles. Am J Physiol 246:H8-H16

    Google Scholar 

  36. Murray PA, Vatner SF (1979) Alpha-adrenoceptor attenuation of the coronary vascular response to severe exercise in the conscious dog. Circ Res 45:654–660

    Google Scholar 

  37. O'Rourke RA, Bishop VS (1971) Cardiovascular hemodynamics in the conscious dog. Am Heart J 81:55–60

    Google Scholar 

  38. Freye E (1974) Cardiovascular effects of high dosages of fentanyl, meperdine, and naloxone in dogs. Anesth Analg 53:40–47

    Google Scholar 

  39. Ostheimer GW, Shanahan EA, Guyton RA, Daggett WM, Lowenstein E (1975) Effects of fentanyl and droperidol on canine left ventricular performance. Anes-thesiology 42:288–291

    Google Scholar 

  40. Goldberg AH, Padget CH (1969) Comparative effects of morphine and fentanyl on isolated heart muscle. Anesth Analg 48:978–982

    Google Scholar 

  41. Strauer BE (1972) Contractile responses to morphine, piritramide, meperdine, and fentanyl: A comparative study of effects on the isolated ventricular myocardium. Anesthesiology 37:304–310

    Google Scholar 

  42. Arndt JO, Mikat M, Parasher C (1984) Fentanyl's analgesic, respiratory, and cardiovascular actions in relation to dose and plasma concentration in unanesthetized dogs. Anesthesiology 61:355–361

    Google Scholar 

  43. Ikemoto Y, Yatani A, Arimura H, Yoshitake J (1985) Reduction of the slow inward current of isolated rat ventricular cells by thiamylal and halothane. Acta Anesth Scand 29:583–586

    Google Scholar 

  44. Lain RF, Hess ML, Gertz EW Briggs FN (1968) Calcium uptake activity of canine myocardial sarcoplasmic reticulum in the presence of anesthetic agents. Circ Res 23:597–604

    Google Scholar 

  45. Malinconico ST, McCarl RL (1982) Effect of halothane on cardiac sarcoplasmic reticulum Ca2+-ATP-ase at low calcium concentrations. Mol Pharmacol 22:8–10

    Google Scholar 

  46. Komai H, Rusy BF (1984) Differences in the myocardial depressant action of thiopental and halothane. Anesth Analg 63:313–318

    Google Scholar 

  47. Blanck TJJ, Stevenson RL (1988) Thiopental does not alter Ca2+ uptake by cardiac sarcoplasmic reticulum. Anesth Analg 67:346–348

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

These studies were supported by United States NIH Research Grant HL 18912.

Deceased August 22, 1989

Rights and permissions

Reprints and permissions

About this article

Cite this article

Snyder, D.S., Harasawa, Y., Sagawa, K. et al. Effects of pentobarbital on inotropic state of isolated canine left ventricle. Heart Vessels 8, 128–135 (1993). https://doi.org/10.1007/BF01744797

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01744797

Key words

Navigation