Abstract

Hypothesis

Rats with Postinfarction Heart Failure: Effects of Propranolol Therapy on Intracellular Calcium Regulation and Left Ventricular Function

Hari Prasad Sonwani*

Published: 28 November, 2023 | Volume 8 - Issue 3 | Pages: 158-163

Patients with heart failure may live longer if they receive chronic treatment with beta-adrenergic blocking medications. Unresolved are the mechanisms underlying the beneficial effects and if they may be applied to ischemic heart failure. Rats (n = 28) underwent echocardiographic-Doppler exams one and six weeks following a simulated operation or myocardial infarction (MI). After the first echocardiography, rats were randomized to either no therapy or 500 mg/l of propranolol in their drinking water. The noninfected left ventricular (LV) papillary muscles were used to record isometric contractions and intracellular Ca transients simultaneously.
Untreated MI rats had a restrictive LV diastolic filling pattern, decreased systolic function (13% ± 2%), and significant LV dilatation (10.6 ± 0.4 mm vs. 8.9 ± 0.3 mm, MI vs. control). The LV chamber diameters of the propranolol-treated MI rats were 10.6 ± 0.5 mm, and systolic performance (13% ± 2%). Higher LV end-diastolic pressures (27 ± 2 mmHg vs. 20 ± 3 mmHg) and a more constrained LV diastolic filling pattern (increased ratio of early to late filling velocities and faster E wave deceleration rate) were seen in the propranolol-treated animals. Papillary muscle contractility in untreated MI rats was lower (1.6 ± 0.3 g mm²). Furthermore, the inotropic response to isoproterenol was attenuated, and Ca transients were extended. During isoproterenol stimulation, beta-adrenergic blocking administration had no effect on force development (1.6 ± 0.3 g mm²) or the length of Ca transients.
Rats with postinfarction heart failure receiving chronic propranolol treatment did not have improvements in systolic function or LV remodeling. Propranolol exacerbated LV diastolic pressures and filling patterns. Additionally, there was no discernible improvement in intracellular contractility following treatment, Calcium control, or beta-adrenergic sensitivity in the myocardium that is not infarcted).

Read Full Article HTML DOI: 10.29328/journal.jccm.1001169 Cite this Article Read Full Article PDF

Keywords:

Beta-adrenergic blocking; Myocardial infarction; Echocardiography; Blood of velocity; Diastole; Calcium; Heart failure; Congestive; Myocardial contractility

References

  1. Heidenreich PA, Lee TT, Massie BM. Effect of beta-blockade on mortality in patients with heart failure: a meta-analysis of randomized clinical trials. J Am Coll Cardiol. 1997 Jul;30(1):27-34. doi: 10.1016/s0735-1097(97)00104-6. PMID: 9207617.
  2. Appleton CP, Hatle LK, Popp RL. Relation of transmitral flow velocity patterns to left ventricular diastolic function: new insights from a combined hemodynamic and Doppler echocardiographic study. J Am Coll Cardiol. 1988 Aug;12(2):426-40. doi: 10.1016/0735-1097(88)90416-0. PMID: 3392336.
  3. Andersson B, Blomström-Lundqvist C, Hedner T, Waagstein F. Exercise hemodynamics and myocardial metabolism during long-term beta-adrenergic blockade in severe heart failure. J Am Coll Cardiol. 1991 Oct;18(4):1059-66. doi: 10.1016/0735-1097(91)90767-4. PMID: 1680132.
  4. Fisher ML, Gottlieb SS, Plotnick GD, Greenberg NL, Patten RD, Bennett SK, Hamilton BP. Beneficial effects of metoprolol in heart failure associated with coronary artery disease: a randomized trial. J Am Coll Cardiol. 1994 Mar 15;23(4):943-50. doi: 10.1016/0735-1097(94)90641-6. PMID: 8106700.
  5. Randomised, placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease. Australia/New Zealand Heart Failure Research Collaborative Group. Lancet. 1997 Feb 8;349(9049):375-80. PMID: 9033462.
  6. Bohm M, Gierschik P, Jacobs K, Pieske B, Schnabel P, Ungerer M, Erdmann E. Increase of Gia in human hearts with dilated but not ischemic cardiomyopathy. Circulation. 1990; 82: 1249 ± 1265.
  7. Bristow MR, Anderson FL, Port JD, Skerl L, Hersh-Berger RE, Larrabee P, O'Connell JB, Renlund DG, Volkman K, Murray J, Feldman AM. Divergences in b-adrenergic neuroreceptor mechanisms in ischemic versus idiopathic dilated cardiomyopathy. Circulation. 1991; 84: 1024-1039.
  8. Haber HL, Simek CL, Gimple LW, Bergin JD, Subbiah K, Jayaweera AR, Powers ER, Feldman MD. Why do patients with congestive heart failure tolerate the initiation of beta-blocker therapy? Circulation. 1993 Oct;88(4 Pt 1):1610-9. doi: 10.1161/01.cir.88.4.1610. PMID: 8104738.
  9. Litwin SE, Katz SE, Morgan JP, Douglas PS. Serial echocardiographic assessment of left ventricular geometry and function after large myocardial infarction in the rat. Circulation. 1994 Jan;89(1):345-54. doi: 10.1161/01.cir.89.1.345. PMID: 8281668.
  10. Litwin SE, Katz SE, Morgan JP, Douglas PS. Long-term captopril treatment improves diastolic filling more than systolic performance in rats with large myocardial infarction. J Am Coll Cardiol. 1996 Sep;28(3):773-81. doi: 10.1016/0735-1097(96)00215-x. PMID: 8772771.
  11. A randomized trial of propranolol in patients with acute myocardial infarction. I. Mortality results. JAMA. 1982 Mar 26;247(12):1707-14. doi: 10.1001/jama.1982.03320370021023. PMID: 7038157.
  12. Bart BA, Shaw LK, McCants CB Jr, Fortin DF, Lee KL, Califf RM, O'Connor CM. Clinical determinants of mortality in patients with angiographically diagnosed ischemic or nonischemic cardiomyopathy. J Am Coll Cardiol. 1997 Oct;30(4):1002-8. doi: 10.1016/s0735-1097(97)00235-0. PMID: 9316531.
  13. Feuerstein GZ, Yue TL, Cheng HY, Ruffolo RR Jr. Myocardial protection by the novel vasodilating beta-blocker, carvedilol: potential relevance of anti-oxidant activity. J Hypertens Suppl. 1993 Jun;11(4):S41-8. PMID: 8104241.
  14. Gilbert EM, Abraham WT, Olsen S, Hattler B, White M, Mealy P, Larrabee P, Bristow MR. Comparative hemodynamic, left ventricular functional, and antiadrenergic effects of chronic treatment with metoprolol versus carvedilol in the failing heart. Circulation. 1996 Dec 1;94(11):2817-25. doi: 10.1161/01.cir.94.11.2817. PMID: 8941107.
  15. Feuerstein G, Liu GL, Yue TL, Cheng HY, Hieble JP, Arch JR, Ruffolo RR Jr, Ma XL. Comparison of metoprolol and carvedilol pharmacology and cardioprotection in rabbit ischemia and reperfusion model. Eur J Pharmacol. 1998 Jun 26;351(3):341-50. doi: 10.1016/s0014-2999(98)00326-4. PMID: 9721026.
  16. Böhm M, Ettelbrück S, Flesch M, van Gilst WH, Knorr A, Maack C, Pinto YM, Paul M, Teisman AC, Zolk O. Beta-adrenergic signal transduction following carvedilol treatment in hypertensive cardiac hypertrophy. Cardiovasc Res. 1998 Oct;40(1):146-55. doi: 10.1016/s0008-6363(98)00099-6. PMID: 9876327.
  17. Gay RG, Raya TE, Goldman S. Chronic propranolol treatment promotes left ventricular dilation without altering systolic function after large myocardial infarction in rats. J Cardiovasc Pharmacol. 1990 Oct;16(4):529-36. doi: 10.1097/00005344-199010000-00003. PMID: 1706793.
  18. Hagar JM, Newman LG, Kloner RA. Effects of amlodipine on myocardial infarction, infarct expansion, and ventricular geometry in the rat. Am Heart J. 1992 Sep;124(3):571-80. doi: 10.1016/0002-8703(92)90261-s. PMID: 1387506.
  19. Hodsman GP, Kohzuki M, Howes LG, Sumithran E, Tsunoda K, Johnston CI. Neurohumoral responses to chronic myocardial infarction in rats. Circulation. 1988 Aug;78(2):376-81. doi: 10.1161/01.cir.78.2.376. PMID: 2899463.
  20. Hu K, Gaudron P, Ertl G. Long-term effects of beta-adrenergic blocking agent treatment on hemodynamic function and left ventricular remodeling in rats with experimental myocardial infarction: importance of timing of treatment and infarct size. J Am Coll Cardiol. 1998 Mar 1;31(3):692-700. doi: 10.1016/s0735-1097(97)00527-5. PMID: 9502655.
  21. Hall SA, Cigarroa CG, Marcoux L, Risser RC, Grayburn PA, Eichhorn EJ. Time course of improvement in left ventricular function, mass and geometry in patients with congestive heart failure treated with beta-adrenergic blockade. J Am Coll Cardiol. 1995 Apr;25(5):1154-61. doi: 10.1016/0735-1097(94)00543-y. PMID: 7897129.

Figures:

Similar Articles

Recently Viewed

Read More

Most Viewed

Read More

Help ?