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Angiotensin II blockade followed by growth hormone as adjunctive therapy after experimental myocardial infarction.

Publication ,  Journal Article
Hongo, M; Sentianin, EM; Tanaka, N; Mao, L; McKirnan, MD; Clark, RG; Won, W; Chien, KR; Ross, J
Published in: J Card Fail
September 1998

BACKGROUND: Recombinant human growth hormone (rhGH) has shown beneficial effects on cardiac function after myocardial infarction (MI) in rats. High-dose angiotensin II (AT1) receptor blockade in normal rats inhibited the hypertrophic effect of growth hormone (GH), therefore we investigated whether GH effects after MI would be enhanced by giving it in sequence after remodeling had been inhibited by prior AT1 blockade (losartan, L). METHODS AND RESULTS: Rats given losartan for 10 weeks after MI followed by rhGH for 2 weeks (2 mg/kg twice a day, GH plus losartan) were compared with rats given losartan for 10 weeks followed by placebo for 2 weeks (placebo plus losartan group) and with untreated controls (n = 17-20/group). Average MI sizes and left ventricular (LV) end diastolic (ED) dimensions (echocardiography) did not differ between groups. In GH and losartan, body weight (BW) was increased but left ventricular weight (LVW)/BW was reduced, and the LV fractional shortening and LV dP/dtmax (catheter tip micromanometer) were increased compared with the control group (20.3 vs 15.4% and 5579 vs 4699 mmHg/s, respectively, P < .05). The cardiac index also was significantly increased. In the placebo plus losartan group, the LVW/BW was also reduced and the cardiac index increased versus controls. Stroke volume was increased in GH plus losartan group compared with both placebo plus losartan and controls, and the systemic vascular resistance was significantly decreased only in the GH plus losartan group. The ED posterior wall thickness (noninfarcted wall) was increased in GH plus losartan compared with both control and placebo plus losartan. Left ventricular end diastolic pressure reduction was not significant in GH plus losartan group versus controls but was reduced in placebo plus losartan group, whereas LV relaxation (tau) was improved in both groups versus control rats. Thus, persistent remodeling effects caused by prior AT1 blockade undoubtedly contributed to some responses, but short-term GH given in sequence after chronic AT1 blockade had favorable actions on the failing heart and peripheral circulation by increasing LV wall thickness with partial reversal of unfavorable remodeling, lowering of vascular resistance, improvement of LV contractility, and enhanced LV systolic function and cardiac index relatively late after experimental MI.

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Published In

J Card Fail

DOI

ISSN

1071-9164

Publication Date

September 1998

Volume

4

Issue

3

Start / End Page

213 / 224

Location

United States

Related Subject Headings

  • Ventricular Remodeling
  • Ventricular Function, Left
  • Spleen
  • Rats, Sprague-Dawley
  • Rats
  • Random Allocation
  • Organ Size
  • Myocardium
  • Myocardial Infarction
  • Losartan
 

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Hongo, M., Sentianin, E. M., Tanaka, N., Mao, L., McKirnan, M. D., Clark, R. G., … Ross, J. (1998). Angiotensin II blockade followed by growth hormone as adjunctive therapy after experimental myocardial infarction. J Card Fail, 4(3), 213–224. https://doi.org/10.1016/s1071-9164(98)80008-0
Hongo, M., E. M. Sentianin, N. Tanaka, L. Mao, M. D. McKirnan, R. G. Clark, W. Won, K. R. Chien, and J. Ross. “Angiotensin II blockade followed by growth hormone as adjunctive therapy after experimental myocardial infarction.J Card Fail 4, no. 3 (September 1998): 213–24. https://doi.org/10.1016/s1071-9164(98)80008-0.
Hongo M, Sentianin EM, Tanaka N, Mao L, McKirnan MD, Clark RG, et al. Angiotensin II blockade followed by growth hormone as adjunctive therapy after experimental myocardial infarction. J Card Fail. 1998 Sep;4(3):213–24.
Hongo, M., et al. “Angiotensin II blockade followed by growth hormone as adjunctive therapy after experimental myocardial infarction.J Card Fail, vol. 4, no. 3, Sept. 1998, pp. 213–24. Pubmed, doi:10.1016/s1071-9164(98)80008-0.
Hongo M, Sentianin EM, Tanaka N, Mao L, McKirnan MD, Clark RG, Won W, Chien KR, Ross J. Angiotensin II blockade followed by growth hormone as adjunctive therapy after experimental myocardial infarction. J Card Fail. 1998 Sep;4(3):213–224.
Journal cover image

Published In

J Card Fail

DOI

ISSN

1071-9164

Publication Date

September 1998

Volume

4

Issue

3

Start / End Page

213 / 224

Location

United States

Related Subject Headings

  • Ventricular Remodeling
  • Ventricular Function, Left
  • Spleen
  • Rats, Sprague-Dawley
  • Rats
  • Random Allocation
  • Organ Size
  • Myocardium
  • Myocardial Infarction
  • Losartan