A histamine H2 receptor blocker ameliorates development of heart failure in dogs independently of β-adrenergic receptor blockade

Hiroyuki Takahama, Hiroshi Asanuma, Shoji Sanada, Masashi Fujita, Hideyuki Sasaki, Masakatsu Wakeno, Jiyoong Kim, Masanori Asakura, Seiji Takashima, Tetsuo Minamino, Kazuo Komamura, Masaru Sugimachi, Masafumi Kitakaze

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Histamine has a positive inotropic effect on ventricular myocardium and stimulation of histamine H2 receptors increases the intracellular cAMP level via Gs protein, as dose stimulation of β-adrenergic receptors, and worsens heart failure. To test whether a histamine H2 receptor blocker had a beneficial effect in addition to β-adrenergic receptor blockade, we investigated the cardioprotective effect of famotidine, a histamine H2 receptor blocker, in dogs receiving a β-blocker. We induced heart failure in dogs by rapid ventricular pacing (230 beats/min). Animals received no drugs (control group), famotidine (1 mg/kg daily), carvedilol (0.1 mg/kg daily), or carvedilol plus famotidine. Both cardiac catheterization and echocardiography were performed before and 4 weeks after the initiation of pacing. Immunohistochemical studies showed the appearance of mast cells and histamine in the myocardium after 4 weeks of pacing. In the control group, the left ventricular ejection fraction (LVEF) was decreased after 4 weeks compared with before pacing (71 ± 2 vs. 27 ± 2%, p < 0.05) and mean pulmonary capillary wedge pressure (PCWP) was increased (8 ± 1 vs. 19 ± 3 mmHg). Famotidine ameliorated the decrease of LVEF and increase of PCWP, while the combination of carvedilol plus famotidine further improved both parameters compared with the carvedilol groups. These beneficial effects of famotidine were associated with a decrease of the myocardial cAMP level. Histamine H2 receptor blockade preserves cardiac systolic function in dogs with pacing-induced heart failure, even in the presence of β-adrenergic receptor blockade. This finding strengthens the rationale for using histamine H2 blockers in the treatment of heart failure.

Original languageEnglish
Pages (from-to)787-794
Number of pages8
JournalBasic Research in Cardiology
Volume105
Issue number6
DOIs
Publication statusPublished - 2010 Nov

Keywords

  • β-Adrenergic receptor blocker
  • Heart failure
  • Histamine
  • Histamine H receptor blocker

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