H<sub>2</sub>Receptor Antagonists and Right Ventricular Morphology: The MESA Right Ventricle Study

Leary, Peter J.; Barr, R. Graham; Bluemke, David A.; Bristow, Michael R.; Kronmal, Richard A.; Lima, João A.C.; Ralph, David; Ventetuolo, Corey E.; Kawut, Steven M.

doi:10.1513/annalsats.201407-344oc

Cited by 20 publications

(16 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are interesting data suggesting that H 2 receptor antagonists reduce the propensity for heart failure in humans. Apparently, the first data in this regard were Japanese register data (Kim et al, 2004); this prompted a better controlled but still retrospective study in the United States (Leary et al, 2014(Leary et al, , 2016b. The authors provided first evidence for a beneficial role of H 2 receptor antagonists by delaying the onset of heart failure and alterations of the morphology of the heart; the development of left ventricular dilation, a hallmark of imminent heart failure, was delayed.…”

Section: Discussionmentioning

confidence: 99%

Initial Characterization of Transgenic Mice Overexpressing Human Histamine H₂Receptors

Gergs

Bernhardt

Buchwalow

et al. 2019

J Pharmacol Exp Ther

119

View full text Add to dashboard Cite

In an integrative approach, we studied the role of histamine H 2 receptors in the mouse heart. We noted that histamine, added cumulatively to the organ bath, failed to affect the force of contraction in left atrial preparations and did not change spontaneous heart rate in right atrial preparations from wildtype mice. By contrast, in the same preparations from mice that overexpressed the human H 2 receptor in a cardiac-specific way, histamine exerted concentration-and time-dependent positive inotropic and positive chronotropic effects. Messenger RNA of the human H 2 receptor was only detected in transgenic mice. Likewise, immunohistology and autoradiography only gave signals in transgenic but not in wild-type cardiac preparations. Similarly, a positive inotropic and positive chronotropic effect was observed with histamine in echocardiography of living transgenic mice and isolated perfused hearts (Langendorff preparation). Phosphorylation of phospholamban was increased in atrial and ventricular preparations from transgenic mice, but not in wild-type animals. The effects of histamine were mimicked by dimaprit and amthamine and antagonized by cimetidine. In summary, we generated a new model to study the physiologic and pathophysiologic cardiac role of the human H 2 receptor.

show abstract

Section: Discussionmentioning

confidence: 99%

Initial Characterization of Transgenic Mice Overexpressing Human Histamine H₂Receptors

Gergs

Bernhardt

Buchwalow

et al. 2019

J Pharmacol Exp Ther

119

View full text Add to dashboard Cite

show abstract

“…A validated medication inventory was used to assess medication use (10,15). Participants were asked to bring all medications used during the 2 weeks prior to a MESA examination.…”

Section: Methodsmentioning

confidence: 99%

“…In men and women with HF and reduced ejection fraction (HFrEF), H2RA use is associated with smaller left ventricular (LV) volumes and less severe symptoms; we have previously shown H2RA use is associated with lower right ventricular mass and smaller volumes (9,10). Alongside the observations in animals, these data suggest histamine signaling may be relevant to the pathogenesis of human heart failure.…”

mentioning

confidence: 99%

Histamine H 2 Receptor Antagonists, Left Ventricular Morphology, and Heart Failure Risk

Leary

Tedford

Bluemke

et al. 2016

Journal of the American College of Cardiology

Self Cite

View full text Add to dashboard Cite

Background Myocardial H2 receptor activation may promote cardiac fibrosis and apoptosis in preclinical models and histamine H2 receptor antagonist (H2RA) use may improve symptoms in participants with heart failure (HF); however, relationships between H2RA use, incident HF, and longitudinal change in left ventricular (LV) morphology are not known. Objectives We sought to determine whether H2RA use is associated with incident HF and change in LV morphology over time. Methods This study included 6,378 men and women from MESA (Multi-Ethnic Study of Atherosclerosis), a multicenter prospective observational cohort of participants without cardiovascular disease at baseline. Cox proportional hazards were used to estimate the association between H2RA use and incident HF in adjusted models. In participants with cardiac magnetic resonance imaging (CMR), associations between H2RA use, baseline LV morphology (n = 4,691), and longitudinal change in the LV (n = 2,806) were estimated using linear regression. Results H2RAs were used by 313 participants but not by the other 6,065 individuals. During a median follow-up of 11.2 years, 236 participants developed HF. In adjusted models, baseline H2RA use relative to nonuse was associated with 62% lower risk for incident HF (p = 0.02). H2RA use was associated with preserved stroke volume, LV end-diastolic volume, and mass/volume ratio as measured by CMR over approximately 10 years (all p < 0.05). There were no associations between H2RA use and LV mass or ejection fraction. Conclusions H2RA use was associated with reduced risk for incident HF. Changes in left heart morphology over time suggest less age-related change in H2RA users. These associations suggest histamine signaling may be important in the pathogenesis of HF.

show abstract

“…This is another novel point. Taken together, the 2 studies potently propose histamine as the provoking factor, as well as a worsening factor, for CHF.Acquired from CHF patients, data from our previous study(10) as well as the MESA Right Ventricle study(11) helped inform the present study in whichLeary et al (3) suggest that histamine may play an important role in the prevention of CVD as well as in its treatment. However, there is theoretically a large gap between the prevention and treatment of CHF.…”

mentioning

confidence: 62%

Clinical Evidence of the Role of Histamine in Heart Failure ∗

Kitakaze

2016

Journal of the American College of Cardiology

View full text Add to dashboard Cite

H₂Receptor Antagonists and Right Ventricular Morphology: The MESA Right Ventricle Study

Abstract: H2RA use was associated with lower RV mass and smaller RV end-diastolic volume. Additional study of histamine and H2 receptors in cardiopulmonary diseases affecting the RV may have direct clinical relevance.

Cited by 20 publications

References 35 publications

Initial Characterization of Transgenic Mice Overexpressing Human Histamine H₂Receptors

Initial Characterization of Transgenic Mice Overexpressing Human Histamine H₂Receptors

Histamine H 2 Receptor Antagonists, Left Ventricular Morphology, and Heart Failure Risk

Clinical Evidence of the Role of Histamine in Heart Failure ∗

Contact Info

Product

Resources

About

H2Receptor Antagonists and Right Ventricular Morphology: The MESA Right Ventricle Study

Abstract: H2RA use was associated with lower RV mass and smaller RV end-diastolic volume. Additional study of histamine and H2 receptors in cardiopulmonary diseases affecting the RV may have direct clinical relevance.

Cited by 20 publications

References 35 publications

Initial Characterization of Transgenic Mice Overexpressing Human Histamine H2Receptors

Initial Characterization of Transgenic Mice Overexpressing Human Histamine H2Receptors

Histamine H 2 Receptor Antagonists, Left Ventricular Morphology, and Heart Failure Risk

Clinical Evidence of the Role of Histamine in Heart Failure ∗

Contact Info

Product

Resources

About

H₂Receptor Antagonists and Right Ventricular Morphology: The MESA Right Ventricle Study

Initial Characterization of Transgenic Mice Overexpressing Human Histamine H₂Receptors

Initial Characterization of Transgenic Mice Overexpressing Human Histamine H₂Receptors