CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Jiyoong Kim, MD and
Masafumi Kitakaze, MD, PhD, FACC, FAHA*
* Cardiovascular Division of Medicine, National Cardiovascular Center, Suita, Osaka 565-8565, Japan (Email: kitakaze{at}hsp.ncvc.go.jp).
We appreciated the important comments of Dr. Kolck and colleagues regarding our study (1) showing that histamine is involved in pathophysiology in the patients with moderate to severe chronic heart failure (CHF). They investigated patients with systemic mastocytosis who have an increased mast cell infiltration in the heart and, hence, an increased myocardial histamine concentration. In such patients, the prevalence of left ventricular (LV) systolic dysfunction was not increased; however, diastolic LV dysfunction occurred in 70% of the patients, and 30% of the patients suffered from LV hypertrophy. They argued that there is a disparity between their observation and our study showing that histamine-H2 blockers improve the severity of CHF pathophysiology (1,2). However, we do not consider that their observation contradicts ours, but rather it supports our findings.
We showed that histamine is deleterious in the process or progression of CHF via activation of H2-receptors, but did not show that histamine is one of the causes of CHF. This is the same as in the role of catecholamine or angiotensin II in the pathophysiology of CHF. Even if catecholamine or angiotensin II is continuously administered to animal models, infusion of catecholamine or angiotensin II only produces LV hypertrophy, but does not produce severe heart failure (3). In the clinical setting, we have seen that in patients with pheochromocytoma or angiotensin-producing tumor, LV hypertrophy is only observed without overt CHF. These observations are consonant with those of Kolck et al., suggesting that catecholamine, angiotensin II, or histamine does not potentially cause CHF such as virus infection, but decreases the threshold to CHF in patients with ventricular dysfunction.
It is intriguing that histamine exposures over a long time can cause LV diastolic dysfunction with LV hypertrophy, suggesting that histamine is able to cause mild ventricular damages. This mechanism may worsen the pathophysiology of pre-existing CHF caused by essential hypertension, myocardial infarction, or cardiac myocarditis/myopathy. Therefore, we believe that histamine-H2 blocker improves some aspects of the pathophysiology of CHF. We are working in a model of canine pacing-induced CHF or the model of pressure overload-induced CHF in histamine-H2 receptor knock-out mice to investigate the potential and novel role of histamine and histamine receptors in CHF.
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References
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1. Kim J, Ogai A, Nakatani S, et al. Impact of blockade of histamine H2 receptors on chronic heart failure revealed by retrospective and prospective randomized studies J Am Coll Cardiol 2006;48:1378-1384.[Abstract/Free Full Text]2. Francis GS, Tand WHW. Histamine, mast cells, and heart failure. Is there a connection?. J Am Coll Cardiol 2006;48:1385-1386.[Free Full Text] 3. Asakura A, Kitakaze M, Takashima S, et al. Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF: metalloproteinase inhibitors as a potential new therapy for cardiac hypertrophy Nat Med 2004;8:35-40.
Related Article
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Cardiac Mast Cells: Implications for Heart Failure
- Ulrich W. Kolck, Kirsten Alfter, Jürgen Homann, Ivar von Kügelgen, and Gerhard J. Molderings
J. Am. Coll. Cardiol. 2007 49: 1107.
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