Blockade of histamine H2 receptors protects the heart against ischemia and reperfusion injury in dogs.
We have previously reported that histamine H(2) blockers may be cardioprotective in patients with chronic heart failure. Since both endogenous histamine and histamine H(2) receptors are present in heart tissue, we tested the hypothesis that the blockade of histamine H(2) receptors mediates protection against reversible or irreversible ischemia and reperfusion injury. In open-chest dogs, the left anterior descending coronary artery was occluded for 90 minutes, followed by reperfusion for 6 hours. Administration of famotidine and cimetidine from 10 minutes before occlusion until after 1 hour of reperfusion reduced infarct size (17.0 +/- 4.1% and 17.8 +/- 2.9% vs. 36.9 +/- 5.9% of the solvent group, respectively) Famotidine administration only during the reperfusion period for 1 hour also attenuated infarct size (22.5 +/- 3.5%). There were no differences in either area at risk or collateral flow among the groups. In another set of experiments, we decreased coronary perfusion pressure in dogs so that the coronary blood flow decreased to 50% of the non-ischemic level. In such conditions, we observed the increases in histamine release compared with non-ischemic conditions (0.04 +/- 0.03 to 0.28 +/- 0.13 ng/ml, p < 0.05). Famotidine improved anaerobic myocardial metabolism gauged by both lactate extraction ratio and myocardial oxygen consumption. We conclude that the blockade of histamine H(2) receptors mediates improvements in the anaerobic myocardial metabolism, and thus protects against ischemia and reperfusion injury.
Asanuma
Hiroshi
H
Cardiovascular Division, National Cardiovascular Center, Suita, Suita City, Osaka Prefacture, Tokai University School of Medicine, Isehara, Japan.
Minamino
Tetsuo
T
Ogai
Akiko
A
Kim
Jiyoong
J
Asakura
Masanori
M
Komamura
Kazuo
K
Sanada
Shoji
S
Fujita
Masashi
M
Hirata
Akio
A
Wakeno
Masakatsu
M
Tsukamoto
Osamu
O
Shinozaki
Yoshiro
Y
Myoishi
Masafumi
M
Takashima
Seiji
S
Tomoike
Hitonobu
H
Kitakaze
Masafumi
M
D000818:Animals; D004285:Dogs; D015738:Famotidine / Q000494:pharmacology; D006333:Heart Failure / Q000378:metabolism; D006439:Hemodynamics; D006635:Histamine H2 Antagonists / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D010101:Oxygen Consumption; D010477:Perfusion; D011312:Pressure; D011970:Receptors, Histamine H2 / Q000378:metabolism*; D015427:Reperfusion Injury / Q000473:pathology*; D013997:Time Factors
D006635:Histamine H2 Antagonists; D011970:Receptors, Histamine H2; D015738:Famotidine