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1 To characterize the histamine receptors in the muscularis mucosae, the isotonic responsiveness of the isolated muscularis mucosae of the guinea-pig oesophagus to histamine receptor agonists and antagonists was examined in vitro. 2 Histamine (0.1-100 M) produced a concentration-dependent contraction of the muscularis mucosae (EC50 = 1.6 ± 0.2 LM). The contractions were rapid in onset, sustained, reversible by washing and the preparation did not show tachyphylaxis. 3 2-Methylhistamine (2-MH), 2-pyridylethylamine (PEA) and 4-methylhistamine (4-MH) produced similar sustained contractions of the muscularis mucosae. The order of sensitivity was histamine > 2-MH > PEA> 4-MH. Impromidine (10-300 LM) and dimaprit (10-300 gM) caused no response in this tissue. 4 The contractile responses to histamine, 2-MH, and PEA were competitively antagonized by diphenhydramine, and the pA2 values were almost the same (approximately 8.1). Cimetidine (I 00 gM)could not modify the contractile response to these agonists. 5 The contractile response to histamine was slightly inhibited by tetrodotoxin (0.3 JM), atropine (1 LM), indomethacin (0.1-3 jAM) or aspirin (30-300 jM), and the EC50 value was increased about [2][3][4][5][6] times by these drugs. 6 When the preparation was incubated in Tyrode solution containing various calcium concentrations (0, 0.45, 0.9 and 1.8 mM), the concentration-response curve to histamine was shifted to the right and downward; the effect was inversely dependent on the calcium concentration, and in a calcium-free medium the response to histamine was abolished. Verapamil (1-10 M) partially inhibited the contractile response to histamine. 7 The present results indicate that the contraction of the guinea-pig oesophageal muscularis mucosae to histamine is mediated mainly by a direct action on the smooth muscle and partly by indirect actions via the stimulation of either endogenous prostaglandin biosynthesis or intramural cholinergic nerves. The histamine receptors responsible for contractions of this tissue are probably mainly of the H,-subtype with H2-receptors having a negligible role.

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Cardiac amyloidosis is characterized by left-ventricular filling defects at a relatively early stage. To investigate such defects more precisely, we studied atrial sound and left-ventricular inflow velocity patterns in 12 patients with cardiac amyloidosis (mean age 60.9 ± 12.5 years). Twelve age-matched cases with hypertrophic cardiomyopathy (HCM) served as controls. We recorded the amplitude of the atrial sound by low-frequency phonocardiography and measured the height of the A wave of apexcardiogram (ACG-A wave) as well as its ratio to the total amplitude of the ACG. Using pulsed Doppler echocardiography, we measured the rapid filling wave (E) and the atrial filling wave (A) and calculated the ratio of A to E. In the amyloidosis group, the atrial sound was weaker and the ACG-A wave was significantly smaller than in the HCM group (p < 0.001; 12.4 ± 3.9 vs. 22.4 ± 5.6%). As concerns the left-ventricular inflow velocity patterns, both the E wave (41.7 ± 16.0 vs. 56.4 ± 12.1 cm/s; p < 0.02) and the A wave (40.5 ± 13.4 vs. 58.1 ± 13.0 cm/s; p < 0.006) were smaller than in the HCM group. The A/E was 1.0 ± 0.34 in the amyloidosis group and 1.1 ± 0.3 in the HCM group (NS). We conclude that disturbed left-ventricular filling, especially in the atrial filling period, decreases the amplitude of both atrial sound and ACG-A wave in cardiac amyloidosis.

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