僧帽弁弁膜症は犬に高率に発生する心疾患であり, 僧帽弁閉鎖不全症の原因として臨床的に重要な意義を持つ. 本症罹患弁膜に特徴的な病理組織学的変化は粘液腫様変性であるとされているが, 弁膜症病変の本態ならびに形成機序に関しては十分に解明されていない. そこで今回, 僧帽弁閉鎖不全症例を含む犬剖検例81例の僧帽弁を用いて弁膜症病変の形成過程を詳細に検索するとともに, vimentin, α-smooth muscle actin (α-SMA), desmin, transforming growth factor-β (TGF-β) およびplatelet derived growth factor (PDGF) に対する免疫組織化学的染色を施し, 弁膜症病変の形態形成について検討した. その結果, 弁膜症の初期には弁膜のventricularis (心室面) あるいはatrialis (心房面) に限局していた粘液腫様変性が, その後進行性に拡大し, 中期ないし末期にはspongiosa (海綿層) とfibrosa (線維層) を広く巻き込んでいた. また, この段階では粘液腫様変性病巣内に線維増生病変の形成が認められた. 正常弁膜組織内に存在する細胞はすべてvimentinのみ陽性であり, 粘液腫様変性病巣でもその多くがvimentinにのみ陽性所見を示したが, ごくまれにα-SMAあるいはdesminの発現も認められた. 一方, 線維増生病巣ではvimentinに加えてα-SMAおよび/またはdesminを発現する細胞, すなわち筋線維芽細胞が多数出現していた. TGF-βおよびPDGFの発現は粘液腫様変性病巣内の細胞に高頻度に認められた. しかしながら, 線維増生病巣ではTGF-βの発現はもはや認められず, PDGFの発現も間質に限られていた. 以上の所見から, 犬の僧帽弁弁膜症病変は病理組織学的に粘液腫様変性と線維増生とからなることが明らかになった. また, 本病変を形成する細胞は, 粘液腫様変性病巣では線維芽細胞, 線維増生病巣では筋線維芽細胞であり, 線維芽細胞から筋線維芽細胞への形質転換にはTGF-βあるいはPDGFが関与している可能性が示唆された. 弁膜症病変にみられるこのような一連の変化は, 粘液腫様変性に伴う抗張力性低下に抗するための弁膜の構造的リモデリングの1つとして捉えられた.

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To determine the chronic effects of β-blocker on hemodynamics, left ventricular (LV) function and geometry in dogs with chronic heart failure due to mitral regurgitation (MR), metoprolol (MP) was administered to dogs with experimentally produced severe (n =4) and mild (n =3) MR. Oral administration of MP was started at a dose of 1.5mg/kg/day and gradually increased up to a maintenance dose of 4.5mg/kg/day. Clinical status, heart rate, arterial blood pressure, and LV function and geometry were evaluated at baseline and after 10 days, 20 days, 1 month, 3 months, and 6 months of treatment. Serum norepinephrine (NE) and atrial natriuretic peptide (ANP) concentrations were also examined. As a result, clinical status was worsened in severe MR group after 3 months of treatment, but not in mild MR group throughout the study. MP reduced heart rate, systolic and diastolic blood pressures, and LV fractional shortening in both MR groups. MP caused a significant increase in regurgitant volume and a decrease in stroke volume in severe MR group. In contrast, such changes were not observed in mild MR group. Relative LV wall thickness to chamber diameter increased in mild MR group, whereas LV chamber dilatation with wall thinning was seen in severe MR group. Serum NE and ANP concentrations were elevated in severe MR group associated with deterioration of clinical status. These results suggest that monotherapy of MP achieve negative chronotrophic and inotrophic effects without aggravation of cardiac function and clinical status in mild MR, whereas these effects may lead to progressive worsening of mitral regurgitation and clinical status in severe MR.

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Thirty-four adult healthy dogs (16 males and 18 females) weighing 4.6 to 18.9 kg (mean±SD, 11.2±3.4 kg) were studied by both two-dimensional and M-mode echocardiography. All tested subjects were mixed-breed companion dogs with the age ranging from 1.3 to 8 years old. During recording, dogs were kept in lateral recumbency without giving any chemical restraint. Two-dimensional echocardiographic images were obtained from left caudal (apical) parasternal location. The M-mode echocardiography was performed from the right parasternal long-axis view. Prior to presenting these values, each set of data was validated by both normality test and descriptive statistics. Parameters were also statistically evaluated to determine whether a correlation to age, gender, heart rate, body weight, and body surface area existed. In conclusion, the presented reference values are useful especially when the tested dogs are fitted in the above categories. Many values, being not correlated to age, sex, and body size, provide good indicators for evaluation of cardiac function. They are ejection fraction, fractional shortening, fractional thickness, interventricular septal thickness/left ventricular posterior wall thickness ratio, left atrial dimension/aortic root dimension ratio, systolic time intervals, indices in MV study (D-E excursion, E-F slope, E-septal separation, E-septal separation/left ventricular diastolic dimension ratio), and stroke volume index.

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Thirty adult healthy dogs (11 males and 19 females) weighing 4.7 to 17.2 kg (mean 10.9±3.3) were studied by spectral Doppler echocardiography. All tested subjects were mixedbreed companion dogs with the age ranging from 1.3 to 8 years old. During recording, dogs were kept in left lateral recumbency without giving any chemical restraint. Blood flows across mitral, tricupsid, pulmonary, and aortic valves were analyzed to understand ventricular systolic and diastolic functions and pressure determination as well. In addition, cardiac output and ventricular stroke volume were calculated. Each set of data was validated with both normality test and descriptive statistics. Parameters were also evaluated to understand whether they were correlated to age, gender, heart rate, body weight, and/or body surface area. The results revealed that Doppler values were correlated to pressure recordings, systolic time intervals, indices of ventricular diastolic function, cardiac output index, and/or stroke volume index. In conclusion, the presented reference values are useful especially when the tested dogs are fitted in the above categories. And the facts that many values either not correlated to age, sex, or body size, appear to be good general references for evaluation of cardiac function for all dogs.

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右心不全により死亡した9歳の犬の三尖弁に心臓粘液肉腫の発生がみられた。剖検では, 三尖弁中隔尖に付着した卵円形の腫瘤は5.5×3×2.5cmの大きさで, 右心房と右心室を占拠していた。腫瘤の割面は灰白色, 黄色, 赤色などさまざまで, 広範な壊死・出血領域を伴っていた。組織学的には, 酸性粘液多糖類に富んだ無定形ないし細線維状の粘液様基質と, 核内に豊富なクロマチンを有し旺盛な増殖活性を示す多形性の細胞からなっていた。これらの腫瘍細胞は免疫組織化学的に平滑筋分化の傾向を示した。

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