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Myocardial ischemia interrupts neurotransmission and causes the depression of norepinephrine release. However, the effects of sympathetic nerve stimulation on neurotransmission and norepinephrine release in post-ischemic myocardium are not well defined. We measured regional myocardial length and norepinephrine (NE) release during sympathetic nerve stimulation in anesthetized dogs. Dogs were divided into 2 groups: Group 1 (n = 14); sympathetic nerve stimulation, Group 2 (n = 9); pre-treatment with alpha-blockade yohimbine hydrochloride (0.2 mg/kg) followed by sympathetic nerve stimulation. The left anterior descending artery was occluded for 15 min. Sympathetic nerve stimulation was performed before coronary occlusion and after reperfusion. In group 1, the decrease in systolic shortening in the ischemic region persisted for more than 60 min. Although sympathetic nerve stimulation caused an increase in systolic shortening, it was lower than the pre-ischemic value. NE release from the post-ischemic myocardium remained decreased for 60 min. The decrease in the post-ischemic myocardial response to sympathetic nerve stimulation was associated with diminished NE release. When the cardiac sympathetic nerve was denervated with an epicardial phenol application, NE release decreased even further. In group 2, NE release did not decrease following reperfusion. These results suggest that sympathetic nerve conduction is not completely impaired in post-ischemic myocardium and that pre-synaptic alpha -2 receptors might play an important role in diminished NE release.

To clarify the relationship between post-ischemic myocardial dysfunction and local cardiac sympathetic nerve function, we measured regional myocardial length and norepinephrine (NE) release during sympathetic nerve stimulation in 32 mongrel dogs. Coronary occlusion was produced by balloon occluder for 15 min and reperfused for 60 min. Dogs were divided into 3 groups as follows; Group 1 (n = 14): Sympathetic nerve stimulation, Group 2 (n = 9): Pre-treatment with yohimbine hydrochloride (0.2 mg/kg) and sympathetic nerve stimulation, Group 3 (n = 9): Exogenous NE administration. Sympathetic nerve stimulation or NE infusion were performed before occlusion and after reperfusion. In group 1, the extent of the increase in systolic shortening during sympathetic nerve stimulation (delta - shortening) lowered at 5 min after reperfusion and augmented progressively. But, delta-shortening at an early reperfusion period did not reduce in group 2 and 3. NE release from the ischemic myocardium decreased in group 1 and did not recover for 60 min. When the cardiac sympathetic nerve was denervated with 90% phenol solution, NE release further decreased in group 1. On the other hand, NE release did not decrease in group 2. These results indicate that the response to sympathetic nerve stimulation decreased in post-ischemic reperfused myocardium and this was due to diminished NE release. It was considered that sympathetic nerve conduction was not completely impaired in post-ischemic myocardium and pre-synaptic alpha-2 receptor mediated negative feedback mechanism would play an important role in these diminished NE release.

18歳以上の精神薄弱者施設に流行したA型肝炎(感染者は精薄者43人と職員15人の計58人)について,流行の実態,IgM型抗HAV抗体の消長,IgA型抗HAV抗体検出の臨床的意義と免疫グロブリンによる予防効果について検討した,精薄者のHAV感染率は69%と高率で,30歳台で高かった.感染経路は接触による連鎖伝播と推定された.A型肝炎の発病初期,肝機能が異常にもかかわらず,IgM型HAV抗体陰性例が21例みられた.A型肝炎の流行に際し,肝機能異常症例は,日をおいてのIgM型HAV抗体再検が必要と思われた.15例が6ヵ月以上の長期にわたり,IgM型HAV抗体陽性を持続した.IgM型HAV抗体陽性例全例に加え,肝炎が流行した寮の関係老33人に,IgA型HAV抗体が検出された.IgA型HAV抗体は,HAV感染規模を推定する上で,有力な手がかりになるものと考えられた.人免疫グロブリン投与は,新たなHAV感染を予防し,潜伏期に投与された場合,症状を軽減するものと思われた.

Cytosolic free calcium concentration ([Ca2+]i) and intracellular pH (pHi) were simultaneously measured with a fluorescence technique using fura-2 and BCECF. Hypochlorous acid (HOC1) increased [Ca2+]i and decreased pHi of single quiescent myocytes isolated from rat ventricles. The HOC1-induced changes in [Ca2+]i and pHi (delta [Ca2+]i and delta pHi) were 129 +/- 18nM and 0.18 +/- 0.02 (mean +/- SD), respectively, with 200 microM HOC1. A positive linear correlation was obtained between delta [Ca2+]i and delta pHi under various extracellular Ca2+, pH, and Na+ conditions. Chelation of extracellular Ca2+ depressed only one-fourth of delta [Ca2+]i, and Ca2+ antagonists (verapamil and nifedipine) did not reduce delta [Ca2+]i, indicating that delta [Ca2+]i originates mainly from intracellular Ca2+ stores. A disulfide-reducing reagent, 1,4-dithiothreitol (DTT), recovered the increased [Ca2+]i and decreased pHi to the control levels. The simultaneous changes in [Ca2+]i and pHi induced by HOC1 and the simultaneous restoration of the normal [Ca2+]i and pHi in cardiac myocytes.

ホルター心電計 (Avionics社製Electrocardiocorder Model 445B) により磁気テープに記録された心電図データをミニコンピュータ (Texas Instruments 980B) に入力し, 独自の波形認識アルゴリズムによって解析を行うホルター心電図の心室期外収縮自動診断システムを開発した。QRS波形の計測パラメータとしてQRS面積, QRS振幅およびQRS面積をQRS振幅で除したQRS time indexを算出し, 患者6名につき各30分間の心電図を用い心室期外収縮判定の有用性を検討した。QRS time indexが最も有用と考えられたが, QRS面積の方が有利な場合があったため, 心室期外収縮の判別, 定量分析にはQRS time indexとQRS面積を症例により使い分けることとした。本システムの精度を評価するため, 心室期外収縮が多発する患者25名, 各2時間の分析を施行したところ, 各症例における心室期外収縮のsensitivity平均99.60%, specificity平均99.95%と満足すべき結果を得た。

原発性肺高血圧症(PPH)における非侵襲的診断法を検討するため, 7例の本症患者(男2,女5,年令14～48才,平均30才)に心エコー図検査を施行,左-右短絡性疾患に続発した肺高血圧症(以下SPHと略す)と比較した. PPH群の肺動脈平均圧は42～90mmHg,平均60mmHg,肺血流量は1.85～3.48l/min/m2,平均2.64l/min/m2であつた.心エコー図所見として右室拡張期径の拡大が全例にみられたに反し,左房,左室径は正常,もしくは小であつた.僧帽弁後退速度は低下し,僧帽弁狭窄症と紛らわしい所見を呈したが,後尖の動きは正常であつた.心室中隔運動の振幅は左室後壁に比し大で, 7例中4例で奇異性運動がみられた.肺高血圧の所見とされる肺動脈弁エコーにおけるe-fslopeの水平化, ‘a’ dipの消失はPPH, SPH両群に共通にみられたが,もう一つの肺高血圧の所見,収縮期弁flutteringは後者で全例にみられたに反し,前者では明らかでない例が多かつた.又,弁エコーは援者で太いのに反し,前看で細く,対照的であつた. 4例のPPH剖検例(年令15～33才,平均25才)では肺動脈弁の肥厚を認めなかつたが, SPHの部検7例(年令1～25才,平均13才)では肺動脈弁の肥厚,膠原線維増殖が認められ,弁エコー厚さが異なる一因として,弁の器質的変化が関連を有すると考えられた.

A method for quantitative detection of tricuspid regurgitation is proposed. In cases without tricuspid insufficiency or intracardiac shunt, 1/slope (ts-fv) of the earpiece dye-dilution curve after injection of dye into the femoreal vein (fv curve) was significantly correlated with that (ts-pa) of the curve after injection into the pulmonary artery (PA curve) within each range of right heart blood volume (rbv) calculated as a product of cardiac output and mean transit time difference between FV curve and PA curve. The relationship among the 3 parameters was expressed as a statistically significant regression equation; log (tsfv) equals 0.9858 log (ts-pa) plus 0.2980 log (RBV) minus 0.6418 (p small than 0.005, sd of predicted ts-fv equals plus or minus 0.591). The assumption was made that tricuspid regurgitation caused prolongation ot ts-fv without any changes in ts-pa or RBV, being based on the concepts of the indicator dispersion and of the path-length distribution. The ratio of tricuspid regurgitation to cardiac output was calculated from (observed ts-fv-predicted ts-fv)/predicted ts-fv, in which predicted ts-fv is the value calculated from ts-pa and RBV using the equation shown above. In 2 patients who manifested clinical tricuspid insufficiency, large amount of tricuspid regurgitant fraction was determined by this method. It is suggested that the present method utilizing double injections--single sampling dye-dilution technique is useful for clinical quantitation of tricuspid regurgitation.

The hemodynamic effects of the site of the artificial cardiac stimulation were studied in 17 open chest dogs. The right atrium and five ventricular sites (the inflow and outflow tracts and apex of the right ventricle, apex and lateral wall of the left ventricle) were stimulated electronically at a given rate, ranging from 130 to 190 per min. When cardiac performance during ventricular pacing was compared with those during right atrial pacing, the former uniformly caused a diminution of cardiac output and systemic blood pressure, without reduction of left ventricular end-diastolic pressure. Ventricular function curves, in which left ventricular stroke work was related to left ventricular end-diastolic pressure, shifted downwards and to the right during ventricular pacing. Stimulation frequency did not alter these variables. It was considered that the left ventricular dysfunction in ventricular pacing resulted from the absence of atrial contribution to ventricular filling, mitral regurgitation present and asynchronous ventricular contraction. No significant difference of cardiac performance was demonstrated by changing the site of ventricular pacing, suggesting that the mode of ventricular depolarization itself was not relevant to a decrease in cardiac performance.

In five anesthetized open chest dogs, contraction patterns of the left ventricle induced by ventricular pacing were analyzed using cineangiocardiography. Left ventriculography was performed with dogs in the right anterior oblique position. The right atrial appendage (RA) and two ventricular sites (RVO: outflow tract of the right ventricle and LVA: apex of the left ventricle) were stimulated electrically at a rate of 150 per min. Contraction patterns and cardiodynamics in response to ventricular pacing were compared with those to RA pacing, which represents a normal sequence and extent of ventricular contraction. RVO pacing resulted in asyneresis of anterior wall and normal contraction of posterior wall, while LVA pacing produced a systolic expansion of the apex associated with enhanced contraction of the posterior wall. Ventricular pacing uniformly caused decreases in left ventricular end-diastolic volume (LVEDV), stroke volume (SV) and ejection fraction (EF), with relatively constant left ventricular end-systolic volume (LVESV). Blood pressure was significantly decreased with ventricular pacing. There were only minor differences of these parameters between RVO and LVA pacing. It was considered that a diminution of SV and EF during ventricular pacing resulted from the asynchronous contraction of the ventricle which was not related to decreased myocardial contractility.

In order to evaluate cardiac sympathetic nerve activity, plasma norepinephrine levels in the coronary sinus (NECS) and in the artery (NEA) were determined in 24 subjects with cardiovascular diseases and in six with functional murmur. The resting NECS was greater than NEA in 14 subjects with normal left ventricular end-diastolic pressure (LVEDP) (p0.001) and/or in 22 with normal cardiac index (p0.04), whereas NECS was not significantly different from NEA in the remaining patients with elevated LVEDP and/or with reduced cardiac index. Isometric handgrip exercise increased both NECS and NEA (p0.001). When subjects were divided into two groups according to the slope of the ventricular function curve (delta stroke work index/delta LVEDP), NECS during exercise was greater then NEA in the group having slopes of 1.0 or more (p0.01), but neither values significantly differed in the group with slopes of less than 1.0. In the latter group, cardiac NE overflow rat calculated from the difference between NECS and NEA multiplied by coronary sinus plasma flow, was significantly less than that of the former group before and during handgrip (p0.05 and p0.01, respectively). These results suggest that cardiac norepinephrine release into the coronary sinus is reduced in patients with impaired cardiac function.

To clarify the effect of blood sampling through the indwelling catheter on indices of platelet function, we measured the levels of plasma β-thromboglobulin (βTG) and platelet factor 4 (PF4). In 12 patients with heart disease, direct sample was obtained by two-syringe technique with a 21-gauge needle inserted into the antecubital vein and catheter sample was also obtained immediately after advancing a 16-gauge Teflon catheter of 50cm length into the superior vena cava. In 4 patients (33%), catheter sample showed extremely high levels (more than 50%) of both βTG and PF4 as compared with those of direct sample. In 7 normal subjects, direct samples were obtained from the right and left antecubital veins immediately before and 45 minutes after catheterization, respectively. Catheter sample was also obtained 45 minutes after catheterization., βTG and PF4 levels of direct sample obtained 45 minutes after catheterization (21±6 and 5±1ng/ml, respectively) were similar to those before catheterization (22±8 and 5±1ng/ml), while their levels of catheter sample (66±36 and 18±10ng/ml) were significantly higher than those of direct samples. In another 4 normal subjects, catheter samples were repetitively withdrawn through a Teflon needle of 6cm length immediately after insertion to the antecubital vein and 10, 15 and 30 minutes thereafter. βTG and PF4 levels increased progressively (βTG: from 19±7 to 106±49, PF4: from 6±1 to 44±28ng/ml). Microscopy of the inner surface of the indwelling catheter disclosed massive platelet aggregates and fibrin strands. This study demonstrated that collection of blood through the catheter of any length caused an artificial elevation of plasma βTG and PF4 levels, which was derived from catheter-induced platelet α-granule release, and that catheter insertion itself had no effect of artificial increase in βTG and PF4 in vivo.

In 13 open chest dogs, the right atrium and various ventricular sites (i. e. the inflow and outflow tracts and apex of the right ventricle, apex and lateral wall of the left ventricle) were stimulated electri-cally at a given rate, ranging from 140 to 210 per min. Coronary circulation and cardiodynamics in response to ventricular pacing were compared with those to right atrial pacing at equivalent heart rate. Stimulation of the ventricle except lateral wall of the left ventricle produced no significant changes in coronary sinus blood flow and myocardial oxygen consumption despite decreased blood pressure and cardiac output. The minor change of coronary sinus blood flow was related to the decrease in coronary vascular resistance. Oxygen content of coronary sinus blood decreased during ventricular pacing, while arterial oxygen saturation remained constant. The response of coronary circulation to ventricular pacing did not differ essentially at faster and slower heart rates. It was considered that when stimuli were applied to the ventricular surface, the relatively constant myocardial oxygen consumption in the presence of lowered cardiac performance was attributed to the asynchrony of fractionate contractions of the ventricular muscle, coronary circulation

By means of cineventriculography, contraction pattern of the ventricular septum was studied during electrical stimulation of the right atrium (RA), outflow tract (RVO) and apex (RVA) of the right ventricle and apex (LVA) and lateral wall (LVL) of the left ventricle. RA pacing produced a monophasic shortening of the septal hemiaxes after initial lengthening for about 40 msec from R wave of ECG. In contrast, ventricular stimulation near the septum (i.e. RVO, RVA and LVA) resulted in a biphasic and decreased contraction of the septal wall, in which an early preejection shortening was followed by a brief lengthening and second shortening. LVL pacing showed a monophasic and increased contraction of the septal wall. The biphasic motion of the septal wall was likely to be related to the abnormal mechanical contraction caused by the abnormal conduction sequence of ventricular depolarization. On the other hand, the lateral wall demonstrated a biphasic and decreased contraction during LVL pacing, and a monophasic and increased contraction during RVO, RVA and LVA pacing. Thus, the biphasic and diminished contraction at the site of electrical stimulation was compensated by the monophasic and forceful contraction of the contralateral wall. It is considered that the ventricular septum plays an important functional role in regulation of cardiac performance.

HANEDA, T., NIWA, T., MIURA, T., MIYAZAWA, K. and TAKISHIMA, T. Echocardiographic and Morphological Features of the Pulmonic Valve in Patients with Primary Pulmonary Hypertension and Those with Secondary Pulmonary Hypertension Resulting from Left-to-Right Shunt. Tohoku J. exp. Med., 1981, 134 (4), 393-400 -In 11 patients with primary pulmonary hypertension (PPH) and 16 with secondary pulmonary hypertension due to left-to-right shunt (SPH), ehocardiographic and morphological features of the pulmonic valve were studied. Mean ages of these patients were 27 and 31 years, respectively. The echo intensity of the pulmonic leaflet was graded as either “strong” or “not strong” by comparison with the adjacent tissue. In the PPH group, the valve echo was “not strong”, while it was “strong” in the majority of the cases of SPH. In autopsy, there were no morphological changes in the pulmonic valves in the former, while these valves were definitely hypertrophic in the latter. The average thicknesses of the valve edges in the two groups of patients were 0.5 and 1.6mm, respectively. The results suggest that the different echo intensities reflect the morphological differences of the pulmonic valve; and this provides a diagnostic value for differentiating the two conditions.

Ten mongrel dogs were used to assess regional myocardial function in response to electrical pacing from the inflow (RVI), outflow tracts (RVO), and apex (RVA) of the right ventricle and apex (LVA) and lateral wall (LVL) of the left ventricle. Straingauge arches were sutured to the epicardial segments of the apical and lateral walls of the left ventricle and their mechanical shortening was measured during right atrial (RA) and during ventricular pacing. The onset of shortening of two segments did not differ significantly in RA and RVI pacing, while the stimulation of RVA and LVA caused the initial contraction of the apical segment, and RVO and LVL pacing caused that of the lateral segment; i. e. RVA and RVO pacing resulted in left ventricular asynchrony of contraction similar to LVA and LVL pacing, respectively. Asynchrony of contraction was not accompanied by a uniform change in peak tension of regional myocardial segments, but pre-ejection tension rose and ejection tension fell at the pacing site. The reduction in mean aortic pressure inversely correlated with the prolongation of the time interval between the onset of shortening of two segments during left ventricular pacing. The decrease in cardiac performance observed during ventricular pacing was related to the severity of asynchrony rather than the direction of the ventricular depolarization or change in regional myocardial tension.

Hemodynamic responses to administration of metaproterenol and deslanoside were studied in 5 and 3 patients with aortic regurgitation, respectively. Metaproterenol produced an increase in forward stroke volume and aortic flow and a reduction in aortic regurgitant flow. In pure aortic regurgitation, these effects were related to a decreased left ventricular work. Deslanoside uniformly increased stroke volume, forward and regurgitant flows. Left ventricular work also increased after deslanoside administration. Calculated regurgitant valve orifice was changeable in association with alteration of inotropy and heart rate following administration of these drugs. The change of regurgitant flow was positively correlated with the change of regurgitant orifice area (r=0.988) and diastolic time (r=0.696). There was no close correlation between the regurgitant flow and systemic vascular resistance or diastolic pressure gradient from the aorta to left ventricle. It was concluded that when the hemodynamics in aortic insufficiency were altered by drug administration, the size of regurgitant orifice area and the duration of diastole were the important determinant of aortic regurgitation.

A case of a syphilitic aneurysm of the ascending aorta compressing the pulmonary artery and producing pulmonic stenosis is presented. The patient was accurately diagnosed by antemortem examination. Surgical correction was unsuccessful. Clinical complexities of this syndrome are discussed and criteria for the clinical diagnosis proposed.

By measuring separately the left and right ventricular outputs using the dye dilution technique, a method for estimating bronchial blood flow was devised. In healthy persons and normal dogs, the average value of the right ventricular output was completely in agreement with the left, and differences between the two outputs in individual cases were not more than 10 per cent of the right output in all but one. It was then demonstrated that in the experimental dogs, the pulmonary collateral circulation can be measured accurately by this method. The method is considered to be preferable and reliable for estimating physiologically bronchial blood flow in man.

Regional difference of the amplitude of respiratory variations (Δp) in pulmonary arterial wedge pressure was investigated at different sites of the lung at various body positions in man and dogs. In 6 patients without pulmonary hypertension and 6 dogs, simultaneously measured Δp of wedge pressures in the right and left lungs was compared in supine, left lateral, right lateral and prone positions. The mean value of Δp of the left lung was always larger than the right one in any body positions. This was statistically significant except for right lateral and left lateral decubitus positions in man. In the other 5 dogs, Δp in the upper lung area and lower lung area in the right lung was compared in supine, head-up and head-down positions, and there was no statistically significant difference between the mean Δp in both wedge pressures in any body positions. No significant differences of the end-expiratory pulmonary arterial wedge pressures were found between the left and right lungs in different body positions in both patients and dogs and between upper and lower lung areas of the right lung in supine, head-up and head-down positions in dogs. The results suggest that the gravitational force does not cause regional difference of Δp of the wedge pressure, and it seems that significant difference of Δp between the left and right lungs is caused by the difference of the respiratory variations in intrathoracic pressure in both lungs.

Selective bronchial artery catheterization was conducted in four healthy subjects and 86 patients with various cardiopulmonary diseases. Satisfactory bronchial arteriograms were obtained in 67 (66 percent) of 101 studied. Three pathologic conditions: inflammation, malignant neoplasm, and diminished pulmonary blood flow resulted in hyperdevelopment of the bronchial arteries. Bronchial arteriograms, although not invariably, showed a typical pattern depending on the disease. Considerable connections between pulmonary and bronchial vascular circulations were proved angiographically in some cases. There was no close correlation between the increase in bronchial blood flow and the hyperdevelopment of bronchial arteries on angiograms.

Aortic regurgitation was measured from the dye dilution curves recorded simultaneously from the left ventricle and femoral artery following continuous injection of dye into the aortic root. In 18 cases with aortic regurgitant murmur, regurgitant fraction ranged from 7.3 to 145.0% of aortic forward flow, and no regurgitant flow was detected in 4 control patients. Comparing the results of continuous injection method with those of rapid injection method performed in succession, there was a considerable difference of the values between both methods. Reproducibility of measurement was excellent in the continuous method (r=0.98), while poor in the rapid method (r=0.38). The defect of the latter method was primarily due to the inadequate timing of dye injection in relation to the phase of the cardiac cycle. Regurgitant fraction was correlated with diastolic valve area (r=0.78), heart rate (r=-0.46), and peripheral vascular resistance (r=-0.45). There was no close correlation between regurgitant fraction and diastolic pressure gradient from aorta to left ventricle or diastolic time. It is concluded that the continuous injection method can be used as a valid means for estimating aortic regurgitant flow in man and for evaluating hemodynamics in aortic valve disease.

The coronary sinus and the aortic root were catheterized in ten patients without heart disease. Cardiogreen dye was injected into the aortic root and the dye-dilution curve was recorded from the coronary sinus. Coronary circulation time calculated as mean transit time of the dye ranged from 4.7 to 11.2 sec with an average of 8.1±2.1 sec. The appearance time and peak concentration time of the dye were 3.8±1.2 sec and 4.7±1.8 sec, respectively. Although coronary circulation time had no significant correlations with age, body surface area, heart rate, aortic blood pressure, arterial oxygen saturation, oxygen content of arterial or coronary sinus blood, myocardial oxygen consumption, coronary vascular resistance, and coronary sinus blood flow, it correlated with coronary arteriovenous oxygen difference. It is suggested that coronary circulation time may be shorter than the circulation time through kidney or liver and longer than that through lung or brain, and that coronary circulation time may be an important index in the evaluation of coronary circulation.

The light from a tungsten lamp was conveyed into a fresh heparinized non-hemolyzed bovine blood by one part of a bundle of fiber optics which contains 800 fiber optics (30 μ in diameter). The reflected light from the blood was guided by the other two parts, through which two electrical outputs (I610 and Ieoo) were obtained by means of photomultipliers with optical filters of maximum transmission at 610 mμ and 800 mμ, respectively. When the oxygen saturation of blood was changed, Iolo was changed, while Ieoo remained constant, and the logarithm of I610/I800 was linearly related to the oxygen saturation. Reflexi-bility (a) of red blood cell was calculated according to the equation derived from an ideal case. α at 610 mμ (aelo) and at 800 mμ (a800) with 100% oxygen satura-tion were 78.5 and 27.3%, when expressed as per cent of the reflexibility of mercury. aelo was 2.9 times as large α800. α800 did not change with the change of oxygen saturation, but aelo increased as oxygen saturation was increased. The relationship between I610 and oxygen saturation was comparable with that between I610/I800 and oxygen saturation. It is suggested that the change of reflected light dependent on oxygen saturation is due to the change in α610.

Plasma catecholamine (CA) levels in the coronary sinus (CS), aorta (Ao) and femoral vein (fv) were simultaneously measured in 22 patients with various heart diseases at rest and during handgrip exercise (IHG). The mean resting levels of plasma norepinephine (NE) in CS, Ao and FV were 359 +/- 49 (SEM) pg/ml, 290 +/- 27 and 234 +/- 24, respectively. The corresponding values of epinephrine (E) were 127 +/- 18 pg/ml, 186+/- 30 and 97 +/- 11, respectively. The E values in Ao were significantly greater than those in CS and in FV (p less than 0.05). IHG exercise induced an obvious elevation of plasma CA levels in every portion of the circulation studied. The mean increments of NE concentration were 81%, 54% and 67% of the resting levels at CS, Ao and FV, respectively, while IHG induced elevation of E were 70% of the resting values at each portion studied. Significant correlations were observed between individual CA concentrations in CS and in Ao, and also between those in Ao and in FV at rest. Under raised sympathoadrenal conditions, however, individual values of NE in CS failed to correlate signficantly to those in Ao and in FV, respectively. The NE output from CS was limited to only 3% and 5% of those in Ao at rest and during IHG, respectively. An actual mean increment of NE on its passing through the coronary circulation was only 2% or less of NE output in ao at both stages. It appears, thus, to be untenable that the cardiac tissue is one of the major source of circulating CA at physiological condition. From these reasons, the direct measurement of NE levels in CS may be mandatory, when plasma CA assay is designed for the purpose of studying the role of the sympathetic nerve activity in the regulation of cardiac function.

MIYAZAWA, K. and YAMAGUCHI, I. Cardiovascular Response to Exercise in the Healthy Male Septuagenarians: With Reference to Plasma Norepinephrine. Tohoku J. exp. Med., 1984, 143(2), 177-183 - Hemodynamics during supine graded exercise were measured in 7 healthy aged and 20 young. The maximal work load in the aged was about one half of that in the young. Cardiac output (CO) increased linearly with increasing work load, but its maximal value was markedly lower in the aged than in the young (11.2±1.1 vs. 19.7±1.0liter/min; M±S.E.) Although CO at each level of submaximal exercise was essentially the same in both groups, the aged had smaller increases in stroke volume (SV) and systemic vascular conductance (SC), corresponding to larger increases in heart rate and mean blood pressure. An increase in SV during exercise was achieved from a greater systolic emptying force rather than Frank-Starling effect. A small increase in SC suggested the decreased arteriolar vasodilation in the working muscles. Thus, in the aged, both the reduced myocardial contraction reserve and increased afterload contributed to a small increase in SV during exercise. Plasma norepinephrine concentration in the aged was higher than in the young at rest (240±37 vs. 159±30pg/ml), and both groups showed similar high levels at exhaustion (715±121 vs. 702±99pg/ml). These demonstrated that the sympathetic activity during exercise remained unchanged and the cardiac response to sympathetic stimulation declined with age.

To investigate the response of locally sympathectomized myocardium to sympathetic stimulation, 90% phenol solution was painted on the left ventricular anterior wall surface in 13 open chest anesthetized dogs. Two pairs of ultrasonic crystals were implanted into the mid-myocardium and the left ansa subclavia was stimulated (LSS) at a frequency of 4 Hz. Heart rate, left ventricular systolic pressure and peak dP/dt increased following LSS before and after phenol application. After phenol application, the increase in peak dP/dt was significantly lower than before phenol application (p < 0.01) despite similar increases in both heart rate and left ventricular systolic pressure. Before phenol application, norepinephrine (NE) overflow was observed following LSS (1.60 ng/ml) but after phenol application NE overflow decreased to 0.45 ng/ml, indicating that phenol interrupted sympathetic nerve conduction. During LSS, in both anterior and posterior walls, %shortening (%dL) increased from 13 ± 1 (mean ± SE) to 22 ± 3% and 12 1 to 20 2%, respectively. After phenol application, LSS caused an increase of %dL in the posterior wall from 10 1 to 17 2%, while in the anterior wall it decreased from 15 2 to 8 3%. At the end of the experiment, when NE was infused to maintain the left ventricular systolic pressure similar to that obtained during LSS, %dL increased from 15 2 to 21 3% in the anterior wall. Pressure-length loop during LSS showed an early systolic expansion in the phenol treated anterior wall which disappeared during NE infusion. These observations indicated that the abnormal pressure-length loop was derived from the delayed contraction in the phenol treated region.

In order to evaluate the cardiac sympathetic nerve tone in cardiomyopathies, plasma norepinephrine concentration in the coronary sinus (NE(CS)) and artery (NE(A)) was measured by THI method in five patients with the hypertrophic type (HCM) and in seven with the congestive type (CCM); six patients with functional murmur served as controls. NE(CS) was 182 +/- 39 ng/liter (SEM) in HCM, 288 +/- 47 in CCM, and 306 +/- 65 in controls. The NE(CS) - NE(A) difference (delta NE) was 9 +/- 22 ng/liter in HCM, -57 +/- 34 in CCM, and 81 +/- 29 in controls. Norepinephrine overflow into the coronary sinus,which was calculated by multiplying coronary sinus plasma flow by delta NE, was 0.54 +/- 0.86 ng/min/100gm, -2.81 +/- 1.47, and 3.73 +/- 1.77, respectively. Norepinephrine overflow and delta NE were significantly lower in CCM than in controls. The results suggest than an excessive sympathetic discharge does not exist in HCM and that cardiac sympathetic activity is reduced in CCM.

To evaluate the effects of propranolol on myocardial metabolism after coronary reperfusion, serial measurements of myocardial creatine kinase (CK) and calcium (Ca) contents and CK and tactic acid (LA) concentrations in coronary sinus blood were carried out in 33 open-chest dogs. The left anterior descending coronary artery was occluded for 60 minutes and was then reopened. Twelve of the dogs were given propranolol before occlusion. Reperfusion for 30 minutes in dogs with and without propranolol pretreatment resulted in reduced myocardial CK in the ischemic region and rapidly elevated plasma CK and LA. However, when compared with the control group, the propranolol-treated group showed smaller changes in myocardial CK and plasma LA. Myocardial Ca in the ischemic region was significantly higher than that in the nonischemic region in the control group, but not in the propranolol-treated group. It was concluded that propranolol was protective against myocardial damage resulting from coronary occlusion followed by reperfusion.

Cardiovascular response to supine exercise was studied in 11 patients with chronic ventricular pacing for complete atrioventricular block whose heart rate was fixed during exercise, and compared with 11 age- and sex-matched normal subjects. Oxygen uptake increased linearly with increasing work rate, and attained maximum values of 15.7 +/- 0.7 and 29.5 +/- 1.1 ml/min.kg, respectively. In both groups, cardiac output increased in association with oxygen uptake, although the maximum value in the patients was less than one half that in the controls (6.8 +/- 0.5 and 15.1 +/- 0.3 l/min). Stroke volume, however, could change in patients, as in the controls under similarly increased afterloads (maximum values were 96 +/- 7 and 93 +/- 3 ml/beat, respectively). During exercise, the systolic arterial pressure elevated to a similar extent in both groups (221 +/- 14 and 235 +/- 12 mmHg, respectively). The increase in stroke volume in the patients was achieved by complete systolic emptying and the Frank-Starling mechanism. It is considered that in patients with ventricular pacing, exercise can produce an increase in stroke volume when myocardial function is not impaired.

Twenty-one patients with various heart diseases undergoing the coronary sinus catheterization had myocardial blood flow studies before and during isometric handgrip exercise. At 30% of the maximal voluntary contraction (MVC), handgrip increased both coronary sinus blood flow by 19.8% and myocardial O2 consumption by 21.0% on the average as compared to those at rest. At 20% of MVC, the increase of the both was slight except for 1 case. The increase in coronary sinus blood flow significantly correlated to the increase of myocardial O2 consumption. Lactate extraction ratio decreased to less than 10% during handgrip in 4 of 19 cases studied despite of normal values at rest. Lactate extraction ratio had significantly positive correlations with coronary sinus blood flow and myocardial O2 consumption during handgrip, while there were not significant ones at rest. It is suggested that isometric handgrip exercise is useful as a stress test for detection of myocardial ischemia in the heart of coronary artery disease.

In order to evaluate the effect of handgrip on left ventricular dynamics, cineventriculography was performed in 16 patients with heart disease and 5 normal subjects at 30% of maximal voluntary contraction. No patient had ventriculographic evidence of asynergy or valve regurgitation. During exercise, left-ventricular end-diastolic volume (LVEDV) insignificantly increased, left ventricular end-systolic volume (LVESV) decreased, and hence stroke volume (SV) and ejection fraction (EF) rose in the normal group, while in the patient group a similar change in LVEDV was associated with increased LVESV, resulting in unchanged SV and decreased EF. It is notable that during exercise LVEDV increased in both groups, despite a shortened diastolic filling period. Mean velocity of fiber shortening (mean VCF) increased in the normal group and remained unchanged in the patient group. The changes in mean VCF during exercise were correlated with the alterations in SV and EF (r=0.46, p less than 0.05 and r=0.90, p less than 0.001), respectively). These data signify that an increased afterload induced by handgrip leads to an enhanced left ventricular myocardial contraction in addition to an increase in preload in the normal group, while the Frank-Starling mechanism is mainly utilized in the patient group.

In an attempt to detect an increased bronchial blood flow in man from the earpiece dye-dilution curve, the reliability of three indexes was investigated by comparing them with the values of bronchial blood flow measured from the left atrial dye-dilution curve following dye injection into the aortic root. The first index is obtained from the Cp method, in which the ratio of the peak concentration of early appearing dye-curve due to bronchial circulation to that of the dye-curve of the first circulation. The second is time index for appearance time of the early dye-curve, and the third is CL/Cr as a representation of elevation of the least dye concentration. Cp method showed a good agreement with the bronchial blood flow irrespective of dye injection sites. The last two indexes were both correlated to the bronchial blood flow at a borderline level of significance. It was noteworthy that there was a sharp separation in the second index without any overlapping between cases with and without increased bronchial blood flow. These suggest usefulness of these indexes for clinical assessment of augmented bronchial circulation.

SUMMARY 1.Measurements of bronchial blood flow were performed by the dye dilution method in 50 patients with various chronic pulmonary diseases including bronchiectasis, pulmonary tuberculosis, silicosis, pulmonary abscess, pulmonary emphysema, and pulmonary neoplasms, and the influences of bronchial circulation on respiration and circulation were studied. 2.In bronchiectasis, the bronchial blood flow showed the greatest increase among these pulmonary diseases and a surprising large value was obtained in one case. 3.In six of eight cases with pulmonary tuberculosis, no increase in bronchial blood flow was observed, but in the other two significantly increased flow was found. In silicosis, the cases with simple silicotic nodules did not show increased flow, while the cases with massive densities proved the significantly increased flow. We were unable to clarify the participation of tuberculous complication to the development of the bronchial collateral vessels. 4.Seven of eight cases with pulmonary emphysema did not indicate any increment in bronchial blood flow, but one with long-standing chronic bronchitis showed slightly increased flow. In pulmonary abscess the increase was insignificant in all four cases. 5.In pulmonary neoplasms, four of five cases with primary bronchogenic carcinoma showed increased bronchial blood flow, while two with metastatic pulmonary tumor did not show this increased flow. However, one case of metastatic lung cancer with an episode of pneumonia showed a large increase in bronchial blood flow. 6.From these results it was deduced that pulmonary infection is a contributing and determining factor in the development of the bronchial vessels. 7.When the bronchial blood flow was increased, irrespective of the cause, oxygen saturation and venous admixture ratio were maintained near the normal value. On the other hand, heart size on teleroentgenogram was enlarged in the cases with greatly increased bronchial blood flow, in the absence of systemic hypertension and without correlation with the elevation in pulmonary artery pressure.

Bronchial blood flow was measured in nine patients with tetralogy of Fallot and in two of these cases after radical operation also. The study was made of simultaneous recording of dye-dilution curves from the left atrium and the ear following dye injection into the aortic root. A method of calculating the bronchial blood flow was devised by combining the dye-dilution method with the Fick principle. The bronchial blood flow was increased in all cases. The mean value was 0.46±0.31 L/min, with a range from 0.14 to 1.27 L/min; this is equivalent to 15.3% of the pulmonary artery flow on the average. This study showed no definite relationships among pulmonary artery blood flow, pulmonary artery pressure, arterial oxygen saturation, severity of disease, and patient's age. The postoperative measurement revealed no significant change in bronchial blood flow though its ratios to the pulmonary artery or aortic blood flows were considerably decreased.