Clinical study on the flow murmurs at the defect area of atrial septal defect by means of intracardiac phonocardiography.

In order to study flow murmurs through atrial septal defects, right heart catheterization was performed on 48 patients of secundum type, four of primum type, and five of probe-patent foramen ovale, with the double-lumen phonocatheter of Lewis, at the tip of which barium titanate was mounted. The flow murmurs at the defect area were classified into three patterns: v murmur, atriosystolic murmur, and mid-diastolic murmur. V murmur was continuous, extending from late systole to diastole, of low to medium pitch, closely related to atrial v wave and augmenting with expiration. It had no significant correlation to the ratio of left-to-right shunt. It was recorded in 32 out of 48 cases of secundum type and one of primum type, but not observed in probe-patent foramen ovale. Atriosystolic murmur was noted in 17 of 48 cases of secundum type and one of primum type. It was connected with atrial a wave. Mid-diastolic murmur was found at the defect area in four subjects of secundum type. It was thought to be an independent entity from v murmur and to be another one due to shunt flow through the septal defect, since it had no relation to v wave but it was localized between v and a waves in the pressure curve of the right atrium. It is different in localization from mid-diastolic murmur due to relative tricuspid stenosis at the inflow tract of right ventricle.     

Apex and subxiphoid approaches to Ebstein's anomaly using cross-sectional echocardiography

Apex and subxiphoid cross-sectional echocardiography was performed with an electronic sector scan on 11 patients having Ebstein's anomaly, isolated or associated with other cardiac diseases. For control study, 10 normal subjects and 10 ASD patients were similarly examined.In the apical four-chamber view, the displacement of the STL was measured in end-diastole using 8 mm. cinematography. It ranged from 1.4 to 3.2 cm., with an average of 2.1 ± 0.5 cm. in eight out of the 11 patients, whereas in control subjects, there was no displacement of the STL.From the apical three-chamber view of the right side of the heart, the downward displacement of the STL into the right ventricular cavity was also clearly visualized, as well as the tricuspid valve ring. Thus, the right-sided heart was seen to be divided into the functional and atrialized right ventricles and the right atrium by the displacement of the STL.In addition, the CT inserting into the ATL was observed in five cases from the three-chamber view and in four instances from the four-chamber view.The interpretable subxiphoid cross-sectional images were obtained in nine of the 11 patients. The right and left sides of the heart were widely visualized and the elongated ATL was fully observed from the tip to the thickened root. Moreover, the CT inserting into the ATL was visualized in six out of the nine patients.     

Cross-sectional echocardiographic study on persistent left superior vena cava

Twelve patients with persistent left superior vena cava (PLSVC) were studied using high speed cross-sectional echocardiography with mechanical sector scanning. The majority of the examined patients had other associated congenital heart diseases.A circular echo with an echo-free space was demonstrated at the posterosuperior region of the posterior mitral leaflet (PML) in the cross-section of the long cardiac axis. It was also recognized as a narrow tubular cavity echo posterior to the left atrium and the left ventricle in the cross-section of the sagittal plane of the chest. This abnormal echo was gradually enlarged during systole and the unusual cavity was largest in early diastole at the E point of the anterior mitral leaflet (AML), and its anterior margin moved back in middiastole. This abnormal echo seems to be correspond to the left atrioventricular sulcus. By the injection of indocyanine green at the left median cubital vein, the positive contrast echo appeared in the cavity which was considered to be PLSVC, whereas it appeareed neither in the left atrium nor in the left ventricle. This abnormal echo was not recognized in normal subjects and other cardiac diseases without PLSVC.In M-mode echocardiography, the unusual linear echo was recorded behind the AML. It moved anteriorly during systole and went back posteriorly in diastole.Consequently, because of the direction of the echo beam, the movement and the location of the unusual echo, it seems to emanate from the lower part of the PLSVC. High speed cross-sectional echocardiography has proved to be useful for noninvasive diagnosis of the PLSVC.     

Correlation between the direction of the interventricular septum estimated with transmission computed tomography and the initial QRS vectors

A correlative study was performed to relate the interventricular septal angle (As^o) evaluated by transmission computed tomography to azimuth of initial QRS vectors in 52 patients. Patients were divided into five groups: RV volume overloading (RVO), RV pressure overloading (RSO), LV volume overloading (LVO), LV pressure overloading (LSO), and normal control with no cardiopulmonary disease. For measurement of As^o, the leftward and forward directions were designated as zero and 90 degrees, respectively. The mean value of As° was significantly smaller in RVO (14.4°) and RSO (41.1°) than in normal controls (50.4°) and in LVO (53.2°). The mean value of the azimuth of the initial 12-msec instantaneous QRS vectors (H₁₂^o) was significantly smaller in RVO (80.5°), RSO (81.7°), and LSO (81.3°) than in normal controls (113.8°) and in LVO (113.7°).A significant linear correlation was shown between As^o and H₁₂^o in a combined group consisting of RVO, LVO, and normal controls (r=0.70, p<0.001), and also in another combined group consisting of RSO, LSO, and normal controls (r=0.52, p<0.01). It was concluded that the orientation of the interventricular septum was one of the major determinants of the direction of initial QRS vectors, especially in patients with ventricular volume overload or without cardiopulmonary disease.     

Effect of the autonomic blockade on the automaticity of the A-V junctional pacemaker in awake dogs.

The effect of the autonomic blockade on the automaticity of the A-V junctional pacemaker was evaluated in 15 awake dogs with experimentally induced A-V junctional rhythm. The duration of asystole after overdrive (D.A.O.) in these dogs was prolonged significantly in accordance with increase in the drive rate, and the mean +/- SD of the D.A.O. reached 4.7 +/- 1.1 seconds (N = 15) after overdrive at 2.5 times the spontaneous heart rate. After administration of atropine (0.4 mg/kg; i.v.) to eight dogs, the mean +/- SD of the D.A.O. at the same rate decreased from 4.5 +/- 0.9 to 3.4 +/- 1.2 seconds. After administration of practolol (0.5 mg/kg; i.v.) to the seven other dogs, the mean +/- SD of the D.A.O. at the same rate increased remarkably from 4.9 +/- 1.3 to 9.4 +/- 3.0 seconds. Intravenous injection of practolol (0.5 mg/kg) had no effect upon the D.A.O. in the five dogs with sinus rhythm. Thus, it is suggested that (1) the sympathetic nerve might play a more important role in regulating the automaticity of the A-V junctional pacemaker than the vagus and (2) it physiologically might take over 5.0 seconds for the A-V junctional pacemaker to initiate an escape beat during longstanding sinus arrest, if a marked dysfunction of the A-V junctional pacemaker occurs due to a decrease in tension of the sympathetic nerve.     

Mechanism of free fatty acid-induced arrhythmias

This study was designed to shed light upon the mechanism of free fatty acid-induced arrhythmias, and to examine the effects of carnitine and its derivatives on such arrhythmias. Forty-two mongrel dogs were anesthetized and divided into six groups of seven animals each. The control group received only isotonic saline, while the lipid 1 ml/kg group and lipid 2 ml/kg group received lipid emulsions of 1 ml/kg and 2 ml/kg, respectively. The carnitine, acetylcarnitine or propionylcarnitine groups were given, respectively, 300 mg/kg of D,L-carnitine, 200 mg/kg of acetylcarnitine, and 100 mg/kg of D,L-propionylcarnitine, 10 min before they received 2 ml/kg infusions of lipid emulsion. The ventricular multiple response threshold (VMRT) of the animals was monitored over the course of time, and after the last measurement of VMRT, myocardial mitochondria were prepared, and their Ca⁺⁺-binding activities were measured. Concentrations of acyl-CoA and free L-carnitine in each mitochondrial sample were also measured. There was no significant difference in VMRT between the control group and the lipid 1 ml/kg group. In the lipid 2 ml/kg group, the VMRT was significantly lower than that of the control group, while it was found that premedication with carnitine or its derivatives significantly protected the VMRT against the effects induced by the infusion of 2 ml/kg of lipid emulsion. The mitochondria of the lipid 2 ml/kg group showed a markedly high accumulation of acyl-CoA, along with a concomitant decrease in Ca⁺⁺-binding activity. The 1 ml/kg infusion caused relatively small increase in acyl-CoA and had little effect on mitochondrial Ca⁺⁺-binding activity. The premedication with carnitine or its derivatives prevented the accumulation of acyl-CoA and preserved mitochondrial Ca⁺⁺-binding activity. These results suggest that free fatty acid-induced arrhythmias are closely related to the disturbance of mitochondrial Ca⁺⁺-binding activity induced by the accumulation of acyl-CoA, and that carnitine, especially propionylcarnitine, is effective in preserving the VMRT and mitochondrial Ca⁺⁺-binding activity despite subsequent 2 ml/kg lipid infusion.     

Renal handling of secretin in dogs: Free and stop flow analyses

Renal handling of secretin was studied in anesthetized dogs. Highly purified porcine secretin was infused into the renal artery and its concentration in plasma and urine was measured by a radioimmunoassay. Free flow experiments demonstrated that secretin appeared in urine above 10 ng/ml of plasma secretin and that its urinary excretion was increased in proportion to the plasma level of the hormone. Clearance of secretin was less than 0.05% of creatinine clearance and nearly constant over the plasma range of 10–170 ng/ml. In stop flow studies secretin appeared in urine in the same manner as inulin when both substances were injected simultaneously. This indicates that the hormone is filtered through glomerular capillary membranes. The maximal fall of secretin concentration during an infusion of the hormone appeared around the distal portion of the nephron where the dip of Na concentration was present. This suggests, although not entirely excludes the possibility of proximal reabsorption of secretin, that the hormone is reabsorbed around the distal portion of the nephron. It may be concluded that secretin, once filtered by the glomerulus, is reabsorbed by the tubular epithelium.     

Mechanism of antiarrhythmic action of beta-blocking agents

We investigated the antiarrhythmic effect of beta-blocking agents. Using 35 anesthetized dogs, the chest was opened and the left anterior descending coronary artery (LAD) was ligated for 30 min and the ventricular multiple response threshold (VMRT) was observed in the time course. The dogs were divided into five groups premedicated intravenously ten min before LAD ligation with either isotonic saline (the control group), D,L-propranolol (0.5 mg/kg), D-propranolol (0.5 mg/kg), D,L-pindolol (0.1 mg/kg), or D,L-acebutolol (2.5 mg/kg). Thirty min after ligation, myocardial mitochondria were prepared from the ischemic and the non-ischemic areas, and then the content of mitochondrial long-chain acyl-CoA and Ca++-binding activity were measured. The value of VMRT 1.59 +/- 0.21 mA before ligation decreased to 0.99 +/- 0.13 mA 30 min after ligation. Content of acyl-CoA in mitochondria from the ischemic area increased significantly compared to those from the non-ischemic area. Mitochondrial Ca++-binding activity in the ischemic area decreased significantly compared to that in the non-ischemic area. Each administration of three beta-blocking agents prevented the decreases in VMRT and Ca++-binding activity and excessive accumulation of acyl-CoA; D-propranolol had no effect. These results suggest that the antiarrhythmic action of beta-blocking agents is based, at least in part, on the protection from decrease in Ca++-binding activity due to mitochondrial dysfunction induced by the excessive accumulation of long-chain acyl-CoA in mitochondria.     

Mechanism of reperfusion arrhythmia prostaglandin as a washout metabolite

This study was designed to clarify the mechanism of reperfusion arrhythmia. In the mongrel dogs, the left anterior descending coronary artery was occluded for 15 min and then the ligation was released. The dogs were divided into two groups: one was the control group, and the other the indomethacin group in which indomethacin, an inhibitor of prostaglandin (PG) biosynthesis, was premedicated at 30 min before ligation. The ventricular multiple response threshold (VMRT), and plasma levels of K⁺, PG E and PG F₂α were measured in the great cardiac vein before and during occlusion, and after reperfusion. In the control group, during occlusion, VMRT decreased and did not return to normal soon after reperfusion. The levels of PG E and PG F₂α in the great cardiac vein did not change significantly during occlusion; however, PG E became significantly elevated after reperfusion. In the indomethacin group, the time course of VMRT was essentially similar to that of the control group during occlusion; however, lowering of VMRT after reperfusion was prevented significantly. The PG F₂α level in the great cardiac vein did not elevate after reperfusion or during occlusion. In both groups, the level of K⁺ in the great cardiac vein was elevated during occlusion, but rapidly decreased to normal after reperfusion.These results suggest that PG E, as a washout metabolite, is a key factor in evoking reperfusion arrhythmia.     

Prognosis in hypertrophic cardiomyopathy

One hundred thirty-six patients with hypertrophic cardiomyopathy were followed up for 1 to 17 years. Twenty-one patients had died, 14 of them suddenly, two from heart failure, two from cerebral embolism, and three from noncardiac causes. Life table analysis revealed that sudden death was significantly associated with young age less than 20 years (relative risk [rr] = 8.63, when compared with those greater than 40 years) and with positive Master's single two-step test (rr = 3.55). Heart failure was more frequent in patients with positive Master's single test (rr = 4.27) and with left ventricular end-diastolic pressure greater than 20 mm Hg (rr = 2.58). Atrial fibrillation, observed in 15 patients, was a poor prognostic sign, resulting in five cardiac deaths and seven heart failures. In contrast, prognosis was favorable in patients with apical hypertrophy with giant negative T wave. Thus Japanese patients with hypertrophic cardiomyopathy showed a prognosis consistent with Western patients, except for excellent outcome of apical hypertrophy.     

Newly developed systolic murmur in patients with a transvenous pacemaker

We encountered four cases in which a transvenous cardiac pacemaker produced a systolic musical murmur in the absence of any complications. This systolic murmur appeared only when the pacing was being cut off and disappeared soon after the pacing had been turned on. Although the exact mechanism of production of the murmur remains uncertain, several possible mechanisms for its occurrence are discussed. It is apparent from this study that a systolic murmur can newly occur without any obvious cause in patients with a transvenous pacemaker.     

Detection of posterior myocardial infarction by body surface mapping: A comparative study with 12 lead ECG and VCG

To examine the diagnostic ability of body surface mapping in posterior myocardial infarction (PMI), mapping was performed in 11 patients with PMI proven by left ventriculography and T1-201 myocardial perfusion imaging (PMI group) and in 44 normal subjects (N group). Map data was analysed by the following methods: (1) potential departure maps at 10, 20, 30, 40 and 50 msec after the onset of QRS; each map indicates the area of decreased potential out of the normal range at the time. (2) AQRS departure map which indicates the area of decreased time-integral value of QRS out of the normal range. True positive (TP) in the PMI group and false positive (FP) in the N group were calculated for each method, and were compared with those of various criteria for PMI with standard 12-lead electrocardiogram (ECG) and Frank lead vectorcardiogram (VCG). The potential departure maps and the AQRS departure map had high TP (10/11 and 8/11) and low FP (0/44 and 0/44). The diagnostic ability of mapping is considered to be higher than that of ECG and VCG. Mapping, especially the departure map technique, is a sensitive and specific method to detect posterior infarction.     

Norepinephrine levels in the coronary sinus in patients with cardiovascular diseases at rest and during isometric handgrip exercise

In order to evaluate cardiac sympathetic nerve activity, plasma norepinephrine levels in the coronary sinus (NE_CS) and in the artery (NE_A) were determined in 24 subjects with cardiovascular diseases and in six with functional murmur. The resting NE_CS was greater than NE_A in 14 subjects with normal left ventricular end-diastolic pressure (LVEDP) (p < 0.01) and/or in 22 with normal cardiac index (p < 0.05), whereas NE_CS was not significantly different from NE_A in the remaining patients with elevated LVEDP and/or with reduced cardiac index. Isometric handgrip exercise increased both NE_CS and NE_A (p < 0.001). When subjects were divided into two groups according to the slope of the ventricular function curve (Δ stroke work index/ΔLVEDP), NE_CS during exercise was greater than NE_A in the group having slopes of 1.0 or more (p < 0.01), but neither values significantly differed in the group with slopes of less than 1.0. In the latter group, cardiac NE overflow rate calculated from the difference between NE_CS and NE_A multiplied by coronary sinus plasma flow, was significantly less than that of the former group before and during handgrip (p < 0.05 and p < 0.01, respectively). These results suggest that cardiac norepinephrine release into the coronary sinus is reduced in patients with impaired cardiac function.     

Electrocardiographic and hemodynamic correlations in patients with idiopathic hypertrophic subaortic stenosis.

The ECG and Frank VCG were compared to the hemodynamic findings in 33 patients with idiopathic hypertrophic subaortic stenosis in whom cardiac catheterization had excluded concomitant valvular heart disease, congenital heart disease, or occlusive coronary artery disease. The patients were divided into two groups according to the absence (Group I) or presence (Group II) of left ventricular hypertrophy on the ECG and/or VCG. The 11 patients in Group I were found to have neither mitral insufficiency nor a resting left intraventricular gradient, and only six patients in whom mitral valve movement was visualized demonstrated systolic anterior movement of the anterior leaflet. The papillary muscles and left ventricular wall were either normal or only mildly hypertrophied in 10 of 11 Group I patients. Group II (22 patients) demonstrated either a resting left intraventricular gradient and/or mitral insufficiency in 18 patients. Twenty-one of the 22 patients showed systolic anterior movement of the anterior leaflet of the mitral valve on a cineangiogram and the papillary muscles and left ventricular wall were moderately to severely hypertrophied in 18 patients. These data suggest that specific hemodynamic and anatomic characteristics of hypertrophic subaortic stenosis may be predicted with reasonable accuracy from the ECG and VCG.     

Theoretical considerations on the electrocardiogram of ventricular hypertrophy.

The electrical effect of ventricular hypertrophy is evaluated with an idealized model. Perfectly symmetrical hypertrophy is expected to enlarge the QRS complex with a certain proportion of the amplitude and duration. If the conduction velocity is unaltered, the QRS area will be increased proportionally to the myocardial mass. 2) Based on the preservation of the ventricular gradient, the secondary T change is expressed as a function of the QRS and G vectors. A theoretically interesting parameter, G/QRS ratio, is defined as a measure of the "ventricular gradient density," which is important for the over-all recovery pattern. This ratio is decreased in ventricular hypertrophy and is closely related to the QRS-T angle. 3) From the viewpoint of the theory, clinical cases with left ventricular hypertrophy are examined. The theory describes the cases with uncompicated hypertension fairly well, although variations from case to case are not small. Underlying assumptions and causes of deviations in actual cases are discussed.