A study on the genesis of the third heart sound (S3) based on the mass-spring model is presented. In such a system the natural frequency of vibration depends on the stiffness constant and the mass according to a physical law. The amplitude versus frequency spectra of S3 of 19 patients were obtained using the FFT algorithm together with mono- and two-dimensional echocardiographic parameters. Each echo parameter was correlated with the relative energy contained in each of the 15 Hz bands in which the normalized average spectrum of S3 of each subject was divided. The relative energy of each band was related to echocardiographic parameters. Significant correlation coefficients were found between the diameter of the left ventricle measured at the end of the rapid filling phase, the thickness of the posterior wall and of the interventricular septum at this moment, and the energy contained in certain frequency bands. The statistical correlations we have revealed are consistent with the model postulated in our hypothesis.

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The prognostic value of low-level exercise testing (EXT) before hospital discharge was assessed in 111 patients with uncomplicated acute myocardial infarction (AMI). Of 111 patients, 94 were followed for 1 year after AMI to find that 22 carried a poor prognosis: reduction in duration of EXT (6 patients), postinfarction angina (2 patients), congestive heart failure (3 patients), coronary bypass graft surgery (7 patients) and reinfarction (4 patients). The prognosis was poor in 3.7% of 54 patients who tolerated exercise for 721 seconds or longer (4.2 METs) and 50% of 40 patients tolerating it no longer than 720sec (p<0.0001). Of 22 patients who turned out to be carriers of a poor prognosis, 12 (54.5%) had an ST segment change during EXT, but 10 of the 12 patients were asymptomatic. Our results suggest that reduction in duration of exercise and asymptomatic ST segment changes during EXT provide important clues to establishing the short-term prognosis of AMI.

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To examine the value of stress and redistribution thallium-201 single photon emission computed tomography (SPECT) for predicting improvement after coronary artery bypass grafting (CABG) and for assessing graft patency, 17 patients underwent SPECT before and after CABG. Preoperatively, 16 patients (94%) showed reversible ischemia with redistribution, and defect score decreased from 16.4±7.6 to 8.3±5.8 (p<0.001) on 2 hour delayed images. Stress electrocardiography was positive in 15 cases (88%). The stress defect score was reduced postoperatively (7.8±6.3) as compared to the preoperative score (16.4±7.6) (p<0.001). Postoperatively, 7 cases (41%) showed reversible ischemia and the defect score decreased from 11.3±6.5 to 6.1±4.7 (p<0.05), while 4 cases (23.5%) showed positive stress electrocardiograms (ECG). Resting left ventricular (LV) ejection fraction (EF) improved in 6 cases (48.3±5.4% preoperatively to 56.8±7.4% postoperatively, p<0.05) and showed a reduction in 11 (58.2±10.5% to 47.5±9.4%, p<0.01). Grafts were occluded in 6 cases, and redistribution was evident on the delayed thallium images in all cases (100%), while stress ECG was positive in only 3 (50%).
Thus, stress and redistribution SPECT is valuable for identifying patients who will improve after surgery and assessing graft patency more accurately than stress ECG. Resting LVEF was less useful for assessing improvement in LV function.

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Multifocal atrial tachycardia (MAT) was observed in 9 patients aged 60-85 (mean 72.1±8.6) years during exacerbation of their chronic lung and/or cardiac disease. Four, in whom the rapid heart rate caused symptoms of pulmonary congestion, were treated with intravenous amiodarone (450-900mg over 2 hours) with restoration of sinus rhythm soon after the termination of the drug infusion. In 1, with recurrence of MAT, the same intravenous dosage was repeated for 2 consecutive days, with final achievement of stable sinus rhythm. Five patients, apart from the conventional management of their underlying disease (digitalis, diuretics, aminophylline) were treated with oral amiodarone (600mg/day). Sinus rhythm was restored in all and remained stable during their hospitalization, under α maintenance dosage of 200-400mg daily. Amiodarone may be the drug of choice for the treatment of MAT, for which up to now no effective therapy has been established.

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A clinical and histologic correlation study was conducted to examine the accessory bypass tracts in 6 cases of Wolff-Parkinson-White syndrome.
(1) Types A, B (Rosenbaum) and C (Ueda) were found in 2 cases each. From the polarity of the delta waves, the site of the bypass tract was assumed to be in the left posterior and left lateral free wall in type A, the right lateral and right posterior paraseptal regions in type B and in the right posterior paraseptal and right anterior paraseptal areas in type C.
(2) In 6 cases 19 bypass tracts were found, consisting of 18 Kent bundles and 1 Mahaim fiber, from a total of 146, 400 serial sections. The site of the bypass tract was the left lateral and left posterior walls in 2 type A cases, and the right lateral and right posterior walls in 2 type B cases, with good correspondence to our assumption. In both type C cases it was biventricular, composed of left posterior paraseptal and right lateral regions with an additional Mahaim fiber in 1 case.
(3) A total of 46 cases of WPW syndrome were collected from the literature and the present paper; they consisted of 16 cases of type A, 20 of type B, 4 of type A+B and 6 of type C. Seventy % of type A cases showed a bypass tract in the left heart, and 64% of type B in the right heart. In 6 cases of type C, the bypass tract was found in various sites and in various combinations, requiring further investigation.

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Three hundred and thirty six Kay-Shiley disc valves were implanted in 323 cases from 1968 to 1975 at the Hacettepe University Hospital, Ankara. Eight patients died during surgery. Of the 328 valve replacements followed postoperatively, 263 were in the mitral (80.2%), 26 in the aortic (8%) and 39 in the tricuspid position (11.9%). Three hundred and fifteen patients were evaluated in the early and late postoperative periods. In the early period 52 patients died (16.5%). The remaining cases were followed up for 1-16 years (3381 patient-years). Twenty eight patients remain alive at the time of this report (10.6%). The longest survivors are 2 of the mitral valve replacement cases. The actuarial survival estimates were 88±2.4% at 1 year, 60.3±3.4% at 5 years, 36.3±3.9% at 10 years for all cases. The incidence of thromboemboli was 4.2% per patient-year in the late period in both the overall and the isolated MVR groups. Valve failure due to thromboses was detected in 8 patients (3%). Six patients were reoperated on in the late period (2.3%).

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The carotid sinus baroreceptor reflex was studied in 15 healthy young men by a variable pressure neck suction chamber. Neck suction produced a reduction in blood pressure and an increase in RR interval, which were augmented by an increase of stimuli. Both responses occurred promptly and were attenuated with time. The reproducibility of the response was examined in 6 subjects. There were no differences in either hypotensive or bradycardiac responses between 2 runs separated by 1 hour, indicating good short-term reproducibility. In a long-term reproducibility study involving 2 runs separated by 2 weeks, hypotensive responses showed similar changes, whereas bradycardiac responses showed a wide variation. Based on this good reproducibility of responses, the effects of diltiazem on baroreflex function were studied in 9 men. Following the administration of diltiazem (20mg, P.O.), the hypotensive responses to neck suction stimuli were significantly augmented compared to preadministration responses. On the other hand, diltiazem did not have a significant influence on heart rate responses. Thus, the present study shows that the neck chamber method is a feasible approach to studying the influence of given interventions on baroreflex function and demonstrates an enhancement of baroreflex-mediated hypotension by diltiazem.

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The effectiveness of using blood temperature change as an indicator to automatically vary heart rate physiologically was evaluated in 3 patients implanted with Model Sensor Kelvin 500 (Cook Pacemaker Corporation, Leechburg, PA, USA) pacemakers. Each patient performed two block-randomized treadmill exercise tests: one while programmed for temperature-based, rate-modulated pacing and the other while programmed without rate modulation. In 1 pacemaker patient and 4 volunteers, heart rates were recorded during exposure to a hot water bath.
Blood temperature measured at 10sec intervals and pacing rate measured at 1min intervals were telemetered to a diagnostic programmer and data collector for storage and transfer to a computer. Observation comments and EGG-derived heart rates were manually recorded.
The temperature-based pacemaker was shown to respond promptly not only to physical exertion but also to emotionally caused stress and submersion in a hot bath. These events cause increased heart rate in the normal heart. Using a suitable algorithm to process the measurement of blood temperature, it was possible to produce appropriate pacing rates in paced patients.

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The effects of sodium intake on blood pressure and platelet function were evaluated in 19 subjects with essential hypertension (10 men and 9 women; mean age 49.7 years). The study was conducted under 3 conditions: (1) normal sodium diet (12g/day of salt was used in cooking), (2) after 5 days of mild sodium restriction diet (6g/day of salt was used in cooking) and (3) after moderate sodium restriction (no salt was used in cooking). Blood pressure was significantly reduced following sodium restriction without any change in heart rate. The ratio of the plasma level of β-thromboglobulin to platelet factor IV, regarded as the most reliable index for platelet activation in vivo, increased significantly after mild sodium restriction; this change was maintained after moderate sodium restriction. Plasma thromboxane B₂, a stable metabolite of thromboxane A₂, increased significantly after sodium restriction; the level of 6-keto-prostaglandin F_1α, a stable metabolite of prostacyclin, was unaffected. These results indicate that dietary sodium restriction induces both a reduction of blood pressure and an activation of platelet function in vivo. Thus, one must consider both antihypertensive effects and effects on platelet function as factors in adjusting the dietary sodium intake in the course of antihypertensive therapy.

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We examined the efficacy of the combination of coronary reperfusion and calcium-activated neutral protease (CANP) inhibitor (E-64c) for the treatment of acute myocardial infarction in dogs. In 34 dogs, the left anterior descending artery (LAD) was occluded and reperfused after 1 hour (Groups A and B). In the remaining 49 dogs, the LAD was ligated (Groups C and D). E-64c (100mg/kg, Groups A and C) or vehicle (Groups B and D) was injected intravenously before and after the coro-nary occlusion or ligation. After 24 hours the hearts were removed.
The proportion of the infarct size in the LAD perfusing area (risk zone) in Group A was 47.3±9.7%, significantly lower than in Group C (54.8±8.2%, p<0.05) or Group D (58.7±10.0%, p<0.01). There was a significant difference between Group B (52.9±8.6%) and Group D as well (p<0.05). The effects of reperfusion (p=0.0016) and E-64c (p=0.0226) per se on infarct size were significant, but the combination of reperfusion and E-64c was not additive. The decrease in CPK activity in the risk zone was significantly lower in the reperfused group (p=0.0001). The mCANP activity was higher in the border zone and lower in the infarct zone. The trend in the μCANP activity was similar to that of mCANP.
Thus, treatment with a CANP inhibitor in the early phase of acute myocardial infarction may be marginally beneficial in combination with reperfusion.

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When a new cardiotonic, OPC-8490 (3, 4-dihydro-6-[4-(4-oxo-4- phenylbutyl)-1-piperazinylcarbonyl]-2(1H)-quinolinone citrate), was administered into the jugular vein of a support dog, at doses of 0.1, 0.3 and 1μmol/kg, decreases in heart rate and arterial blood pressure were dose-dependently induced in intact support dogs. One and a half min after administration, positive inotropic and slight negative chronotropic responses were observed in isolated right atria perfused with arterial blood of support dogs. Administration of OPC-8490 into the sinus node artery of the isolated atrium induced positive inotropic and biphasic chronotropic effects, an initial brief positive (Ph1) followed by a longlasting negative (Ph2) chronotropic effect in a dose-related manner. OPC-8490 at 1000nmol caused a triphasic, Phl followed by Ph2 and slight positive (Ph3) chronotropic effects and an inotropie effect. In the left ventricular muscle preparation driven electrically at 2Hz, 10-3000 nmol of OPC-8490 increased contractile force in a dose related manner. OPC-8490-induced responses were not significantly modified by propranolol or atropine. When isoproterenol (0.04nmol/min) increased the basal sinus rate and contractile force of isolated atria, the Ph1 was suppressed and the Ph3 became clear, although the negative phase (Ph2) was not changed. The positive inotropic effect was not significantly changed. When intramural vagal nerve stimulation decreased sinus rate and contractile force, the positive inotropic and negative (Ph2) chronotropic effects were depressed. Verapamil significantly depressed the positive inotropic but not the chronotropic responses to OPC-8490. The positive inotropic effect of OPC-8490 was depressed by pinacidil but not changed by ouabain, although the chronotropic responses to OPC-8490 were not changed. These results suggest that cardiac responses to OPC-8490 involve several mechanisms including cyclic AMP dependent, Ca channel-dependent, potassium current-inhibitory and/or other mechanisms in the dog heart.

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The distribution of norepinephrine (NE), cyclic AMP (cAMP) and cyclic GMP (cGMP) and the activities of related enzymes in the atrioventricular (A-V) conducting tissue of the bovine heart were examined. The concentration of NE in the atrium was about twice that in the ventricle. In the A-V conducting tissue, the concentration of NE was highest in the atrioventricular node (AVN) and lowest in the false tendon (FT), with intermediate levels in the bundle of His (HIS) and the right and left bundle branches (RLBB). The activity of monoamine oxidase (MAO) in the atrium was about 2.2 times that in the ventricle. In the A-V conducting tissue, the activity of MAO was highest in the HIS and lowest in the FT. The activity of catechol-o-methyltransferase (COMT) in the atrium and ventricle was similar, and that in the HIS was slightly, but not significantly, higher than that in other regions of the A-V conducting tissue. The concentration of cAMP in the ventricle was about twice that in the atrium. In the A-V conducting tissue, the concentration of cAMP was higher in the AVN and FT than in the HIS and RLBB. The distribution of adenylate cyclase (AC) was similar to that of NE. The phosphodiesterase (PDE) activity in the atrium and ventricle was similar. No significant difference was found in the level of PDE activity in different regions of the A-V conducting tissue. The concentration of cGMP was slightly, but not significantly, higher in the A-V conducting tissue than in the atrium or ventricle. In the A-V conducting tissue, the concentration of cGMP was highest in the FT and the concentrations in the HIS, RLBB and AVN were similar. These findings suggest that in the A-V conduction tissue, the regions that have the higher spontaneous pacemaker rates have higher NE content and AC activity, that is sensitivity to NE. Furthermore, the sensitivity for muscarinic cholinergic stimulation is higher in the conducting tissue (especially in the FT) than in the atrium and ventricle.

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It is well known that a short rest period during the regular stimula-tion of isolated cardiac muscle induces a transient increase of subsequent twitch tension, although the mechanism of postextrasystolic potentiation (PESP) is still unclear. This paper is concerned with the contribution of an extrasystole to the PESP using isolated papillary muscle of guinea pigs.
We have found that the length of the coupling interval of the extrastimulation prior to the rest interval affected the degree of PESP in a coupling interval-dependent way at the same rest period, and the PESP of the same coupling ratio increased and decreased as the rest period was prolonged. Theophylline increased the strength of steady-state twitch tensions, whereas the dependency of PESP on a coupling ratio of extrastimulation was removed and the PESP decreased with prolonged rest periods. The evidence suggests that the coupling ratio of extra-stimulation might vary the relative contributions of trans-sarcolemmal Ca influx and Ca release from the sarcoplasmic reticulum.

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Definitive clinical diagnosis of congenital pulmonary arteriovenous fistula is extremely difficult. In order to evaluate the diagnostic value of echocardiography, 2 cases with suspected pulmonary arteriovenous fistula were studied.
In the first case, there was a solitary pulmonary arteriovenous fistula, while in the second multiple minute pulmonary arteriovenous fistulas were illustrated. The solitary lesion was demonstrated by two-dimensional and peripheral vein contrast echocardiography. However, in the second case direct visualization of the lesion was not possible but peripheral vein contrast echocardiography showed abnormal filling of the left atrium with echo contrast material.

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