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Research on effort and motivation commonly assesses how the sympathetic branch of the autonomic nervous system affects the cardiovascular system. The cardiac pre-ejection period (PEP), assessed via impedance cardiography, is a common outcome, but assessing PEP requires identifying subtle points on cardiac waveforms. The present research examined the psychometric value of the RZ interval (RZ), which has recently been proposed as an indicator of sympathetic activity, for effort research. Also known as the initial systolic time interval (ISTI), RZ is the time (in ms) between the ECG R peak and the dZ/dt Z peak. Unlike PEP, RZ involves salient waveform points that are easily and reliably identified. Data from two experiments evaluated the suitability of RZ for effort paradigms and compared it to a popular automated PEP method. In Studies 1 (n = 89) and 2 (n = 71), participants completed a standard appetitive task in which each correct response earned a small amount of cash. As expected, incentives significantly affected PEP and RZ in both experiments. PEP and RZ were highly correlated (all rs ≥ 0.89), and RZ consistently yielded a larger effect size than PEP. In Study 3, a quantitative synthesis of the experiments indicated that the effect size of RZ's response to incentives (Hedges's g = 0.432 [0.310, 0.554]) was roughly 15% larger than PEP's effect size (g = 0.376 [0.256, 0.496]). RZ thus appears promising for future research on sympathetic aspects of effort-related cardiac activity.

Transcranial Direct Current Stimulation (tDCS) has shown that stimulation of Dorsolateral Prefrontal Cortex (DLPFC) facilitates task performance in working-memory tasks. However, little is known about its potential effects on effort. This study examined whether tDCS affects effort during a working-memory task. Participants received anodal, cathodal and sham stimulation over DLPFC across three sessions before carrying out a 2-back task. During the task, effort-related cardiovascular measures were recorded—especially the Initial Systolic Time Interval (ISTI). Results showed that anodal stimulation produced a shorter ISTI, indicating a greater effort compared to cathodal and sham conditions, where effort was lower. These findings demonstrate that anodal stimulation helps participants to maintain engagement in a highly demanding task (by increasing task mastery), without which they would otherwise disengage. This study is the first to show that tDCS impacts the extent of effort engaged by individuals during a difficult task.

The usefulness of automated measurements of the systolic time intervals in community screening deserves investigation. The systolic time intervals, including pre-ejection period (PEP), the left ventricular ejection time (LVET), and PEP/LVET were automatically and rapidly determined from signals of electrocardiography, phonocardiography, and pulse volume recording in 1087 residents agedor = 40 years in a community of homogeneous Chinese. Receiver operating characteristics analysis was performed to determine the cutoff values for PEP, ET, and PEP/LVET in predicting high N-terminal pro-brain natriuretic peptide (NT-proBNP). The prevalence of high NT-proBNP was 12.3% in men and 8.3% in women. NT-proBNP was linearly related to both PEP and PEP/LVET, while there was a U-shaped relationship between NT-proBNP and LVET. In men, the sensitivity and specificity in predicting high NT-proBNP levels were 60% and 60%, respectively, for PEPor = 89 ms; 60% and 62% for PEP/LVETor = 0.31; and 63% and 60% for LVET272 ms or LVETor = 310 ms. Various combinations of the criteria further improved either sensitivity or specificity. Women had slightly different cutoff values and performance for the various criteria of abnormal systolic time intervals and their combinations. Automated systolic time intervals appear to be useful in the screening of subjects with high NT-proBNP in a community.

Right ventricular systolic time intervals (RVSTI) and noninvasive Doppler-derived pulmonary blood flow were measured before and after surgical ductus ligation in 18 otherwise healthy infants and children who were older than 3 months of age. Right ventricular preejection period (PEP) and the ratio of preejection period and right ventricular ejection time (PEP/RVET), both corrected or uncorrected for heart rate, decreased significantly following surgery (PEP 71 +/- 14 vs. 50 +/- 13, p0.001 and PEP/RVET 0.29 +/- 0.06 vs. 0.21 +/- 0.05, p0.001). The volume of pulmonary blood flow correlated with PEP/RVET (r = 0.48, p = 0.003). The magnitude of the change in pulmonary blood flow correlated with the change in PEP/RVET (r divided by 0.56, p = 0.016). The velocity of circumferential fiber shortening (VCFc) increased after surgery, but not significantly. We speculate that patent ductus arteriosus has a similar effect on right ventricular performance when other congenital heart defects are present.

Heart rate-corrected STI integrate and reflect changes in ventricular inotropy, preload and afterload. STI represent a global method for the evaluation of cardiovascular performance, provided very well controlled study designs, including positive and negative controls and strictly standardised conditions are followed. STI are accurate, economic, reproducable and are very sensitive. They represent a useful non-invasive tool in clinical pharmacology for assessing the influence of drugs, their dose-effect relationships, and the time course of their effects on the cardiovascular system.

As part of a multicentre double-blind comparative study of the effects of metoprolol and nebivolol in patients with hypertension in Czechoslovakia, systolic time intervals (STIs) were used to evaluate the effects of these drugs after 3 months. Examination of STIs was performed in 29 subjects with essential hypertension before and after 1, 2 and 3 months’ treatment with either metoprolol 100mg twice daily or nebivolol 5mg once daily.

β-Adrenoceptor antagonists could paradoxically provide long term benefit to patients with heart failure. They have been shown to improve left ventricular function and symptoms after a 6-month period of treatment with progressively administered doses. Several mechanisms, such as restoration of cardiac β-adrenergic responsiveness, could be involved.

In a double-blind clinical study, electrocardiogram, blood pressure and systolic time intervals were measured in 40 depressive patients treated with either paroxetine (30 mg/day) or amitriptyline (150 mg/day) for 6 weeks. While amitriptyline significantly increased the heart rate, the QTc interval and the PEP/LVET ratio, paroxetine did not alter any of the cardiovascular parameters measured.

The effects of anesthetic induction by diazepam, flunitrazepam and midazolam on cardiac performance were evaluated in 33 ASA class I surgical patients (average age was 36 years). The patients were divided according to the 3 drug groups, and the effects of each drug assessed utilizing measurements of systolic time intervals. An increase in heart rate and decrease in blood pressure was observed following flunitrazepam and midazolam induction. There was no changes in PEPI (pre-ejection period index) and LVETI (left ventricular ejection time index) by benzodiazepines induction. The PEP/LVET ratio was increased by diazepam while the DPTI (diastolic pressure time index)/TTI (tension time index) was reduced by flunitrazepam and midazolam. However, these changes in PEP/LVET and DPTI/TTI were within normal limits. These data indicate that in healthy humans the induction dose of either diazepam, flunitrazepam or midazolam does not extremely influence either PEP/LVET for cardiac performance or DPTI/TTI for cardiac oxygen balance. The results also suggest that the simultaneous use of PEP/LVET and DPTI/TTI is more informative than any single variable for the evaluation of cardiac effects of anesthetics.

The left ventricular systolic function of 32 patients with insulin-dependent diabetes mellitus was investigated by measurement of systolic time intervals. Patients with clinical signs of sclerosis in the coronary arteries were excluded. Twenty-nine sex- and age-matched healthy people served as controls. Resting values of PEP/LVET ratio and of the corrected pre-ejection period were significantly higher in diabetics than in controls. The alterations of systolic time intervals during volume-loading induced by passive leg-raising as well as by isometric handgrip test indicated an increase in left ventricular performance in healthy people. The unchanged systolic time intervals observed in diabetics during the same loadings indicated a decrease in the functional reserve of the diabetic left ventricle. The systolic time intervals observed in patients with type-1 diabetes could be evaluated as a preclinical abnormality of left ventricular performance and as early signs of diabetic cardiomyopathy.

Thirty-six premature infants with respiratory distress syndrome and clinically significant patent ductus arteriosus (PDA) were studied by M-mode echocardiography before and after closure of the ductus. Before closure the ratio of left ventricular preejection period to left ventricular ejection time (LPEP/LVET) was .26±.03 (mean±SD). After closure of the ductus, LPEP/LVET was .38±.04 (mean±SD), significantly different from the value before closure but not significantly different from the value found in 21 control infants; also, a ratio < .30 was always associated with a clinically significant shunt. The combination of systolic time interval measurement with standard M-mode measurement of the left side of the heart enhanced echocardiographic detection of PDA in our series. Serial evaluation of systolic time interval measurements may provide a further index of left-to-right shunt through a PDA and be a valuable adjunct to the clinical management of these patients.

Systolic time intervals (STI) were measured from simultaneous high speed recordings of electrocardiogram, phonocardiogram, and carotid artery trace in 47 children of anemia with or without congestive heart failure (CHF), and in 20 healthy normal children. Group I comprised 20 healthy controls with a mean Hb level of 13.65±0.73 gm percent, group II of 37 anemic children with a mean Hb level of 7.3±1.01 gm percent, without any evidence of CHF: Group III of 10 severely anaemic children with a mean Hb level of 2.75±0.82 gm percent with overt CHF. Electromechanical systole (QS2) pre-ejection period (PEP), left ventricular ejection time (LVET) and the ratio of PEP/LVET were studied and compared in various groups. PEP/LVET ratio was found to be 0.265±0.04, 0.363±0.07 and 0.407±0.06 in groups I, II, III cases respectively. The mean PEP/LVET ratio was significantly prolonged in groups II and III when compared with group I (p

Blood samples and skeletal muscle biopsies (m. quadriceps femoris, vastus lateralis) were taken from 15 patients during digitalization or during withdrawal of digoxin treatment for analysis of serum and skeletal muscle digoxin concentrations. A percutaneous needle biopsy technique was used for muscle sampling and digoxin was analysed by radioimmunoassay. During "slow" digitalization with 0.25 mg digoxin daily the skeletal muscle digoxin concentrations after 2 and 4 days were 45% (range 19%--62%; n = 3) and 78% (range 56%--92%; n= 3) respectively, of the steady state concentration (defined as the digoxin concentration after 25--40 days of treatment). After 9 and 11 days of treatment the skeletal muscle digoxin concentrations were 106% (range 84%--133%; n = 5) and 116% (range 72%--164%; n = 3) respectively, of the steady state concentration. A doubling of the digoxin dose gave a proportional increase in skeletal muscle digoxin concentration (three patients). The magnitude of the estimated half-life of skeletal muscle digoxin was the same as previously reportedly in healthy subjects. No significant correlations were found between changes in systolic time intervals and steady state serum or skeletal muscle digoxin concentrations.

This study was undertaken to determine the cardiac response of Nigerian hypertensives to anaesthesia and surgery, using systolic time intervals as an indication of ventricular function. Nine hypertensive and eight normotensive patients who were admitted for various operations had carotidogram, phonocardiogram and electrocardiogram recorded simultaneously before induction of anaesthesia, after induction and during operation. The pre-ejection phase, (PEP) and the left ventricular ejection time (LVET) were measured from the tracings and the ratio PEP/LVET was calculated. The results showed that for both normotensive patients and hypertensive patients there was a mean increase of the PEP/LVET ratio under anaesthesia and surgery, indicating deterioration of ventricular function. Hypertensive patients showed a much greater deviation from normal, approaching heart failure values. It is concluded that hypertensive patients seemed to be at greater risk during anaesthesia and surgery. The implication is that hypertensive patients should be adequately treated before operation.

An 219 Kindern zwischen 3 und 15 Jahren mit den haufigsten angeborenen und erworbenen Herzfehlern wurde untersucht, in welcher gesetzmasigen Weise die STI von den entsprechenden Normalwerten abweichen. Dabei fand sich, das alle STI bei kindlichen Aniokardiopathien gegenuber den frequenzbezogenen Normalwerten verandert sein konnen, auch bei Rechtsherzvitien. Die groste diagnostische Bedeutung kommt diesen Meswerten selbstverstandlich bei der Beurteilung von Linksherszfehlern zu, bes. Aortenklappenfehlern (verlangerte QS2 und LVET, verkurzte PEP), sowie von Septumdefekten (verkurzte LVET, verlangerte PEP, normale QS2). Hauptursache fur die Abweichungen der STI von den Normalwerten bei kindlichen Angiokardiopathien sind die Druck- und Volumenbelastungen des Herzens. In statistischer Hinsicht lassen sich einzelne Herzfehlergruppen mittels der STI gut voneinander differenzieren. Davon kann vor allem die Unterscheidung zwischen einem Ventrikelseptumdefekt und einer Pulmonalstenose sowie zwischen einer valvularen Aortenstenose und einer Pulmonalstenose klinisch bedeutungsvoll sein.

DurchWeissler u. Mitarb. wurde der Begriff der „systolic time intervals” in die nichtinvasive Herzdiagnostik eingefuhrt; im einzelnen sind dies folgende Meswerte: the total electromechanical systole = QS2, the left ventricular ejection time = LVET, the preejection period = PEP und der Quotient PEP/LVET. Diese Meswerte stellen prinzipiell keine neuen Parameter dar; QS2 ist im deutschen Schrifttum bekannt als Systolendauer, LVET entspricht der Austreibungszeit und PEP der Anpassungszeit. Die Bestimmung der PEP (=QS2-LVET ist der ublichen Berechnung der Anspannungszeit nachBlumberger insofern vorzuziehen, als grosere Strecken gemessen werden mussen und daher der statistische Fehler geringer wird. Bei 96 herzgesunden Kindern zwischen 3 und 15 Jahren wurden polygraphische Kurven registriert und die „systolic time intervals” gemessen; es wurden Normalwerte ermittelt und statistisch ausgewertet. QS2 und LVET korrelieren positiv linear mit dem Alter (hochsignifikant) und negativ linear mit der Herzfrequenz (hochsignifikant). Fur PEP erwies sich nur die negativ lineare Korrelation mit der Herzfrequenz als hochsignifikant, fur PEP/LVET ergab sich keine signifikante Korrelation. Madchen haben eine signifikant langere PEP (+6 msec) und einen hochsignifikant groseren PEP/LVET-Quotienten (+0,04) als Jungen. Die Normalbereiche der STI sind relativ gros (Grenzen fur QS2: 278 und 386 msec, fur LVET: 200 und 285 msec, fur PEP: 65 und 114 msec, fur PEP/LVET: 0,27 und 0,47), so das zur Untersuchung von Einzelfallen besser die mittels der Regressionsgeraden bestimmten Normalwerte zum Vergleich herangezogen werden sollten.

Measurements of systolic time intervals were obtained by simultaneous recordings of ECG and first derivative transthoracic electrical impedance curves, at rest in the supine and upright body positions and during exercise while sitting on a bicycle ergometer. The same schedule was applied to 70 normal males divided into 3 groups: 20 boys 11–14 years, 25 yound adults 20–30 years, and 25 middle-aged men 45–55 years.

Impedance cardiography was used to determine the classical systolic time intervals (STI's) (i.e., pre-ejection period (PEP), left ventricular ejection time (LVET) and the quotient PEP/LVET), in young, healthy, male subjects during supine and seated exercise. With increasing exercise, there was a tendency toward decreases in PEP, LVET, and PEP/LVET. In the seated position, there was an increase in transthoracic Zo incident to the caudal migration of thoracic blood--a result of the postural change. With seated exercise, there were--in contrast to supine exercise-greater decreases in PEP/LVET and greater increases in the Heather index. Similarly, there was a tendency toward increases in dZ/dtmin and the Rapid Ejection Index. We suggest that these differences are related to increased myocardial contractility resulting from the postural augmentation of cardio-sympathetic activity, added to that of exercise per se. This study, as well as previous ones, indicates that impedance cardiography is reliable, effective, and more practicable than the arteriographic method for monitoring STI's. We also believe that certain impedance-derived indices (i.e., transthoracic Zo, dZ/dtmin and the Heather Index) have considerable potential value for physiologic and clinical investigation.

Pre-operative assessment of PEP/LVET ratio was as reliable as invasively measured ejection fraction in separating patients with normal ventricular performance from those with abnormal indices. Our study demonstrates significant impairment of ventricular performance following aorto-coronary bypass procedures. The duration of this dysfunction is between two and five days following operation and is maximal in the first 48 hours. Meaningful interpretation of systolic time interval changes requires measurement of pre-load and after-load. Changes in these variables account for at least some of the increase in PEP/LVET ratio noted in our study. On the basis of a shortened QS2I these patients are thought to exhibit increased adrenergic activity for the entire period of their hospitalization.

Systolic time intervals according the method of Weissler were measured in nine females (mean age: 55.1 years) with mammary carcinoma on the left, prior to, during and 3 months after postoperative radiation therapy. The average load to the anterior cardiac wall amounted to 36 Gy. We found a reversible statistically highly significant decrease of left ventricular function (increase of PEP/LVET) during radiation therapy, which seems to be related to a radiation-induced acute pancarditis known from animal experiments.

Current techniques utilize data derived from the aortic valve (AV) to determine the ratio between the pre-ejection (PEP) and ejection period (EP) of left ventricle (LV) in children. Mitral valve (MV), septum (S) and posterior LV wall (LVW) motion, can also be obtained and may be of value in the measurement of systolic time intervals (STI) by echograms (E). Thus, we studied a group of 40 normal school children by E to establish normal standards for PEP/EP for 4 reference points at MV, AV, S and LVW. PEP was measured from the onset of Q wave of the EKG to: 1-coaptation of MV (MPEP), 2-to the opening point of AV (APEP), 3-to the onset of systolic posterior excursion of S (SPEP) and 4-to the onset of anterior systolic motion of LVW (LVWPEP). EP was measured for: 1-total coaptation time of MV (MEP), 2-seperated interval of AV (AEP), 3-from the onset to the point of maximum systolic posterior excursion of S (SEP) and 4-similar to S for LVW anterior motion (LVWEP). PEP/EP ratios were computed for several cardiac cycles and averaged. Results of mean and standard error of mean were: MPEP/MEP 0.154±0.005, APEP/AEP 0.275±0.012, SPEP/SEP 0.304±0.009 and LVWPEP/LVWEP 0.390±0.011. Our study establishes normal standards for ratios of STI of 4 different reference points of LV in children which do not appear to be interchangable as they reflect different intracardiac events. (Sponsor: Eli Gold)

Systolic time intervals (STI) are recorded in 48 children with chronic renal failure (CRF) for quantitative determination of impaired myocardial performance as a result of uraemic cardiomyopathy under conservative treatment or on haemodialysis (HD). Duration of total systole (DTS), pre-ejection-phase (PEP), ejection time (ET) and systolic quotient (SQ = ET/PEP) are estimated from simultaneous high speed tracings of the EKG, PKG and the external carotid pulse. The measured values are compared to the calculated values related to age and heart rate according to GOLDE. In non-dialysed children (mean SCR 9 mg%) there is a prolongation in PEP of 32% above normal (p < 0.05), indicating a reduced myocardial performance. The SQ is found shortened to 80% of normal (p < 0.05) corresponding to a diminished left ventricular ejection fraction. A correlation is also found between PEP, SQ and serum haemoglobin (r = 0.75/0.76). Following administration of digitalis PEP decreases (p < 0.05) and SQ increases (p < 0.05). On HD PEP and SQ improve significantly (p < 0.05) in the case that they have indicated a negative inotropic myocardial state before HD.

We compared left ventricular systolic time intervals (L STI's) derived from pulsed Doppler(D) and from conventional(C) carotid pulse tracing(CPT) and phonocardiography(PCG) in 24 subjects, aged 1.7 to 18.5 yrs, median=12.1 yr. Using the apical 2-chamber view, D frequency-time curves from the proximal ascending aorta were recorded simultaneously with CPT,PCG and ECG. L STI's from the D tracings were measured as follows: pre-ejection period (PEP)-beginning of QRS to onset of D systolic upstroke; ventricular ejection time(VET)-onset of D systolic upstroke to maximal end-systolic flow reversal. The difference in pulse transmission time between onset and end of systole resulted in a systematically shorter PEP and longer VET by C. C PEP was best predicted by the regression equation C PEP=1.03(D PEP)-14, and C VET by C VET=0.99(D VET)+8. The cumulative distribution of the error of the predicted values and correlation coefficients(r) using these formulae were

Echocardiographic (E) assessment of cardiac function (CF) was carried out preoperatively and at 1, 4, and 24 hours (h) post-operatively (PO) in 20 pediatric patients (pts) with varied congenital heart defects. Simultaneous measurements of cardiac out-put (CO) and clinical and hemodynamic data were obtained. The pts were divided into 3 groups: (I) sustained CO≥2.2L/min/m2 without pressors (P)(N=9); (II) low CO

Diminished pulmonary vascular compliance (PVC) is believed to be a major determinant of the widened splitting of the second heart sound (S2) in atrial septal defect (ASD). However in association with the decreased PVC in ASD, the right ventricular ejection time (RVET) is prolonged. We tested the thesis that RVET shortens in the immediate post-op ASD period and that this shortening is directly associated with narrowed splitting of S2. Right and left pre-ejection periods (RPEP. LPEP) and ejection times (RVET, LVET) were measured pre-op both at cardiac catheterization (cath) and by echocardiographic semilunar valve recordings (echo) in 14 children with ASD. Repeat echo systolic time intervals (STI) were measured on the seventh post-op day. Pre-op and post-op phonocardiograms (phono) were recorded at the second left intercostal space. The maximum expiratory interval between the two high frequency components of S2 were recorded as A2-P2. All pre-op echo STI correlated highly with cath STI (r=0.87). RPEP changed from 0.073±.01 S.D. (seconds) pre-op to 0.065±.01 post-op; LPEP 0.073±.01 pre-op to 0.071±.01 post-op; and LVET 0.26±.01 pre-op to 0.27±.04 post-op. The RVET changed from 0.29±.04 pre-op to 0.24±.02 post-op.* The A2-P2 changed from 0.060±.007 pre-op to 0.014±.005 post-op.* Conclusions: We have demonstrated that RVET shortens in the early post-op period after ASD closure. Because PVC changes demand anatomic alterations, immediate shortening of A2-P2 suggests that RVET may be the major determinant of the width of splitting of S2. *p

1408 PROSTAGLANDINS AND SYSTOLIC TIME INTERVALS (LVSTI) IN THE DIAGNOSIS OF PATENT DUCTUS ARTERIOSUS (PDA)