Arnold M. Weissler

Systolic Time Intervals in Heart Failure in Man

The duration of the systolic time intervals in nondigitalized patients with heart failure was determined from simultaneous fast speed recordings of the electrocardiogram, phonocardiogram, and carotid arterial pulsation. These were compared with the systolic time intervals corrected for heart rate and sex in 211 normal subjects. The failing left ventricle is characterized by a prolongation in the systolic pre-ejection period and a diminution in the left ventricular ejection time while total electromechanical systole remains relatively unaltered. Both components of the pre-ejection period, the Q-1 interval and the isovolumic contraction time, were prolonged. These alterations in the phases of systole occur in the absence of a measurable change in ventricular depolarization time. The prolongation in the pre-ejection period is well correlated with the reduced stroke volume and cardiac output in heart failure and is independently augmented by high levels of arterial pressure. The abbreviation in left ventricular ejection time is also correlated significantly with the stroke volume and cardiac output. It is postulated that a defect in the mechanical performance of the heart is responsible for the abnormal systolic time intervals in human heart failure.

Bedside Technics for the Evaluation of Ventricular Function in Man

Abstract Characteristic changes in the systolic intervals of the left ventricle have been demonstrated among patients with arteriosclerotic, hypertensive and primary myocardial disease. These consist of a prolongation of the pre-ejection period and an abbreviation in the ejection time, while total electromechanical systole remains unaltered. The changes in the pre-ejection period and the left ventricular ejection time correlate well with the level of cardiac output and stroke volume. The ratio of the pre-ejection period to the left ventricular ejection time (PEP/LVET) lends a convenient expression of these changes in the systolic intervals. The ease with which these measures can be obtained, using a noninvasive technic, suggests their use in the bedside evaluation of cardiac performance in man.

The Relationship of Alterations in Systolic Time Intervals to Ejection Fraction in Patients with Cardiac Disease

The relationships between the systolic time intervals determined from simultaneous recordings of the electrocardiogram, the phonocardiogram, the carotid arterial pulse tracing, and direct measures of left ventricular performance as assessed angiographically by measurement of left ventricular stroke volume (SV), end-diastolic volume (EDV), and ejection fraction (EF) were studied in 68 patients with a wide variety of cardiac diseases. The systolic intervals, the pre-ejection period (PEP), the left ventricular ejection time (LVET), and the ratio PEP/LVET, each correlated significantly with angiographically determined EF and EDV. Closest correlation was observed between PEP/LVET and EF (r = -0.90). The systolic intervals correlated only slightly with the angiographically determined SV. These data lend additional evidence supporting the use of systolic time intervals as a non-invasive measure of left ventricular performance in patients with cardiac disease.

Changes in diastolic time with various pharmacologic agents: implication for myocardial perfusion.

Diastolic time (DT) is calculated as the cycle length (RR) minus electromechanical systole (QS2). The ratio of DT (RR-QS2) to RR interval times 100, or the percent diastole (%D), varies nonlinearly with heart rate (HR), increasing rapidly with decreasing HR. The effect of commonly used cardioactive agents on %D was studied in five groups of normal subjects.In group I (n = 12), propranolol (160 mg daily) increased %D from 55.9 ± 1.7 to 64.7 i 1.3 (p < 0.001) by slowing HR. In group 2 (n = 12), dobutamine (2.5 Ag/kg/min) increased %D from 56.4 i 1.4 to 61.8 1.3 (p < 0.005) by shortening the QS2. In group 3 (n = 10), Cedilanid-D (1.6 mg i.v.) increased %D from 55.5 ± I to 63.2 ± 0.7 (p < 0.001), both by slowing the HR and shortening the QS2. In group 4 (n = 12), isoproterenol (2 Ag/min) increased HR and shortened the QS2 significantly. The net result was a significant reduction of%D from 56.1 ± 1.4 to 53.5 ± 1.1, (p < 0.05). In group 5 (n = 15), a 100-mg bolus of i.v. lidocaine did not have a significant effect on %D. This study indicates that cardiovascular drugs may have significant effects on the relative duration of diastole either by affecting HR or the duration of systole. This may have clinical implications for patients with coronary artery disease and patients with left ventricular hypertrophy, since in both cases coronary flow is mostly diastolic.

Assay of digitalis glycosides in man

Abstract The administration of digitalis glycosides is followed by a consistent and dose-dependent abbreviation of the duration of left ventricular ejection in normal individuals. The changes in left ventricular ejection time determined from the indirect carotid arterial tracing and corrected for heart rate (ejection time index) offer an easily derived measure of the myocardial response to digitalis. In the present studies, this effect of the cardiac glycosides was employed in comparing the temporal course of the action of four digitalis glycosides in man. Deslanoside (1.6 mg.) and ouabain (1.0 mg.) intravenously induced a temporally equivalent onset of action which reached a maximum 20 minutes after administration. Onset of the effect of digoxin (1.6 mg. intravenously) was similarly rapid. The initial response to digoxin was followed by a secondary delayed effect which reached its maximum six hours after drug administration. Digitoxin (1.6 mg. intravenously) evoked a slight initial effect followed by a slowly developing, late response which reached a maximum six hours after its administration. A logarithmic temporal dissipation of the effects of the digitalis glycosides on the ejection time index occurred. From the dissipation curves the physiologic half-lives of the glycosides were calculated: ouabain, 22 hour; digoxin, 33 hour; deslanoside, 36 hour; and digitoxin, 102 to 112 hour. When administered orally, digoxin elicited a response characterized by a late onset, delayed maximum and diminished potency when compared to the intravenously administered agent. The effects of digitoxin on the ejection time index were virtually identical by the intravenous and oral routes. The action of digitalis glycosides on ejection time index was demonstrated in patients with heart failure and in individuals with complete heart block. These effects on ejection time index offer a new, objective and quantitative approach to the measurement of the cardiac response to digitalis in man.

Left Ventricular Systolic Time Intervals as Indices of Postural Circulatory Stress in Man

The effects of graded increments of passive head-up tilt on the duration of the systolic time intervals corrected for heart rate were investigated in 15 normal subjects. Head-up tilt caused a prolongation of the pre-ejection period and a shortening of the left ventricular ejection time, while total electromechanical systole diminished minimally. The lengthening of the pre-ejection period and abbreviation of the left ventricular ejection time increased progressively with stepwise increments of head-up tilt. The application of venous occlusive tourniquets produced changes in the systolic intervals directionally similar to those observed with head-up tilt. In contrast to the normal subjects, three patients with congestive heart failure demonstrated no change in the systolic time intervals during head-up tilt. After diuresis in two of the patients with heart failure, the responses of their systolic time intervals to head-up tilt returned toward normal.

Effect of beta adrenergic blockade on the hemodynamic responses to epinephrine in man

Abstract The effects of beta adrenergic receptor blockade by propranolol on the hemodynamic responses to isoproterenol and epinephrine were investigated in 10 supine normal volunteers. Intravenous propranolol (10 mg.) lowered heart rate, cardiac output and stroke volume, raised mean right atrial pressure and total peripheral resistance without affecting arterial pressure, and blocked almost completely the hemodynamic responses to 2 or 2.5 μg./min. of isoproterenol. An infusion of isoproterenol at 12.5 μg./min. partially overcame the beta blockade. During beta blockade most of the responses to an infusion of epinephrine at 5 μg./min. were reversed, with heart rate, cardiac output and stroke volume decreasing, and arterial and mean right atrial pressures and total peripheral resistance increasing. Before beta blockade the isometric period of left ventricular systole was shortened by isoproterenol and epinephrine. After beta blockade it was unaffected by isoproterenol but lengthened by epinephrine. The changes in control data produced by propranolol are consistent either with the blockade of pre-existing beta adrenergic activity or with a nonspecific direct, possibly depressant, action on the heart. The data demonstrate that beta adrenergic receptor blockade by propranolol may be used to unmask the potent alpha (vasoconstrictive) action of epinephrine in man.

The effect of deslanoside on the duration of the phases of ventricular systole in man

Abstract In the present investigation we studied the effect of deslanoside on the duration of the phases of left ventricular systole as derived indirectly from simultaneous tracings of the electrocardiogram, the heart sounds and the external carotid arterial tracing. The phases of systole measured included the interval between the beginning of electrical activity and the second heart sound (Q-S 2 ), the interval between the first and second heart sound S 1 -S 2 and the interval between beginning ejection and the trough of the incisura of the carotid pulse tracing (LVET). All data were expressed relative to the regression relationships between heart rate and each of the measured intervals. Deslanoside, administered intravenously (1.6 mg.), induced a decrease in the duration of each of the measured phases of left ventricular systole. The abbreviation in Q-S 2 and S 1 -S 2 exceeded that in LVET, lending evidence for a decrease in both the pre-ejection and ejection phases of the cardiac cycle. Studies on the temporal course of this action of deslanoside demonstrated the presence of an effect at 10 minutes, with progression to a maximum at one to two hours, after which the abbreviation in systole remained relatively constant for eight hours. Studies over the ensuing five days revealed a serial dissipation of the drug effect. The mean response in the duration of each of the phases of systole during the first eight hours following administration of deslanoside proved to be dose-dependent. A significant diurnal abbreviation in the duration of the phases of left ventricular systole was observed. This diurnal effect must be considered in all studies involving serial measurements of the duration of the phases of the cardiac cycle. The determination of the duration of the phases of left ventricular systole offers a useful means for assaying digitalis effects on the human ventricle.

Shortening of Electromechanical Systole as a Manifestation of Excessive Adrenergic Stimulation in Acute Myocardial Infarction

The relationship between shortened electromechanical systole (QS2I) and 24-hour urinary catecholamine excretion (E+NE) was studied in 51 patients admitted to the coronary care unit with suspected acute myocardial infarction. Among these patients, 24 had a documented acute myocardial infarction while 27 had chest pain without evidence of recent myocardial infarction. Patients receiving cardioactive drugs or with impaired renal function were excluded. Initial elevation of catecholamine excretion was found in 22 of 24 subjects with myocardial infarction and 14 patients without documented myocardial infarction. A close linear correlation (r = -0.82, P < 0.001) was noted between shortening of the QS2I and catecholamine excretion among all patients irrespective of the presence of documented infarction. Patients with serious arrhythmias had significantly higher levels of catecholamine excretion. In 13 patients with a short QS2I, 2.5 mg of propranolol given intravenously produced a significant lengthening of the QS2I while no change in the QS2I occurred in normal controls. This test provided useful corroborative evidence that the short QS2I was related to excessive adrenergic stimulation. In view of the current availability of effective beta-adrenergic blocking agents, these results may improve the selection of patients for antiarrhythmic therapy with these drugs.

The Onset and Magnitude of the Contractile Response to Commonly Used Digitalis Glycosides in Normal Subjects

Controversy exists over the rapidity of onset of the inotropic effect of various digitalis glycosides. Shortening of the systolic time intervals (STI) provides a quantitative measure of the inotropic effect of digitalis glycosides in human subjects. Total electromechanical systole corrected for heart rate (QS2I) is the most sensitive of the STI since it combines the shortening effect of digitalis glycosides on both the pre-ejection period and ejection time. Normal volunteer subjects were studied serially following i.v. injection of 1.6 mg cedilanid-D (C) (n = 18), 1.0 mg ouabain (O) (n = 12), 1.6 mg digoxin (D) (n = 16), and 1.6 mg digitoxin (DT) (n = 9). The shortening of QS2I was corrected for the molecular weight of the digitalis glycoside. The onset of shortening of the QS2I/ mole proved to be exponential for each digitalis glycoside. This allowed estimation of the maximum shortening of QS2I/mole (A) which would occur assuming zero excretion, from which the time constant (tc) of the curves could be determined. There was no significant difference in A among the digitalis glycosides. The tc, were 5.8 min (O), 7.2 min (C), 23 min (D), and 56 min (DT). These tc were significantly different except for O and C. Thus both C and O have a rapid onset of activity which is significantly shorter than either D or DT. The tc for C in patients with congestive heart failure is the same as normals. This study provides a heretofore unavailable, accurate measure of the differences among commonly used glycosides.