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The Effect of Steady-State Increases in Systemic Arterial Pressure on the Duration of Left Ventricular Ejection Time

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The Effect of Steady-State Increases in Systemic Arterial Pressure on the Duration of Left Ventricular Ejection Time The effect of steady-state increases in systemic arterial pressure on the duration of left ventricular ejection time James A. Shaver, … , James J. Leonard, H. W. Paley J Clin Invest. 1968;47(1):217-230. https://doi.org/10.1172/JCI105711. Research Article The effect of steady-state increases in systemic arterial pressure on the duration of left ventricular ejection time was studied in 11 normal male subjects. Methoxamine, a pressor amine of predominantly vasoconstrictor activity but lacking significant inotropic effect, was administered intravenously resulting in an average increase in mean arterial pressure of 27 mm Hg. Heart rate was held constant by high right atrial pacing, and there was no significant change in cardiac output. During methoxamine infusion, when stroke volume, heart rate, and inotropic state were held constant, left ventricular ejection time increased as mean arterial pressure increased. There was a highly significant correlation between the increase in mean systolic blood pressure and the prolongation of left ventricular ejection time (r = 0.870). In one subject, an increase in mean systolic pressure of 75 mm Hg prolonged left ventricular ejection time 55 msec, producing paradoxical splitting of the second heart sound. The prolongation of left ventricular ejection time during infusion was not blocked by the prior intravenous administration of atropine sulfate or propranolol hydrochloride, thus ruling out both vagal inhibition of the left ventricle and reflex withdrawal of sympathetic tone as its cause. In three subjects, left ventricular end diastolic pressure was measured and found to be significantly increased. This finding suggests that the normal left ventricle maintains a constant stroke volume […] Find the latest version: https://jci.me/105711/pdf The Effect of Steady-State Increases in Systemic Arterial Pressure on the Duration of Left Ventricular Ejection Time JAMES A. SHAvER, FRANK W. KROETZ, JAmES J. LEONARD, and H. W. Pmiry From the University of Pittsburgh School of Medicine, Department of Medicine, Pittsburgh, Pennsylvania A B T R A C T The effect of steady-state increases sured and found to be significantly increased. This in systemic arterial pressure on the duration of finding suggests that the normal left ventricle left ventricular ejection time was studied in 11 maintains a constant stroke volume in the pres- normal male subjects. Methoxamine, a pressor ence of an increased pressure load by the Frank amine of predominantly vasoconstrictor activity Starling mechanism. This study concludes that ar- but lacking significant inotropic effect, was ad- terial pressure must be included as a prime deter- ministered intravenously resulting in an average minant of left ventricular ejection time along with increase in mean arterial pressure of 27 mm Hg. stroke volume, heart rate, and inotropic state in Heart rate was held constant by high right atrial intact man. pacing, and there was no significant change in cardiac output. During methoxamine infusion, INTRODUCTION when stroke volume, heart rate, and inotropic state were held constant, left ventricular ejection time The effect of stroke volume, heart rate, and ino- increased as mean arterial pressure increased. tropic state on the duration of left ventricular ejec- There was a highly significant correlation between tion time has been extensively studied in both the increase in mean systolic blood pressure and man and animals and the results by various in- the prolongation of left ventricular ejection time vestigators are consistent (1-6). However, the (r = 0.870). In one subject, an increase in mean effect of increasing systemic arterial pressure has systolic pressure of 75 mm Hg prolonged left ven- been variably reported to increase, decrease, or tricular ejection time 55 msec, producing paradoxi- have no significant effect on left ventricular ejec- cal splitting of the second heart sound. The pro- tion time. In the metabolically supported, isolated longation of left ventricular ejection time during heart preparation of Braunwald, Sarnoff, and infusion was not blocked by the prior intravenous Stainsby (4), substantial changes in mean arterial administration of atropine sulfate or propranolol pressures had little influence on the duration of hydrochloride, thus ruling out both vagal inhibi- left ventricular ejection time in six of seven tion of the left ventricle and reflex withdrawal of hearts. However, Wallace, Mitchell, Skinner, and sympathetic tone as its cause. In three subjects, Sarnoff (5), in a right heart by-pass preparation, left ventricular end diastolic pressure was mea- showed that as mean blood pressure was increased left ventricular ejection time decreased, isometric A partial report of this work appeared in abstract contraction time increased, and the total duration form. 1966. J. Clin. Res. 14: 261. of systole remained unchanged. Weissler, Peeler, Dr. Paley's present adress is the Mt. Zion Hospital, San Francisco, Calif. and Roehl have reported that when compared to Received for publication 23 September 1966 and in re- normal controls, no significant difference was vised form 1 September 1967. found in left ventricular ejection time in a group The Tournal of Clinical Investigation Vnlume 47 1968 217 of 11 patients with severe hypertension (6). tid pulse were made on a multichannel, photographic re- Nevertheless, hypertensive cardiovascular disease cording unit 3 at a paper speed of 100 mm/sec, with time markers indicating 0.02 sec (Fig. 1). All pressure mea- been as a cause of paradoxical splitting has cited stirements were made with P23G Statham pressure trans- of the secondlheart sound (7-9) which presumably ducers.4 The zero level for pressure was taken as 5 cm is due to prolongation of left ventricular ejection below the angle of the sternum with the subject in the time. supine position. Mean systolic pressure was obtained by The purpose of this investigation was to study )lanimetry of the systolic portion of five consecutive brachial artery pressure curves. The standard lead II of the effect of steady-state increases in systemic the electrocardiogram was selected. Heart sounds at the arterial pressure on the duration of left ventricular base were recorded with a contact microphone,5 and care ejection time in the intact human left ventricle. was taken to maintain a constant position on the chest The technique of high right atrial pacing was used wall at a point where clear inscription of both heart to maintain a constant heart rate. By preventing sounds could be made. The indirect carotid pulse was obtained with a standard, funnel-shaped pick-up con- the reflex bradycardia associated with an acute in- nected to a P23D transducer. The pick-up was placed crease in arterial pressure, cardiac output was over the point of maximal pulsation of the carotid artery, maintained; and, therefore, stroke volume was held and left ventricular ejection time was measured as the in- constant. It was possible, then, to study the effect terval from the beginning of the upstroke to the trough of of arterial pressure alone on the duration of left the incisural notch. The QA2 interval was measured from the onset of the Q wave on the electrocardiogram to the ventricular ejection time when heart rate, stroke first major vibration of the second heart sound. Each deter- volume, and inotropic state were held constant. mination of left ventricular ejection time, QA2 interval, and RR interval was determined from the average of 10 METHODS well-inscribed complexes taken in close succession. Heart 12 studies were performed on 8 healthy male volunteers rate was calculated dividing 60 by the average RR in- and 3 male subjects with functional murmurs, whose ages terval. The difference between measured and derived data ranged from 15 to 29 yr. No premedication was adminis- was evaluated by the method of paired means (11). tered and all studies were performed in the supine posi- Care was taken to familiarize all subjects with the ex- tion. A No. 8, bipolar, Zucker 1 catheter was placed at perimental design before the procedure. When all cathe- the superior vena cava-right atrial junction. Right atrial ters were in place the patient rested for 10-15 min, and pressure was monitored through this catheter while heart control measurements were recorded, after which high rate was held constant by pacing. Arterial pressure was right atrial pacing was instituted through the bipolar recorded through a 15 cm polyethylene catheter (PE No. catheter with a battery powered, external pacing unit.8 160, 0.045 inch I.D.) that was introduced percutaneously Pacing was accomplished at the slowest possible rate at into the left brachial artery. In three subjects, left ven- which complete atrial capture occurred. After a mini- tricular pressure was recorded through a radiopaque, mum of 5 min of atrial pacing, repeat observations polyethylene catheter (PE No. 160) placed retrograde were made. Methoxamine [jP-hydroxy-jS (2,5 dimethoxy- through the right femoral or brachial artery. Cardiac phenyl)-isoprophylamine], a pressor amine of predomi- output was determined by the indicator dilution technique. nantly vasoconstrictor activity but lacking significant ino- Indocyanine green dye (1.5 mg) was injected through a tropic effect (12-15), was then administered intrave- 90 cm polyethylene catheter (PE No. 50, 0.023 inch I.D.) nously (0.3-0.7 mg/min), which resulted in an average that had been introduced percutaneously through an ante- increase of 27 mm Hg in mean arterial pressure. When cubital vein into the superior vena cava. Blood was a new steady state was apparently reached, complete ob- sampled from the brachial artery catheter and delivered to servations were again recorded. Pacing was then discon- a cuvette densitometer 2 by means of a constant rate, tinued, whereas blood pressure was maintained, elevated motor driven syringe. Cardiac outputs were performed in with methoxamine, and final measurements were then duplicate and recorded as the average of the two deter- made. In two subjects, after control observations 2 mg minations in all but two observations.
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