Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Heart failure wikipedia , lookup
Electrocardiography wikipedia , lookup
Antihypertensive drug wikipedia , lookup
Hypertrophic cardiomyopathy wikipedia , lookup
Atrial septal defect wikipedia , lookup
Dextro-Transposition of the great arteries wikipedia , lookup
Quantium Medical Cardiac Output wikipedia , lookup
Arrhythmogenic right ventricular dysplasia wikipedia , lookup
Induced Pressure Gradients Across Infundibular Zone of Right Ventricle in Normal Dogs By John R. Tobin, Jr., M.D., Peter E. Blundell, M.D., Ralph G. Goodrich, and H. J. C. Swan, M.B., Ph.D., M.R.C.P. Downloaded from http://circres.ahajournals.org/ by guest on April 30, 2017 • During investigations of the effects of sympathomimetic amines on ventricular function in normal dogs, significant pressure gradients were observed frequently across the right ventricular outflow tract. The magnitude of these pressure gradients was greatest in anesthetized animals infused with isopropylarterenol. Since no detailed description of such functional right ventricular outflow-tract pressure gradients was found in the literature, studies on the occurrence and mechanism of this phenomenon were initiated. These experiments demonstrated that infusions of isopropylarterenol induce pressure gradients, which are largest in late systole, between the sinus of the right ventricle and the pulmonary artery; that the magnitude of these pressure gradients always is increased by the prior administration of either acetyl strophanthidin or calcium chloride, and that the genesis of these pressure gradients apparently depends on early vigorous contraction of the infundibulum of the right ventricle. Methods PREPARATION OF DOGS Mongrel dogs weighing 12 to 18 kg were anesthetized with pentobarbital and restrained in the supine position. One carotid artery and both jugular veins were exposed. Number 6 Lehman catheters were introduced and, under fluoroscopic and manometric control, manipulated into the pulmonary artery, the sinus of the right ventricle, and the aortic arch. Number 5 Lehman catheters From the Mayo Clinic and the Mayo Foundation, Rochester, Minnesota. Supported in part by Grant HE-06249 from the National Institutes of Health, U. S. Public Health Service. Received for publication August 7, 1964. 162 were introduced into the superior vena cava for the injection- of indocyanine green and into a jugular vein for the infusion of drugs. INSTRUMENTATION Statham strain-gauge transducers with equal sensitivities were used to measure simultaneous pressures which were recorded on the same base line. The assembly for calibration of zero reference levels at midthorax and the sensitivities of multiple manometers in situ have been described.1 The catheter-manometer systems used have frequency responses which are uniform to between 15 and 20 cycles/sec. When three pressure pulses were recorded simultaneously and at the same sensitivities from three sites (the sinus and infundibulum of the right ventricle and the pulmonary artery) in open-chest dogs, special catheter-manometer systems were used. These consisted of flanged, 19gauge, thin-walled needles, 1 cm long; nylon tubing with an internal diameter of 0.039 inch and a length of 12 cm; P23DB Statham straingauge transducers; and 40-350 Heiland galvanometers which were electrically damped by 300 ohms resistance. The frequency response of such systems is uniform to 35 cycles/sec with variability of ± 10*. Cardiac output was measured by the indicator dilution technic. Indocyanine green (cardiogreen), 1.0 to 1.5 ml, was injected into the superior vena cava in a concentration of 1.25 mg/ ml. Arterial blood was sampled continuously from the aortic arch by a vacuum suction system and drawn through a densitometer, model XC-100, Waters Corporation, for recording of the dilution curves. After each experiment, the densitometer was calibrated with aliquots of the animal's blood containing known concentrations of indocyanine dye. Values for cardiac output were calculated by standard methods.2 Stroke volume was obtained by dividing the cardiac output by the heart rate. To determine the exact time of pulmonary valve closure, a phonocardiogram was recorded from the right parastemal area at the level of the third interspace by means of a Sanborn impedance CircnUiion Resetrcb, Vol. XVI, ttbrutrj 196) 163 INFUNDIBULAR PRESSURE GRADIENTS IN DOGS Downloaded from http://circres.ahajournals.org/ by guest on April 30, 2017 microphone with a diaphragm, a Sanborn logarithmic amplifier, and a HeMand-C galvanometer with a frequency response from 0 to 225 cycles/sec and a variability of ± 4%. Lead n of the electrocardiogram was recorded and used as an additional timing reference to the cardiac cycle. interval was permitted to elapse and variables were recorded again (control 3). Isopropylarterenol infusions and subsequent experimental procedures were done also in the manner just described. EXPERIMENTAL PROCEDURE Figure 1 iHustrates the method used to measure the systolic ejection period. The mean right ventricular (sinus) pressure (RVsm) and the mean pulmonary arterial pressure (PAsm) during systolic ejection were calculated by conventional planimetry. The mean pressure gradient during systolic ejection (SGm) was obtained by subtraction of the mean pulmonary arterial pressure from the mean right ventricular (sinus) pressure. The mean pressure gradient was divided by the mean right ventricular (sinus) pressure to express the magnitude of the pressure gradient in relationship to the ventricular pressure. When relative stability was attained, control observations (control 1), which included the recording of indicator dilution curves and pressure pulses, were made during a ten-minute period. Then, isopropylarterenol (Isuprel hydrochloride, Winthrop Laboratories) was infused at a constant rate of 2.5 /xg/min by means of a Harvard syringe. After six minutes of infusion, indocyanine green-dye curves and pressure pulses were again recorded. The rate of infusion was increased to 5.0 jitg/min, ar>d after a second six-minute interval of infusion, the same variables were recorded. An exact twelve-minute time interval was permitted to elapse and another set of records (control 2) was obtained. When acetyl strophanthidin or calcium chloride was used, control 2 was followed bv the injection of 0.5 mg of acetyl strophanthidin or 40 mg/kg of calcium chloride. A twelve-minute 40 - 20 - CALCULATIONS Results ISOPROPYLARTERENOL (TABLE 1) The effects of isopropylarterenol infusion on right ventricular outflow-tract pressure gradients in a normal dog are illustrated in figure 2. PULMONARY ARTERY RIGHT VENTRICLE Q Phonocordiogram EC6 "** Base Line FIGURE 1 Systolic ejection period (S.E.P.) is time between onset of ejection (wlien ventricular pressure first exceeds pulmonary arterial pressure) and end of ejection (when vibration consequent to pulmonary valve closure appears on phonocardiogram). CircmUlio* Rtltsrcb, Vol. XVI, February 196) TOBIN, BLUNDELL, GOODRICH, SWAN 164 TABLE 1 Isopropylarterenol-induced Right Ventricular Outflow-tract Pressure Gradients in Nine Normal Dogs Experimental period A. Control Average Standard deviation B. Isopropylarterenol, 2.5 Mg/min Average Standard deviation Downloaded from http://circres.ahajournals.org/ by guest on April 30, 2017 Difference between A and B Mean of differences^ Standard deviation C. Isopropylarterenol, 5.0 jig/min Average Standard deviation Difference between A and C Mean of differences^ Standard deviation Heart rate Stroke volume beat«/min ml Cardiac output Syitolic ejection period literg/min RVsm* PAim* mm Hg mm Hg Preuure gradient mm Hg % of RVim 160 13.5 2.13 0.143 21 19 18 3.5 0.62 0.016 5 5 2 9 178 15.1 2.75 0.136 27 19 8 30 16 3.9 0.83 0.016 8 6 4 14 18t 1.9} 0.62} 6} 0 6t 4.3 5.1 0.596 0.0184 5.9 3.8 3.9 -0.008 192 16.9 3.26 0.132 26 16 10 36 17 4.6 0.99 0.024 5 3 5 14 321 3.5} Lilt -0.012 20.6 3.62 0.863 6} 0.0306 6.1 -3 3.6 8t 3.4 *RVsm is the mean systolic right ventricular (sinus) pressure; PAsm is the mean systolic pulmonary arterial pressure. tP<0.01. tP<0.05. § Discrepancies between the mean of individual differences and the apparent arithmetic mean difference are the result of rounding numbers for average values. Responses of this magnitude were found in one third of the studies. The data which describe the effects of isopropylarterenol infusion in nine normal dogs are listed in table 1. The infusion of isopropylarterenol at 2.5 /xg/min increased right ventricular pressure by an average of 6.0 mm Hg and increased the mean pressure gradient by an average of 6.0 mm Hg. The pulmonary arterial pressure was unaltered. A significant increase of heart rate resulted in an average increase of cardiac output by 0.62 liter/min. The systolic ejection period was unchanged. When the infusion rate of isopropylarterenol was increased to 5.0 /xg/min, the average increase of the outflowtract pressure gradient during systolic ejection was 8.0 mm Hg. ACETYL STROPHANTHIDIN AND ISOPROPYLARTERENOL (TABLE 2) The effects of isopropylarterenol infusion on right ventricular outflow-tract pressure gradients in a normal dog 12 minutes after the infusion of 0.5 mg of acetyl strophanthidin are illustrated in figure 3. The data which describe the effects of isopropylarterenol infusion in four normal dogs, after the infusion of 0.5 mg of acetyl strophanthidin, are listed in table 2. The infusion of isopropylarterenol at a rate of 2.5 /xg/min increased right ventricular pressure by an average of 21 mm Hg and increased the mean pressure gradient by an average of 19 mm Hg. There was a small and inconsistent increase of pulmonary arterial pressure (average 3.0 mm Hg). A consistent increase of heart rate (average 36 per minute) was primarily responsible for the average increase in cardiac output of 0.65 liter/min and for a shortened systolic ejection period. When the infusion rate of isopropylarterenol was increased to 5.0 /ig/min, the average increase Circulation Resttrcb, Vol. XVI, Ftbrmtry 196) 165 INFUNDIBULAR PRESSURE GRADIENTS IN DOGS illustrated in figure 4. The data which describe the effects of isopropylarterenol infusion in three normal dogs after the infusion of 40 mg/kg of calcium chloride are listed in table 3. The infusion of isopropylarterenol at a rate of 2.5 /u,g/min increased right ventricular pressure by an average of 20 mm Hg and increased the mean pressure gradient by an average of of the outflow-tract pressure gradient during systolic ejection was 26 mm Hg. CALCIUM CHLORIDE AND ISOPROPYLARTERENOL (TABLE 3) The effects of isopropylarterenol infusion on right ventricular outflow-tract pressure gradients in a normal dog 12 minutes after the infusion of 40 mg/kg of calcium chloride are Control (mm Hg) 60 i— Isopropylarterenol (fig /minute) 2.5 5.0 Control 40 Downloaded from http://circres.ahajournals.org/ by guest on April 30, 2017 20 PULMONARY ARTERY RIGHT VENTRICLE -f-f- Phonocardiogram Base Line RV(m) = 24 SG(m) - 4 27 13 FIGURE 2 Isopropylarterenol-induced right ventricular outflow-tract pressure gradients in normal dog weighing 12.5 kg. Two control gradients also shown. Control (mm Hg) Isopropylarterenol 2.5 (fig/min) Control 5.0 60 40 RIGHT VENTRICLE 20 PULMONARY ARTERY 0 C Phonocardiogram -J ECG Base Line RV(m) = 26 SG (m) • 12 46 27 45 33 4IB 6 FIGURE 3 Effects of acetyl strophanthidin on isopropylarterenol-induced right ventricular outflow-tract pressure gradients in normal dog weighing 12.5 kg. Infusion of isopropylarterenol administered 12 minutes after infusion of acetyl strophanthidin, 0.5 mg. Circulation Rtsurch, Vol. XVI, Ftknury 196} ownloaded from http://circres.ahajournals.org/ by guest on April 30, 2017 TABLE 2 132 to 156 Range 24 to 38 36 162 to 192 0.74 - 0 . 0 9 to 1.20 — 3.9 to 4.3 30 to 51 2.88 to 3.58 1.0 15.5 to 21.3 40 168 to 186 3.34 0.35 to 1.30 - 1 . 9 to 4.3 18.6 0.65 2.45 to3.70 3.15 1.90 to 3.30 2.50 Cardiac output liters/ min 0.4 13.2 to 20.2 17.9 13.9 to 21.1 17.6 ml Stroke volume -0.045 t o - 0 . 0 0 7 — 0.027 0.137 to 158 0.150 -0.049 to—0.003 -0.027 0.144 to 0.155 0.149 0.158 to 0.200 0.176 sec Systolic ejection period RVsm* 14 to 40 24 38 to 58 46 15 to 27 21 39 to 46 43 18 to 26 22 mm Hg PAsm* - 7 to 3 —1 12 to 17 15 — 1 to 5 3 17 to 22 19 14 to 19 16 mm Hg 21 to 37 26 25 to 41 31 12 to 24 19 17 to 28 24 1 to 12 6 60 to 73 68 44 to 62 56 5 to 46 25 % of RVsm Pressure gradient mm Hg *RVsm is the mean systolic right ventricular (sinus) pressure; PAsm is the mean systolic pulmonary arterial pressure. t Discrepancies between the mean of individual differences and the apparent arithmetic mean differences are the result of rounding numbers for average values. Range Difference between A and C Mean of differencest Range C. Isopropylarterenol, 5.0 jiig/min 181 Average Range Difference between A and B Mean of differencest Range 13. Isopropylarterenol, 2.5 Mg/min Average 177 141 Heart rate A. Control Average Experimental period Effects of Acetyl Strophanthidin on Isopropylarterenol-induced Right Ventricular Outfiow-tract Pressure Gradients in Four Normal Dogs > I/I SO n o o o o z o C o ov Downloaded from http://circres.ahajournals.org/ by guest on April 30, 2017 n TABLE 3 132 to 156 142 Heart rate - 1 8 to 66 28 138 to 204 170 12 to 54 30 156 to 192 3.0 to 11.7 6.0 19.9 to 24.0 22.1 4.8 to 7.1 5.7 19.4 to 23.7 21.7 12.3 to 18.9 16.0 Stroke volume ml 0.13 to 3.20 1.51 3.08 to 4.90 3.81 1.03 to 2.03 1.42 3.43 to 3.98 3.71 1.70 to 2.95 2.29 Cardiac output liters/min -0.046 to 0.18 -0.029 0.137 to 0.170 0.153 -0.033 to-0.011 -0.022 0.150 to 0.177 0.159 0.174 to 0.188 5 to 31 19 29 to 43 38 14 to 28 20 38 to 40 39 12 to 24 19 — 6 to 5 1 11 to 17 15 60 to 63 18 to 27 11 to 26 19 62 23 13 to 23 1 to 5 47 to 60 18 to 24 16 53 8 to 29 1 to 7 21 21 4 Pressure gradient % RVsm mm Hg 4 16 to 20 18 11 to 17 14 sec 0.182 PAsm* mm Hg RVsm* mm Hg Systolic ejection period •RVsm is the mean systolic right ventricular (sinus) pressure; PAsm is the mean systolic pulmonary arterial pressure. t Discrepancies between the mean of individual differences and the apparent arithmetic difference are the result of rounding numbers for average values. Range Difference between A and C Mean of differencest Range C. Isopropylarterenol, 5.0 Average Range Difference between A and B Mean of differences Range B. Isopropylarterenol, 2.5 Mg/min Average 172 Range A. Control Average Experimental period Effects of Calcium. Chloride on Iso)>roi)ijlarterenol-induced Right Ventricular Outflow-tract Pressure Gradients in Three Normal Dogs O\ 8 o Z m u 73 o 71 m «/> v> 7) 00 z o c 168 TOBIN, BLUNDELL, GOODRICH, SWAN Control Isopropylarterenol (jig /min) Control 2.5 5.0 (mm Hg) 60 40 20 PULMONARY ARTERY RIGHT VENTRICLE 0 •J Phonocardiogram Downloaded from http://circres.ahajournals.org/ by guest on April 30, 2017 Base Line «*« RV(m)=>20 SG(m)=S 38 18 42 25 24 5 FIGURE 4 Effects of calcium chloride on isopropylarterenol-induced right ventricular outflow-tract pressure gradients in normal dog weighing 15 kg. Infusion of isopropylarterenol administered 12 minutes after infusion of calcium chloride, 40 mg/kg. 16 mm Hg. There was a small but consistent increase of pulmonary arterial pressure (average, 4.0 mm Hg). A larger cardiac output was the product of consistent increases of heart rate and stroke volume. When the infusion rate of isopropylarterenol was increased to 5.0 /ng/min, the average increase of the outflow-tract pressure gradient during systolic ejection was 19 mm Hg. The means of the differences between values obtained at the two levels of isopropylarterenol infusion were evaluated for all experiments. In each instance the differences were small and inconsistent excepting for the small increases in the outflow-tract pressure gradients. Comment " . . . I do not think that either clinicians or physiologists have yet fully perceived the bearings which this theory (incorporation of the bulbus cordis into the right ventricle as the infundibulum) has on the constitution and action of the normal heart."—Sir Arthur Keith.3 At the conclusion of our initial experiments (table 1), it was apparent that right ventricular outflow-tract pressure gradients could be induced by isopropylarterenol in normal dogs; but if the genesis of such pressure gradients was to be investigated, an invariably successful method of producing them was desirable. The infusion of epinephrine or norepinephrine at 10 /xg/min induced significant right ventricular outflow-tract pressure gradients in 10% of studies, but the magnitudes of such responses were invariably less than those attained with isopropylarterenol. Left ventricular outflow-tract pressure gradients have been induced in normal dogs by several investigators.4-0 These investigators either infused sympathomimetic amines4 or combined such infusions with a procedure which reduced the stroke volume/''" Our right ventricular outflow-tract pressure gradients were not effectively magnified by either prior phlebotomy or infusion of massive concentrations of isopropylarterenol. Isopropylarterenol enhances the rate and force of myocardial contraction.7 If the inotropic effect were primarily responsible for the development of the right ventricular outflow-tract pressure gradients in normal dogs, other agents which enhance the force of myocardial contraction might be additive and magnify those pressure gradients. The experiCircuUlion Reiurcb. Vol. XVI, F«4r«rj 1963 INFUNDIBULAR PRESSURE GRADIENTS IN DOGS 169 Downloaded from http://circres.ahajournals.org/ by guest on April 30, 2017 ments detailed in tables 2 and 3 showed that the right ventricular outflow-tract pressure gradients induced by isopropylarterenol in normal dogs are indeed enhanced by the prior administration of either acetyl strophanthidin or calcium chloride. Figure 5 summarizes graphically the average results of these experiments. The pressure gradients varied for different experimental periods, with respect to both the absolute values and their percentage relationship to the ventricular pressures. When the pressure gradient increased, right ventricular pressure increased simultaneously, but the pulmonary arterial pressure did not rise. The infusion of isopropylarterenol at 5.0 /jLg/min produced responses which did not differ substantially from those obtained with 2.5 /xg/min. The infusion of acetyl strophanthidin or calcium chloride alone did not induce right ventricular outflow-tract pressure gradients which differed significantly from those observed during control periods. Yet, the ad- ministration of either acetyl strophanthidin or calcium chloride, prior to the infusion of isopropylarterenol at 2.5 fig/min, resulted in responses which greatly exceeded those accompanying the infusion of isopropylarterenol alone. These observations indicate that isopropylarterenol was primarily • responsible for the genesis of these gradients and its effect was probably maximal, but pretreatment with acetyl strophanthidin and calcium chloride resulted in a substantially greater infundibular contraction. Thus, a mechanism other than simple inotropic stimulation may be induced by the addition of these substances. The data indicate that the relatively small increases in cardiac output were not major factors in the genesis of these pressure gradients, Braunwald and co-workers,8'9 in reporting studies of hypertrophic subaortic stenosis in man, emphasized the variable nature of the pressure gradients between the left ventricle and the brachial artery and suggested that this variability depends on changes in the Controls (9, Mean and ± I S.D.) Calcium Chloride Acetylstrophanthidin (3, Mean and Range) (4, Mean and Range) IsopropylorterenoH/ig) Isopropylarterenol l/iq.) Control 2.5 5.0 Control 60 MEAN PRESSURES 30 (mm Kg) 0 SO PRESSURE/ GRADIENT/ RV * (%) 1%J 40 - y CARDIAC ^ OUTPUT (L./minute) Y y Y V FIGURE S Hemodynamic features of isopropylarterenol-induced right ventricular outflow-tract pressure gradients in normal dogs (average values). Circulation Resurcb. Vol. XVI. Ptbrusry 1961 170 TOBIN, BLUNDELL, GOODRICH, SWAN A ' JU JU -UL ANGIO MARKER >MMAl|MMAl M l A ANGIOCARDIOGRAM (On« Cardiac Cycle) (mm Hg) 80 — AORTA 40 PULMONARY ARTERY Downloaded from http://circres.ahajournals.org/ by guest on April 30, 2017 RIGHT VENTRICLE - m m FIGURE 6 Simultaneously recorded pressure pulses from sinus and infundibulum of right ventricle and from pulmonary artery during filming of cineangiogram of outflow tract of right ventricle of a 14-kg dog. Cineangiogram marker (above) identifies timing of individual frames (1-1V) reproduced to right. Note the contraction of infundibulum (frame 111) associated with rising sinus pressure and falling infundibular pressure. Diagonal line traversing record indicates syringe travel during injection of Renovist (mixture of sodium and methylglucamine diatrizoates) 30 ml. force of ventricular contraction. Such pressure gradients have been magnified with both isopropylarterenol10 and ouabain.11 Selective left ventricular angiograms have demonstrated systolic narrowing of the left ventricular outflow tract and have suggested that the obstruction is maximal in late systole. Figure 6 illustrates the simultaneous recording of a cineangiogram and three pressure pulses. The pressure pulses were recorded directly from the sinus and infundibulum of the right ventricle and from the pulmonary artery of an open-chest dog. The animal had received 0.5 mg of acetyl strophanthidin and was being infused with 5.0 /u.g/min of isopropylarterenol. This experiment demonstrated that a right ventricular outflow-tract pressure gradient exists between the sinus of the right ventricle and the infundibulum of the right ventricle during systole and that the cross-sectional area of the lowest portion of the outflow tract is smallest in late systole. The classic studies of Keith'' demonstrated that the bulbus cordis appears in a developmental stage of the heart in all vertebrate embryos and that it does not disappear from the mammalian heart but becomes incorporated into the right ventricle, forming the outflow tract or infundibulum. There is ample evidence that in normal sequence the sinus of the right ventricle is activated and contracts before the infundibulum.12 If the sequence of right ventricular activation or contraction were altered, premature contraction of the infundibulum might be responsible for the right ventricular outflow-tract pressure gradients induced in these normal dogs. The sequence of ventricular activation was Circulation Research, Vol. XVI, February 1965 INFUNDIBULAR PRESSURE GRADIENTS IN DOGS 171 CONTROL 19.7 msec ISOPROPYLARTERENOL 19.6 msec Control /6.5 Acetylstrophanthidin Downloaded from http://circres.ahajournals.org/ by guest on April 30, 2017 22.0 Calcium Chloride FIGURE 7 Effects, in a 20-kg dog, of isopropylarterenol-induced pressure gradients on temporal relationships of peak electromyographic potentials recorded directly from body (A) and infundibulum of right ventricle (B). investigated by implanting bipolar electrodes in the right ventricular wall of two open-chest dogs (fig. 7). One electrode (A) was placed in the anterior wall in the region of the anterior papillary muscle, and the second (B) was placed in the outflow tract immediately beneath the pulmonary valve. Under controlled conditions, the maximum peak potential recorded from electrode A preceded the maximum peak potential from electrode B by 19 msec. When large gradients were produced in the manner previously described, the sequence of ventricular activation was not altered. The nature of right ventricular contraction was also investigated by analysis of the pressure pulses recorded directly from the sinus and infundibulum of the right ventricle and from the pulmonary artery in open-chest dogs (fig. 8). When pressure gradients were induced, the initiation sequence of contraction was not altered, but the contours of the pressure pulses and the time intervals between them were altered. The interval between the onset of contraction in the sinus and in the infundibulum decreased to 10 msec, and the CircuUtion Reietrcb, Vol. XVI, ftbrtury 196) interval between the peak pressures (infundibular peak preceding sinus peak) increased to 46 msec. The infundibular systolic pressure became similar to the systolic pulmonary arterial pressure, rising sharply to an attenuated peak and falling abruptly to the level of pulmonary arterial diastolic pressure as the pressure in the sinus of the ventricle continued to rise to a delayed peak. These pressure pulse contours are similar to those described by Rodbard and Shaffer13 and Johnson14 in patients with muscular (functional) infundibular stenosis. Altered tonus of the infundibular portion of the right ventricle has been suggested as a mechanism involved in the "cyanotic spells" associated with tetralogy of Fallot,lr> in the reduction of left-to-right shunts associated with ventricular septal defects,10 and in the persistence of right ventricular outflow-tract pressure differences after pulmonary valvulotomy.17 It has been assumed that these findings were characteristic of the hypertrophied infundibulum of the diseased heart. However, our experiments demonstrate that severe right ventricular outflow-tract pressure gradients TOBIN, BLUNDELL, GOODRICH, SWAN 172 ACETYLS TROPHA N THIDIN Control Isopropylorterenol Control Isopropylorterenol 27 25 43 25 27 24 53 22 25 22 24 22 (mm Hg) 60 r- 40 - PULMONARY ARTERY 2 0 RIGHT VENTRICLE Downloaded from http://circres.ahajournals.org/ by guest on April 30, 2017 Base Line R.V.(m) Sinus Infundibulum P.A.(m) FIGURE 8 Simultaneously recorded pressure pulses from sinus and infundibulum of right ventricle and from pulmonary artery of a 15-kg open-chest dog. Effects of isopropylarterenol alone and after administration of acetyl strophanthidin. can be induced in normal dogs by drugs which alone or in combination alter the rate and force of cardiac contraction. of intravascular and intracardiac pressures. In Medical Physics, vol. 3, ed. by O. Classer. Chicago, Year Book Publishers, I960, pp. 641651. Summary 2. HAMILTON, W. F., MOORE, J. W., KINSMAN, J. M., AND SPURLINC, R. G.: Studies on the cir- In these experiments we have demonstrated that: 1. Right ventricular outflow-tract pressure gradients of significance can be induced in normal dogs by a sympathomimetic amine which increases the rate and force of ventricular contraction. 2. Such outflow-tract pressure gradients are magnified by the addition of other inotropic drugs, such as acetyl strophanthidin and calcium chloride. 3. These outflow-tract pressure gradients are not the result of an increase in the volume and rate of blood flow but are due to forceful contraction of the infundibulum. culation. IV. Further analysis of the injection method, and of changes in hemodynamics under physiological and pathological conditions. Am. J. Physiol. 99: 534, 1932. 3. KEITH, A.: Fate of the bulbus cordis in the human heart. Lancet 2: 1267, 1924. References 1. SUTTERER, W. F., AND WOOD, E. H.: Strain- gauge manometers: Application to recording 4. KRASNOW, N., ROLETT, E., HOOD, W. B., JR., YURCHAK, P. M., AND GORLJN, R.: Reversible obstruction of the ventricular outflow tract. Am. J. Cardiol. 11: 1, 1963. 5. GAUER, O. H.: Evidence in circulatory shoclc of an isometric phase of ventricular contraction following ejection. Federation Proc. 9: 47, 1950. 6. CROSS, C. E., AND SALISBURY, P. F.: Functional subaortic stenosis produced in animals. Am. J. Cardiol. 12: 394, 1963. 7. LANDS, A. M., AND HOWARD, J. W.: A com- parative study of the effects of 2-arterenol, epinephrine and isopropylarterenol on the heart. J. Pharmacol. Exptl. Therap. 106: 65, 1952. Circmttsioi, Rtsurcb, Vol. XVI, Fthnutry 196} INFUNDIBULAR PRESSURE GRADIENTS IN DOGS 8. BRAUNWALD, E., MORBOW, A. C , CORNELL, W. P., AYCE.V, M. M., AND HILBISH, T. F.: Idio- pathic hypertrophic subaortic stenosis: clinical, hemodynamic, and angiographic manifestations. Am. T. Med. 29: 924, 1960. 9. BRAUNWALD, E., BROCKENBROUCH, E. C , AND MORROW, A. C : Hypertrophic subaortic stenosis—a broadened concept. (Editorial) Circulation 26: 161, 1962. 10. BRAUNWALD, E., AND EBERT, P. A.: Hemodynam- ic alterations in idiopathic hypertrophic subaortic stenosis induced by sympathomimetic drugs. Am. J. Cardiol. 10: 489, 1962. 11. BRAUNWALD, E., BROCKENBROUCH, E. C , AND Downloaded from http://circres.ahajournals.org/ by guest on April 30, 2017 FRYE, R. L.: Studies on digitalis. V. Comparison of the effects of ouabain on left ventricular dynamics in valvular aortic stenosis and hypertrophic sulwortic stenosis. Circulation 26: 166, 1962. 12. MARCH, H. W., ROSS, J. K., AND LOWER, R. R.: Observations on the behavior of the right ventricular outflow tract, with reference to its de- Circtlttion Reittrcb, Vol. XVI, Ftbrnrn 196} 173 velopmental origins. Am. J. Med. 32: 835, 1962. 13. RODBARD, S., AND SHAFFER, A. B.: Muscular contraction in the infundibular region as a mechanism of pulmonic stenosis in man. Am. Heart J. 51: 885, 1956. 14. JOHNSON, A. M.: Functional infundibular stenosis: Its differentiation from structural stenosis and its importance in atrial septal defect. Cuy's Hosp. Rept. 108: 373, 1959. 15. WOOD, P.: Symposium on congenital heart disease: Attacks of deeper cyanosis and loss of consciousness (syncope) in Fallot's tetralogy. Brit. Heart J. 26: 282, 1958. 16. CASUL, B. M., DILLON, R. F., VHLA, V., AND HAIT, G.: Ventricular septal defects: Their natural transformation into those with infundibular stenosis or into the cyanotic or noncyanotic type of tetralogy of Fallot. J. Am. Med. Assoc. 164: 847, 1957. 17. BROCK, R.: Control mechanisms in the outflow tract of the right ventricle in health and disease. Guy's Hosp. Rept. 104: 356, 1955. Induced Pressure Gradients Across Infundibular Zone of Right Ventricle in Normal Dogs JOHN R. TOBIN, Jr., PETER E. BLUNDELL, RALPH G. GOODRICH and H. J. C. SWAN Downloaded from http://circres.ahajournals.org/ by guest on April 30, 2017 Circ Res. 1965;16:162-173 doi: 10.1161/01.RES.16.2.162 Circulation Research is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1965 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7330. Online ISSN: 1524-4571 The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circres.ahajournals.org/content/16/2/162 Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation Research can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Circulation Research is online at: http://circres.ahajournals.org//subscriptions/