Frequency potentiation and postextrasystolic potentiation in patients with and without coronary arterial disease.

Frequency potentiation and postextrasystolic potentiation of myocardial contractility were induced in 17 patients found not to have cardiac disease (group 1) and in 10 patients with coronary arterial disease (group 2). Atrial stimulation was performed starting at a rate of 110/min and going up to 200/min (frequency potentiation). Single, premature venriculr beats with decreasing coupling intervals were induced every fifteenth beat during basal atrial stimulation at 125/min, after which compensatory pauses were provided (posts used an an idex of contractility. With increasing heart rate dp/dt max was augmented equally, in both groups of patients, by frequency increases and premature beats (the coupling interval of the extrasystole being expressed as heart rate). dp/dt min and left ventrricular systolic pressure remained unchanged while left ventricular end-diastolic pressure decreased in both groups of patients with the two forms of potententiation. It was concluded that both these forms of potentiation have the same augmenting effect on myocardial contractility. Shortening the coupling intervals of premature beats caused a decreased in left ventricular end-diastolic pressure, suggesting that the Frank-Starling mechanism was not involved in postextrasystolic potentiation. Patients with coronary arterial disease had lower values of dp/dt max, dp/dt min, and higher values of left ventricular end-diastolic pressure during rest and stimulation procedures, while the systolic pressures equalled those in the control group. Though individual case values fromthe healthy and diseased hearts might be similar, it was only under the stress of potentiation that the true state of contractility was made apparent. Impairment of dp/dt min was not found without an impairment of dp/dt max in the presence of myocardial ischaemia.     

Frequency potentiation and postextrasystolic potentiation in patients with and without coronary arterial disease.

Frequency potentiation and postextrasystolic potentiation of myocardial contractility were induced in 17 patients found not to have cardiac disease (group 1) and in 10 patients with coronary arterial disease (group 2). Atrial stimulation was performed starting at a rate of 110/min and going up to 200/min (frequency potentiation). Single, premature venriculr beats with decreasing coupling intervals were induced every fifteenth beat during basal atrial stimulation at 125/min, after which compensatory pauses were provided (posts used an an idex of contractility. With increasing heart rate dp/dt max was augmented equally, in both groups of patients, by frequency increases and premature beats (the coupling interval of the extrasystole being expressed as heart rate). dp/dt min and left ventrricular systolic pressure remained unchanged while left ventricular end-diastolic pressure decreased in both groups of patients with the two forms of potententiation. It was concluded that both these forms of potentiation have the same augmenting effect on myocardial contractility. Shortening the coupling intervals of premature beats caused a decreased in left ventricular end-diastolic pressure, suggesting that the Frank-Starling mechanism was not involved in postextrasystolic potentiation. Patients with coronary arterial disease had lower values of dp/dt max, dp/dt min, and higher values of left ventricular end-diastolic pressure during rest and stimulation procedures, while the systolic pressures equalled those in the control group. Though individual case values fromthe healthy and diseased hearts might be similar, it was only under the stress of potentiation that the true state of contractility was made apparent. Impairment of dp/dt min was not found without an impairment of dp/dt max in the presence of myocardial ischaemia.     

Characterization of left ventricular mechanical function during arrhythmias with two dimensional echocardiography: I. premature ventricular contractions

Two dimensional echocardiography was applied experimentally in the closed chest dog to quantitate left ventricular function during and immediately after single premature ventricular contractions induced through threshold stimulation at the apex. Coupling intervals were varied over a range from 35 to 85 percent of the R-R interval during normal sinus rhythm (920 to 980 ms). The quality of tomographic echocardiographic images during premature as well as postextrasystolic beats was found to be satisfactory for quantitating short axis section areas at end-diastole and end-systole. A systolic fractional area change was computed from two dimensional echocardiographic measurements to characterize mid ventricular cardiac function, which correlated significantly with peak left ventricular pressure and maximal first derivative of left ventricular pressure (dP/dt). Marked shortening of coupling intervals reduced fractional shortening during premature systole and enhanced the degree of potentiation during the postextrasystolic beat. By contrast, premature beats with relatively long coupling intervals caused less reduction in contraction and only minor postextrasystolic potentiation.Systolic shortening of left ventricular length as well as transverse diameters were studied in a two dimensional echocardiographic long axis cross section. During long coupling intervals contraction was normal except for distinct regional systolic outward “bulging” in the apical region. In contrast, short coupling intervals were associated with a more significant generalized derangement of ventricular wall motion during systole. It is concluded that the two dimensional echocardiographic method can be used to portray and quantitate global as well as regional left ventricular function during disturbances of cardiac rhythm.     

The influence of ectopic beats and tachyarrhythmias on stroke volume and cardiac output

The potentially adverse influence of premature ectopic beats or tachyarrhythmias on cardiac performance was studied by assessing the echocardiographic left ventricular stroke volume in 21 patients with cardiac rhythm disturbances. The beat to beat stroke volume correlated closely with end-diastolic volume in each patient, (averge R=.9). Premature ventricular contractions decreased stroke volume by an average of 48±8 ml (−71%) compared with sinus beats; whereas the postextrasystolic beats, although preceded by a pause and higher end-diastolic volume, increased stroke volume by only 16±7 ml (18%) over the sinus, beats. Those postextrasystolic beats with equivalent timing and end-diastolic volume to the sinus beats had a mean stroke volume only 8 ml higher, suggesting that postextrasystolic potentiation plays only a minor role in augmenting stroke volume. Transient aberrant ventricular conduction of intermittent left bundle branch block, ectopic beats or atrial fibrillation failed to alter stroke volume. Ventricular bigeminy, trigeminy and quadrigeminy lowered cardiac output by 1.3, .9 and .7 l/min. The onset, of tachyarrhythmias was oftentimes associated with a continuously changing end-diastolic volume and stroke volume, with either alternation or progressive increment of these variables.It is apparent that premature contractions decrease stroke volume by virtue of their infringement on diastolic, filling, the principle beat to be determinant of stroke volume in arrhythmias being left ventricular end-diastolic volume. Since premature beats decrease stroke volume to an extent greater than postextrasystolic beats increase it, they may reduce cardiac outpout by a substantial degree, depending on their frequency of occurrence and degree of prematurity.     

The effect of premature ventricular contraction on left ventricular relaxation, chamber stiffness, and filling in humans

To investigate the influence of single spontaneous premature ventricular ectopic beats on left ventricular contraction, relaxation, chamber stiffness, and filling, we examined 21 patients with simultaneous micromanometer left ventricular pressure tracings and echocardiograms. Instantaneous left ventricular diameter and mitral valve inflow velocity were obtained by using of M-mode and pulsed Doppler echocardiography, respectively. The isovolumic relaxation time constants (TL and TD) were calculated by mean of a zero (TL) and variable (TD) asymptote pressure. The chamber stiffness constants were derived from the diastolic pressure-diameter (kd) and pressure-volume (kv) relationships. The extrasystolic beat was associated with marked impairments of relaxation, systolic function, and diastolic filling as seen by an increased TL (53 to 71 msec; p less than 0.001), TD (59 to 89 msec; p less than 0.005), time from maximum negative dp/dt to the lowest diastolic pressure (147 to 170 msec; p less than 0.05), and decreased number of elasped TDs (3.1 to 2.4; p less than 0.05), end-systolic pressure-diameter ratio (2.4 to 1.7; p less than 0.001), maximum positive dp/dt (1904 to 1326 mm Hg/sec; p less than 0.001), shortening fraction (31% to 21%; p less than 0.001), and peak early filling velocity (59 to 49 cm/sec; p less than 0.001). Chamber stiffness constants were unchanged. Relaxation and chamber stiffness were unchanged during the postextrasystolic beat as reflected by TL, TD, maximum negative dp/dt, and kd and kv.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationships between beat-to-beat interval and the strength of contraction in the healthy and diseased human heart

Twenty-six adult patients, classified by clinical and catheter criteria into groups of those with normal and abnormal left ventricular function, were studied during cardiac catheterization. Right heart pacing was established, and left ventricular dP/dt was measured with end-catheter manometers. By varying the interval preceding a test beat after periods of steady pacing it was confirmed that recovery of left ventricular mechanical function (maximum dP/dt) occurs approximately 800 msec (optimum interval) after a beat. The augmentation of maximum dP/dt of the first 2 beats after an extrasystole, each spaced at the optimum interval, was also studied; the amount of potentiation was varied by alterations in extrasystolic interval. Potentiation decayed from the first to the second postextrasystolic beat with a ratio that was fixed in each individual patient. The ratio (recirculation fraction) was higher in patients with normal than in those with abnormal left ventricular function (mean +/- SD 0.52 +/- 0.10 vs 0.37 +/- 0.11, p less than .005). There was an inverse relationship between this ratio and the degree of potentiation of the first postextrasystolic beat (r = .80, p less than .001). We postulate a disturbance of excitation-contraction coupling mechanisms to explain these effects.     

Cardiac function and myocardial contractility: a perspective

An experimental study was designed to validate postextrasystolic potentiation assessment of myocardial viability or functional reserve of cardiac segments after acute coronary occlusion. Segmental systolic fractional area changes and wall thickening in pacing-induced postextrasystolic beats were mapped in 12 closed chest dogs by two-dimensional echocardiography during a control period and from 20 minutes to 3 hours after occlusion of the left anterior descending coronary artery. The extent of myocardial ischemic and necrotic zones was evaluated in left ventricular slices and subsegements corresponding to echographic cross sections. During two-dimensional echocardiography, left ventricular segments that were found to be neither ischemic nor necrotic always exhibited a significant augmentation of both fractional area change and wall thickening during the postextrasystolic beat that followed an induced premature contraction with a 42.4% coupling interval. In segments without necrosis but with varying degrees of ischemia, significant postextrasystolic potentiation was also demonstrated, even after 3 hours of occlusion. In contrast, segments that developed more than 80% necrosis failed to potentiate systolic fractional area change after 2 hours, and systolic wall thickening, even after 20 minutes of coronary occlusion. Statistical evaluation revealed a characteristic threshold at 41 to 60% necrosis, beyond which no potentiation of function could be elicited 3 hours after occlusion. Extrapolation from the experimental data suggests that when two-dimensional echographic studies in myocardial ischemia indicate postextrasystolic augmentation of segmental left ventricular function, the latter segments may be assumed to contain only small infarcts or to consist of reversibly ischemic and normal myocardium. Conversely, segments that fail to exhibit postextrasystolic potentiation can be assumed to be more than 60% necrotic.     

Evaluation of left ventricular residual function using postextrasystolic potentiation. Relation between systolic time intervals and angiographic study

The effects of postextrasystolic potentiation (PESP) on systolic time intervals and left ventricular wall motion were studied during diagnostic cardiac catheterization in 20 patients (4 normal individuals, 11 patients with coronary artery disease and 5 patients with idiopathic dilated cardiomyopathy). Postextrasystolic changes in the aortic pressure and systolic time intervals were measured from the electrocardiogram and aortic pressure tracing. After a micromanometer-tipped catheter was positioned in the ascending aorta just above the aortic valve, a single ventricular premature beat was introduced using an R-wave coupled stimulator. PESP was then studied during left ventriculography which was undertaken simultaneously in the right anterior oblique 30 degrees and left anterior oblique 60 degrees positions. Following two or three normal sinus beats, a right ventricular extrastimulus was delivered again under the same stimulating condition. PESP in all patients caused a decrease in the ratio of the preejection period to the left ventricular ejection time (PEP/ET). The average percent decrease was 21% (from 0.429 +/- 0.162 to 0.339 +/- 0.102, p less than 0.001). The left ventricular ejection fraction (EF) increased in all patients with PESP from 0.52 +/- 0.20 to 0.61 +/- 0.17 (p less than 0.001). The postextrasystolic changes in the PEP/ET ratio and EF were greater in patients with low cardiac performance. There was a good correlation (r = -0.85, p less than 0.001) between the changes in the EF and those in PEP/ET in PESP. Thus, it is possible to determine left ventricular residual function (the postextrasystolic change in the global EF) using the postextrasystolic change in PEP/ET in patients with coronary artery disease and dilated cardiomyopathy.     

Effects of postextrasystolic potentiation on systolic time intervals

The changes in systolic time intervals associated with postextrasystolic potentiation were studied in 48 patients whose left ventricular function was categorized angiographlcally into four groups—normal function (I) and mlld (II), moderate (III) and severe (IV) left ventricular dysfunction. Postectopic potentiation in all groups caused a decrease in preejection period/left ventricular ejection time (PEP/LVET) ratio. The greatest potentiation and decreases in PEP/LVET ratio were noted in beats where the difference in compensatory pause and coupling interval (both expressed as percent of basic cycle length [CP percent — CI percent]) exceeded 40. The decrease in the ratio was least in the normal subjects (Group I) and maximal in Group IV patients. The pattern of response of the rate-corrected left ventricular ejection time and preejectlon period was also different at the four levels of ventricular function. Marked shortening of ejection time with minimal shortening of preejection period occurred in Group I, but in Group IV patients there was marked shortening of preejection period and minimal shortening of ejection time. An intermediate response was seen in Group II and III patients. The amount of shortening of ejection time exceeded that of preejection period in Group II patients; the reverse was true in Group III patients. The group responses differed with a significance of 2P <0.001 except when Group II was compared with Group III, when the significance was 2P <0.025. Thus, measurement of changes in systolic time intervals associated with postextrasystolic potentiation is of value as a noninvasive means of assessing resting left ventricular function.     

Influence of post-extrasystolic potentiation on left ventricular function estimated by means of systolic time intervals.

Systolic time intervals were measured in 50 patients with frequent premature ventricular beats. The patients were divided into two groups: group I included those which showed in the beat that preceded an extrasystole a pre-ejection period/left ventricular ejection time (PEP/LVET) ratio greater than or equal to 0.43, and group II with PEP/LVET ratio greater than 0.44. Systolic time intervals recorded during post-extrasystolic potentiation were compared with those measured in the preextrasystolic complex. Also the measured intervals were tested against the hourly rate of premature beats obtained by electrocardiographic telemetric monitoring. The results confirmed the following results of previous reports: a) ventricular premature beats are followed by sinus-potentiated contractions inversely related to the coupling interval and dependent on adequate compensatory pauses; b) potentiated contractions are greater in patients with ventricular dysfunction. No relationship was found between left ventricular performance and the rate of premature beats. It is concluded that the effect of an antiarrhythmic intervention on the left ventricular function might be adequately evaluated by means of systolic time intervals and provoked post-extrasystolic potentiation, with the advantage of using totally non-invasive procedures.     

'Programmed' left ventricular angiography: a new method for assessing left ventricular compliance

In the present study a new method for evaluating left ventricular chamber compliance is reported. We induced a programmed postextrasystolic beat during routine left ventricular angiography through a temporary pacing catheter, placed at the sinoatrial junction (S1-S1 = 600 ms; S1-S2 = 400 ms; S2-S3 = 800 ms). Thirty-two patients with documented critical coronary artery disease and 5 normal subjects represent the study group. The method allows to have two couples of end-diastolic pressure and end-diastolic volume and we calculated the modulus of chamber stiffness with the formula: K = (1n EDP 3 - 1n EDP 1)/(EDVI 3 - EDVI 1), where EDP 1-3 and EDVI 1-3 are end-diastolic pressure and end-diastolic volume index in basal beat and in the postextrasystolic pause, respectively. Left ventricular chamber compliance (dV/dP) and specific compliance (dV/VdP) were also calculated. In order to assess the clinical value of the method, we divided the patients with coronary artery disease into three groups: 12 patients had angina and no previous myocardial infarction; 15 had a previous myocardial infarction and responded to postextrasystolic potentiation with an increase in left ventricular ejection fraction greater than or equal to 0.08 and 5 patients had myocardial infarction and did not respond to postextrasystolic potentiation. Diastolic indices showed significant differences between subgroups; patients with more severe disease and with systolic dysfunction had the highest values of the modulus of chamber stiffness and the lowest values of chamber compliance. Moreover, these indices were not correlated with basal end-diastolic volumes, but they were directly and significantly correlated with the actual increase in left ventricular filling.     

Radionuclide evaluation of postextrasystolic potentiation of left ventricular function induced by atrial and ventricular stimulation

Postextrasystolic potentiation of left ventricular function induced by ventricular and atrial stimulation was compared in 10 patients using radionuclide ventriculography. After insertion of pacing wires, a preliminary radionuclide ventriculogram was obtained and then ventricular and atrial trigeminy was induced in random order, each with identical R-R coupling intervals, each for 6 to 10 minutes. During the stimulation studies, radionuclide data were acquired in electrocardiographic gated list mode format. Left ventricular ejection fraction and relative end-diastolic and end-systolic volume changes were measured for each reformatted composite sinus, atrial and ventricular premature beat and potentiated beat. The volume changes were normalized to the count-based values obtained for the sinus beat of the appropriate study. Postextrasystolic potentiation induced by either ventricular or atrial stimulation was characterized by similar significant increases in left ventricular ejection fraction (mean ± standard deviation 7 ± 3 percent, p < 0.01 versus 7 ± 5 percent, p < 0.01; difference not significant [NS]) and decreases in relative end-systolic volume (?12 ± 12 percent, p < 0.01 versus ?12 ± 8 percent, p < 0.01; NS) but little change in relative end-diastolic volume (+5 ± 10 percent, NS versus +4 ± 7 percent, NS; NS). This was despite a longer compensatory pause (1,120 ± 220 versus 1,050 ± 190 ms, p < 0.01) after the ventricular premature beat. It is concluded that there is no difference in the postextrasystolic potentiation induced by atrial or ventricular premature stimulation.     

Haemodynamic effects of intravenous amrinone in patients with impaired left ventricular function.

The effects of intravenous amrinone on resting haemodynamic function were investigated in 15 patients with impaired left ventricular function. All patients received 1 X 5 mg/kg and 10 received a further 2 mg/kg. We observed dose related increases in heart rate and cardiac index, and reductions in mean arterial pressure, left ventricular end-diastolic pressure, and systemic vascular resistance. A small reduction in left ventricular end-diastolic volume and a 36% increase in ejection fraction occurred. No significant change in max dp/dt, min dp/dt, (Max dp/dt/P), max (dp/dt/P), KVmax or the ratio of left ventricular end-systolic pressure to left ventricular end-systolic volume was detected. It is concluded that the beneficial effects of intravenous amrinone on the resting haemodynamics in our patients were attributable to vasodilatation, with the drug having no demonstrable positive inotropic effect.     

Changes in hemodynamics and bradykinin concentration in coronary sinus blood in experimental coronary artery occlusion.

The following parameters were studied before and after acute occlusion of the anterior descending branch of the left coronary artery in 17 dogs: bradykinin (BK) in the coronary sinus blood, heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), left ventricular max dp/dt (LV max dp/dt), and an index of myocardial contractility (LV max dp/dt/IP). BK levels increased, reaching a maximum of 30 +/- 13 ng/ml 2 min after coronary ligation, accompanied by a significant elevation of LVEDP, and lowering of the myocardial contractility index. HR and LV max dp/dt showed no significant changes. A positive correlation obtained between the level of BK and LVEDP, as well as a negative correlation between the level of BK and of both LVSP and myocardial contractility index. Pretreatment with aprotinine (Trasylol), an inhibitor of kinin forming enzyme, prevented the increase in both BK and LVEDP after coronary artery ligation and caused an elevation of myocardial contractility index. These results suggest that BK formed within ischemic myocardium exerts a negative inotropic action on the heart.     

Pressure-dimension analysis of the poststimulation potentiation--influence of heart rate and ventricular function (author's transl)

The mechanism of poststimulation potentiation (PSP) was studied in 17 patients with coronary artery disease by simultaneous pressure-dimension analysis. The left ventricular pressure (LVP) was measured by catheter-tip-micromanometer and LV diameter by M-mode echocardiography. The pressure signals were digitised and analysed on line by 400 Hz. The pressure-dimension tracings were additionally analysed half-automatically. Measurements were done during right atrial pacing at 80, 120, 140 beats/min and during the poststimulation period. 1. Right atrial pacing increased the rate of LV pressure development (dp/dt max), the rate of pressure fall (dp/dt min), the velocity of circumferential fiber shortening (VCF mn), and fiber dilatation (vcf mx) dependent on heart rate and cardiac function. 2. LV enddiastolic diameter (LVEDD) reached during the first poststimulation period the starting point independent on pacing rate and cardiac function. LV enddiastolic pressure (LVEDP) showed a slight overshoot. PSP resulted in an increase of LVP, dp/dt max, VCF mn, and the velocity of posterior wall motion, dp/dt min, VCF mx, and the velocity of posterior wall relaxation decreased, however, with the first post-stimulation beat. 3. The PSP was dependent on atrial pacing rate. The higher the pacing rate the higher the PSP. dp/dt max increased after cessation of 120/min for +29% and after 140/min for +38%. The PSP for the preload independent parameter of contractility, V-40, was, however, equal for both heart rates +25% and +28% respectively. 4. Another determinant of PSP was cardiac function. The PSP was relatively higher in patients with reduced ejection fraction than in patients with a normal ejection fraction: dp/dt max +55% and 25%, VCF mn +18% and +7% respectively. From the derived ventricular function curves, it could be shown, that atrial pacing reflected an increase in LV contractility (Bowditch effect), whereas PSP reflected an increase in LV performance by the Frank-Straub-Starling (Woodworth staircase) effect on a new left ventricular function curve, which was shifted to the left by atrial pacing.     

Postextrasystolic aortic pressure pulse response in coronary artery disease.

The response of the aortic systolic pressure after an extrasystole was evaluated in 100 consecutive patients with coronary artery disease. The patients were divided into four groups depending on the response of the first postextrasystolic beat. Group IA (45 patients), had lower systolic pressure, whereas group IB (40 patients), had a similar systolic pressure in the postextrasystolic beat, as compared to beats preceding the extrasystole. Group IIA (12 patients) and group IIB (3 patients), demonstrated an increased systolic pressure in the first postextrasystolic beat with subsequent beats in group IIB, also demonstrating pulsus alternans. Congestive heart failure and cardiomegaly were significantly more frequent in group II, as compared to group I patients. In group IIA and IIB, triple vessel disease was present in 83 and 100 per cent, respectively, as compared to 44 per cent in group I patients. Left ventricular end-diastolic pressure (mm. Hg) was 14 ± 6 and 12 ± 7 in group IA and IB respectively, as compared to 19 ± 9 (p < 0.025) in group IIA and 31 in group IIB. Comparing groups IA and IB with each other for cardiac output, stroke volume, end-diastolic volume and ejection fraction, revealed no significant difference. The cardiac output (L./min./M.²) was 2.2 ± 0.6 for group IIA, as compared (p < 0.01) to 2.8 ± 0.5 and 2.9 ± 0.5 in groups IA and IB. Stroke volume (ml./M.²) and ejection fraction were 30 ± 10 and 0.30 ± 0.08, respectively, for group IIA, which is signficantly less, as compared to group I patients. The end-diastolic volume (ml./M.²) in group IIA was 102 ± 28, which is significantly (p < 0.001) higher, as compared to group IA and IB. All patients in group IIB had an abnormal cardiac output, end-diastolic volume and ejection fraction. Thus, the differences in response between group I and group II patients to an extrasystole clearly define two distinct hemodynamic groups. The responses observed to an extrasystole are best explained by variable response of each group to postextrasystolic potentiation and aortic impedance.     

Effect of procainamide and lidocaine on ventricular automaticity and reentry during acute coronary occlusion

A model was developed to study ventricular automaticity and reentry in the heart of open chest dogs during myocardlal ischemia. Atrioventricular (A-V) block and the resultant idioventricular rhythm were induced by surgical destruction of the His bundle, and acute myocardial ischemia was produced by ligation of the left anterior descending coronary artery. The ventricle was paced by basic stimuli, and one or two premature beats were introduced at various coupling Intervals after the 10th basic beat. Two different types of response to these premature beats could be observed: (1) rapidly repetitive beats or fibrillation due to reentry after early premature beats, and (2) the appearance of escape beats from idioventricular automatic fibers after late premature beats.With this model of ventricular reentry and automaticity, the effect of procainamide (group I antiarrhythmic agent) was studied in 12 dogs, and that of lidocaine (group II) in 13 dogs. Both procainamide and lidocaine were effective in decreasing automaticity since they significantly increased postextrasystolic escape intervals of idloventricular beats. Although procainamide failed to abolish the reentrant beats induced by early premature beats in all 12 dogs, lidocaine abolished these beats in 10 of 13 dogs. The results indicate that lidocaine is much more effective than procainamide in preventing ventricular reentrant activity induced by early premature beats.     

Action of magnesium salts on the toxic effects of calcium overload in the isolated and perfused rat heart

The toxic effect of calcium overload and the action of magnesium sulfate (4 mM) and magnesium chloride (4 mM) on heart rate, coronary flow rate, left ventricular systolic pressure, dp/dt max and voltage epicardial electrogram were studied in the isolated and perfused rat heart. Increasing calcium load by increasing [Ca]o from 1 to 6 mM we observed a progressive increase in heart rate coronary flow rate, left ventricular systolic pressure, dp/dt max and a decrease in voltage epicardial electrogram. During the exposure to [Ca]o 8 mM the toxic manifestations of calcium overload developed and we observed a reduction in heart rate, coronary flow rate, left ventricular systolic pressure, dp/dt max and an increase in voltage epicardial electrogram. Magnesium sulfate and magnesium chloride had similar effect: in fact, in both procedures we observed a decrease in heart rate, left ventricular systolic pressure, dp/dt max, voltage epicardial electrogram and an increase in coronary flow rate at [Ca]o 2 mM. When magnesium salts were administered at the same time as the heart was exposed to [Ca]o 8 mM, we observed a reduction in the toxic effect of calcium overload. When magnesium salts were administered after the appearance of the calcium overload, they did not revert the toxic effect of calcium overload but prevented the insurgence of cardiac standstill. Thus, in the isolated perfused rat heart, the toxic manifestations of calcium overload develop at [Ca]o 8 mM and magnesium salts are able to reduce the toxic effects of calcium overload and the appearance of cardiac standstill according to their calcium-antagonism mechanism.     

First derivative of the apex cardiogram and systolic time intervals in evaluation of myocardial contractility in man

The sensitivity of various systolic time intervals and measurements derived from the first derivative (dp/dt) of the calibrated apex cardiogram were investigated to assess the value of this noninvasive method for detecting changes in myocardial contractility in man. The electrocardiogram, carotid arterial pulse tracing, phonocardiogram and calibrated apex cardiogram were simultaneously recorded on frequency modulated magnetic tape in 15 normal subjects before and after administration of angiotensin, isoproterenol and propranolol. All measurements, including the ratio (dp/dt)/P, a new variable derived from the apex cardiogram, were obtained by computer wave recognition and measurement programs.

Significant changes occurred mainly in the early phases of the cardiac contraction cycle. Whereas systolic time intervals provided indirect information in regard to the rate of rise of intraventricular pressure, more direct information on changes in myocardial contractility was obtained from the rate of rise of the apex cardiogram. Mean control values for (dp/dt)/P derived from the calibrated apex cardiogram ranged between 29 and 35. These values are comparable with reported (dp/dt)/P ratios derived from left ventricular pressure data. A significant increase in (dp/dt)/P of the apex cardiogram was provoked by isoproterenol. The results of our study suggest that (dp/dt)/P of the calibrated apex cardiogram may be useful as a new noninvasive index of myocardial contractility.     

Pulsus alternans induced by inferior vena caval occlusion in man

To assess the effect of rapid preload reduction on left ventricular performance in nonischemic cardiomyopathy, 11 patients were studied during inferior vena caval (IVC) balloon occlusion. Five developed sustained pulsus alternans. During pulsus alternans, the strong beats demonstrated systolic performance characteristics similar to baseline values, despite a drop in both left ventricular (LV) end-diastolic diameter (66 +/- 13 to 61 +/- 13 mm; p less than 0.05) and LV end-diastolic pressure (21 +/- 8 to 9 +/- 6 mmHg; p less than 0.05). In contrast, the weak beats demonstrated a reduction in peak systolic pressure (130 +/- 36 to 109 +/- 33 mmHg; p less than 0.02), fractional shortening (20% +/- 4% to 17% +/- 9%; p less than 0.05) and peak positive dP/dt (1,006 +/- 224 to 921 +/- 287 mmHg; p less than 0.05). Measures of diastolic performance (peak negative dP/dt, the time constant of LV relaxation, the length of diastasis, and LV end-diastolic stress) were not different between baseline beats and the strong beats; and only LV end-diastolic stress differed when baseline beats were compared to the weak beats. When the strong beats were compared to the weak beats during induced pulsus alternans, significant differences were observed in peak systolic pressure, peak positive dP/dt, and fractional shortening, but no differences in any measured diastolic parameter was observed. A slight difference was noted in the left ventricular end-diastolic diameters, with the weak beat consistently beginning at a slightly smaller diameter (61 +/- 13; mm vs 59 +/- 13; p less than 0.05). In summary, these data are consistent with an augmentation and deletion of intrinsic contractile forces in association with an alternation in preload on a beat-to-beat basis as best describing left ventricular performance during pulsus alternans.