Evaluation of indices of left ventricular contractility and relaxation in evolving canine experimental heart failure.

OBJECTIVE: The aim was to evaluate changes in indices of left ventricular contractility and relaxation in relation to changes in loading conditions in dogs with rapid pacing induced heart failure. METHODS: 14 conscious male mongrel dogs were paced at 250 beats.min-1 to severe heart failure, which occurred at 4.2(SD1.9) weeks. Six sham operated dogs served as controls. Right sided pressures were obtained by a thermodilution catheter. Left ventricular pressure and its derived variables were obtained by a high fidelity manometer tipped catheter. Rate corrected velocity of circumferential fibre shortening--end systolic wall stress relations were obtained by simultaneous haemodynamic and echocardiographic studies. RESULTS: In the paced dogs, baseline right atrial pressure, 6.4(2.0) mm Hg, and pulmonary capillary wedge pressure, 7.1(2.5) mm Hg, increased to 13.3(3.1) mm Hg and 34.5(7.1) mm Hg respectively at severe heart failure (both p less than 0.0001). The peak first derivative of left ventricular pressure dP/dt decreased from 1515(274) mm Hg.s-1 at baseline to 975(321) mm Hg.s-1 at severe heart failure (p less than 0.05) while baseline left ventricular end diastolic pressure, 4.4(3.7) mm Hg, and relaxation time constant tau, 18.0(4.5) ms, increased to 37.2(6.6) mm Hg (p less than 0.01) and 51.9(21.4) ms (p less than 0.05) respectively. The shortening-wall stress relation was markedly displaced downward from baseline. Furthermore, weekly studies revealed a major downward displacement of this relation by one week of pacing with no significant further shift at severe heart failure, whereas both end diastolic diameter (preload) and end systolic wall stress (afterload) increased significantly further from one week. In the sham operated dogs, there was no change over time in any of these study variables. CONCLUSIONS: In pacing induced heart failure, there is impairment of left ventricular contractility and relaxation. The major downward shift of the shortening-wall stress relation at one week suggests that left ventricular contractility is impaired early and may be the initiating mechanism of heart failure in this model.     

Effects of aminophylline in the conscious dog after coronary occlusion

The effects of aminophylline were examined in 19 conscious dogs subjected to coronary arterial occlusion. Measurements were made of left ventricular pressure and its first derivative (dP/dt), segment length and the velocity of segment length shortening in normal and severely ischemic zones. Regional blood flow was measured in these zones using the radioactive microsphere technique. Coronary occlusion increased heart rate, mean arterial pressure and left ventricular end-diastolic pressure but did not change left ventricular systolic pressure or dP/dt significantly. It also resulted in increased end-diastolic segment length and reduced segment length shortening (114 ± 6 percent, that is, paradoxical bulging) associated with marked reduction of blood flow to ischemic myocardium. Aminophylline, 1 mg/kg per min for 9 to 15 minutes administered after occlusion, increased heart rate 6 ± 2 beats/min, mean arterial pressure 5 ± 1 mm Hg, left ventricular systolic pressure 9 ± 2 mm Hg and left ventricular dP/dt 670 ± 50 mm Hg/s while reducing left ventricular end-diastolic pressure by 3.4 ± 0.3 mm Hg. In severely ischemic zones aminophylline increased transmural blood flow by 21 ± 8.0 percent (p < 0.02), reduced end-diastolic segment length by 0.23 ± 0.05 mm (p < 0.01) and reduced paradoxical bulging by 0.15 ± 0.06 mm (p < 0.02). Thus, in the presence of coronary arterial occlusion, aminophylline increased mean arterial pressure, left ventricular dP/dt and heart rate while reducing left ventricular end-diastolic pressure. In severely ischemic myocardium aminophylline appeared to exert a salutary effect and improved both regional perfusion and function.     

Effects of exercise stress on left ventricular end diastolic pressure-length strain relations in dogs with and without coronary stenosis.

OBJECTIVE: The aim was to elucidate the alterations of left ventricular diastolic properties, taking into account changes in unstressed length during exercise stimuli with and without coronary stenosis. METHODS: Left ventricular end diastolic pressure-length strain relations using segment length normalised to Lagrangian strain, and the rate of relaxation, were studied in seven open chest anaesthetised dogs with and without coronary stenosis on both left anterior descending and circumflex coronary arteries (approximately 30% resting flow reduction) during simulated dynamic exercise. Regional segment length was measured with ultrasonic crystals placed in the left anterior descending subendocardial region, and unstressed segment length at zero transmural pressure was obtained by occluding the vena cava. RESULTS: Peak negative dP/dt was decreased and isovolumetric left ventricular relaxation time constant increased by coronary stenoses; however neither changed significantly during simulated exercise. Left ventricular end diastolic pressure was significantly increased by coronary stenoses, from 3.1(SEM 0.8) to 7.0 (0.9) mm Hg (p < 0.05), and further increased to 15.5(1.1) mm Hg (p < 0.01) during simulated exercise, although right ventricular end diastolic pressure did not change. Unstressed length was increased in coronary stenoses from 9.03(0.08) to 9.89(0.13) mm (p < 0.01), and further increased to 10.34(0.14) mm (p < 0.01) during exercise, whereas it tended to decrease without coronary stenosis, from 9.03(0.08) to 8.79(0.11) mm during exercise. Left ventricular end diastolic pressure-length strain relations progressively shifted upward and leftward with coronary stenoses and subsequent exercise, but shifted downward and rightward during exercise without coronary stenosis. CONCLUSIONS: The increase in unstressed length or volume may contribute to exercise induced left ventricular dilatation observed in patients in effort angina. End diastolic distensibility decreases in both mild supply induced and exercise induced ischaemia, whereas in the normal heart, left ventricular end diastolic distensibility increases during exercise.     

Acute effects of gallopamil on left ventricular systolic and diastolic function in patients with ischaemic heart disease

In 13 patients with chronic stable angina, left ventricular pressures were measured by catheter-tip micromanometer, and left cineventriculography was performed at matched atrial paced rates before and 20 min after administration of intravenous gallopamil (3 mg). Mean plasma concentration of gallopamil at the second haemodynamic and angiographic assessment was 18.6 +/- 5.7 ng.ml-1. Left ventricular peak systolic pressure decreased from 134 +/- 12 to 125 +/- 13 mmHg (P less than 0.005) and mean aortic pressure from 94 +/- 11 to 91 +/- 9 mmHg (ns). Peak positive first derivative of left ventricular pressure (+dP/dt) and maximal velocity of the contractile element (Vcemax) significantly decreased (from 1828 +/- 334 to 1702 +/- 304 mmHg.s-1, P less than 0.002, and from 51 +/- 11 to 43 +/- 5 s-1, P less than 0.001, respectively). Left ventricular protodiastolic pressure decreased from -0.6 +/- 2.9 to -2.8 +/- 2.9 mmHg (P less than 0.005) and left ventricular end-diastolic pressure from 9.5 +/- 3.4 to 8.9 +/- 4.6 mmHg (ns). No changes occurred in peak negative dP/dt, while a significant reduction was observed in the exponential time constant of the first 40 ms of isovolumetric relaxation (t-constant decreased from 38 +/- 8 to 34 +/- 7 ms, P less than 0.01). No changes were observed in end-diastolic and end-systolic left ventricular volume indices and ejection fraction. Thus, intravenous gallopamil induced a moderate afterload reduction and a slight negative inotropic effect resulting in a net effect of unchanged left ventricular pump function. The observed improvement of early relaxation seems to be a potentially beneficial effect of gallopamil in patients with coronary artery disease.     

Quantitative Doppler tissue imaging as a correlate of left ventricular contractility

Doppler tissue imaging is a new noninvasive imaging modality that allows quantitation of the low intensity, high amplitude Doppler shifts in the range of myocardial tissue motion. This study was performed to test the hypothesis that Doppler tissue imaging may provide unique information reflecting left ventricular systolic function, and to test the relationship between myocardial tissue velocity and noninvasive measures of ventricular contractility. Nine patients with mild or moderate mitral insufficiency and no regional wall motion abnormality were studied during dobutamine stress echocardiography. Left ventricular ejection fraction and peak systolic velocity of the sub- endocardial left ventricular posterior wall were quantified at baseline and at peak stress and compared with estimated peak dP/dt. During dobutamine infusion, ejection fraction increased from 41.7±22.2 (range 14 to 70) % to 56.6±27.9 (range 17 to 84) % (p=0.001), peak systolic velocity increased from 22.7±4.2 (range 18 to 28) mm/sec to 35.3±10.1 (range 20 to 47) mm/sec (p=0.004), and dP/dt increased from 1050±322 (range 613 to 1574) mm Hg/sec to 1766±768 (range 936 to 3000) mm Hg/sec (p=0.01). Although there were good correlations between left ventricular dP/dt and both ejection fraction (R=0.75) and peak systolic velocity (R=0.81), the correlation between change in dP/dt and change in myocardial velocity (R=0.75) was better than that between change in dP/dt and change in ejection fraction (R=0.36). These data support the hypothesis that myocardial velocity determined with Doppler tissue imaging reflects myocardial contractility, and that catecholamine- induced alteration in contractility is better reflected by changes in myocardial velocity than by changes in ejection fraction.     

Acute haemodynamic and metabolic effects of felodipine in congestive heart failure.

Felodipine is a new calcium antagonist with a high degree of vascular selectivity. To examine its potential value as an afterload reducing agent in congestive heart failure 11 patients were studied. Substantial increments in cardiac index were associated with a fall in systemic vascular resistance. Left ventricular end diastolic pressure was also significantly reduced. Although left ventricular maximum dP/dt remained unchanged, maximum dP/dt/P increased. Left ventricular unloading was reflected by a reduction in cavity dimensions and a shift in the relation between end systolic pressure and dimension downwards and to the left. The myocardial oxygen supply to demand ratio was also improved: coronary sinus flow increased significantly despite a decline in myocardial oxygen consumption. These beneficial haemodynamic and metabolic effects suggest that felodipine may extend the clinical application of calcium antagonists to include the treatment of congestive heart failure.     

Effects of verapamil and nifedipine on rate of left ventricular relaxation in coronary arterial disease patients

We have evaluated the effects of nifedipine and verapamil on rate of left ventricular relaxation in 26 patients having coronary arterial disease with normal ejection fraction and normal left ventricular contractility. None of the patients had myocardial infarction. All patients showed normal contractile indices and abnormally high values of T constant, neg, dP/dt and left ventricular protodiastolic pressure, suggesting an impairment of left ventricular relaxation. Nifedipine, injected intravenously (15 micrograms/kg) in 14 patients induced a significant reduction of afterload parameters and an increase of contractility. Nifedipine also improved left ventricular relaxation, as it induced a reduction of the T constant from 42 +/- 2 msec to 33 +/- 2 msec (P less than 0.01). It induced a tendency to a reduction of negative dP/dt and protodiastolic pressure without reaching statistical significance. Verapamil, injected intravenously in the remaining 12 patients (0.1 mg/kg as a bolus followed by chronic infusion of 0.005 mg/kg/min for 3 min) induced a reduction of the T constant from 43 +/- 10 to 37 +/- 6 msec (P less than 0.01). It reduced the negativity of dP/dt from 2302 +/- 273 to 2021 +/- 252 mm Hg/sec (P less than 0.05) and of left ventricular protodiastolic pressure from 3.2 +/- 1.4 to 1.5 +/- 1.1 mm Hg (P less than 0.01). Verapamil, like nifedipine, reduced the afterload parameters although to a lesser extent. It did not substantially affect the left ventricular contractility. These data suggest that abnormalities of left ventricular relaxation may precede changes in systolic function and that nifedipine and verapamil favourably modify the indices of left ventricular diastolic function in patients with coronary arterial disease.     

Direct effects of dopamine, orciprenaline and norepinephrine on the right and left ventricle of isolated canine hearts.

In 31 canine heart-lung preparations the direct cardiac effects of dopamine were compared to those of norepinephrine and orciprenaline. All three agents increased heart rate by 50-60% to a maximum of 240-250 beats/min. The inotropic effects of the three drugs were not significantly different. Even with the highest doses cardiac arrhythmias were rarely observed. To achieve maximal chronotropic and inotropic effects, dopamine required four times higher doses than norepinephrine and orciprenaline. All three drugs increased right ventricular dP/dt max by about twice as much as left ventricular dP/dt max. Peak systolic pressure (P max) in the right ventricle was increased 4-5 times more than P max in the left ventricle while mean aortic pressure was elevated by 12-16 mm Hg and mean pulmonary pressure by 6-14 mm Hg. The positive inotropic effect of all three sympathomimetics and of CaCl2 was substantially more pronounced on the right than on the left ventricle.     

Load dependence of the single beat maximal pressure (stress)/volume ratios in humans

To determine whether the slopes of the single beat maximal pressure (stress)/volume ratios are sensitive to changes in loading conditions in humans, 16 patients without cardiac disease were studied with simultaneous micromanometer-determined left ventricular pressures and biplane contrast cineangiograms under control conditions and during methoxamine and nitroprusside infusions. Left ventricular volumes were calculated with use of a Simpson's rule algorithm, wall thickness was obtained iteratively, and both midwall circumferential and meridional stresses were computed frame by frame. The maximal pressure/volume and both circumferential and meridional maximal stress/volume ratios were calculated using a single beat from each loading condition assuming a zero volume-axis intercept. Mean left ventricular systolic pressure increased 47% during the methoxamine infusion and decreased 22% during the nitroprusside infusion compared with control (p less than 0.001 for both). Despite these changes in left ventricular systolic pressure, heart rate was eliminated as a confounding variable by right atrial pacing; and mean maximal rate of change of left ventricular pressure [(+)dP/dtmax] and rate of change at developed pressure 40 mm Hg [(+)(dP/dt) per DP40] values did not differ significantly. Mean single beat maximal pressure/volume ratios also did not differ significantly among the three loading conditions. In contrast, mean single beat circumferential and meridional maximal stress/volume ratios were 3.15 +/- 1.83 and 1.40 +/- 0.82 g/cm2 per ml at control; they increased to 4.47 +/- 2.44 and 2.21 +/- 1.25 g/cm2 per ml during the methoxamine infusion (p less than 0.001 for both), and they decreased during the nitroprusside infusion to 2.58 +/- 1.47 and 1.14 +/- 0.57 g/cm2 per ml (p less than 0.05 and p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Contractile and relaxation reserve of the left ventricle. II. Patients with rheumatic valvular disease (author's transl)

The function of the left ventricle is important for the success of surgery. To differentiate between normal and abnormal ventricular function, the contractile and relaxation reserve was measured. In 19 patients, 10 with mitral and 9 with aortic valve disease, max dP/dt and min dP/dt were measured at rest and during exercise (ergometer). Max dP/dt increased in 7 patients above 3200 mm Hg/s and dP/dt/P above 60 s-1 (normal contractile reserve). Only 3 of these patients reached a normal increment of relaxation velocity (min dP/dt above 2400 mm Hg/s). In 12 patients the contractile and relaxation reserve was decreased. All patients with mitral stenosis had abnormal relaxation reserve despite normal contractile function in 4 cases. Left ventricular enddiastolic pressure did not correlate well with myocardial dysfunction. Isovolumic contractility during exercise was decreased in patients with aortic valve disease. Enddiastolic pressure increased from 18 +- 8 to 22 +- 14 mm Hg during exercise.     

Experimental model of chronic global left ventricular dysfunction secondary to left coronary microembolization

A model of chronic left ventricular dysfunction characterized by left ventricular dilation, elevated filling pressures and histologic changes has been lacking. In this study the use of coronary microsphere embolization-induced ischemia was explored as a method of producing chronic left ventricular dysfunction. Acute ischemic left ventricular dysfunction was induced in 13 mongrel dogs with 50 microns plastic microspheres until the peak positive first derivative of left ventricular pressure (dP/dt) decreased by 25% and the left ventricular end-diastolic pressure increased to greater than or equal to 12 mm Hg. After 8 weeks of observation, hemodynamic and echocardiographic variables were measured in each dog. Acute left ventricular dysfunction resulted in a dilated left ventricle with systolic dysfunction (area ejection fraction 24 +/- 6% vs. 57 +/- 9% initially, p less than 0.01) and elevated left ventricular filling pressures. Isovolumetric relaxation was prolonged and the peak rapid filling/atrial filling velocity and integral ratios were reduced. Eight weeks after embolization, there was an increased left ventricular size (end-diastolic area 15.1 +/- 2.1 cm2 at 8 weeks vs. 13.5 +/- 1.4 cm2 early after microsphere injection, p less than 0.05), unchanged end-systolic area, improved area ejection fraction and increased left ventricular mass. Left ventricular end-diastolic pressure increased and, despite continued abnormal relaxation, the peak rapid filling/atrial filling velocity and integral ratios increased to above baseline values, demonstrating a "restrictive" pattern. Gross and histologic examination revealed diffuse, patchy scarring associated with perivascular fibrosis. Thus, coronary microsphere embolization resulted in a model of chronic moderate left ventricular systolic dysfunction and abnormal diastolic function characterized by a "restrictive" filling pattern.     

Contraction-excitation feedback in an ejecting whole heart model--dependence of action potential duration on left ventricular diastolic and systolic pressures

STUDY OBJECTIVE--Contraction-excitation feedback may play a role in arrhythmogenesis in heart failure. The aims of this study were to determine whether contraction-excitation feedback has a significant effect on action potential duration within a physiological range of pressures, and to investigate the individual effects of left ventricular end diastolic and peak systolic pressures on action potential duration. DESIGN--A new model was developed for studying contraction-excitation feedback in a physiologically ejecting isolated heart preparation. Hearts were perfused via the left atrium, ejecting against an aortic afterload. By varying left atrial and aortic pressures, left ventricular end diastolic pressure and left ventricular peak systolic pressure were controlled independently. Intracellular potentials were recorded from the epicardium. EXPERIMENTAL MATERIAL--Hearts (n = 33) were obtained from guinea pigs weighing 300-350 g. MEASUREMENTS AND MAIN RESULTS--Increasing left ventricular end diastolic pressure from 0.3 to 1.1 kPa (2.2 to 8.3 mm Hg), at constant left ventricular peak systolic pressure, shortened action potential duration by 11.3(SEM 1.5) ms (p less than 0.0005). Action potential duration achieved a new steady state within 30 s of a change in end diastolic pressure. The changes were fully reversible. The effects of left ventricular peak systolic pressure variation at constant left ventricular end diastolic pressure were less marked. Increasing left ventricular peak systolic pressure from 10.3 to 13.1 kPa (75 to 100 mm Hg) shortened action potential duration by 2.1(0.7) ms (p less than 0.01). Reduction of aortic pressure below 8 kPa had variable effects on action potential duration, reflecting the development of ischaemia. CONCLUSION--The results show the existence of contraction-excitation feedback in a physiologically ejecting whole heart preparation and suggest that raised end diastolic pressure may contribute to arrhythmogenesis in heart failure.     

Quantitative data on the afterload dependence of left ventricular dP/dtmax in isolated canine hearts

Summary In 15 canine heart-lung preparations the effect of an increase in aortic pressure on left ventricular dP/dt_max was tested. Abrupt elevation of aortic pressure by 20–80 mm Hg during diastole without change in enddiastolic pressure did not influence left ventricular dP/dt_max in the following heart beat. Left ventricular circumference increased slightly.Stepwise elevation of aortic pressure from 60 to 130 mm Hg (LVEDP maintained constant) resulted in an augmentation of the steady-state values of dP/dt_max by only 42 mm Hg/s per 10 mm Hg pressure rise.If the enddiastolic pressure was not maintained constant, the increase in dP/dt_max was 77 mm Hg/s per 10 mm Hg pressure rise.Aortic pressure alterations exhibit a slight but significant influence on left ventricular contractility in the steady-state phase, while an acute effect is not detectable, thus demonstrating that a sudden increase in coronary perfusion pressure is without immediate effect on the cardiac performance.A preliminary report was given at the 51st meeting of the German Physiological Society 1979.     

Contractile and relaxation reserve of the left ventricle. IV. Patients with coronary heart disease (author's transl)

51 patients with coronary heart disease had exercise tests on a bicycle ergometer (86 +/- 32 watts). Compared to a normal control group, only 13 patients had normal contractile reserve (group 4.1). In 32 patients the increase in contractility during exercise was reduced (max dP/dt below 3200 mm Hg/s, group 4.2). Patients with reduced contractile reserve were graded according to the height of left ventricular enddiastolic pressure during exercise: In patients with grade 1, enddiastolic pressure was normal. In patients with grade 2, enddiastolic pressure increased between + 4 and + 15 mm Hg and in the patients with grade 3a a above + 15 mm Hg. Contractile and relaxation reserve decreased along with a rise in enddiastolic pressure and an increase in the complaints of the patients. Severe chest pain led to termination of exercise in patients of grade 3b. Enddiastolic pressure increased above + 15 mm Hg. During ischemia, peak-measured velocity of contractile elements (dP/dt/P) and the maximal rate of left ventricular pressure fall (min dP/dt) decreased. In conclusion, with increasing chest pain a decrease of contractile reserve was observed. Left ventricular enddiastolic pressure rose excessively. This has to be taken as a sign of myocardial failure due to ischemic dyskinesia and impeded relaxation.     

Left ventricular function before and after diltiazem in patients with coronary artery disease

Left ventricular contraction, relaxation and diastolic mechanics were investigated before and after intravenous administration of 15 mg of diltiazem in 15 patients with coronary artery disease. High fidelity left ventricular pressure measurements were performed in all 15 patients, with simultaneous biplane cineangiography in 13. The time constant of left ventricular isovolumic pressure decay was calculated from the linear relation of left ventricular pressure and its rate of change with time (negative dP/dt). Frame by frame volume analysis through one cardiac cycle was completed to construct volume-time and pressure-volume curves before and after the administration of diltiazem. After diltiazem, left ventricular peak systolic pressure decreased from 124 to 113 mm Hg (p less than 0.001), while left ventricular end-diastolic pressure and heart rate were not altered. Maximal positive dP/dt also remained unchanged. End-diastolic volume was not changed after diltiazem, but end-systolic volume increased from 48 to 52 ml/m2 (p less than 0.025); as a result, ejection fraction decreased slightly from 57 to 55% (p less than 0.025). The time constant of left ventricular pressure decay and maximal negative dP/dt decreased from 58 to 54 ms (p less than 0.025) and from -1,404 to -1,321 mm Hg/s (p less than 0.025), respectively. Peak early diastolic filling rate increased from 621 to 752 ml/s (p less than 0.01) in association with an increase in filling volume during the first half of diastole from 60 to 68% (p less than 0.005). No consistent displacement of the diastolic pressure-volume curve was observed after diltiazem.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional and global biventricular function during dipyridamole stress testing

This study assesses the relation between regional ventricular performance (using 2-dimensional echocardiography) and global systolic and diastolic indexes of biventricular myocardial function (using hemodynamic monitoring) during dipyridamole stress testing. Simultaneous 2-dimensional echocardiographic and biventricular hemodynamic monitoring during dipyridamole infusion (0.56 mg/kg over 4 minutes) was performed in 19 patients. All patients had a normal resting function. Eleven of the 19 patients had a positive echocardiography test (new wall motion dyssynergy with dipyridamole) and they formed group 1. Eight patients had a negative echocardiography test (group 2). During baseline conditions, no significant differences were found in the 2 groups: rate pressure product (107 +/- 16 vs 108 +/- 13 mm Hg x beats/min x 1/100), positive left ventricular (LV) dP/dt (1,950 +/- 473 vs 2,262 +/- 430 mm Hg/s), negative LV dP/dt (-2,069 +/- 620 vs -2,205 +/- 245), LV end-diastolic pressure (8.2 +/- 4.4 vs 9.6 +/- 4.0 mm Hg), right ventricular positive dP/dt (368 +/- 133 vs 400 +/- 190 mm Hg/s) and negative dP/dt (-281 +/- 89 vs -383 +/- 147). At peak dipyridamole, the 2 groups were different for LV end-diastolic pressure (20 +/- 10 vs 8 +/- 5 mm Hg, p less than 0.01), LV positive dP/dt (2,100 +/- 688 vs 3,013 +/- 851 mm Hg/s, p less than 0.01) and negative dP/dt (-1,868 +/- 518 vs -2,564 +/- 272, p less than 0.01). At peak ischemia, LV positive dP/dt increased slightly, but not significantly, while negative dP/dt decreased significantly (p less than 0.01) in comparison with resting values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Haemodynamic effects of short term intravenous amiodarone for hypertrophic cardiomyopathy

The haemodynamic effects of an intravenous amiodarone infusion (5 mg/kg for 10 minutes) were measured in ten patients with hypertrophic cardiomyopathy (two with a left ventricular outflow gradient at rest) five, 15, and 30 minutes after drug administration. Mean (SD) pulmonary capillary wedge pressure rose significantly at five and 15 minutes (from 12.3 (6.2) mm Hg to 17.6 (9.2) and to 16.2 (8.6] with a subsequent tendency to fall to control values at 30 minutes. Mean right atrial and right ventricular end diastolic pressures increased from 3.6 (1.8) mm Hg to 7.3 (3.1) and from 6.3 (2.4) to 9.8 (3.2) mm Hg respectively at 30 minutes. The increase in filling pressures was paralleled by a decrease of left ventricular max dP/dt from 1522 (414) to 1372 (327) to 1316 (338) and to 1326 (379) five, 15, and 30 minutes after infusion. Despite this slight negative inotropic effect, cardiac index and stroke volume index were unchanged or slightly increased, possibly because of the decrease in systemic vascular resistance (from 1326 (330) dyn s cm-5/m2 to 1152 (285]. In both patients with outflow gradient the pressure gradient at rest decreased (from 110 to 65 and from 85 to 65 mm Hg) through a reduction of left ventricular systolic pressure. Thus short term intravenous infusion of amiodarone is safe in patients with hypertrophic cardiomyopathy. The main changes were a mild depression of ventricular contractility, which was well tolerated and adequately compensated for by a decrease in afterload.     

Effects of negative pleural pressure on left ventricular hemodynamics

Negative pleural pressure alters left ventricular (LV) function. LV volume changes have been studied in human subjects, but little is known of the hemodynamic effects. The effect of changes of pleural pressure on LV hemodynamics during a Mueller maneuver (inspiration against an obstruction) was studied in 11 subjects and during quiet, unobstructed inspiration in 3. During the Mueller maneuver, there was an initial decrease in pulmonary wedge pressure and aortic systolic pressure, almost as great as the decrease in pleural pressure. Thereafter, these pressures increased despite a sustained reduction in pleural pressure. Toward the end of the Mueller maneuver, pulmonary wedge transmural pressure averaged 31 ± 12 mm Hg and in 6 patients large v waves developed. The increase in aortic transmural pressure averaged 30 ± 16 mm Hg. Aortic pulse pressure decreased on the first beat from control levels of 59 ± 21 to 47 ± 21 (p < 0.001) and then returned to control levels.During normal breathing in 3 subjects, studied with intraesophageal balloons, there was a similar increase in both transmural aortic and transmural pulmonary wedge pressures with a decrease in pleural pressure 6 mm Hg during inspiration.Thus, increased negative pleural pressure was associated with a marked increase in pulmonary wedge transmural pressure; the increase was approximately proportionate to the decrease in pleural pressure. It is suggested that this increase was due to increased impedance to LV ejection and to right ventricular expansion interfering with LV diastolic filling.     

Contractile and relaxation reserve of the left ventricle. III. Patients with cardiomyopathy (author's transl)

Seven of 22 patients with cardiomyopathy increased maximal rate of left ventricular pressure rise (max dP/dt) above 3200 mm Hg/s and dP/dt/P above 60/s. Relaxation reserve was normal with an increase of min dP/dt above 2400 mm Hg/s.--In 15 patients contractile and relaxation reserve was reduced. In congestive cardiomyopathy, contractility and relaxation reserve were equally reduced. Left ventricular enddiastolic pressure increased during exercise slightly or not (grade 1). Enddiastolic volume was elevated to 173 +/- 50 ml/1.73 m2 and endsystolic volume to 63 +/- 22 ml/1.73 m2; ejection fraction and mean circumferential fiber shortening were reduced (61 +/- 17%; 1.3 +/- 0.9 circ/s). In hypertrophic cardiomyopathy without obstruction, contractile and relaxation reserve and ejection phase parameters could be found to be normal. Enddiastolic pressure at rest was elevated. In severe cases, contractile and relaxation reserve were markedly reduced and enddiastolic pressure increased to a greater extent than in congestive cardiomyopathy. In addition, relaxation reserve was reduced, especially in patients with excessive hypertrophy of the myocardium. These had abnormal (grade 2) and pathological reaction to exercise: contractile and relaxation reserve were decreased and enddiastolic pressure (grade 3) increased. Left ventricular contractility was found to be almost normal in patients with hypertrophic obstructive cardiomyopathy. This was the case despite increases in enddiastolic pressure. Contractile reserve was reduced, however, in patients with excessive hypertrophy. Diastolic filling was impeded during exercise.--Measuring left ventricular function during exercise, different types of cardiomyopathy correlate with typical hemodynamic alterations.     

Haemodynamic effects of short term intravenous amiodarone for hypertrophic cardiomyopathy.

The haemodynamic effects of an intravenous amiodarone infusion (5 mg/kg for 10 minutes) were measured in ten patients with hypertrophic cardiomyopathy (two with a left ventricular outflow gradient at rest) five, 15, and 30 minutes after drug administration. Mean (SD) pulmonary capillary wedge pressure rose significantly at five and 15 minutes (from 12.3 (6.2) mm Hg to 17.6 (9.2) and to 16.2 (8.6] with a subsequent tendency to fall to control values at 30 minutes. Mean right atrial and right ventricular end diastolic pressures increased from 3.6 (1.8) mm Hg to 7.3 (3.1) and from 6.3 (2.4) to 9.8 (3.2) mm Hg respectively at 30 minutes. The increase in filling pressures was paralleled by a decrease of left ventricular max dP/dt from 1522 (414) to 1372 (327) to 1316 (338) and to 1326 (379) five, 15, and 30 minutes after infusion. Despite this slight negative inotropic effect, cardiac index and stroke volume index were unchanged or slightly increased, possibly because of the decrease in systemic vascular resistance (from 1326 (330) dyn s cm-5/m2 to 1152 (285]. In both patients with outflow gradient the pressure gradient at rest decreased (from 110 to 65 and from 85 to 65 mm Hg) through a reduction of left ventricular systolic pressure. Thus short term intravenous infusion of amiodarone is safe in patients with hypertrophic cardiomyopathy. The main changes were a mild depression of ventricular contractility, which was well tolerated and adequately compensated for by a decrease in afterload.