The Influence of Myocardial Systolic Shortening on Action Potential Duration Following Changes in Left Ventricular End-Diastolic Pressure

APD and Systolic Shortening. Introduction: Contraction-excitation feedback may he an important factor in arrhythmogenesis in patients with heart failure. We have previously demonstrated the contrasting effects of raising left ventricular end-diastolic pressure on action potential duration in dog and guinea pig hearts. The current study was undertaken to assess whether these differing effects might reflect differences in the effect of varying left ventricular end-diastolic pressure on systolic shortening in the two models. Methods and Results: Two models were studied and compared. In open chest dog hearts and isolated guinea pig hearts, measurements of myocardial segment length were made while left ventricular end-diastolic pressure was raised and lowered at constant left ventricular peak systolic pressure. Action potentials were also recorded while left ventricular end-diastolic pressure was changed. The dog hearts were studied further in a manner aimed at reproducing the contraction pattern of the guinea pig hearts. In the in situ dog heart, elevation of left ventricular end-diastolic pressure, and the consequent increase in end-diastolic segment length, was accompanied by a marked increase in systolic shortening, such that minimum systolic segment length remained unchanged. Elevation of left ventricular end-diastolic pressure was accompanied by a prolongation of action potential duration. In the in vitro guinea pig model, elevation of left ventricular end-diastolic pressure was accompanied by more modest changes in systolic shortening, which were not sufficient to compensate for increased diastolic segment length. Consequently, minimum systolic segment length increased as the hearts dilated. Elevation of left ventricular end-diastolic pressure was accompanied by a shortening of action potential duration. In a further series of experiments, the effects of increased left ventricular end-diastolic pressure were studied in the dog model while allowing aortic pressure to rise, thereby restricting systolic shortening. Under these circumstances, the dog model was similar to the guinea pig model, with an increase in left ventricular end-diastolic pressure causing a shortening of action potential duration. Conclusion: Our results suggest that the effects of preload changes on action potential duration depend on accompanying changes in systolic shortening. This suggests a possible role for contraction-excitation feedback in arrhythmogenesis in patients with regional wall-motion abnormalities.     

Changes in myocardial repolarization in patients undergoing balloon valvuloplasty for congenital pulmonary stenosis: evidence for contraction-excitation feedback in humans

Alterations in ventricular loading conditions lead to changes in action potential duration and arrhythmias via contraction-excitation feedback; a decrease in load leads to prolongation of repolarization. To determine whether changes in right ventricular load alter ventricular repolarization in man, the corrected QT interval, a measure of overall ventricular repolarization, was measured in 32 patients before and after valvuloplasty for pulmonary stenosis. Right ventricular systolic pressure decreased (82.5 +/- 30.7 to 40.5 +/- 9.5 mm Hg, p less than .001) and the QTc increased concurrently (409.1 +/- 24.3 to 440.7 +/- 28.0 msec, p less than .001) after successful valvuloplasty. The increase in QTc was most marked for those patients with a greater than 30 mm Hg decrease in right ventricular pressure (40.0 +/- 23.3 vs 16.3 +/- 21.3 msec, p = .006). In a subset of seven patients in whom monophasic action potentials were recorded, monophasic action potential duration, a measure of local repolarization, was prolonged (230.0 +/- 24.3 vs 216.9 +/- 21.9, p less than .001) after successful valvuloplasty, confirming that the QTc prolongation reflected changes in local ventricular repolarization. In addition, during nine acute right ventricular outflow tract occlusions in a subset of six patients, monophasic action potential duration shortened (206.6 +/- 17.6 vs 221.7 +/- 20.9 msec, p less than .01) and early afterdepolarizations developed consistent with contraction-excitation feedback. These data suggest that, in humans, changes in mechanical load are associated with changes in ventricular repolarization consistent with contraction-excitation feedback.     

Effects of changes in airway pressure on the left ventricle and left atrium of dogs

The effects of negative and positive airway pressure were examined in eight closed chest, chronically instrumented dogs to determine beat to beat changes in left ventricular pressure, left ventricular dP/dt, left ventricular dimensions, and oesophageal pressure. As an index of afterload, systolic transmural pressure was calculated by subtracting oesophageal pressure from left ventricular pressure. With each change in airway pressure left ventricular end systolic minor axis diameter and left ventricular end diastolic minor axis diameter increased significantly. Left atrial end diastolic dimension increased significantly with negative airway pressure and did not change with positive airway pressure. Left ventricular dP/dt and left ventricular fractional shortening did not change. With the Mueller manoeuvre left ventricular systolic pressure decreased significantly from 106(4.2) mm Hg to 100.9(4.2) mm Hg and systolic transmural pressure increased significantly from 105.1(4.6) mm Hg to 110.4(4.3) mm Hg. With a transient increase in positive airway pressure of 30 mm Hg (4.0 kPa), left ventricular pressure increased significantly from 106.9(4.8) mm Hg to 113.9(5.9) mm Hg and systolic transmural pressure decreased significantly from 106.6(4.9) mm Hg to 99.8(4.6) mm Hg. The addition of positive end expiratory pressure of 10 cm H2O (0.98 kPa) or autonomic blockade with atropine and propranolol did not alter these results. Thus manoeuvres which cause opposite effects on systolic transmural pressure produce similar increases in left heart dimensions, suggesting that increases in pulmonary venous return and not changes in afterload may be the important determinants of left ventricular dimensional changes during changes in airway pressure.     

Echocardiographic assessment of the relation between left ventricular wall and cavity dimensions and peak systolic pressure in children with aortic stenosis

Echocardiographic measurements of the left ventricular end diastolic minor axis and posterior and septal wall thickness were obtained in 19 children with congenital aortic stenosis with left ventricular peak systolic pressures ranging from 110 to 225 mm Hg at cardiac catheterization. From these measurements were derived (1) the left ventricular peak circumferential wall stress, (2) the end-diastolic h?/r ratio (that is, mean of septal and posterior wall thickness (h?) to minor semiaxis (r) ratio), and (3) the LVM/LVV ratio (that is, left ventricular mass (LVM) to left ventricular end-diastolic volume (LVV) ratio). The peak stress was found to be within the normal range and independent of the left ventricular peak systolic pressure. The end-diastolic h?/r and LVM/LVV ratios had highly significant linear relations to the left ventricular peak systolic pressure. It is concluded that these easily determined echocardiographic measurements provide a useful noninvasive means of assessing left ventricular peak systolic pressure in patients with aortic stenosis without myocardial decompensation.     

Effect of changes in load on monophasic action potential and segment length of pig heart in situ

There is increasing evidence that mechano-electric feedback, defined as a change in mechanical state that precedes and alters transmembrane potential, operates in a wide variety of preparations and species including man. Load reduction is becoming a common therapeutic tool in a variety of clinical settings but the electrophysiological effects of these manoeuvres is not known. In this study the effect of changes in loading conditions on the time course of ventricular repolarisation were examined in the in situ heart in 13 pigs anaesthetised with halothane. Monophasic action potentials, electrocardiograms and segment length changes were recorded from the left ventricular epicardium using suction operated devices. Afterload was decreased by intravenous infusion of sodium nitroprusside, and increased by aortic cross clamping. Infusion of sodium nitroprusside resulted in a rise in action potential duration (measured at 70% repolarisation) in all 21 infusions (mean 3.4 ms), which was linearly related to the fall in systolic left ventricular pressure (r = 0.72, p less than 0.001) and the change in minimum systolic segment length (r = 0.46, p less than 0.05), but not to the change in maximum diastolic length (r = 0.33, NS). Aortic constriction, sufficient to elevate peak systolic left ventricular pressure back to the control level, restored the changes in action potential duration to normal. In addition, there were concomitant changes in the QT interval and T wave of the epicardial ECG. These findings show that mechano-electric feedback operates in the in situ heart and has potential importance in the clinical setting where changes in systemic blood pressure may directly alter cardiac electrophysiology.     

Early detection of myocardial alterations in mitral insufficiency with the angiotensin test

Left ventricular function was assessed at rest and after increasing systemic arterial resistance by angiotensin in 40 patients with isolated mitral insufficiency. Angiotensin was administered intravenously at a dose of 0,4 micrograms/mn until the systolic blood pressure rose by at least 30 mm Hg. Left ventricular and aortic pressures, cardiac index and left ventriculography in the 30 degree right anterior oblique projection (50 frames per second) were recorded before and during angiotensin infusion. The mean rise in systolic left ventricular pressure was 40 +/- 2,8 mm Hg; the heart rate increased slightly but significantly; left ventricular and diastolic pressure rose from 12,0 +/- 1,0 to 24,0 +/- 1,2 mmHg. The systolic index (Fick's method) was significantly decreased (37 +/- 1,6 ml/m2 to 26 +/- 1,6 ml/m2) though the angiographic systolic index remained unchanged. This is explained by an increase in the regurgitant fraction (51 +/- 2,5% ao 65 +/- 3%). The end diastolic volume index was unchanged; the ejection fraction was significantly decreased. The resting hemodynamic status was only slightly disturbed in 29 patients (mean capillary pressure less than 15 mm Hg, 8,8 +/- 0,52 mmHg). The left ventricular function curves with angiotensin distinguished two groups of patients: Group A (20 patients) with left ventricular dysfunction induced by angiotensin, Group B (9 patients) who maintained the systolic index despite the increase in left ventricular end diastolic pressure. These results suggest that the angiotensin test may be useful for detecting early left ventricular dysfunction in patients with isolated mitral insufficiency and virtually normal resting hemodynamic parameters.     

Diastolic aortic pressure rise during percutaneous transluminal coronary angioplasty: an index of left ventricular systolic dysfunction.

OBJECTIVES--To investigate the relation between diastolic aortic pressure response and left ventricular systolic dysfunction during percutaneous transluminal coronary angioplasty. BACKGROUND--The abnormal diastolic blood pressure rise during exercise in patients with coronary artery disease probably reflects left ventricular systolic dysfunction rather than the number of stenosed coronary arteries. METHODS--Aortic blood pressures and left ventricular systolic function indices were estimated in 26 patients with single proximal stenosis of the left anterior descending coronary artery both before and during angioplasty. RESULTS--During coronary angioplasty all patients presented an increase in diastolic aortic pressure (P << 0.001), 8-12s before intracoronary electrocardiographic changes. During acute ischaemia there was a decrease in left ventricular ejection fraction (P << 0.001) and stroke volume (P << 0.001) and an increase in end systolic volume (P << 0.001) and left ventricular end diastolic pressure (P << 0.001). No statistically significant changes were observed in systolic blood pressure or heart rate. The aortic diastolic pressure increase was correlated with the decrease in ejection fraction (r = -0.95, P << 0.001) and with the increases in end systolic volume (r = 0.86, P << 0.001) and left ventricular end diastolic pressure (r = 0.85, P << 0.001). CONCLUSIONS--The rise in diastolic aortic pressure during percutaneous transluminal coronary angioplasty occurs earlier than intracoronary electrocardiographic changes and is related to ischaemic left ventricular systolic dysfunction.     

Diastolic function in patients with aortic stenosis: influence of left ventricular load reduction

Pressure overload hypertrophy of the left ventricle due to aortic stenosis is associated with abnormalities of left ventricular isovolumic relaxation and early diastolic filling. The relative contribution of the hemodynamic load on the left ventricle to the impairment of diastolic function observed in this disorder remains poorly understood. To study this relation, the vasodilator nitroprusside was administered to eight patients with aortic stenosis and normal systolic function. The effect of a short-term reduction in left ventricular preload and afterload on left ventricular isovolumic relaxation and early diastolic filling was assessed by analysis of simultaneous micromanometer left ventricular pressure and radionuclide angiographic volume measurements. At baseline, left ventricular systolic and end-diastolic pressures were markedly elevated, and associated with prolongation of the time constant of left ventricular relaxation and depression of the left ventricular peak filling rate. Infusion of nitroprusside resulted in reduction of left ventricular systolic (204 +/- 31 to 176 +/- 31 mm Hg, p less than 0.05) and end-diastolic (31 +/- 8 to 18 +/- 6 mm Hg, p less than 0.05) pressures, with no associated improvement in time constant of left ventricular pressure decay (T) (68 +/- 25 to 80 +/- 37 ms, p = NS), T 1/2 (34 +/- 8 to 34 +/- 14 ms, p = NS), left ventricular peak filling rate (2.3 +/- 0.5 to 2.3 +/- 0.8 end-diastolic volume/s, p = NS) or time to left ventricular peak filling rate (150 +/- 50 to 144 +/- 37 ms, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hysteresis of left ventricular end ejection pressure-dimension relations after acute pressure loading in the intact canine heart

The left ventricular end systolic pressure-volume relation of the isolated canine heart is linear and independent of the loading conditions. The effects of acute pressure loading on the left ventricular end ejection pressure-length relations were studied in the intact canine heart. The lengths of two wall segments of the left ventricle parallel to the minor axis were measured with pairs of miniature piezoelectric crystals. At two levels of filling pressure, with and without control of heart rate, acute increases in left ventricular afterload were produced for six successive beats by occluding the thoracic aorta. After abrupt release of this occlusion, at left ventricular end diastolic pressure less than 10 mmHg, end ejection lengths were longer than before the occlusion for both segments despite the same or lower end ejection pressures. When heart rate was not controlled the mean(SD) difference in end ejection length was 0.46(0.21) mm (n = 100). When heart rate was controlled by atrial pacing after autonomic blockade the difference was 0.37(0.11) mm (n = 80). In contrast, at left ventricular end diastolic pressure greater than 10 mmHg there was no significant difference between end ejection lengths before and after release of the aortic occlusion. Gradual release of the aortic occlusion over 4-5 beats produced clockwise hysteresis of the left ventricular end ejection pressure-length relation when left ventricular end diastolic pressure was less than 10 mmHg. No hysteresis occurred when left ventricular end diastolic pressure was greater than 10 mmHg. Hysteresis of the end systolic pressure-dimension relation was also seen when major and minor axis dimensions of the left ventricular were measured.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypertrophic remodeling: gender differences in the early response to left ventricular pressure overload

Objectives. To identify gender differences in left ventricular remodeling, hypertrophy, and function in response to pressure overload due to ascending aortic banding in rats.Background. Gender may influence the adaptation to pressure overload, as women with aortic stenosis have greater degrees of left ventricular hypertrophy and better left ventricular function than men.Methods. Fifty-two weanling rats underwent ascending aortic banding (16 males, 18 females), or sham surgery (9 males, 9 females). At 6 and 20 weeks, rats underwent transthoracic echo Doppler studies, and closed-chest left ventricular pressures with direct left ventricular puncture. Perfusion-fixed tissues from eight rats were examined morphometrically for myocyte cross-sectional area and percent collagen volume.Results. At 6 weeks after aortic banding, left ventricular remodeling, extent of hypertrophy, and function appeared similar in male and female rats. At 20 weeks, male but not female rats showed an early transition to heart failure, with onset of cavity dilatation (left ventricular diameter = 155% vs. 121% of same-sex sham), loss of concentric remodeling (relative wall thickness = 102% vs. 139% of sham), elevated wall stress (systolic stress = 266% vs. 154% of sham), and diastolic dysfunction (deceleration of rapid filling = 251% vs. 190% of sham). Left ventricular systolic pressures were higher in female compared with male rats (186 ± 20 vs. 139 ± 13 mm Hg), while diastolic pressures tended to be lower (14 ± 4 vs. 17 ± 4 mm Hg).Conclusions. Gender significantly influences the evolution of the early response to pressure overload, including the transition to heart failure in rats with aortic stenosis.     

The differential effects of positive inotropic and vasodilator therapy on diastolic properties in patients with congestive cardiomyopathy

Symptoms of congestive heart failure frequently reflect abnormalities in both systolic and diastolic performance. While much work has been reported regarding the mechanisms by which positive inotropic and vasodilator therapy affect systolic performance, little is known about their effect on diastolic function. In 12 patients with diffuse congestive cardiomyopathy micromanometer left ventricular and aortic pressure measurements were recorded simultaneously with two-dimensionally targeted M mode echocardiograms and thermodilution-determined cardiac output. Each patient received dopamine (2, 4, and 6 micrograms/kg/min), and dobutamine (2, 6, and 10 micrograms/kg/min), and 10 received nitroprusside (0.125 to 2.0 micrograms/kg/min). Baseline hemodynamics were characterized by low cardiac index (2.1 +/- 0.7 liter/min/m2, mean +/- SD), high left ventricular end-diastolic pressure (24 +/- 10 mm Hg), and increased end-diastolic (6.8 +/- 1.0 cm) and end-systolic dimensions (6.0 +/- 1.0 cm). All patients had abnormal left ventricular pressure decay with a prolonged time constant (67 +/- 20 msec) and reduced peak diastolic lengthening rates. Dopamine and dobutamine decreased the time constant of relaxation and increased the peak lengthening rate. Dobutamine also reduced the minimum diastolic pressure from 14 +/- 7 to 10 +/- 9 mm Hg (p less than .01); neither drug reduced end-diastolic pressure. In fact, dopamine elevated end-diastolic pressures in seven patients, despite more rapid pressure decay. Diastolic pressure-dimension relations after dopamine and dobutamine showed a leftward shift with a reduced end-systolic chamber size, but no significant changes in passive chamber stiffness. Nitroprusside decreased left ventricular minimum diastolic pressure by 4 +/- 2 mm Hg and end-diastolic pressure by 7 +/- 4 mm Hg (p less than .01). It did not consistently accelerate left ventricular pressure decay at the doses tested. The decreased end-diastolic pressure with nitroprusside was due to a reduced end-diastolic dimension in five patients. In the other patients, all of whom had elevated right atrial pressures, diastolic pressure-dimension relations showed a parallel downward shift after nitroprusside. Thus, positive inotropic therapy with beta 1-adrenoceptor agonists enhances early diastolic distensibility by accelerating relaxation, augmenting filling, and reducing end-systolic chamber size. Vasodilator therapy is much more effective in lowering diastolic pressures.(ABSTRACT TRUNCATED AT 400 WORDS)     

Synchronization of the contraction of the right ventricle against an acute afterload increase. Left ventricle-like mechanical function of the right ventricle

AIM: The aim of this study was to demonstrate right ventricular contraction synchronization during acute and moderate afterload increase. MATERIAL AND METHOD: Right and left ventricular pressures, pulmonary and aortic pressures, pulmonary flow, and ventricular volumes by sonomicrometry were measured in seven anesthetized sheep. Pulmonary arterial hypertension was induced by Escherichia coli endotoxemia. RESULTS: Acute increase of the right ventricular afterload, measured as the mean arterial pulmonary pressure (11.9 1.3 to 24 3.6 mmHg) produced the following changes in the right ventricle without preload and contractility changes: a) maximal elastance shifted towards the end of the ejection (127.5 18.5 ms) and the ejection time shortened (57.5 20.3 ms), so that the negative peak of the first ventricular pressure derivative occurred at the end of the ejection; b) the pressure-volume loop became rectangular, i.e.; the systolic and diastolic phases were isovolumic, and c) the ejection showed a single phase. CONCLUSIONS: Asynchronous and sequential right ventricular contraction with normal afterload changed to a synchronic contraction pattern as in the left ventricle during an acute and moderate afterload increase. This left ventricle-like mechanical property establishes a novel mechanical reserve mechanism of the right heart, since it allows the right ventricle to maintain its systolic function during an afterload increase, independently of the preload and contractility.     

Long-term hemodynamic function of the transplanted heart

The aim of this study was to identify the long-term haemodynamic changes of the transplanted heart. Between 1987 and 1997, 136 patients required cardiac transplantation at Dijon hospital. During follow-up, 76 patients aged 51.2 +/- 9.46 years underwent catheter studies (12 women, 15.8%; and 64 men, 84.2%). Right and left heart catheterisation was performed at 3 months, 1, 2, 3 and 5 years after transplantation. Right heart catheterisation included measurement of mean pulmonary artery and pulmonary capillary pressures and pulmonary arteriolar resistances. During left heart catheterisation, cardiac output, mean aortic pressure, the ejection fraction, the dp/dt max of the left ventricular wall, systemic arterial resistances and left ventricular end diastolic pressures were measured. At each catheter study, the indexed myocardial mass, indexed end systolic and end diastolic left ventricular volumes, the mass/volume ratio, the residual serum cyclosporine concentrations and the serum creatinine were analysed. In addition, an endomyocardial biopsy was also performed. Initially raised, the mean pulmonary artery and pulmonary capillary pressures decrease from the 3rd month to the 2nd year. From the 3rd year onwards, they readjust to the upper limits of normal. The pulmonary artery resistances underwent the same changes. The left heart parameters remained constant over the period of follow-up but with a heart rate, mean aortic pressure and left ventricular end diastolic pressure higher than normal. The indexed myocardial mass was increased at all periods. The indexed left ventricular end systolic and diastolic volumes decreased with a M/V ratio which increased. Cyclosporine concentrations decreased whereas serum creatinine increased. The frequency of severe rejection and of coronary atherosclerosis was low. Significant correlations were observed between different parameters at different periods. In the long-term, the function of the transplanted heart is not normal in the strict sense of the term. The apparent normality is obtained by anti-hypertensive treatment. The transplanted heart adapts to the increase in cyclosporine-induced afterload by permanent myocardial hypertrophy, and increased diastolic pressure probably relates to diastolic dysfunction without noticeable intracardiac fibrosis.     

Mechanism of nitroglycerin effect in valvular aortic stenosis

The hemodynamic effects of nitroglycerin taken sublingually were studied during cardiac catheterization in 10 patients with valvular aortic stenosis. Hemodynamics and cineangiographic left ventricular volumes were determined before administration of nitroglycerin and at peak nitroglycerin effect. Diastolic pressure-time and ejection pressure-time product were used to evaluate left ventricular energy supply and demand. Pressurevolume loops and left ventricular wall tension were calculated. There was a decrease (P < 0.05) in aortic systolic pressure, but heart rate and aortic diastolic pressure did not change significantly. Left ventricular ejection pressure-time declined by more than 20 percent and diastolic pressuretime did not show a significant change. Thus, the ratio of diastolic pressure-time to ejection pressure-time increased from 0.59 ± 0.07 (mean ± standard error) to 0.71 ± 0.09 (P < 0.05). There were significant declines in left ventricular peak systolic and end-diastolic pressures, endsystolic and end-diastolic volumes and peak left ventricular wall tension. Thus, the peripheral unloading effects of nitroglycerin were reflected in the left ventricle despite the fixed aortic valve obstruction. There was no significant change in any measure of left ventricular contractility after administration of nitroglycerin.

It is concluded that sublingual nitroglycerin in aortic valve stenosis: (1) improves indirect indexes of left ventricular energy supply/demand ratio, (2) decreases left ventricular preload and afterload, and (3) does not change left ventricular contractility.     

Hemodynamics of the Mueller maneuver in man: right and left heart micromanometry and Doppler echocardiography

Ten subjects with normal hemodynamics were studied during elective cardiac catheterization with right and left heart multisensor micromanometry to assess hemodynamic responses to the Mueller maneuver. Simultaneous right and left circulatory hemodynamics and left ventricular, pulmonary arterial, and aortic pressures were recorded, in addition to pulmonary arterial and aortic flow velocities. Steady-state cardiac outputs were determined by thermal dilution. Aortic systolic and mean pressures were not significantly changed during the Mueller maneuver, in contrast to a lower diastolic (p = .019) and higher pulse pressure (p = .016). Mean right atrial pressure (+/- SE) decreased from 7 +/- 1 to -17 +/- 4 mm Hg (p = .0002) and the right atrial "x" descent was markedly accentuated. Left ventricular end-diastolic pressure decreased from 12 +/- 4 to -3 +/- 13 mm Hg (p = .0025). Systemic vascular resistance and left ventricular peak positive dP/dt were increased during the Mueller maneuver (p less than .02), cardiac output and stroke volume were reduced (p less than .05), and there was no significant change in heart rate. Right and left peak flow velocities showed a trend toward a bilateral decrease (right, p = .054; left, p greater than .1), and times to peak flow velocity were increased in the pulmonary artery (p = .007) and reduced in the aortic root (p = .03). Normal subjects were studied separately by pulsed Doppler echocardiography. During the sustained Mueller maneuver, the internal jugular and right ventricular dimensions decreased, and superior vena cava Doppler flow was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)     

Abnormal exercise hemodynamics in patients with normal systolic function late after aortic valve replacement

We studied the hemodynamic response to supine bicycle exercise in 20 patients late (10 +/- 2 years) after aortic valve replacement (for aortic stenosis in 12 patients, aortic insufficiency in six patients, and for combined stenosis and insufficiency in two patients). The pulmonary artery wedge pressure was obtained with a pulmonary artery balloon catheter, and left ventriculography was performed by digital-subtraction angiography after injection of radiographic contrast into the pulmonary artery. These patients were compared with 11 control subjects with no or minimal cardiac disease studied routinely for evaluation of chest pain in whom left ventricular end-diastolic pressure and a direct contrast ventriculogram were obtained. Compared with the control population, the study population had similar left heart filling pressures (7 +/- 3 vs 9 +/- 3 mm Hg, NS), but higher left ventricular ejection fractions (75 +/- 7% vs 67 +/- 7%, p less than .02) and higher left ventricular muscle mass indexes (106 +/- 28 vs 85 +/- 9 g/m2, p less than .01). Elevated myocardial muscle mass led to lower systolic wall stress in the study population than in the control subjects (254 +/- 65 vs 320 +/- 49 10(3).dynes/cm2, p less than .01) and might explain the higher ejection fraction observed. Fourteen patients had a normal response to exercise (with left heart filling pressures of 16 +/- 4 vs 18 +/- 2 mm Hg for control subjects, NS; and left ventricular ejection fraction of 77 +/- 8% vs 73 +/- 5% for control subjects, NS). However, while the remaining six patients had a normal exercise left ventricular ejection fraction (72 +/- 9%, NS), they had an abnormal rise in left heart filling pressure (33 +/- 8 mm Hg, p less than .01). Preoperatively these patients also had higher left ventricular mid- and end-diastolic pressures at similar diastolic volumes, suggesting a decrease in chamber compliance. Thus, late after aortic valve replacement there is a subgroup of patients who, despite normal hemodynamics and normal left ventricular systolic function as assessed by the left ventricular ejection fraction at rest, have an abnormal response to exercise characterized primarily by a substantial rise in left heart filling pressures. Preoperatively this group also has a decrease in diastolic chamber compliance despite nearly normal left ventricular ejection fractions. This abnormality appears to result from a primary derangement of diastolic function that is not evident at rest.     

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.     

Pressure tracings in obstructive Tako-Tsubo cardiomyopathy

A 70-year-old female experienced severe anxiety due to an incident with a stranger when she was home alone at night. Immediately after the event, she had an oppressive chest sensation; 16 h later she was admitted to hospital. Left ventriculography showed akinesia of the mid-to-distal portion and hyperkinesia of the basal portion of the left ventricular chamber. However, coronary angiography showed no significant coronary artery disease. We diagnosed her as having Tako-Tsubo cardiomyopathy. Subsequently, left ventricular and central aortic pressures were recorded simultaneously. Initial recording showed a peak systolic gradient of 60 mm Hg. On the first sinus beat after a premature ventricular contraction, the peak systolic gradient increased to 130 mm Hg, and the pulse pressure decreased. Shortly after intravenous administration of nitroglycerin (0.5 mg), central aortic pressure decreased and the peak systolic gradient increased to 100 mm Hg. On the first sinus beat after a premature ventricular contraction, the peak systolic gradient increased to 160 mm Hg, and the pulse pressure decreased. Five minutes after intravenous nitroglycerin, the peak systolic gradient returned to 70 mm Hg. Follow-up transthoracic echocardiography 13 days later showed normal left ventricular wall motion with no pressure gradient through the left ventricular outflow tract.     

Comparison of two calcium blockers on hemodynamics, left ventricular mass, and coronary vasodilatory in advanced hypertension

Dihydropyridine and nondihydropyridine calcium channel blockers (CCB) differ in pharmacologic characteristics. Few clinical studies distinguish effects of CCB as monotherapy. We conducted a comprehensive comparison of two CCB on patients with moderate to severe hypertension. Thirty patients with pretreatment diastolic blood pressures > or = 100 mm Hg were randomly assigned to either nifedipine-GITS or verapamil-SR. Dose titration achieved a diastolic blood pressure of < or = 95 mm Hg or a decrease of > or = 15 mm Hg over 4 weeks. Clinic blood pressure (BP), 24-h ambulatory BP, exercise BP, left ventricular mass, systolic and diastolic function by echocardiography, and coronary flow reserve by split-dose thallium-201 imaging with adenosine were assessed at baseline, end of titration, 3 months and 6 months of treatment. Plasma renin activity, atrial natriuretic peptide, norepinephrine, and epinephrine were assayed. Both drugs caused similar reductions in clinic and 24-h ambulatory BP and similar reductions in left ventricular mass index. Compared to nifedipine-GITS, verapamil-SR produced a significantly lower resting and peak exercise heart rate. Nifedipine-GITS elicited a lower peak exercise systolic BP. At end titration nifedipine-GITS produced lower plasma atrial natriuretic peptide levels, no longer apparent by 6 months. Plasma norepinephrine was lower with verapamil-SR, also at end titration and at 3 months, but not at 6 months. Plasma epinephrine and plasma renin activity were unchanged by either drug. There was no difference for systolic or diastolic left ventricular function or coronary flow reserve between the two treatments. Once daily nifedipine-GITS and verapamil-SR are equally effective for reduction of arterial pressure in moderate to severe hypertension. Differences in their hemodynamic profiles and neurohormonal responses are consistent with preclinical pharmacologic characteristics. The clinical implications of their similarities and differences remain to be fully evaluated in outcome studies.     

The physiology of external cardiac massage: high-impulse cardiopulmonary resuscitation

In intact chronically instrumented dogs, left ventricular dynamics were studied during cardiopulmonary resuscitation (CPR). Electromagnetic flow probes measured cardiac output and coronary blood flow, ultrasonic transducers measured cardiac dimensions, and micromanometers measured left ventricular, right ventricular, aortic, and intrathoracic pressures. The dogs were anesthetized with morphine, intubated, and fibrillated by rapid ventricular pacing. Data were obtained during manual external massage with dogs in the lateral and supine positions. Force of compression was varied from a peak intrathoracic pressure of 10 to 30 mm Hg, and compression rate was varied from 60 to 150/min. Increasing force of compression increased stroke volume up to a peak intrathoracic pressure of approximately 20 mm Hg, beyond which stroke volume remained constant or declined. Stroke volume appeared to result primarily from direct transmission of manual compression force to the heart rather than from positive intrathoracic pressure because peak cardiac or vascular pressures or the change in these pressures were consistently two to four times greater than the corresponding intrathoracic pressures during manual compression. With increasing compression rate, stroke volume remained relatively constant, and total cardiac output increased significantly: 425 +/- 92 ml/min at 60/min, 643 +/- 130 ml/min at 100/min, and 975 +/- 219 ml/min at 150/min (p less than .05). Left ventricular dimensions decreased minimally at higher manual compression rates. In four patients undergoing CPR, systolic and diastolic arterial blood pressure increased with faster compression rates, correlating well with data obtained in the dog. Dynamic coronary blood flow in canine experiments decreased to zero or negative values during compression. Antegrade coronary flow occurred primarily during noncompression periods and seemed to be related to diastolic aortic perfusion pressure; coronary flow at a compression rate of 150/min averaged 75% of control. Therefore stroke volume and coronary blood flow in this canine preparation were maximized with manual chest compression performed with moderate force and brief duration. Increasing rate of compression increased total cardiac output while coronary blood flow was well maintained. Direct cardiac compression appeared to be the major determinant of stroke volume during manual external cardiac massage.