Comparative effects of ionic and nonionic contrast materials on indexes of isovolumic contraction and relaxation in humans

The effects of contrast media on left ventricular (LV) relaxation as assessed by the time constant of isovolumic relaxation have not previously been studied. A new nonionic contrast agent (iohexol) has been shown to have fewer deleterious effects than standard ionic agents. Nineteen patients received iohexol and sodium meglumine diatrizoate (Renografin-76) in a double-blind, crossover study during left and right coronary arteriography and with simultaneous high-fidelity micromanometer measurements of LV pressure. Neither agent induced significant changes in LV end-diastolic pressure after right or left coronary arteriography. After right coronary arteriography, neither agent produced significant deterioration of peak positive dP/dt or (dP/dt)/DP40 (dP/dt at a developed pressure of 40 mm Hg). However, after right coronary arteriography both agents caused a transient deterioration in peak negative dP/dt and the time constant of isovolumic relaxation (p less than 0.05 at 20 seconds after arteriography). After left coronary arteriography, sodium meglumine diatrizoate induced deterioration of systemic blood pressure (p less than 0.05), peak positive dP/dt (p less than 0.01), (dP/dt)/DP40 (p less than 0.05), peak negative dP/dt (p less than 0.01) and the relaxation time constant (p less than 0.01). These effects were not induced by iohexol. Thus, nonionic contrast media exert negligible alterations on LV function when used for coronary arteriography. The findings are of potential clinical importance in view of the large number of patients with depressed LV function who undergo coronary arteriography.     

Mechanical loads and the isovolumic and filling indices of left ventricular relaxation

In this report we have emphasized the significant influence of loading conditions on LV relaxation. Changes in inotropic state, ischemia, hypertrophy, and a host of other factors were not discussed herein. Ventricular asynchrony is likewise beyond the scope of this review, but it should be recognized that complex loading interactions among fibers within the LV wall influence relaxation and filling in ventricles that contract and relax nonsynchronously. Intact heart and isolated muscle experiments indicate that changes in preload do not influence relaxation rates when systolic pressure or total load remains constant. It appears, therefore, that the relaxation changes that occur with volume loading are primarily due to changes in systolic pressure or load. Indeed, an increase in systolic pressure may cause a substantial decrease in isovolumic relaxation rate, especially if there is a slow rise and a late peak in LV pressure. By contrast, an abrupt increase in late systolic load augments relaxation rate. Intact heart studies indicate that an abrupt load increment near the end of ejection results in premature and more rapid isovolumic relaxation, while an increase in left atrial pressure increases the filling rate; isolated muscle studies indicate that a load increment at the end of isometric relaxation causes an increase in isotonic relaxation rate. Thus, loading conditions during the periods of ejection, isovolumic relaxation, and filling can influence relaxation parameters and should be considered in clinical and experimental studies of LV relaxation.     

Noninvasive estimation of the instantaneous first derivative of left ventricular pressure using continuous-wave Doppler echocardiography

BACKGROUND. The complete continuous-wave Doppler mitral regurgitant velocity curve should allow reconstruction of the ventriculoatrial (VA) pressure gradient from mitral valve closure to opening, including left ventricular (LV) isovolumic contraction, ejection, and isovolumic relaxation. Assuming that the left atrial pressure fluctuation is relatively minor in comparison with the corresponding LV pressure changes during systole, the first derivative of the Doppler-derived VA pressure gradient curve (Doppler dP/dt) might be used to estimate the LV dP/dt curve, previously measurable only at catheterization (catheter dP/dt). METHODS AND RESULTS. This hypothesis was examined in an in vivo mitral regurgitant model during 30 hemodynamic stages in eight dogs. Contractility and relaxation were altered by inotropic stimulation and hypothermia. The Doppler mitral regurgitant velocity spectrum was recorded along with simultaneously acquired micromanometer LV and left atrial pressures. The regurgitant velocity profiles were digitized and converted to VA pressure gradient curves using the simplified Bernoulli equation. The instantaneous dP/dt of the VA pressure gradient curve was then derived. The instantaneous Doppler-derived VA pressure gradients, instantaneous Doppler dP/dt, dP/dtmax, and -dP/dtmax were compared with corresponding catheter measurements. This method of estimating dP/dtmax from the instantaneous dP/dt curve was also compared with a previously proposed Doppler method of estimating dP/dtmax using the Doppler-derived mean rate of LV pressure rise over the time period between velocities of 1 and 3 m/sec on the ascending slope of the Doppler velocity spectrum. Both instantaneous Doppler-derived VA pressure gradients (r = 0.95, p less than 0.0001) and Doppler dP/dt (r = 0.92, p less than 0.0001) correlated well with corresponding measurements by catheter during systolic contraction and isovolumic relaxation (pooled data). The Doppler dP/dtmax (1,266 +/- 701 mm Hg/sec) also correlated well (r = 0.94) with the catheter dP/dtmax (1,200 +/- 573 mm Hg/sec). There was no difference between the two methods for measurement of dP/dtmax (p = NS). Although Doppler -dP/dtmax was slightly lower than the catheter measurement (961 +/- 511 versus 1,057 +/- 540 mm Hg/sec, p less than 0.01), the correlation between measurements by Doppler and catheter was excellent (r = 0.93, p less than 0.0001). The alternative method of mean isovolumic pressure rise (896 +/- 465 mm Hg/sec) underestimated the catheter dP/dtmax (1,200 +/- 573 mm Hg/sec) significantly (on average, 25%; p less than 0.001). CONCLUSIONS. The present study demonstrated an accurate and reliable noninvasive Doppler method for estimating instantaneous LV dP/dt, dP/dtmax, and -dP/dtmax.     

Pharmacologic alterations of the isovolumic index: a study of the effects of isoproterenol, propranolol and verapamil

The isovolumic index has been proposed as a noninvasive index of left ventricular function which, unlike the traditional systolic time index, incorporates the period of isovolumic relaxation. The responses of the isovolumic index and the systolic time index to three cardioactive drugs (isoproterenol, propranolol and verapamil) were assessed by measurements of ejection time (ET), isovolumic contraction time (IVC) and isovolumic relaxation time (IVR) in 23 dogs instrumented with high fidelity micromanometers and ultrasonic crystals. Isoproterenol infusions resulted in improvements in both the isovolumic and systolic time indices as a result of significant shortening of ET, IVC and IVR. Propranolol infusions caused significant and parallel increases of IVC (P less than 0.01) and ET (P less than 0.05) but failed to cause prolongation of either the systolic time index, defined as (IVC/ET) or deterioration of regional function. A higher propranolol dose caused significant increases in ET, IVC (P less than 0.001) and IVR (P less than 0.05), yet neither the systolic time index or the isovolumic index (IVC + IVR/ET) were prolonged, and regional function remained normal. Verapamil infusion caused an upward, nonsignificant trend in the isovolumic index and no change in the systolic time index. Stepwise multiple linear regression analysis demonstrated a similar load dependency of both indices and a higher inverse correlation of the isovolumic index with fractional shortening. The systolic time index showed a higher dependency on peak positive dP/dt whereas only the isovolumic index showed dependency on the isovolumic relaxation time constant. When altered loading conditions are accounted for, the isovolumic index shows directional changes that reflect changes in peak positive dP/dt, the isovolumic relaxation time constant and regional shortening.     

Left ventricular isovolumic relaxation is a predictor of left ventricular end-diastolic pressure

BACKGROUND: The relationship between isovolumic left ventricular (LV) relaxation and LV filling pressures remains incompletely explored. If there is a relationship between the rate of early diastolic LV relaxation and LV end-diastolic pressure, this would have important implications concerning both our understanding and, potentially, our treatment of LV diastolic dysfunction. OBJECTIVE: To examine the baseline hemodynamic correlates of LV end-diastolic pressure in patients with both normal and abnormal LV function. METHODS: The relationships between LV end-diastolic pressure, a variety of hemodynamic parameters (tau, the rate of LV isovolumic relaxation, LV peak positive+dP/dt, LV peak systolic pressure and heart rate), measures of LV end-systolic and end-diastolic volume, and age were determined using regression analysis techniques in 104 patients with normal LV systolic function and 90 patients with an LV ejection fraction of less than 40%. RESULTS: Univariate analysis demonstrated a correlation between tau and LV end-diastolic pressure (r=0.743, P<0.001). There were significant univariate relationships between a number of other hemodynamic variables and LV end-diastolic pressure. A multiple regression model demonstrated that tau made the most important contribution to a model where LV end-diastolic pressure is the dependent variable. LV peak systolic pressure and heart rate also made significant contributions to the model. In 33 of these patients, when LV end-diastolic pressure was reduced using an inferior vena cava occlusion balloon, tau did not change. The acute administration of clonidine (n=11) caused an increase in LV end-diastolic pressure that was closely correlated with an observed increase in tau (r=0.843, P<0.001). CONCLUSIONS: These observations suggest that the rate of LV isovolumic relaxation is a predictor of LV end-diastolic pressure.     

Monophasic transmitral flow pattern with less increase in heart rate indicates left ventricular dysfunction.

When heart rate (HR) increases, mitral flow can become monophasic. Prolonged isovolumic contraction and relaxation time (ICT and IRT), directly related to left ventricular (LV) function, can potentially influence the HR with monophasic mitral flow. The present study investigated the relation between HR that causes monophasic flow and LV function. During diagnostic catheterization, HR was increased using right atrial pacing by 2 beats/min every 2 min in a stepwise manner until the development of monophasic mitral flow in 17 patients with normal sinus rhythm. ICT, IRT, end-diastolic and end-systolic LV volumes, LV ejection fraction, LV peak + and -dP/dt, peak (+dP/dt)/P, and the relaxation time constant (tau) were measured by Doppler echocardiography or catheterization when monophasic mitral flow developed. The monophasic HR varied from 74 to 106 beats/min. By univariate analysis, ICT (p<0.01, r2=0.73), LV peak +dP/dt (p<0.05, r2=0.37), peak (+dP/dt)/P (p<0.01, r2=0.71), peak -dP/dt (p<0.05, r2=0.25), and tau (p<0.05, r2=0.33) had a significant correlation with monophasic HR. By multivariate analysis, prolonged ICT and reduced LV peak -dP/dt independently contributed to monophasic mitral flow with less increase in HR. Monophasic mitral flow with less increase in HR indicates impaired LV systolic and diastolic function during isovolumic contraction and relaxation.     

Nisoldipine, a new calcium antagonist: its effect on systolic function and relaxation in the dog

The effect of calcium-blockers on left ventricular (LV) relaxation is still a matter of debate. In 7 open-chest dogs we studied the effect of 0.01 mg/kg Nisoldipine intravenously on LV systolic function and relaxation. LV long and short axes and LV wall thickness were measured by ultrasonic crystals. LV high-fidelity pressure and aortic pressure were recorded at rest, and 2 and 30 min after i.v. Nisoldipine. Partial obstruction of the ascending aorta was performed to keep LV peak systolic pressure close to control values. LV systolic wall stress and LV ejection fraction were calculated in all dogs. The time constant of LV pressure decay (T; ms) was determined from a linear regression of LV pressure and neg. dP/dt. Heart rate and LV end-diastolic pressure remained unchanged following the administration of Nisoldipine. LV peak systolic pressure and wall stress decreased significantly 2 and 30 min after Nisoldipine but were in the normal range with partial obstruction of the ascending aorta. Max. dP/dt decreased slightly although not significantly after Nisoldipine. LV ejection fraction increased, however, significantly from 30% to 39% at 2 min and to 35% at 30 min after Nisoldipine. The time constant T increased from 27 ms to 40 ms (P less than 0.05) at 2 min and amounted to 28 ms at 30 min following Nisoldipine. It is concluded that Nisoldipine is associated with a persistent decrease of LV afterload and a transitory increase in T.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic correlates for timing intervals, ejection rate and filling rate derived from the radionuclide angiographic volume curve

This study was designed to more clearly define the relation between various invasive hemodynamic measurements and left ventricular (LV) timing intervals, ejection rate and filling rate derived from the radionuclide angiographic volume curve. Twenty-eight patients were studied with simultaneous intracardiac micromanometer pressure and dP/dt recordings, gated radionuclide angiography and M-mode echocardiography. These techniques permitted multiple variables of systolic and diastolic function to be measured at a constant atrial paced rate of 100 beats/min. There was a strong correlation between peak ejection rate and ejection fraction (r = -0.97) and between peak ejection rate and maximum positive dP/dt (r = -0.85). There also was a strong correlation between peak filling rate and maximum negative dP/dt (r = -0.85). A weaker correlation existed between the time constant of LV relaxation and the peak filling rate (r = -0.49) and between the LV end-diastolic pressure and the peak filling rate (r = -0.62). There was no correlation between the modulus of chamber stiffness and filling rates, and no association was observed between the time to peak filling rate and the hemodynamic variables. Thus, under the conditions studied, the measured peak ejection and filling rate, determined from the radionuclide angiographic volume curve, correlated well with accepted invasive hemodynamic measurements.     

Correlation between left ventricular contractility and relaxation in patients with idiopathic dilated cardiomyopathy

Background and hypothesis: It is not fully understood whether alterations in left ventricular (LV) relaxation in patients with idiopathic dilated cardiomyopathy (DCM) precede or follow alterations in LV systolic function. Accordingly, we investigated the relationship between LV systole and diastolic relaxation in patients with DCM using LV pressure-volume analysis. Methods: Hemodynamic data were collected for 38 consecutive patients with DCM in normal sinus rhythm and in the resting steady state (New York Heart Association functional class II to III). Continuous simultaneous pressure-volume relationships were obtained by conductance catheter. Left ventricular end-systolic elastance (Ees) was determined during transient occlusion of the inferior vena cava. Results: Left ventricular ejection fraction, peak negative dP/dt, and peak positive dP/dt were depressed (31 ± 11%, - 1242 ± 351 mmHg/s, and 1118 ±253 mmHg/s, respectively ). The LV end-diastolic volume index, the time constants of isovolumic LV pressure decay Tl and Td were increased (141 ±38 ml/m², 54+14 ms, and 69 ± 17 ms, respectively). Ees was markedly depressed (0.9 ± 0.5 mmHg/ml) and was not correlated with established systolic or diastolic indices except for peak positive dP/dt. Our results showed that abnormalities of relaxation were not correlated with contractile dysfunction in patients with DCM in the resting steady state however, most patients (79%) had both prolonged relaxation and extremely depressed contractility. Abnormal relaxation may have been transient or compensated in some patients (21%) with DCM who had preserved relaxation despite severely depressed contractility.     

Diastolic vibration improves systolic function in cases of incomplete relaxation.

BACKGROUND. Incomplete relaxation of the left ventricle (LV) affects LV filling, but the subsequent effect on LV systolic function remains unclear. We attempted to improve relaxation by applying oscillatory mechanical perturbation during diastole (diastolic vibration) and examined the extent to which systolic function improved. METHODS AND RESULTS. Using 10 open-chest canine preparations, pacing tachycardia and administration of propranolol were imposed to induce various levels of incomplete relaxation. Myocardial length perturbation was induced with an oscillator attached to the LV surface (50 Hz, 1-mm amplitude) and was restricted to the period from the beginning of isovolumic relaxation to end diastole. At resting heart rates, diastolic vibration caused an immediate decrease in the time constant (T) of LV pressure fall without any influence on heart rate, LV peak systolic pressure (peak LVP), stroke volume (SV), LV peak positive dP/dt, and total systemic vascular resistance. With pacing tachycardia, diastolic vibration increased both peak LVP and SV at 160 beats per minute (before) and 120 beats per minute (after propranolol), simultaneously decreasing both T and LV diastolic pressures and increasing end-diastolic segment length. The increase in peak LVP and SV caused by diastolic vibration correlated with the T/diastolic interval (r = 0.82), the assumed index of severity of incomplete relaxation. CONCLUSIONS. These results suggest that diastolic vibration accelerates the LV relaxation rate and that this increased relaxation improves systolic function through the Frank-Starling mechanism.     

Contribution of left ventricular contraction to the generation of right ventricular systolic pressure in the human heart

To determine whether left ventricular (LV) contraction contributes to the generation of right ventricular (RV) systolic pressure in humans, LV and RV pressures and their first derivative (dP/dt) were recorded simultaneously with micromanometer-tipped catheters in 11 conscious subjects. Seven subjects had normal LV and coronary angiograms. Four subjects had moderate LV dysfunction (resting ejection fraction 0.40 to 0.50), and three of these had coronary artery disease. During normal sinus rhythm, LV contraction slightly preceded RV contraction (mean 20 msec), and LV and RV dP/dt recordings showed single positive systolic peaks that were coincident. During endocardial pacing of the RV free wall, RV contraction preceded LV contraction (mean 23 msec) and two systolic RV dP/dt peaks were recorded, the first (peak I) occurring significantly before (mean +/- SD = 67 +/- 23 msec, p less than .01), and the second (peak II) coincident with the single systolic LV dP/dt peak. RV ectopic beats produced a similar RV dP/dt pattern, with peak I occurring 63 +/- 11 msec (p less than .01) before, and peak II coincident with the single LV dP/dt peak. Conversely, during LV ectopic beats, LV contraction preceded RV contraction (mean 63 msec) and two systolic RV dP/dt peaks were recorded, but peak I was coincident with the single LV dP/dt peak, while peak II occurred significantly later (63 +/- 26 msec, p less than .01). In two subjects right bundle branch block produced similar findings. In three subjects left bundle branch block produced little ventricular asynchrony (mean 14 msec), but did delay the development of peak LV dP/dt after LV contraction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Usefulness of negative dP/dt upstroke pattern for assessment of left ventricular relaxation in coronary artery disease

It has been reported that regional asynchrony due to acute ischemia disturbs the exponential nature of left ventricular (LV) pressure reduction and may alter the pattern of (-)dP/dt upstroke curve. If LV pressure decreases exponentially during the isovolumic relaxation period (P = Ae-t/T + B, where A and B = constants, t = time and T = time constant), the (-)dP/dt upstroke curve should also be exponential and upward-convex because dP/dt = A(-t/T)e-t/T. To test this theory in humans, the LV (-)dP/dt upstroke curve was analyzed in 9 normal subjects, 12 patients with effort angina pectoris (AP) and 15 with old myocardial infarction (MI) under the basal conditions. The (-)dP/dt upstroke was convex-upward in all normal subjects, but convex-downward in 9 of 12 patients with AP and in all patients with MI, which suggests nonexponential decrease in LV pressure in the groups with AP and MI. The dP/dt (20/60), which is the ratio of the (-)dP/dt value at 20 ms after peak (-)dP/dt to that at 60 ms after peak (-)dP/dt, was significantly lower in the group with AP (1.70 +/- 0.07) and in the group with MI (1.61 +/- 0.13) than in normal subjects (2.08 +/- 0.18) (p less than 0.005). This indicates that (-)dP/dt upstroke 20 to 60 ms after peak (-)dP/dt increases more slowly in the groups with AP and MI than in normal subjects. Theoretical consideration showed that such a slower increase of the upstroke resulted from impaired early to midrelaxation.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of left ventricular wall motion during isovolumetric relaxation period in coronary artery disease

The effect of the left ventricular (LV) regional wall motion during isovolumetric relaxation period (IRP) were studied in 9 patients with old anteroseptal myocardial infarction (OMI) and 8 normal subjects (NOR). There were no significant differences in heart rate, peak LV systolic pressure and peak (+) dP/dt between the groups. LV cavity was divided into the anterior and inferior sides by a long axis, which was equally divided with 3 perpendicular lines, creating 4 areas in each side. The sums of the 2 middle areas in each side were defined as Aa and Ab, respectively. During IRP the pattern of (-) dP/dt at the upstroke phase was convex-downward in OMI, but convex-upward in NOR. Time constant (T) was significantly prolonged in OMI compared with NOR (50 +/- 9 vs 37 +/- 6 msec; p less than 0.01). On NOR, Aa increased significantly after 33.4 msec from peak (-) dP/dt, while Ab remained unchanged. In OMI, Ab increased after 50.1 msec from peak (-) dP/dt, associated with decrease in Aa, suggesting the passive shortening of the anterior wall by the active expansion of the inferior. Such asynchronous LV wall motions during IRP might impair LV relaxation and influence the upstroke pattern of (-) dP/dt.     

Correlation between Doppler derived dP/dt and left ventricular asynchrony in patients with dilated cardiomyopathy: A combined study using strain rate imaging and conventional Doppler echocardiography

AIM: To evaluate the relationship between Doppler-derived left ventricular (LV) dP/dt and the degree of LV mechanical asynchrony measured by strain rate imaging. METHODS AND RESULTS: The study group consisted of 69 patients with variable degree of LV dysfunction and mitral regurgitation (MR). Conventional echo variables and LV dP/dt were calculated from the MR Doppler spectrum by rate-pressure-rise method. Strain rate traces were obtained by 12-segment model and LV long axis images were analyzed off-line. The longest time intervals between the peak negative strain rate waves at isovolumic contraction period and peak systole from reciprocal segments were defined as asynchrony index AIc or AIs, respectively. The maximum differences in time-to-peak systolic velocities between opposing walls were also measured as asynchrony index by tissue Doppler (AItd). The dP/dt, mean QRS duration, AIc, AIs, and AItd were 836 +/- 266 mmHg/sec, 125 +/- 31, 38 +/- 28, 64 +/- 44, and 52 +/- 32 m, respectively. No significant correlation between the dP/dt and the LV dimension, ejection fraction or QRS duration was observed. However, dP/dt correlated negatively with AIc, or AIs (r:-0.78, -0.72, P < or = 0.0001) and AItd (r:-0.65, P < or = 0.001). A cutoff dP/dt value of under 700 mmHg/sec can discriminate patients over median AIs (55 ms) or patients with AIc over 30 ms with high sensitivity and specificity. CONCLUSIONS: Doppler-derived LV dP/dt is related to the degree of LV dyssynchrony rather than the conventional systolic function indices such as EF% in patients with severe heart failure. Noninvasive dP/dt assessment in addition to advanced imaging techniques can be used to define patients for cardiac resynchronization therapy (CRT).     

Early segmental thinning of the left ventricular wall following regional ischemia

To explore possible mechanisms of left ventricular early segmental relaxation, complete occlusion of the left anterior descending coronary artery (LAD) was produced in seven open-chest dogs and partial occlusion of the LAD was produced in six openchest anesthetized dogs. Regional wall thickness was measured both in an ischemic and a normally perfused zone using implanted ultrasonic crystals. Two to three seconds following complete LAD occlusion, thinning of the ischemic wall occurred prematurely during isovolumic relaxation. The extent of premature thinning became more prominent 5 to 10 sec following LAD occlusion. Early thinning of the ischemic wall preceded thinning of the normally perfused wall by 110 ± 10 msec. Partial occlusion of the LAD produced a 33 ± 6% reduction of coronary flow and a 23 ± 4% reduction of systolic wall thickening in the ischemic region. Systolic thickening of the nonischemic wall was unchanged relative to the preocclusion period. Premature early thinning of the mildly ischemic wall preceded thinning of the normally perfused segment by 90 ± 8 msec. The observation that ischemia can produce segmental early thinning of the ventricular wall may have implications in understanding the mechanism of the angiographic observation of the segmental early relaxation phenomena in patients with coronary artery disease.     

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)     

Sensitivity of isovolumic relaxation to hypothermia during myocardial infarction

Effects of moderate spontaneous hypothermia on left ventricular systolic and diastolic function during acute myocardial infarction were documented in 17 anesthetized dogs with micromanometric pressure and ventriculographic dimension recordings acquired at baseline and at 1 and 3 h after coronary occlusion. In Group 1 (n = 5), core temperature was allowed to decline spontaneously. In Groups 2 (n = 6) and 3 (n = 6), core temperature was maintained at normothermic levels. Hypothermia impaired isovolumic relaxation markedly despite its lack of effect on ventricular volumes or ejection fraction. At 32.3 degrees C, tau 1/2, defined as the time needed for the left ventricular pressure at the time of peak negative rate of change of left ventricular pressure (dP/dt) to fall by 50%, was increased by 129% 3 h after occlusion. In addition, at this temperature significant changes were found in heart rate, cardiac output, minute work, peak positive and peak negative dP/dt, systolic ejection time, mean velocity of circumferential fiber shortening, mean aortic pressure and end-diastolic pressure. Thus, hypothermia evolving under conditions of general anesthesia profoundly alters left ventricular function in the setting of acute myocardial infarction, a phenomenon that requires consideration and control in studies of myocardial ischemia and left ventricular function in experimental animals.     

Wide-range load shift of combined aortic valvuloplasty-arterial vasodilation slows isovolumic relaxation of the hypertrophied left ventricle

To assess the effects of left ventricular (LV) load on isovolumic relaxation rate of the hypertrophied LV, wide range LV load shifts were imposed by the sequential use of balloon aortic valvuloplasty (BAV) and arterial vasodilation in 14 patients with severe sclerocalcific aortic stenosis (aortic valve area, 0.45 +/- 0.16 cm2). Micromanometer tip-catheter LV pressure recordings (n = 14) and simultaneous LV angiograms (n = 9) were obtained before BAV, during nitroprusside infusion (NIT) before BAV, 48 hours after BAV, and 48 hours after BAV during NIT. LV peak systolic pressure (LVPSP) decreased from 237 +/- 33 mm Hg before BAV to 200 +/- 33 mm Hg (p less than 0.01) during NIT before BAV, to 201 +/- 27 mm Hg (p less than 0.01) after BAV and to 165 +/- 26 mm Hg (p less than 0.01) during NIT after BAV.LV end-systolic volume (LVESV) decreased from 55 +/- 34 ml before BAV to 25 +/- 23 ml (p less than 0.01) during NIT before BAV, to 30 +/- 32 ml (p less than 0.025) after BAV and to 15 +/- 12 ml (p less than 0.025) during NIT after BAV. LV end-systolic wall stress (LVESs) decreased from 90 +/- 30.10(3) dyne/cm2 before BAV to 41 +/- 13.10(3) dyne/cm2 (p less than 0.01) during NIT before BAV, to 55 +/- 16.10(3) dyne/cm2 (p less than 0.025) after BAV and to 26 +/- 6.10(3) dyne/cm2 (p less than 0.01) during NIT after BAV. Only after sequential BAV-NIT was the time of LV electromechanical systole (LVEST), which marked the onset of the LV isovolumic relaxation period, significantly reduced (from 419 +/- 26 msec before BAV to 363 +/- 28 msec after BAV-NIT [p less than 0.01]). The time constants of LV pressure decay with zero or nonzero asymptote pressure (TO and TPB) remained unchanged after BAV and during NIT before BAV. At the lowest LVPSP, LVESV, and LVESs after sequential BAV-NIT, both TO and TPB significantly prolonged from 35.7 +/- 6.3 to 46.7 +/- 12.6 msec (p less than 0.025) and from 46.6 +/- 12.5 to 73.2 +/- 23.3 msec (p less than 0.01). Phase-plane plots (LV dP/dt vs. LVP) of the LV pressure (P) signal during isovolumic relaxation were constructed for the four different loading states by matching corresponding LVP and LV dP/dt points. For a given LVP value, the corresponding LV dP/dt values on the phase plane plots were comparable before BAV, during NIT before BAV, and after BAV. The corresponding LV dP/dt value was higher during NIT after BAV, impling a slower relaxation rate at the same LVP after sequential BAV-NIT. A shift in the control of isovolumic LV relaxation kinetics from myofilamentary detachment to myoplasmic calcium removal, which proceeds slower in hypertrophied myocardium, could explain the observed slowing of LV isovolumic relaxation after drastic LV unloading of sequential BAV-NIT.     

Effects of a cardioselective beta 1 partial agonist (corwin) on left ventricular function and myocardial metabolism in patients with previous myocardial infarction

Corwin is a new selective beta 1 partial agonist, able to stabilize the beta 1 adrenoceptors at approximately 43% of their maximal activity. The aim of the study was to determine the effects of this agent in patients with coronary artery disease (CAD) and previous myocardial infarction (MI). In a first group of 14 patients, corwin increased significantly the peak (+)dP/dt (+35%; p less than 0.005), the global ejection fraction, and the ejection fraction of abnormally contracting segments (from 20 +/- 18 to 26 +/- 19%; p less than 0.02). Corwin also induced significant decreases in mean systolic (-8%; p less than 0.05) and mean diastolic (-38%; p less than 0.001) wall stress and accelerated the relaxation rate. In a second group of 11 patients, a metabolic study indicated that neither myocardial oxygen consumption (15 +/- 7 versus 15 +/- 7 ml/min; difference not significant) nor lactate extraction was modified by the drug. In this group, increases in peak (+)dP/dt, acceleration in ventricular relaxation (-8 ms in time constant of isovolumic pressure decrease; p less than 0.01), and decreases in left ventricular end-diastolic pressure also were noted after administration of corwin, both under basal conditions and during a cold pressor test. In conclusion, corwin is a positive inotrope which, in patients with CAD and left ventricular dysfunction, improves left ventricular systolic and diastolic function without inducing myocardial ischemia.     

Influence of acute changes in preload, afterload, contractile state and heart rate on ejection and isovolumic indices of myocardial contractility in man.

To determine the sensitivity of several isovolumic and ejection phase indices of myocardial contractility to loading, inotropic stimulation and heart rate in man, 14 patients (pts) were studied during cardiac catheterization with simultaneous recordings of left ventricular (LV) pressures and ultrasound dimensions. Measurements were made of instantaneous and mean circumferential fiber shortening velocity (VCF), maximal (max) rate of LV pressure rise (dP/dt), dPHdt divided by end-diastolic circumference [(dP/dt)/C], (DP/dt)/C divided by aortic valve opening pressure [(dP/dt/CP], PEAK CONTRACTILe element velocity (VCE) using total LV pressure, VCE extrapolated to zero total pressure (Vmax), VCE at a developed pressure of 10 mm Hg (VCEDP10) and dP/dt at a common isovolumic developed pressure of 40 mm Hg [(dP/dt)/DP40]. Resulta are expressed in per cent change of the mean for the group. Acute preload increase (8.6% increase in end-diastolic circumference) with volume expansion at constant heart rate in 7 pts produced insignificant changes in VSF, an 8.3% increase in max dP/dt, no change in (dP/dt)/C, a variable response in (dP/dt)/CP, 18% reduction in peak VCE, 16% reduction in Vmax, 14% increase in VCEDP10, and a 10% increase in (dP/dt)/DP40. An acute increase in afterload produced by angiotensin in 8 pts (44% increase in peak stress) led to a 38% decrease in VCF, a 2.5% increase in max dP/dt, no significant change in (dP/dt)/C, a 26% reduction in (dP/dt)/CP, variable responses in peak VCE and Vmax, an 11% increase in VCEDP10 and minor changes in (dP/dt)/DP40. All of the contractility indices were augmented significantly by isoproterenol and atrial pacing. In a given patient, max, dP/dt appears to be useful in the assessment of acute changes in inotropic state since the magnitude of its response to abrupt changes in preload is small and to afterload insignificant. Normalizing max dP/dt for end-diastolic circumference assures better stability during loading with good sensitivity to inotropic stimulation. VCF may be used whenever changes in afterload are minimal. The isovolumic measurements of VCE (regardless of whether total or developed pressure is used) lack sufficient stability during acute changes in loading conditions to warrant their use in the quantitative assessment of acute changes in inotropic state.