Toshiaki Kumada

Importance of left atrial function in patients with myocardial infarction.

Left atrial function was evaluated in patients with and without remote myocardial infarction. The simultaneous left atrial pressure recording and left atrial and left ventricular cineangiograms were obtained with a catheter-tip micromanometer. The pressure-volume curve of the left atrium was composed of an A-loop and a V-loop. The ratio of active atrial emptying to left ventricular stroke volume in patients with myocardial infarction was significantly larger than that in normal subjects (42 + 12% vs 29 + 10%, p < 0.05). The left atrial work was also significantly greater in patients with myocardial infarction (1690 + 717 mm Hgml) than in normal subjects (940 426 mm Hg-ml, p < 0.05). The ratio of active atrial emptying to left ventricular stroke volume and left atrial work were significantly related in both normal subjects and patients with myocardial infarction (y = 0.72, p < 0.01). The left ventricular ejection fraction correlated inversely with left atrial work (y = - 0.5, p < 0.05). Left atrial work also showed a significant linear correlation with left atrial volume before active atrial emptying (y = 0.82, p < 0.01). We conclude that the left atrial contribution to left ventricular function is increased in patients with remote myocardial infarction. This left atrial contribution to the left ventricle is attributed to the Frank- Starling mechanism in the left atrium.

Asynchronous left ventricular diastolic filling in patients with isolated disease of the left anterior descending coronary artery: assessment with radionuclide ventriculography.

To study the relationship between global and regional filling of the left ventricle, we conducted resting gated radionuclide ventriculographic studies in 15 control subjects (group 1) and 22 patients with isolated disease of the left anterior descending coronary artery (group 2). None had had a previous myocardial infarction. A computer program subdivided the image of the left ventricle into four regions. The time-activity and first-derivative curves of the global and regional left ventricles were computed. In the global left ventricle, the normalized peak filling rate (PFR) was decreased (p less than .01) and the ratio of the time to PFR (time interval from global end-systole to PFR) to the diastolic time, TPFR/DT, was greater (p less than .02) in group 2 than in group 1. In the regional left ventricle, in the side perfused by the stenosed vessel (septal and apical), PFR was slightly decreased in the apical (p less than .05), but not the septal region (p = NS); TPFR/DT was greater in the apical (p less than .02) and in the septal region (p less than .01) in group 2. In the normally perfused lateral side, there were no significant differences in PFR or in TPFR/DT between group 1 and group 2. Total delta t/DT, which was defined as the ratio of the sum of the absolute values of the time differences from global PFR to regional PFR (septal, apical, and lateral) to the diastolic time, was significantly greater in group 2 (0.09 +/- 0.05 vs 0.16 +/- 0.05; p less than .001). This indicates the existence of asynchronous diastolic filling in the different regions of the left ventricle in group 2. A negative correlation existed between total delta t/DT and global PFR (r = -.64, p less than .001). Thus, in patients with one-vessel disease, asynchronous diastolic filling occurs due to the filling disturbance in the affected regions, which may cause impairment of the filling of the global left ventricle.

Quantitative analysis of contraction band and coagulation necrosis after ischemia and reperfusion in the porcine heart.

To assess the importance of contraction band necrosis (CBN) in reperfusion, CBN, coagulation necrosis (CN), and infarct size, expressed as CBN + CN, were quantitatively analyzed in 25 porcine hearts without collateral circulation. The left anterior descending coronary artery was ligated for 20, 30, 60, and 120 min and then reperfused for 8 hr (groups 1 to 4, respectively). Five hearts were not reperfused (group 5). The areas of CBN and CN were traced at a magnification of X 100 under an inverted microscope and quantified with use of an image analyzer. There was no change in hemodynamics with either occlusion or reperfusion. Regional myocardial blood flow, measured by the generated hydrogen gas clearance method, decreased to almost zero after occlusion but recovered during reperfusion. Percent of risk area infarcted in groups 1 to 4 was 0 +/- 0%, 11 +/- 7%, 80 +/- 9%, and 96 +/- 2%, respectively, and the percent of risk area infarcted in group 4 was the same as that in hearts subjected to permanent occlusion (95 +/- 3%). The percent area of CBN was 100 +/- 0% in group 2, 68 +/- 11% in group 3, 2 +/- 1% in group 4, and 2 +/- 2% in group 5. In group 3, the inner third of the ischemic left ventricular wall showed CN and the middle and outer third CBN. These findings show that in pig hearts without collateral circulation, the transmural infarct, two-thirds of which is occupied by CBN, is evident even when reperfusion is achieved after 1 hr occlusion. Therefore, protection against CBN might reduce infarct size after reperfusion.

Change in Aortic End-Systolic Pressure by Alterations in Loading Sequence and Its Relation to Left Ventricular Isovolumic Relaxation

BACKGROUNDnA brief, sustained constriction of the descending and the ascending aortas produces systolic loads at different times during ejection, and descending intervention prolongs left ventricular (LV) relaxation more than ascending intervention. Although alterations in the sequence of loading the ventricle have been suggested as a cause of such load-induced relaxation abnormalities, the relation of the loading system to relaxation has been unclear.nnnMETHODS AND RESULTSnLV peak systolic pressure was elevated by approximately 40 mm Hg by constricting the descending and ascending aortas in seven anesthetized dogs. The descending intervention increased aortic end-systolic pressure (AoESP, 110.4 +/- 9.3 to 150.8 +/- 11.5 mm Hg; P < .05), reduced aortic flow (P < .05), and prolonged LV relaxation (time constant [T], 31.9 +/- 4.4 to 69.8 +/- 12.8 ms; P < .05). LV ejection time was reduced, but the systolic time interval was unchanged. In contrast, ascending intervention decreased AoESP (111.9 +/- 11.4 to 101.5 +/- 10.3 mm Hg; P < .05), reduced aortic flow (P < .05), and prolonged T (31.2 +/- 5.4 to 42.2 +/- 8.3 ms; P < .05), whereas ejection time and systolic time interval increased (both P < .01). Prolongation of T was significantly greater during descending intervention (P < .05) and was associated with an increase in AoESP during descending intervention but a decrease in AoESP during ascending intervention.nnnCONCLUSIONSnDescending intervention induced greater prolongation of T than ascending intervention. Prolongation of T was closely related to an increase in AoESP in the descending intervention but a decrease in AoESP in the ascending intervention. These data suggest that not only the loading sequence but also the pressure level at the onset of isovolumic relaxation determines LV relaxation.

Left ventricular regional wall stress in dilated cardiomyopathy

Left ventriculography with simultaneous pressure micromanometry was performed in 11 normal control subjects and 17 patients with dilated cardiomyopathy (DCM). Left ventricular silhouettes in the right anterior oblique projection were divided into eight areas, and regional wall stress was computed by Janzs method in each area excluding the two most basal areas. Wall stress was higher in DCM patients than in control subjects (p less than 0.01). The percent area changes from end diastole to end systole in each area were lower in DCM patients than in control subjects (mean for six areas, 22 +/- 14% versus 54 +/- 9%, respectively, p less than 0.01), but the coefficient of variation for the percent area changes in the six areas of the left ventricle in DCM patients was greater than that in control subjects (32 +/- 17% versus 15 +/- 4%, respectively, p less than 0.01), indicating regional differences in hypokinesis. There was a significant negative correlation between end-systolic regional wall stress and percent area change (r = -0.60 to -0.86, p less than 0.05) in each area. Thus, excessive regional afterload may play an important role in causing regional hypokinesis in DCM.

Importance of left ventricular systolic function in the assessment of left ventricular diastolic function with doppler transmitral flow velocity recording

To study the effect of left ventricular systolic function on the Doppler transmitral flow velocity pattern, Doppler echocardiographic variables were correlated with hemodynamic indexes in 11 control subjects and 58 patients with heart disease. All underwent cardiac catheterization performed with use of a Millar micromanometer. The time constant of left ventricular isovolumetric pressure decrease and left ventricular end-diastolic myocardial stiffness was calculated. The 58 patients were classified into two groups according to ejection fraction: group I (n = 30; ejection fraction greater than 55%) and group II (n = 28; ejection fraction less than 50%). Compared with the control subjects, patients in group I had impairment only of left ventricular relaxation (time constant 47 +/- 9 vs. 38 +/- 3 ms; p less than 0.01), whereas patients in group II had, in addition to impaired left ventricular relaxation (time constant 52 +/- 11 vs. 38 +/- 3 ms; p less than 0.01), increased preload, increased pulmonary capillary pressure (12 +/- 8 vs. 5 +/- 3 mm Hg; p less than 0.01) and increased myocardial stiffness (2,018 +/- 980 vs. 1,050 +/- 218 g/cm2; p less than 0.01). In group I, there was a significant partial correlation coefficient between the time constant and deceleration half-time (r = 0.54). In group II, a strong correlation existed between myocardial stiffness and peak atrial filling velocity (r = -0.71) and between myocardial stiffness and the ratio of peak atrial to peak rapid filling velocity (r = -0.71).(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular regional relaxation and its nonuniformity in hypertrophic nonobstructive cardiomyopathy.

BackgroundRegional nonuniformity has been suggested to be closely related to left ventricular (LV) relaxation in diseased heart. The purpose of the present study was to assess LV global and regional relaxation in patients with nonobstructive hypertrophic cardiomyopathy (HCM). Methods and ResultsLeft ventriculography was conducted simultaneously with pressure micromanometry in 10 normal control subjects and 11 patients with nonobstructive HCM. LV silhouettes in the right anterior oblique projection were divided into eight regions, and regional wall stress during isovolumic relaxation was computed for six regions from the midventricle to the apex. In HCM patients, isovolumic relaxation time (IRT) and the time constant of LV pressure decrease (Tp) were greater than in control subjects (IRT, 84 ± 13 versus 66 ± 6 msec; Tp, 51 ± 8 versus 36 ± 5 msec, respectively, p < 0.01). In HCM patients, the (−)dP/dt upstroke pattem was convexdownward, and dP/dt(20/60), the ratio ofdP/dt values 20 and 60 msec after peak (−)dP/dt, was less than in control subjects (1.46 ± 0.16 versus 2.15 + 0.14, p < 0.01). These findings suggest that there is impaired LV relaxation in HCM patients. End-systolic regional wall stress was lower, and the time constant ofregional stress decrease (Tst) was prolonged for each region in HCM patients compared with control subjects. In the HCM group, Tst tended to be more prolonged in regions with increased wail thickness than in regions with normal wall thickness (60 ± 15 versus 50 ± 11 msec, p < 0.01). The coefficient of variation for Tst values in six areas of the left ventricle was calculated in each subject and was greater in HCM patients than in control subjects (13 ± 7% versus 7 + 3%, p < 0.05), indicating regional nonuniformity in Tst during isovolumic relaxation in HCM patients. CondusionsSignificant correlations existed between the coefficients of variation for Tst and Tp (r = 0.80, p < 0.01), IRT (r = 0.79, p < 0.01), and dP/dt(20/60) (r = −0.67, p < 0.05) in the HCM group. Thus, regional nonunifonnity is closely related to the impairment of LV relaxation in HCM.

Post-exercise oxygen uptake kinetics in patients with left ventricular dysfunction

We assessed the kinetics of oxygen uptake (VO2) after symptom-limited maximal exercise by use of cardiopulmonary exercise testing with a bicycle ergometer in normal subjects and patients with left ventricular dysfunction due to dilated cardiomyopathy. During the first few minutes after the cessation of exercise, the VO2-time relationship showed an exponential-like decrease. A monoexponential curve was fitted to this relationship of the first 3 min after exercise to obtain the time constant of the decrease in VO2 (T(VO2)). The results of exercise testing in 37 normal subjects (25 male and 12 female) revealed that T(VO2) was relatively independent of age and gender. Then, 30 male patients with dilated cardiomyopathy (10 in New York Heart Association functional class I, 12 in class II, and 8 in class III) were evaluated and the results were compared with those of 16 age-matched male control normal subjects. Although the amount of the estimated oxygen debt was smaller in the patient group, the time constant T(VO2) was 117 +/- 8 s for the controls as compared with 130 +/- 14 s for the patients in class I, 153 +/- 13 s for those in class II, and 219 +/- 49 s for those in class III. There were significant correlations between T(VO2) and anaerobic threshold (r = -0.68, p < 0.001), peak VO2 (r = -0.74, p < 0.001), and the increase in VO2 per work rate (r = -0.88, p < 0.001). T(VO2) also correlated with the ventilatory equivalent for carbon dioxide output (VE/VCO2) at peak exercise (r = 0.70, p < 0.001) and the time course of minute ventilation during the early phase of the post-exercise period (r = 0.67, p < 0.001). Thus, the time course of VO2 decrease after symptom-limited exercise is considered to be closely related to exercise capacity and also to the degree of exercise-induced hyperpnea in patients with left ventricular dysfunction.

Left ventricular relaxation in dilated cardiomyopathy: Relation to loading conditions and regional nonuniformity

OBJECTIVESnThe purpose of the present study was to investigate how loading conditions and regional nonuniformity affect left ventricular relaxation in dilated cardiomyopathy.nnnBACKGROUNDnLeft ventricular relaxation is impaired in dilated cardiomyopathy. It has been suggested that relaxation abnormality is related to loading conditions and regional nonuniformity in the diseased heart.nnnMETHODSnLeft ventriculography with simultaneous pressure manometry was performed in 10 patients with dilated cardiomyopathy before and during nitroprusside infusion. Ten normal subjects served as a control group. Left ventricular hemodynamics, regional wall motion (assessed by the area method) and regional wall stress (Janz method) were analyzed.nnnRESULTSnWhen compared with control subjects, the patients with dilated cardiomyopathy had a reduced left ventricular ejection fraction (p < 0.01) and prolonged relaxation time constants (p < 0.01). Left ventricular wall motion was both hypokinetic and asynchronous in the patient group. In addition, systolic regional wall stress was significantly greater, the time to peak wall stress was longer and the regional myocardial relaxation time constant was greater for each ventricular area assessed in the patient group (each p < 0.01). Administration of nitroprusside reduced left ventricular pressure and increased ejection fraction in the 10 patients with dilated cardiomyopathy. For each region, systolic regional wall stress and the time to peak wall stress decreased, and both regional hypokinesia and asynchrony lessened. These changes in loading conditions and regional nonuniformity were accompanied by an improvement in both regional and global ventricular relaxation that was significant, particularly during the early to midrelaxation phase when regional asynchrony was greatest.nnnCONCLUSIONSnThese results suggest that myocardial relaxation is sensitive to loading conditions and regional nonuniformity in dilated cardiomyopathy and that load reduction can improve both relaxation and systolic performance of the left ventricle.

Acute effects of sublingual isosorbide dinitrate on global and regional left ventricular diastolic filling in normal persons

To study the acute effects of isosorbide dinitrate (ISDN) on global and regional left ventricular (LV) diastolic filling, gated radionuclide ventriculographic studies were conducted in 21 normal persons before and after sublingual administration of ISDN. ISDN treatment caused significant increases in ejection fraction and peak LV ejection rate and it caused a delay in occurrence of peak LV filling, without statistically significant changes in peak LV filling rate globally and regionally. The ratios of peak LV filling rate to peak LV ejection rate decreased significantly both globally and regionally. These alterations induced by ISDN could be interpreted as indicating a failure of improvement of the early diastolic filling despite increased systolic function and heart rate in the global left ventricle and in regions of the left ventricle. Furthermore, ISDN caused early diastolic asynchronous filling. There was a negative correlation between this early diastolic asynchronous filling and the ratio of global peak LV filling to global peak LV ejection rate (r = -0.66, p less than 0.001), indicating that administration of ISDN to normal persons may produce early diastolic asynchronous filling associated with failure of improvement of diastolic filling despite increased systolic function and heart rate.