Motoshi Takeuchi

Single-beat estimation of the slope of the end-systolic pressure-volume relation in the human left ventricle.

This study assessed a new method of estimating the slope (Ees) of the end-systolic pressurevolume relation (ESPVR) from a single beat of the human heart. Left ventricular pressure was recorded with a high-fidelity micromanometer in patients with heart disease during left ventriculography. Peak isovolumic pressure at the end-disastolic volume was estimated by a curve-fitting technique from an isovolumic left ventricular pressure curve. The ESPVR line was drawn from the estimated peak isovolumic pressure-volume point tangential to the left upper corner of the pressure-volume loop. The slope of this estimated ESPVR line from single-beat analysis was compared with the slope of the ESPVR line obtained from three pressure-volume loops in 16 patients given angiotensin II or nitroglycerin infusion. The estimated Ees was 5.0 ± 2.2 mm Hg/m1/m2, and the conventional Ees was 4.9 ± 2.7 mm Hg/mlm2. The estimated Ees showed a positive correlation with the conventional Ees (r = 0.91, p < 0.001, SEE= 1.2 mm Hg/ml/m2). In the other 13 patients, after dobutamine infusion (5, μg/kg/min i.v.) the estimated Ees increased significantly from 5.6 ± 1.4 to 7.4 ± 2.0 mm Hg/ml/m2 (p < 0.01). Thus, the estimated Ees approximated the conventional Ees and was sensitive to a positive inotropic intervention. We conclude that this single-beat analysis method facilitates assessment of the beat-by-beat ESPVR of the human heart.

Comparison of hemodynamic determinants for myocardial oxygen consumption under different contractile states in human ventricle.

BackgroundRecently, several indexes such as tension-time index (TII), tension-time or force-time integral (FfM), rate-pressure product (RPP), pressure-work index (PWI), and systolic pressure-volume area (PVA) have been developed as predictors of myocardial oxygen consumption in experimental and clinical studies. However, it is still unclear whether these indexes are reliable predictors of myocardial oxygen consumption under various contractile states in human hearts. Methods and ResultsWe assessed the relation between TTI, FTI, RPP, PWI, and PVA and myocardial oxygen consumption per beat (&OV0622;O2) in 13 patients with heart disease during volume loading. Left ventricular (LV) volume and pressure were measured simultaneously by the conductance catheter with the tipped micromanometer technique. &OV0622;O2 was calculated from arterial coronary sinus oxygen content difference, and coronary sinus blood flow was measured by the thermodilution method. After z transformation of the correlation coefficients, mean z value for the &OV0622;O2-PVA relation (1.83±0.60) was greater than those for the &OV0622;O2-TII relation (1.22±O.66; p<0.005), &OV0622;O2-FTI] relation (1.18±O.61;p <0.05), &OV0622;O2-RPP relation (0.95±0.65; p<0.05), and &OV0622;O2-PWI relation (1.24±0.58;p<0.05). During dobutamine infusion (5 μ·kg−1·min−1) in five of the 13 patients, &OV0622;O2 also correlated best with PVA (z=1.70±0.89) compared with TII (z=1.43±0.86), FTI (z=1.48±0.95), RPP (z=1.00±0.53), and PWI (z=0.88±0.80). The contractile efficiency (38±14% to 38±20%), the reciprocal of the slope of the &OV0622;O2-PVA relation, remained unchanged, whereas the &OV0622;O2, PVA 0.8 (&OV0622;O2 at PVA=0.8 J per beat/100 g LV) increased from 1.48±1.16 to 2.06±1.13 J per beat/100 g LV (p<0.05). These results show the parallel upward shift of the &OV0622;O2-PVA relation during dobutamine infusion. Because increases in the &OV0622;O2-intercept represent the &OV0622;O2 for the increased excitation-contraction (E-C) coupling associated with the augmented contractile state, the parallelism of the &OV0622;O2-PVA relation could discriminate between &OV0622;O2 for mechanical work (PVA-dependent &OV0622;O2) and &OV0622;O2 for E-C coupling (PVA-independent &OV0622;O2). ConclusionsThe results of the present study indicate that PVA is a reliable and valuable predictor of myocardial oxygen consumption under different contractile states in human hearts. The &OV0622;O2-PVA relation could provide useful information about mechanoenergetics in diseased human hearts.

Nitric Oxide Spares Myocardial Oxygen Consumption Through Attenuation of Contractile Response to β-Adrenergic Stimulation in Patients With Idiopathic Dilated Cardiomyopathy

BACKGROUND The results of recent studies suggest that NO synthase may increase in the failing myocardium and that NO modulates the myocardial contractile response to beta-adrenergic stimulation. However, there are few data regarding the physiological role of NO in patients with heart failure. The aim of the present study was to address the role of NO in left ventricular (LV) contractile response to beta-adrenergic stimulation and corresponding oxygen expenditure in human heart failure. METHODS AND RESULTS We studied 15 patients with heart failure due to idiopathic dilated cardiomyopathy (mean ejection fraction 0.33). We examined LV contractility (E(max), the slope of end-systolic pressure-volume relation), LV external work (EW), myocardial oxygen consumption (MVO(2)), and mechanical efficiency (measured as EW/MVO(2)) with the use of conductance and coronary sinus thermodilution catheters before and during dobutamine (DOB) infusion via a peripheral vein (4. 8+/-0.3 microg. kg(-1). min(-1) IV). Heart rate was kept constant with atrial pacing. We carried out a similar protocol during the intracoronary infusion of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA; 200 micromol). DOB increased E(max), EW, and MVO(2) (by 77+/-17%, 39+/-5%, and 21+/-5%, respectively), leading to an increase in mechanical efficiency (25.4+/-3.1% to 29.6+/-4.1%). L-NMMA alone did not significantly change these variables. Although the concurrent infusion of DOB with L-NMMA increased E(max), EW, and MVO(2) (by 140+/-21%, 64+/-9%, and 35+/-5%, respectively) more than DOB alone, mechanical efficiency did not increase further (24.3+/-3.3% to 29.5+/-4.5%) because EW and MVO(2) increased in parallel. Conclusions-These data suggest that in patients with idiopathic dilated cardiomyopathy, endogenous NO spares MVO(2) through attenuation of LV contractile response to beta-adrenergic stimulation while maintaining LV energy-converting efficiency.

Comparison of the effects on arterial-ventricular coupling between phosphodiesterase inhibitor and dobutamine in the diseased human heart

OBJECTIVES The aim of this study was to compare the effects of a phosphodiesterase inhibitor and catecholamine on arterial-ventricular coupling and myocardial energetics in the diseases human heart. BACKGROUND Recent experimental studies have indicated that the arterial-ventricular coupling analysis using the time-varying elastance model could discriminate between inotropic and vasoactive effects of the two agents. METHODS With the use of a conductance catheter, left ventricular contractility and arterial afterload were measured from the slope of the end-systolic pressure-volume relation, Emax, and the slope of the end-systolic pressure-stroke volume relation, Ea. Arterial-ventricular coupling was assessed by Ea/Emax before and after administration of a new phosphodiesterase inhibitor, E-1020 (0.3 microgram/kg per min), and a beta 1-stimulant, dobutamine (5 micrograms/kg per min), in 20 patients with heart disease. Left ventricular mechanical efficiency was assessed as the ratio of stroke work to myocardial oxygen consumption per beat measured by the thermodilution method. RESULTS The slope of the end-systolic pressure-volume relation increased comparably with both E-1020 (39%, p < 0.01) and dobutamine (47%, p < 0.01), but Ea/Emax decreased with E-1020 (1.25 to 0.78, -37%, p < 0.01) more than with dobutamine (1.23 to 0.99, -16%, p < 0.05). Although stroke work index increased with both agents, myocardial oxygen consumption remained unchanged with E-1020 but increased with dobutamine (p < 0.05). Consequently, left ventricular mechanical efficiency increased with E-1020 (0.30 to 0.36, p < 0.05) but remained unchanged with dobutamine (0.27 to 0.29, p = NS). CONCLUSIONS The phosphodiesterase inhibitor E-1020 improved arterial-ventricular coupling more than did dobutamine, with a resultant increase in mechanical efficiency. These data were in accordance with the theoretic prediction of the coupling analysis in the diseases human heart.

Alteration in Energetics in Patients With Left Ventricular Dysfunction After Myocardial Infarction Increased Oxygen Cost of Contractility

BACKGROUND Although the use of inotropic agents to treat congestive heart failure (CHF) in patients with coronary artery disease has yielded short-term hemodynamic improvement, long-term mortality has shown less improvement. The loss of cardiac muscle as a result of infarction not only decreases the pumping ability of the heart but also leads to some dramatic changes in myocardial energetics. However, little is known about the mechanoenergetics of the heart in patients with left ventricular (LV) dysfunction after myocardial infarction. METHODS AND RESULTS The present study was designed to compare by means of the Vo2-pressure-volume area relation (PVA, a measure of total mechanical energy) and Emax (LV contractility index), the incremental oxygen cost of contractility measured as nonmechanical energy per unit increment in contractility in patients with various kinds of LV dysfunction. We assessed Emax, Vo2, and PVA using conductance and Webster catheters under control conditions and during different rates of dobutamine infusion (3 and 6 micrograms x kg-1 x min-1) in 30 patients with coronary artery disease. Patients were divided into three groups according to LV ejection fraction (EF): 10 without LV dysfunction (EF>/= 60%), 10 with mild LV dysfunction (40% </= EF < 60%), and 10 with severe LV dysfunction (EF < 40%). Under control conditions, the Vo2-PVA relation was linear in each group. Contractile efficiency, the reciprocal of the slope of this relation, was comparable among the three groups. The oxygen cost of contractility in the severe LV dysfunction group was significantly greater than in the groups without and with mild LV dysfunction (0.022 +/- 0.014 versus 0.005 +/- 0.002 and 0.0012 +/- 0.005 mL O2 x mL x mm Hg-1 per beat, P <.05). CONCLUSIONS These findings suggest that the alteration in mechanoenergetics in patients with severe LV dysfunction after myocardial infarction may result from the increased oxygen cost of excitation-contraction coupling rather than from a reduction in the efficiency of chemomechanical energy transduction.

Negative Chronotropic Effect of β-Blockade Therapy Reduces Myocardial Oxygen Expenditure for Nonmechanical Work

BACKGROUND The negative chronotropic effect of beta-blocking agents is likely to provide hemodynamic and energetic advantages. However, the negative chronotropic effect on cardiac energetics observed on the initiation of beta-blockade therapy has not been fully elucidated. METHODS AND RESULTS In 18 patients with heart failure, left ventricular pressure and volume, external work (EW), myocardial oxygen consumption per beat (total Vo2), mechanical efficiency (EW/total Vo2), and Vo2 for nonmechanical work (total Vo2-2.EW) were measured with the use of conductance catheter and Webster catheter at the following three states: under control conditions and after beta-blockade (0.15 +/- 0.07 mg/kg propranolol IV) with and without atrial pacing to keep the heart rate at control levels. Heart rate decreased after atrial pacing was stopped. EW decreased during beta-blockade with pacing and returned to the control level after pacing was stopped. Total Vo2 did not change during beta-blockade with or without pacing, whereas Vo2 for nonmechanical work increased with pacing and returned to the control level after pacing was stopped. As a result, mechanical efficiency decreased during beta-blockade with pacing and returned to the control level after pacing was stopped. CONCLUSIONS The negative chronotropic effect of a beta-blocking agent may offset the mechanoenergetical deterioration resulting from its negative inotropic effect through a reduction in oxygen expenditure for nonmechanical work. These findings suggest that the negative chronotropic effect is an important aspect of beta-blockade therapy.

Effects of left ventricular asynchrony on time constant and extrapolated pressure of left ventricular pressure decay in coronary artery disease

To elucidate the effects of ventricular asynchrony with or without myocardial ischemia on the time constant of left ventricular pressure decay and asymptote, that is, the level to which pressure would decrease if isovolumic pressure decrease continued infinitely, left ventriculography and pressure measurements were investigated in 14 normal subjects and 25 patients with coronary artery disease. Ventricular asynchrony was quantitated by the segmental area-time curve. This study consisted of two parts. 1) After a right atrial pacing stress test, the time constant and asymptote remained unchanged in eight normal subjects. In 18 patients with coronary artery disease and pacing-induced angina, asynchrony increased, the time constant was prolonged (64 +/- 13 to 94 +/- 17 ms, p less than 0.01) and the asymptote decreased (-22 +/- 10 to -46 +/- 20 mm Hg, p less than 0.01) after the pacing. 2) During right ventricular pacing at 80, 100 and 120 beats/min in the patients, asynchrony increased and the time constant was prolonged (55 +/- 7 versus 70 +/- 10, 47 +/- 11 versus 66 +/- 19, 36 +/- 7 versus 53 +/- 13 ms, respectively, p less than 0.01 versus right atrial pacing), whereas the asymptote was unchanged in six normal subjects compared with the value during right atrial pacing at each pacing rate. In seven patients with coronary artery disease, right ventricular pacing at 80, 100 and 120 beats/min also produced an increase in the time constant, while the asymptote was unchanged. Thus, prolongation of the time constant of left ventricular pressure decay may result from ventricular asynchrony even in the absence of myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Deep negative T waves and abnormal cardiac sympathetic image (123I-MIBG) after the Great Hanshin Earthquake of 1995.

The authors report the increased incidence of patients with deep negative T waves without Q wave after the Great Hanshin Earthquake of 1995. Subjects underwent cardiac metaiodobenzyl guanidine (123I-MIBG) imaging, 201Tl scintigraphy, and coronary angiography. Among 2,756 inpatients of the preceding 5-year period, 33 (1.2%) showed the deep negative T waves, whereas 6 of 94 (6.4%; P < 0.001) showed it after the earthquake. Four of six patients had an episode of chest pain. Cardiac metaiodobenzyl guanidine imaging revealed the extent defects in all six patients despite a minimal change of 201Tl image. In addition, cardiac metaiodobenzyl guanidine imaging washout rate was hastened not only in the defect area but also in the nondefect area, which suggested augmented sympathetic activation. Natural disasters can affect the frequency of deep negative T waves, which relate abnormal cardiac sympathetic imaging.

Effect of NKH477, a new water-soluble forskolin derivative, on arterial-ventricular coupling and mechanical energy transduction in patients with left ventricular systolic dysfunction: comparison with dobutamine.

We examined the effects of a novel water-soluble forskolin derivative, NKH477 (0.5 microgram/kg/min), on arterial-ventricular (A-V) coupling and mechanical energy transduction from heart to circulatory bed in comparison with those of dobutamine (3 micrograms/kg/min) in 8 patients with left ventricular (LV) systolic dysfunction using a conductance catheter method. A-V coupling was assessed as the ratio of the effective arterial elastance (E(a)) to the slope of the end-systolic pressure-volume relation (ESPVR) (E(max), left ventricular contractility index), and the ratio of mechanical energy transduction was obtained as the fraction of PV area (PVA) comprised of stroke work (SW). E(max) (2.59 mm Hg/ml/m2), E(a)/E(max) (1.62), and SW/PVA (0.58) were impaired in control contractile state. NKH477 increased Emax to the same extent as dobutamine. E(a) decreased with NKH477 but not with dobutamine. As a consequence, the decrease in E(a)/E(max) with NKH477 was greater than that with dobutamine (52 vs. 47%, p < 0.05); the increase in SW/PVA with NKH477 was also greater than that with dobutamine (28 vs. 21%, p < 0.05). These findings suggest that NKH477 may be a superior alternative to dobutamine in A-V coupling and mechanical energy transduction in patients with LV systolic dysfunction.

Oxygen-Saving Effect of a New Cardiotonic Agent, MCI-154, in Diseased Human Hearts

OBJECTIVES The aim of this study was to examine the left ventricular mechanoenergetic effects of a novel Ca2+ sensitizing agent, MCI-154, on diseased human hearts compared with dobutamine. BACKGROUND Unlike conventional cardiotonic agents, a Ca2+ sensitizer that could produce a positive inotropic action by altering the responsiveness of myofilament to Ca2+ could generate force with smaller amounts of Ca2+; thus, it may potentially save energy expenditure. METHODS The left ventricular pressure-volume relation and myocardial oxygen consumption per beat (Vo2) were measured by a conductance (volume) catheter and a Webster catheter. Left ventricular contractility (Emax), systolic pressure-volume area (PVA [index of left ventricular total mechanical energy]) and Vo2 were assessed before and after infusion of MCI-154 or dobut-amine. The PVA-independent Vo2 (Vo2 mainly for excitation-contraction coupling) was assessed as the Vo2 at zero PVA. RESULTS Both agents increased Emax comparably (dobutamine: from 3.55 +/- 1.10 [mean +/- SD] to 5.04 +/- 1.16 mm Hg/ml per m2, p < 0.0001; MCI-154: from 3.36 +/- 1.26 to 5.37 +/- 2.14 mm Hg/ml per m2, p < 0.0001); dobutamine increased total Vo2 (from 0.22 +/- 0.08 to 0.27 +/- 0.09 ml O2, p < 0.05) and PVA-independent Vo2 (from 0.019 +/- 0.019 to 0.091 +/- 0.051 ml O2, p < 0.005); but MCI-154 did not change these variables significantly. Consequently, the oxygen cost of contractility (delta PVA-independent Vo2/delta Emax) was less with MCI-154 than with dobutamine (0.14 +/- 0.18 vs. 1.10 +/- 0.80 J/mm Hg per ml per m2, p < 0.05). CONCLUSIONS These results suggest that the cardiotonic action mediated by MCI-154 could provide an energetic advantage over the conventional cardiotonic action with currently used inotropic agents.