Efficiency of energy transfer from pressure-volume area to external mechanical work increases with contractile state and decreases with afterload in the left ventricle of the anesthetized closed-chest dog

We studied the effects of ventricular end-systolic elastance (Ees) and effective arterial elastance (Ea) on the efficiency of energy transfer from pressure-volume area (PVA) to external mechanical work (EW) in the left ventricle of anesthetized closed-chest dogs. PVA represents the total mechanical energy generated by ventricular contraction, which is an intermediate form of energy between oxygen consumption, the total energy input, and EW, the effective energy output. PVA and EW were determined from ventricular pressure and volume, which were continuously measured with a volumetric conductance catheter. Measurements of Ees were obtained by transiently increasing afterload by an inflation of a Fogarty catheter in the thoracic descending aorta. Ea was determined as the ratio of end-systolic pressure to stroke volume. The EW/PVA efficiency of a steady-state contraction increased from 55% to 64%, with a 58% increase in Ees after dobutamine. Ees, which was smaller than Ea before dobutamine, became nearly equal to Ea after dobutamine, maximizing EW for a given end-diastolic volume. EW/PVA efficiency decreased with an abrupt increase in afterload before and after dobutamine. The sensitivity of the decrease in the EW/PVA efficiency to an increase in end-systolic pressure was significantly less after than before dobutamine. We could account for all these changes in EW/PVA efficiency by the relative changes in Ees and Ea in the pressure-volume diagram.     

Left ventricular performance, ventriculo-arterial coupling and mechanical output in hypertensive patients with and without left ventricular hypertrophy]

Left ventricular hypertrophy (LVH) is a physiological process of adaptation of the heart to mechanical load increase. Despite depression of left ventricular (LV) contractile performance, work efficiency is preserved and ventriculoarterial coupling is almost normal in hypertensive patients with LVH. To assess the differences between patients with and without LVH, LV contractile performance, the ventriculoarterial coupling and mechanical efficiency were compared in 2 groups of hypertensive patients with similar body surface area and arterial pressures, 23 without LVH (group 1) and 30 with LVH (group 2) and compared to data of 20 normotensive subjects. Left ventricular angiography coupled with simultaneous recording of pressures with micromanometer were used to determine end-systolic stress-to-volume ratio (ESSVR), end-systolic elastance (Ees), effective arterial elastance (Ea), external work (EW) and pressure-volume area (PVA). Left ventricular contractile performance assessed by Ees/100 g myocardial mass and EESVR were lower in group 2 than in group 1 (1.23 +/- 0.28 vs 1.89 +/- 0.48 mmHg/mL/100 g and 6.22 +/- 1.07 vs 9.56 +/- 0.97 g/cm2/mL/m2, respectively, both p < 0.0001, control subjects: 1.47 +/- 0.41 and 6.97 +/- 1.22, respectively). Ventriculoarterial coupling evaluated through Ea/Ees ratio (0.51 +/- 0.05 in group 1 vs 0.53 +/- 0.08 in group 2, 0.49 +/- 0.09 in control subjects), and work efficiency evaluated through EW/PVA ratio (0.80 +/- 0.02 in group 1 vs 0.78 +/- 0.03 in group 2, 0.80 +/- 0.03 in control subjects), were similar in the 2 groups and were comparable to control subject values. In conclusion, this study shows that ventriculoarterial coupling and work efficiency are comparable in hypertensive patients with and without LVH. These results suggest that in patients without LVH the matching between left ventricle and arterial receptor is preserved through an enhancement of myocardial contractility which is energetically costly. Conversely, LVH seems to be a useful adaptation which minimizes the energetical cost of high pressure generation.     

Left ventricular mechanical efficiency in hypertensive patients with and without increased myocardial mass and with normal pump function

Left ventricular hypertrophy (LVH) is a physiologic process of adaptation of the heart to mechanical load increase. Despite depression of left ventricular contractile performance, mechanical efficiency and ventriculoarterial coupling are preserved in hypertensive patients with LVH. To assess the differences between patients with and without LVH, left ventricular contractile performance and the ventriculoarterial coupling were compared in two groups of hypertensive patients with similar body surface area and arterial pressures, and normal pump function: 30 patients with LVH (group 1) and 23 without LVH (group 2). Left ventricular angiography coupled with simultaneous recording of pressures with a micromanometer were used to determine end-systolic stress-to-volume ratio (ESSVR), end-systolic elastance (Ees), effective arterial elastance (Ea), external work (EW), and pressure–volume area (PVA). Myocardial contractile performance, assessed by Ees normalized by myocardial mass and by ESSVR, was lower in group 1 than in group 2 (1.23 ± 0.28 v 1.89 ± 0.48 mm Hg/mL/100 g, and 3.85 ± 0.99 v 5.13 ± 0.56 g/cm²/mL, respectively, both P < .001). Ventriculoarterial coupling evaluated through Ea/Ees ratio, and mechanical efficiency evaluated through EW/PVA ratio, were similar in the two groups (0.53 ± 0.08 v 0.51 ± 0.05, and 0.78 ± 0.03 v 0.80 ± 0.02, respectively, NS). In conclusion, this study shows that ventriculoarterial coupling and mechanical efficiency are comparable in hypertensive patients with and without LVH. These results suggest that in hypertensive patients, the matching between left ventricular performance and arterial load and the energy transfer are preserved either through left ventricular hypertrophy with moderate depression of myocardial contractile performance or through enhancement of myocardial contractile performance in patients with normal left ventricular mass.     

Effect of dobutamine on ventriculo-arterial coupling and ventricular work efficiency in patients with cardiac failure

In nine patients with cardiac dysfunction (ejection fraction less than or equal to 50%), we evaluated the effects of dobutamine (5 micrograms/kg/min) on ventriculo-arterial coupling by monitoring direct arterial pressures and simultaneously-recorded M-mode echocardiograms guided with two-dimensional images. Left ventricular end-diastolic volume (EDV) and end-systolic volume (ESV) were calculated by the formula of Teichholz, and left ventricular end-systolic pressure (ESP) was approximately from the arterial dicrotic pressure. Arterial pressure was altered by phenylephrine or nitroprusside and the slope (Ees) and volume axis intercept (Vo) of the end-systolic pressure-volume relationship were determined as the contractile properties of the ventricle. The arterial system properties were expressed by the slope (Ea) of the end-systolic pressure-stroke volume relationships. Ees during dobutamine infusion was derived assuming that the Vo was unchanged from the baseline state. The left ventricular pressure-volume area (PVA), the sum of external work (EW) and end-systolic potential energy (PE), and ventricular work efficiency (EW/PVA) were determined from a time-varying elastance model. The EDV and ESV were significantly decreased by dobutamine (-4%, p less than 0.05; -22%, p less than 0.01), while the ESP and heart rate remained unchanged. Dobutamine increased the Ees markedly (+41%, p less than 0.01) and decreased the Ea (-23%, p less than 0.01). These changes resulted in a substantial decrease in the ratio of Ea to Ees (-44%, p less than 0.01). The EW was augmented (+22%, p less than 0.01), but the PE was reduced (-33%, p less than 0.01) by dobutamine, while the PVA remained the same as in the baseline state.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventricular energetics in aortic root replacement for annuloaortic ectasia with aortic regurgitation

Aortic root replacement (Bentall operation) is the standard operation for patients who have lesions of the ascending aorta associated with aortic valve disease. We analyzed the mid-term results for left ventricular energetics after the Bentall operation for annuloaortic ectasia with aortic regurgitation. We measured left ventricular contractility (end-systolic elastance; Ees), afterload (effective arterial elastance; Ea), and efficiency (ventriculoarterial coupling; Ea/Ees, and the ratio of stroke work and pressure-volume area; SW/PVA) based on transthoracic echocardiography data before, after, and approximately 1 year after the Bentall operation in 15 patients with annuloaortic ectasia with aortic regurgitation. Left ventricular volume was calculated by the Teichholz M-mode method. Ees and Ea were approximated as follows: Ees = mean blood pressure/minimal left ventricular volume, and Ea = systolic blood pressure/(maximal left ventricular volume — minimal left ventricular volume). Ea/Ees and SW/PVA were then calculated. Left ventricular volume was normalized with body surface area. Ees increased after the Bentall operation and around 1 year later (from 2.17 ± 1.09 to 3.92 ± 2.26 and 5.33 ± 1.90 mmHg·m²/ml, P < 0.001), thus resulting in an improvement in SW/PVA (from 68.8 ± 8.2 to 70.9 ± 9.5 and 74.7 ± 5.2%, P = 0.045). Ea also increased after the Bentall operation and 1 year later (from 1.77 ± 0.61 to 2.88 ± 1.28 and 3.54 ± 1.43 mmHg·m²/ml, P < 0.001). The mid-term results for ventricular contractility and efficiency after the Bentall operation for annuloaortic ectasia with aortic regurgitation are excellent and satisfactory.     

Dynamic effects of carotid sinus baroreflex on ventriculoarterial coupling studied in anesthetized dogs.

We evaluated dynamic effects of the carotid sinus baroreflex on ventriculoarterial coupling. In seven anesthetized, vagotomized dogs, we bilaterally isolated carotid sinuses and randomly changed carotid sinus pressure while measuring aortic pressure, aortic flow, and left ventricular pressure. Estimating left ventricular end-systolic elastance (Ees) and effective arterial elastance (Ea) on a beat-to-beat basis, we determined transfer functions from the carotid sinus pressure to Ees (HEes) and from the carotid sinus pressure to Ea (HEa) over the frequency range spanning 0.002-0.25 Hz. Both HEes and HEa exhibited characteristics of a second-order low-pass filter. The gains of HEes and HEa were 0.085 +/- 0.065 (mean +/- SD) and 0.081 +/- 0.049 mm Hg/ml/mm Hg, respectively. There were no significant differences in natural frequencies (0.039 +/- 0.013 versus 0.039 +/- 0.007 Hz) or damping ratios (0.65 +/- 0.11 versus 0.64 +/- 0.24). The results indicated that the carotid sinus baroreflex dynamically altered Ees and Ea to the same extent in the process of stabilizing arterial pressure. Because the arterial system extracts maximal external work from a given heart when Ea equals Ees, the carotid sinus baroreflex appeared to be designed to regulate the ventricular and arterial properties to optimize the energy transmission from the left ventricle to the arterial system in anesthetized, vagotomized dogs.     

Pressure-volume analysis as a method for quantifying simultaneous drug (amrinone) effects on arterial load and contractile state in vivo

Pressure-volume relation analysis was used to independently quantify changes in ventricular contractile performance and vascular loading in intact anesthetized dogs before and after a single bolus of intravenous amrinone. Ventricular systolic property changes were characterized by the end-systolic elastance (Ees = slope of the end-systolic pressure-volume relation) and arterial properties by the effective arterial elastance (Ea = end-systolic pressure/stroke volume ratio). Pressure-volume data were obtained by the conductance catheter technique with loading varied by transient inferior vena cava occlusion. Amrinone induced a 27% increase in ejection fraction at 10 min (from 44% to 56%) as a result of both a significant rise in contractility (mean Ees 4 +/- 2 to 6 +/- 3 mm Hg/ml, p less than 0.001) and simultaneous reduction in arterial loading (Ea reduction from 6 +/- 2 mm Hg/ml to 5 mm Hg/ml, p less than 0.001). Over the subsequent 30 min, Ea revealed a significant recovery toward baseline, whereas Ees was less altered. Mean percent changes (% delta) in both variables were linearly correlated: % delta Ea = -1.6 x % delta Ees + 3.1, r = 0.96, p less than 0.001. In addition to separating ventricular from vascular property changes, the pressure-volume coupling framework was used to predict net pump performance (ejection fraction). Model predictions showed good agreement with experimental data. Thus, pressure-volume relations can be used to separately quantitate simultaneous changes in ventricular and vascular loading properties in vivo produced by pharmacologic agents with complex actions. Use of this approach in drug testing in humans should simplify data interpretation regarding mechanisms of action in specific clinical settings.     

Xanthine oxidase inhibition ameliorates cardiovascular dysfunction in dogs with pacing-induced heart failure

We hypothesized that chronic xanthine oxidase inhibition (XOI) would have favorable effects on both ventricular and vascular performance in evolving heart failure (HF), thereby preserving ventricular-vascular coupling. In HF, XOI reduces oxidative stress and improves both vascular and myocardial function. Dogs were randomized to receive either allopurinol (100 mg/day p.o.) or placebo following surgical instrumentation for chronic measurement of left-ventricular pressure and dimension and during induction of HF by rapid pacing. In the placebo group (n = 8), HF was characterized by increased LV end-diastolic pressure (LVEDP, 10.2 +/- 5.5 and 29.8 +/- 3.9 mmHg, before and after HF, respectively, P < 0.05), end-diastolic dimension (LVEDD, from 29.5 +/- 3.2 to 34.3 +/- 3.2 mm, P < 0.001), and afterload (arterial elastance, Ea, from 17.9 +/- 1.2 to 42.6 +/- 7.9 mmHg/mm, P < 0.05), and reduced contractility (End-systolic ventricular elastance, Ees, from 10.8 +/- 1.3 to 5.6 +/- 2.3 mmHg/mm, P < 0.05). Thus, ventricular-vascular coupling (Ees/Ea ratio) fell 57.6+/-9% (0.61 +/- 0.1 to 0.16 +/- 0.1, P < 0.05). Allopurinol (n = 9) profoundly attenuated both the Ea increase (from 22.3 +/- 3 to 25.6 +/- 4.6 mmHg/mm, P = NS) and the fall in Ees (from 11.8+/-1.1 to 11.7+/-1, P = NS), thereby preserving the Ees/Ea ratio (from 0.58 +/- 0.1 to 0.56 +/- 0.1, P < 0.001 vs. placebo). Allopurinol did not affect the increase in preload (LVEDP and LVEDD). XO cardiac mRNA and protein were similarly upregulated approximately fourfold in both groups. Allopurinol ameliorates increases in afterload and reductions in myocardial contractility during evolving HF, thereby preserving ventricular-vascular coupling. These results demonstrate a unique and potent hemodynamic profile of XOI, thereby providing further rationale for developing XOIs as a novel HF therapy.     

Partial left ventriculectomy improves left ventricular end systolic elastance in patients with idiopathic dilated cardiomyopathy

OBJECTIVE: To assess the effect of partial left ventriculectomy (PLV) on estimate of left ventricular end systolic elastance (Ees), arterial elastance, and ventriculoarterial coupling. PATIENTS: 11 patients with idiopathic dilated cardiomyopathy before and two weeks after PLV, and 11 controls. INTERVENTIONS: Single plane left ventricular angiography with simultaneous measurements of femoral artery pressure was performed during right heart pacing before and after load reduction. RESULTS: PLV increased mean (SD) Ees from 0.52 (0.27) to 1.47 (0.62) mm Hg/ml (p = 0.0004). The increase in Ees remained significant after correction for the change in left ventricular mass (p = 0.004) and end diastolic volume (p = 0.048). As PLV had no effect on arterial elastance, ventriculoarterial coupling improved from 3.25 (2.17) to 1.01 (0.93) (p = 0.017), thereby maximising left ventricular stroke work. CONCLUSION: It appears that PLV improves both Ees and ventriculoarterial coupling, thus increasing left ventricular work efficiency.     

Value of cardiovascular interaction by exercise echocardiography according to gender

Background The cardiovascular interaction is important for the heart to achieve maximal cardiac work.The cardiovascular stiffness contributes to exercise intolerance. However, the difference in cardiovascular stiff-ness between genders is seldom reported when the objects do exercise. This study was to evaluate the ventricu-lar and arterial stiffness at rest and exercise according to gender. Methods Forty healthy volunteers were studied. The left ventricular function, structure and blood flow were measured by echocardiograph at rest and exercise. The derived variables including left ventricular end-systolic and diastolic elastance（Ees and Ed）, arterial elastance（Ea）, ventricular-vascular coupling index（VVI） and total stiffness index（TSI） were calculated.Results During exercise, all of the Ed, Ees, Ea and TSI showed significant increase, but VVI was no difference compared with them at rest. Both at rest and exercise, Ed, VVI and TSI had significantly higher in women than in men. The area under the receiver operating characteristic curves showed the area of Ed, Ees, Ea and TSI was greater than that of VVI. There were significant differences in Ed, Ees, Ea and TSI（P 〈 0.05）, but no significant difference in VVI（P 〉 0.05） between rest and exercise. Only in women, the Ed, Ees and Ea were correlated with the TSI, rate pressure product, E/e and EF. Conclusions Exercise leads to synchronous increase in ventricular and arterial stiffness, and ventriculoarterial coupling is maintained for healthy objects. The exercise intolerance is lower in women than in men.     

Vascular ventricular coupling in patients with malignant phase hypertension: the West Birmingham malignant hypertension project

Patients with malignant hypertension (MHT) have persistent vascular dysfunction and a much worse clinical prognosis than non-MHT hypertensive patients, despite good long-term blood pressure (BP) control. We hypothesized that abnormal arterial (arterial elastance (Ea); arterial elastance index (EaI)) and ventricular (End-systolic elastance (Ees) and End-diastolic elastance (Eed)) elastances are present in treated MHT patients, compared with non-MHT hypertensive controls. Echocardiographic parameters of cardiac and vascular stiffness (EaI, Ees and Eed) were quantified in patients with stable MHT and treated 'high-risk' hypertension patients (HHT, but non-MHT). All patients had well-controlled BP, with a median follow-up time for MHT of 144 months. Ea was calculated from stroke volume and systolic BP and adjusted by body area (EaI). Ees was calculated using systolic and diastolic BP, stroke volume, ejection fraction, time intervals and estimated normalized ventricular elastance at arterial end diastole. Eed was calculated from Doppler parameters and the diastolic filling volume. Both study groups had preserved left ventricular contractility, with no significant differences on 3D-echocardiography (P=0.10) There were no significant differences in EaI (P=0.83), Ees (P=0.32), Eed (P=0.23) and arterial-ventricular interaction (Ees/Ea, P=0.69). In the MHT group, Eed positively correlated with age (r=0.56, P=0.38) and systolic BP (r=0.68, P=0.008). On multivariable regression analysis, MHT status was not predictive of the ventricular and Ea. Despite documented vascular dysfunction in patients with previously diagnosed stable MHT, the arterial and systolic elastances were similar to HHT patients, suggesting that adequate BP control in MHT patients allows preservation or restoration of normal arterial-ventricular coupling.     

Impact of arterial elastance as a measure of vascular load on left ventricular geometry in hypertension.

OBJECTIVE: Effective arterial elastance (Ea), integrating the pulsatile component of left ventricular (LV) afterload, is an estimate of aortic input impedance. We evaluated relationships of Ea with left ventricular anatomy and function in essential hypertension. DESIGN: A cross-sectional analysis in 81 normotensive and 174 untreated hypertensive individuals enrolled in a referral hypertension centre. METHODS: Using echocardiography we determined left ventricular mass index (LVMI), relative wall thickness (RWT), stroke volume (SV), endocardial (FSe) and midwall (FSm) fractional shortening and total peripheral resistance (TPR). Carotid pressure waveforms were obtained by arterial tonometry, and end-systolic pressure (Pes) was measured at the dicrotic notch. Ea index (EaI) was calculated as Pes/(SV index); LV elastance (Ees) was estimated as Pes/LV end-systolic volume, and ventriculo-arterial coupling was evaluated by the Ea/Ees ratio. RESULTS: EaI was higher in hypertensives than in normotensives (3.02 +/- 0.63 versus 2.40 +/- 0.52 mmHg/l per m2; P< 0.0001). Using the 95% upper confidence limit in normotensives, hypertensives were divided in two groups with normal or elevated EaI. The 38 hypertensives with elevated EaI had higher RWT (0.41 +/- 0.06 versus 0.37 +/- 0.05), lower LVMI (87.5 +/- 18.5 versus 96.8 +/- 19.3 g/m2), higher TPR (2247 +/- 408 versus 1658 +/- 371 dynes/cm s(-5)) and lower FSe and FSm (35 +/- 5 versus 39 +/- 5 and 16 +/- 2 versus 18 +/- 2%; all P< 0.05) than patients with normal EaI. Ea/Ees ratio was increased and cardiac output was reduced in hypertensives with elevated EaI. CONCLUSIONS: High values of EaI identify a minority of hypertensive patients characterized by elevated TPR, left ventricular concentric remodelling, depressed left ventricular systolic function and impaired ventriculo-arterial coupling.     

Comparison of cardiac and peripheral arterial stiffening and ventriculovascular uncoupling in patients with uncomplicated hypertension versus patients with hypertension after heart transplantation

Despite normal ejection fractions, patients who undergo heart transplantation (HT) have low peak aerobic capacity and reduced arterial compliance, suggesting "ventriculovascular uncoupling." To what extent this is related to post-transplantation hypertension versus the unique characteristics of the donor-recipient relation remains poorly understood. Echocardiograms were retrospectively reviewed from 126 normal subjects, 309 patients with uncomplicated hypertension (UH), and 58 consecutive patients with HT >1 year after the procedure who were stable without evidence of rejection. Left ventricular (LV) end-systolic elastance (Ees), a measure of LV systolic performance; effective arterial elastance (Ea), a measure of vascular stiffness; and Ea/Ees, a parameter describing ventriculovascular coupling, were obtained. Compared with normal subjects, tandem increases in Ea (+24% and +85%, all p values <0.0001) and Ees (+23% and +33%, all p values <0.0001) were observed in patients with UH and HT, respectively, with patients with HT having significantly higher values than those with UH (both p values <0.05). Although the Ea/Ees ratio remained similar between normal subjects and patients with UH, patients with HT exhibited increases in the Ea/Ees ratio (all p values <0.01) and reduced stroke volume indexes (-20% and -22%, respectively, all p values <0.05). These changes were associated with a doubling of LV concentric remodeling in patients with HT compared with those with UH (67% vs 34%, p <0.0001). In conclusion, HT is associated with increases in Ees, Ea, and the Ea/Ees ratio, suggesting ventriculovascular uncoupling and maximal LV stroke work. These aberrations, which determine cardiovascular performance in the setting of HT, are not simply explained by vascular age or post-transplantation hypertension but may adversely affect functional capacity.     

Impact of atrial septal defect closure on right ventricular performance.

BACKGROUND: Atrial septal defect (ASD) closure is one of the most representative cardiac operations, but there have been few assessments of right ventricular (RV) performance during the perioperative period. METHODS AND RESULTS: Using transesophageal echocardiography with automated border detection system, the RV pressure - area (P-A) loops were measured in 6 patients immediately before and after an ASD closure. Multiple RV P-A loops obtained by the inferior vena cava occlusion technique were used to evaluate end-systolic maximal elastance (Ees), preload recruitable stroke work (MEW), external work (EW) and the systolic P-A area (PAA). Ees and MEW are indices of contractility, and PAA represents the total mechanical energy. RV Ees and MEW did not change after the operation (from 3.36 +/- 2.20 to 3.70 +/- 2.04 mmHg/cm2, p = 0.4; and from 10.3 +/- 5.0 to 10.5 +/- 4.5 mmHg, p = 0.8, respectively), whereas EW and PAA were significantly reduced (from 121.4 +/- 77.4 to 48.7 +/- 26.6 mmHg/cm2, p < 0.05; and from 274.8 +/- 212.8 to 92.7 +/- 52.8 mmHg/cm2, p < 0.05, respectively). ASD closure reduced the EW and total mechanical energy of the right ventricle without influencing contractility. CONCLUSIONS: These results indicate that ASD closure preserved RV function and reduced RV myocardial oxygen consumption. Assessment of the RV P-A relationship in the operating room demonstrates the beneficial effects of ASD closure on RV performance.     

Ventricular load optimization by unloading therapy in patients with heart failure

The effects of unloading a depressed heart were assessed in terms of optimal coupling between the ventricle and arterial system. To assess the effects of preload on ventricular load coupling, preload was reduced with a lower body negative pressure of -20 mm Hg. Nitroprusside was used to evaluate the effects of afterload on the coupling under the condition that preload reduction was comparable to that with lower body negative pressure. In 13 patients with heart failure (ejection fraction 32 +/- 3%, mean +/- SE), direct arterial pressure was simultaneously recorded with the left ventricular echocardiogram as the pressure was elevated by phenylephrine. Left ventricular contractile properties were defined by the slope (Ees) of the end-systolic pressure-volume relation. The effective arterial elastance (Ea) was expressed by the slope of the end-systolic pressure-stroke volume relation. Left ventricular external work, end-systolic potential energy and work efficiency, defined as external work per pressure volume area (external work + potential energy), were determined. Baseline ventricular load coupling in these patients was characterized by an increase in the ratio of arterial elastance to ventricular elastance (Ea/Ees) (1.96 +/- 0.31). This ratio decreased significantly, to 1.45 +/- 0.22, with nitroprusside, and increased to 2.37 +/- 0.34 with lower body negative pressure. Therefore, end-systolic potential energy was decreased by nitroprusside but was unaltered by lower body negative pressure while external work was comparably decreased by both manipulations, indicating that work efficiency was significantly augmented with nitroprusside but declined with lower body negative pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventriculo-arterial coupling during aerobic and anaerobic exercise in normal subjects

Physiological differences in aerobic and anaerobic exercise were assessed within the coupling framework between the left ventricle and the arterial system. In 10 normal men, the anaerobic threshold was estimated using sequential breath gas analysis during incremental ergometer tests. Direct arterial pressure and left ventricular echocardiograms were simultaneously recorded as its pressure was changed by phenylephrine or nitroprusside, and the slope (Ees) and volume axis intercept (Vo) of the end-systolic pressure (ESP)-volume relationship were determined. The effective arterial elastance (Ea) was expressed by the slope of the ESP-stroke volume relationship. Assuming that the Vo was unchanged from the resting state, the Ees and Ea were determined during exercise at aerobic and anaerobic work levels for each subject. During aerobic exercise, an increase in left ventricular end-diastolic volume and the tendency to decrease in ESP caused a significant fall in Ea by 30%. There was no significant change in Ees. Consequently, Ea/Ees which correlates inversely with left ventricular pump efficiency, decreased by 35%. During anaerobic exercise, Ea remained the same as during aerobic exercise, but Ees rose substantially by 89%. This caused a further reduction in Ea/Ees (-54%). Thus, ventriculo-arterial coupling during exercise is characterized by a decrease in Ea/Ees, indicating an augmentation of pump efficiency. This is primarily mediated by changes in loading conditions (decrease in Ea) during aerobic exercise, and by enhanced contractility (increase in Ees) during anaerobic exercise.     

Effects of carvedilol on ventriculo-arterial coupling in patients with heart failure.

BACKGROUND: Ventriculo-arterial coupling, defined as the ratio of the effective afterload (Ea) to contractility (Ees), reflects the mechano-energetic performance of the heart and is increased in chronic heart failure (CHF); the aim of treatment is to reduce its value. We studied the effect of carvedilol on the Ea/Ees ratio in patients with CHF treated with ACE-inhibitors, diuretics, and digoxin. METHODS: Between November 1999 and October 2001, 36 consecutive ambulatory patients (aged 31 to 76 years) with stable CHF and idiopathic or hypertensive cardiomyopathy, in sinus rhythm and with a left ventricular ejection fraction < or = 40%, were started on carvedilol and the dose was increased to the maximum tolerated. Ees was calculated as the left ventricular systolic pressure--taken as the systolic arterial pressure measured using the cuff manometer simultaneously with two-dimensional echocardiographic recordings--divided by the left ventricular end-systolic volume. Ea was measured as the ratio of the left ventricular systolic pressure to the stroke volume. All patients were investigated prospectively after 6 and 12 months of treatment. RESULTS: Out of 36 patients, 4 did not tolerate the drug and were dropped out. At 6.35 +/- 1 months, the daily dosage of carvedilol was 49.7 +/- 21 mg. The NYHA functional class improved from 1.52 +/- 0.67 to 1.29 +/- 0.53 (p = 0.017), the heart rate markedly diminished from 73.6 +/- 13.3 to 60.8 +/- 10.8 b/min (p < 0.001) and so did Ea (3.35 +/- 0.91 to 2.84 +/- 0.93, p = 0.001). Peripheral resistances and Ees did not change. Therefore, the decrease in the Ea/Ees ratio (2.61 +/- 0.78 vs 2.19 +/- 0.89, p = 0.004) and the related increase in left ventricular ejection fraction (28.8 +/- 5.68 vs 33.3 +/- 7.5%, p < 0.001) were due to the decrease in Ea, while Ees did not vary significantly. Moreover, the Ea reduction was related linearly to the decrease in heart rate (r = 0.46, p = 0.001). There was no change in diuretic or ACE-inhibitor dosing during carvedilol titration. At 14.7 +/- 2 months of follow-up, no further variation occurred, short of a trend toward a slight increase in Ees (1.38 +/- 0.49 to 1.58 +/- 0.65, p = 0.07). CONCLUSIONS: Carvedilol, added to the conventional therapy of CHF, improves left ventricular performance and reduces the Ea/Ees ratio by decreasing Ea, mainly through a reduction in heart rate. This effect is already evident at 6 months and persists later on, while only after 12 months does Ees tend to increase slightly.     

Dipyridamole-induced decrement of functional recovery of postischemic reperfused myocardium in conscious dogs with well-developed coronary collateral circulation

The effects of dipyridamole (20 and 40 micrograms/kg/min intravenously) on the time course of functional recovery of myocardium after five 5-minute coronary artery occlusions and four 5-minute reperfusions and a subsequent 5-hour reperfusion period were studied in chronically instrumented, conscious dogs with well-developed coronary collateral circulation. In comparison with vehicle-treated control dogs, those given dipyridamole (20 and 40 micrograms/kg/min, respectively) 15 minutes before and during coronary occlusion had a greater depression of regional segment shortening (38 +/- 7% and 19 +/- 4%, respectively, vs control levels of 69 +/- 10% of preocclusion values) during acute coronary artery occlusion. After a 5-hour reperfusion period, segment shortening returned to preocclusion values in the control group but remained decreased in the dipyridamole groups (87 +/- 4% and 75%, respectively). These results suggest that dipyridamole in a dose-dependent manner exacerbates recovery of contractility of postischemic reperfused myocardium in dogs with well-developed coronary collateral circulation.     

The effect of prostaglandin E1 on acute pulmonary artery hypertension during oleic acid-induced respiratory dysfunction

This study examined the general effect of intravenous PGE1 on RV Ees and effective PA elastance (EA) during acute pulmonary hypertension associated with oleic acid infusion. In eight pigs, RV end-systolic elastance was quantified with the Ees and Ea was defined with reference to the Windkessel model. Oleic acid infusion increased mean PAP and Ea. Prostaglandin E1 reduced PAP and decreased Ea. Ees did not change throughout the study. Mean arterial pressure was reduced and the pulmonary shunt was increased after PGE1 infusion. The PaO2 was reduced. Data from this study suggest that although PGE1 is effective in reducing PAP, it is not as effective in reducing RV afterload. Furthermore, PGE1 does have significant side effects such as reduction of systemic arterial pressure and an increase in pulmonary shunt.     

Macrophage colony-stimulating factor treatment after myocardial infarction attenuates left ventricular dysfunction by accelerating infarct repair.

OBJECTIVES: We aimed to determine the effects of macrophage colony-stimulating factor (M-CSF) and granulocyte colony-stimulating factor (G-CSF) treatment on both the repair process and ventricular function after myocardial infarction (MI). BACKGROUND: The M-CSF and G-CSF have multiple potential effects on cells involved in wound repair. METHODS: Myocardial infarction was induced by 45- or 90-min coronary occlusion and reperfusion in rats with or without subsequent injection of M-CSF (10(6) IU/kg/day) or G-CSF (50 microg/kg/day) for five days. We examined histology and messenger ribonucleic acid (mRNA), and assessed left ventricular function in situ using a conductance catheter. RESULTS: Five days after MI, M-CSF increased the number of ED-1-positive cells, mRNA levels of transforming growth factor-beta-1, collagen I and III, and collagen fibers within the infarct. Fourteen days after MI, induced by 45-min ischemia, left ventricular end-systolic elastance (Ees) was reduced (1,191 +/- 87 mm Hg/ml vs. 1,812 +/- 150 mm Hg/ml) and both isovolumic relaxation time constant (tau) (11.9 +/- 0.9 ms vs. 8.5 +/- 0.4 ms) and left ventricular end-diastolic volume (LVEDV) (0.225 +/- 0.014 ml vs. 0.172 +/- 0.011 ml) increased versus sham-operated rats. These alterations after MI were attenuated by M-CSF (Ees = 1,650 +/- 146, tau = 9.7 +/- 0.7, LVEDV = 0.199 +/- 0.012) but not by G-CSF. This beneficial effect of M-CSF on Ees was also detected in hearts with MI induced by 90-min ischemia. Furthermore, M-CSF increased collagen content within infarcts and reduced the proportion of thin collagen fibers 14 days after MI. The Ees significantly correlated with infarct collagen content. Nevertheless, neither M-CSF nor G-CSF modified infarct size. CONCLUSIONS: The M-CSF treatment attenuates deterioration of left ventricular function after MI by accelerating infarct repair.