Cardiomyoplasty reduces myocardial oxygen consumption: implications for direct mechanical compression

BACKGROUND: This study investigates the possibility of reducing myocardial oxygen consumption by dynamic cardiomyoplasty in chronic heart failure. The sheep model used is relevant for cardiac assist using direct mechanical cardiac compression. METHODS: In 7 sheep, heart failure was induced by staged intracoronary microembolization followed by dynamic cardiomyoplasty. Six months later, the effect of latissimus dorsi muscle stimulation in the 2:1 mode (on, cardiomyoplasty; off, control) was studied. Left ventricular pressure-volume loops were obtained by conductance, micromanometer, and inferior vena cava occlusion catheter. Myocardial oxygen consumption was derived from left main coronary artery blood flow and oxygen content of arterial and coronary sinus blood. RESULTS: Cardiomyoplasty had no significant effect on left ventricular hemodynamic variables such as end-systolic pressure. However, cardiomyoplasty increased stroke volume and ejection fraction significantly by 11% +/- 12% and 11% +/- 10%, respectively. Although pressure-volume area and external work did not increase with cardiomyoplasty, myocardial oxygen consumption decreased by 21% +/- 11%. Therefore, cardiomyoplasty increased myocardial efficiency (external work/myocardial oxygen consumption) by 16% +/- 13%. CONCLUSIONS: Despite limited hemodynamic improvement from dynamic cardiac compression by cardiomyoplasty in sheep with chronic heart failure, myocardial oxygen consumption was significantly reduced. These findings provide a rationale for reverse remodeling of the failing heart using direct mechanical compression.     

Direct compression of the failing heart reestablishes maximal mechanical efficiency

BACKGROUND: In failing hearts, homeostatic mechanisms contrive to maximize stroke work and maintain normal arterial blood pressure at the expense of energetic efficiency. In contrast dobutamine reestablishes maximal mechanical efficiency by promoting energetically optimal loading conditions. However, dobutamine also wastefully increases nonmechanical oxygen consumption. We investigated whether direct mechanical cardiac compression would reestablish maximal mechanical efficiency without the oxygen-wasting effect. METHODS: The pressure-volume relationship and myocardial oxygen consumption were derived in sheep using left ventricular pressure and volume from manometer-tipped and conductance catheters, and coronary flow from Transonics flow probe. RESULTS: Propranolol hydrochloride and atropine sulfate were administered to reduce ejection fraction to 21% when ventricular elastance fell to 1.35 mm Hg/mL and mechanical efficiency to 79% of maximal. Low-pressure direct mechanical compression of the failing heart restored mechanical efficiency to 94% of maximal and realigned optimal left ventricular end-systolic pressure with operating left ventricular end-systolic pressure without altering nonmechanical oxygen consumption. CONCLUSIONS: We conclude that direct cardiac compression restores mechanical efficiency to normal maximum without wasting energy on additional nonmechanical activity.     

Myocardial oxygen consumption of fibrillating ventricle in hypothermia. Successful account by new mechanical indexes--equivalent pressure-volume area and equivalent heart rate.

We studied the effects of cardiac hypothermia on myocardial oxygen consumption of a fibrillating ventricle and evaluated whether myocardial oxygen consumption of a fibrillating ventricle in hypothermia can be accounted for by new mechanical indexes: equivalent pressure-volume area and equivalent heart rate in the isolated cross-circulated canine heart preparation. Equivalent pressure-volume area is the area that is surrounded by a horizontal pressure-volume line at the pressure of a fibrillating ventricle and the end-systolic and end-diastolic pressure-volume relations in the beating state in the pressure-volume diagram. Equivalent pressure-volume area is an analog of the pressure-volume area of a beating heart and has been proposed to be a measure of the total mechanical energy of a fibrillating ventricle. Equivalent heart rate was calculated from myocardial oxygen consumption per minute in both beating and fibrillating states under unloaded conditions as an estimate of the frequency of contractions of individual myocytes on the assumption that individual myocytes during ventricular fibrillation have the same contractility as that in the beating state. We estimated myocardial oxygen consumption per minute of the fibrillating ventricle at various ventricular volumes as a function of both equivalent pressure-volume area and equivalent heart rate. The myocardial oxygen consumption-equivalent pressure-volume area relation during ventricular fibrillation in hypothermia was highly linear, with a correlation coefficient of 0.90 (mean). The relation between estimated and directly measured myocardial oxygen consumption values of a fibrillating ventricle in hypothermia was highly linear (r = 0.98), and the regression line (y = 0.80x + 0.48) was close to the identity line in the working range. Therefore we conclude that equivalent pressure-volume area is the primary determinant of myocardial oxygen consumption during ventricular fibrillation in hypothermia, and myocardial oxygen consumption of a fibrillating ventricle in hypothermia can be accounted for by the combination of equivalent pressure-volume area and equivalent heart rate as in normothermia.     

Effects of Intracoronary Fentanyl on Left Ventricular Mechanoenergetics in the Excised Cross-circulated Canine Heart (Revised Publication)

Background: It is still unclear whether fentanyl directly alters left ventricular (LV) contractility and oxygen consumption. This is because of the difficulty in defining and evaluating contractility and energy use independently of ventricular loading conditions and heart rate in beating whole hearts.

Methods: This study was conducted to clarify the mechanoenergetic effects of intracoronary fentanyl in six excised cross-circulated canine hearts. The authors used the framework of the Emax (a contractility index)-PVA (systolic pressure-volume area, a measure of total mechanical energy)-VO2 (myocardial oxygen consumption per beat) relationship practically independent of ventricular loading conditions. The authors measured LV pressure, volume, coronary flow, and arteriovenous oxygen content difference to calculate Emax, PVA, and VO2. They first obtained the VO2 -PVA relationship for varied LV volumes at control Emax. The authors then obtained the VO2 -PVA relationship at a constant LV volume, whereas coronary blood fentanyl concentration was increased in steps up to 240 ng/ml. Finally, they obtained the VO2 -PVA relationship for varied LV volumes at the final dose of fentanyl.

Results: Fentanyl at any concentrations did not significantly change Emax, PVA, and VO2 from the control. The linear end-systolic pressure-volume relations and their slopes were virtually the same between the control and fentanyl volume loading in each heart. Further, either the slope (oxygen cost of PVA) or the VO2 intercept (unloaded VO2) of the linear VO2 -PVA relationship remained unchanged by fentanyl.     

Effects of Intracoronary Fentanyl on Left Ventricular Mechanoenergetics in the Excised Cross-circulated Canine Heart

Background: It is still unclear whether fentanyl directly alters left ventricular (LV) contractility and oxygen consumption. This is because of the difficulty in defining and evaluating contractility and energy use independently of ventricular loading conditions and heart rate in beating whole hearts.

Methods: This study was conducted to clarify the mechanoenergetic effects of intracoronary fentanyl in six excised cross-circulated canine hearts. The authors used the framework of the Emax (a contractility index)-PVA (systolic pressure-volume area, a measure of total mechanical energy)-VO2 (myocardial oxygen consumption per beat) relationship practically independent of ventricular loading conditions. The authors measured LV pressure, volume, coronary flow, and arteriovenous oxygen content difference to calculate Emax, PVA, and VO2. They first obtained the VO2 -PVA relationship for varied LV volumes at control Emax. The authors then obtained the VO2 -PVA relationship at a constant LV volume, whereas coronary blood fentanyl concentration was increased in steps up to 240 ng/ml. Finally, they obtained the VO2 -PVA relationship for varied LV volumes at the final dose of fentanyl.

Results: Fentanyl at any concentrations did not significantly change Emax, PVA, and VO2 from the control. The linear end-systolic pressure-volume relations and their slopes were virtually the same between the control and fentanyl volume loading in each heart. Further, either the slope (oxygen cost of PVA) or the VO2 intercept (unloaded VO2) of the linear VO2 -PVA relationship remained unchanged by fentanyl.     

Left ventricular volume reduction surgery for heart failure: a physiologic perspective

BACKGROUND: Ventricular volume reduction surgery for idiopathic cardiomyopathy fails to improve cardiac output and is associated with a high incidence of recurrent heart failure. Volume reduction surgery achieved by removing akinetic or dyskinetic myocardium after myocardial infarction appears to be associated with better outcomes. The reasons for the differences in outcomes are not clear. METHODS AND RESULTS: The hemodynamic effect of the major forms of volume reduction surgery were predicted by using a composite model of the left ventricle in which 20% of the myocardium was given properties of either weak but contracting muscle, an akinetic scar, or a dyskinetic scar (aneurysm). The end-systolic and end-diastolic pressure-volume relationships were determined numerically for each simulated operation. Any volume reduction procedure reduced chamber size, shifting end-systolic and end-diastolic pressure-volume relationships leftward. With resection of weak but contracting muscle, the leftward shift was greater for the end-diastolic than for the end-systolic pressure-volume relationship. Conversely, with resection of dyskinetic scar, the leftward shift was greater for end-systolic than for end-diastolic pressure-volume relationships. In contrast, resection of stiff scar shifted the 2 relationships equally. The effect on overall pump function was indexed by the relationship between total ventricular mechanical work and end-diastolic pressure. There was a beneficial effect on this relationship of resecting dyskinetic tissue, an equivocal effect of akinetic scar resection, and a negative effect of removing contracting myocardium. CONCLUSIONS: The effect of volume reduction surgery on overall ventricular pumping characteristics is determined by the differential effects on end-systolic and end-diastolic properties, which in turn are determined by the material properties of the region being removed.     

Left ventricular mechanics and energetics in the dilated canine heart: acute versus chronic mitral regurgitation.

The effects of volume overload associated with mitral regurgitation on left ventricular systolic mechanics, energetics, mechanical to external stroke work efficiency, and ventriculoarterial coupling were examined in 11 conscious, closed-chest dogs. Miniature radiopaque tantalum markers were implanted into the myocardium to measure left ventricular volume, and biplane cinefluoroscopic images were obtained 1 week and 3 months after creation of mitral regurgitation. Echocardiographically determined left ventricular mass increased from 116 +/- 28 to 152 +/- 29 gm (p less than 0.001). Left ventricular end-diastolic and end-ejection volumes increased by 24% and 27%, respectively. Global left ventricular systolic performance was assessed by the slopes (linear regression) of the end-systolic pressure-volume and end-systolic stress-volume relationships corrected for change in end-diastolic volume; normalized end-systolic pressure-volume relationships fell by 36% (p less than 0.001), and normalized end-systolic stress-volume relationships declined by 21% (p less than 0.005). The normalized end-systolic volume at 100 mm Hg end-systolic left ventricular pressure increased from 0.63 to 0.75 (p less than 0.05). Similar results were observed based on a nonlinear (quadratic) fit of the end-systolic pressure-volume data. In terms of energetics, the slopes of the stroke volume-end-diastolic volume and pressure-volume area-end-diastolic volume relationships fell significantly, indicating reduced external stroke work and mechanical energy at any given level of preload. Additionally, the efficiency of energy transfer from pressure-volume area to external pressure-volume work at matched end-diastolic volume was 25% lower (p = 0.006) at 3 months compared with the 1-week measurements. While overall effective arterial (or total vascular) elastance tended to decrease after a period of time, the effective ventriculovascular coupling ratio increased from 1.6 +/- 0.6 to 2.7 +/- 1.1 (p less than 0.005), indicating a greater degree of mismatch between the left ventricle and the total (forward and regurgitant) vascular load. Therefore the low pressure-volume overload of mitral regurgitation not only resulted in depressed left ventricular systolic mechanics but also was associated with deterioration of global left ventricular energetics and efficiency and exacerbated mismatch in coupling between the left ventricle and the systemic arterial bed and left atrium.     

The effects of cardiac cooling under surface-induced hypothermia on the cardiac function in the in situ heart

It has been reported that in the excised cross-circulated dog heart model, cardiac cooling increases Emax (contractility index) and the external work (EW) of the left ventricle without affecting the systolic pressure volume area (PVA)-independent myocardial oxygen consumption (VO2). However, it remains unclear whether this cooling inotropism and oxygen-saving effect can also be demonstrated in an in situ heart. In the present study, we investigated the effect of cardiac cooling under surface-induced hypothermia in the in situ heart to assess the practical application of this method. Adult mongrel dogs were examined under surface-induced hypothermia with or without vasodilator. Using conductance catheter, pressure-volume relationship were obtained and mechanoenergetical parameters were measured. Optimal temperature for cardiac cooling was also examined. Simple hypothermia increased Emax compared with normothermia without affecting PVA-independent VO2, but EW did not increase. However, with concurrent vasodilator administration, cardiac cooling increased not only Emax but also EW without affecting PVA-independent VO2 compared with normothermia. However, at temperature below 32 degrees C, Tau increased significantly and diastolic dysfunction was noted. Cardiac cooling with concurrent vasodilator administration in the in situ heart has inotropic and oxygen-saving effects and optimal temperature for cardiac cooling is thought to be 34 degrees C.     

Ventricular energetics after the Fontan operation: contractility-afterload mismatch

OBJECTIVE: Fontan-type operations offer the opportunity to create pulmonary and systemic circulation in series with a single pumping chamber. The effectiveness of such a circulatory pattern determines resting and exercise hemodynamics in these patients. The present study investigated cardiac performance after the Fontan operation by using ventricular-vascular coupling framework analysis. METHODS: In 12 anesthetized open-chest dogs, Fontan circulation was established by using a cavopulmonary anastomosis. Left ventricular hemodynamic variables were measured by using a combined pressure-volume-conductance catheter. Additionally, aortic flow and pressure were recorded continuously. Ventricular contractility was quantified by using the load-independent slope of the end-systolic pressure-volume relationship. Arterial system properties were quantified by using the end-systolic pressure/stroke volume ratio. The coupling between the left ventricle and arterial system was expressed by using the ratio of end-systolic pressure/stroke volume to slope of the end-systolic pressure-volume relationship. Additionally, external stroke work, total mechanical energy and mechanical efficiency (Mechanical efficiency = Stroke work/Total mechanical energy) were calculated. Impedance spectra were determined by means of Fourier analysis. RESULTS: During Fontan circulation, the slope of the end-systolic pressure-volume relationship (5.3 +/- 0.6 vs 7.5 +/- 0.6 mm Hg/mL, P <.05) decreased, and the end-systolic pressure-stroke volume relationship (4.2 +/- 0.7 vs 3.3 +/- 0.5 mm Hg/mL, P =.23) increased with parallel increased characteristic impedance. Furthermore, the end-systolic pressure-stroke volume/slope of the end-systolic pressure-volume relationship ratio increased significantly (0.76 +/- 0.04 vs 0.42 +/- 0.03, P <.005). Simultaneously, stroke work (1846 +/- 146 vs 1389 +/- 60 mm Hg/mL, P <.05) and mechanical efficiency (0.82 +/- 0.09 vs 0.56 +/- 0.05, P <.05) were significantly reduced. CONCLUSIONS: Fontan circulation leads to contractility-afterload mismatch by means of increased impedance caused by additional connection of the pulmonary vascular bed to the systemic vasculature and by means of deterioration of myocardial contractility. The increased ventriculoarterial coupling ratio and reduced mechanical efficiency predict limited cardiac functional reserve after the Fontan operation.     

Static cardiomyoplasty with synthetic elastic net suppresses ventricular dilatation and dysfunction after myocardial infarction in the rat: an acute study

BACKGROUND: Wrapping around the heart (static cardiomyoplasty) may help prevent a failing left ventricle (LV) from dilatation but may also interfere with diastolic relaxation, resulting in restrictive hemodynamics and diastolic heart failure. We developed a synthetic net with a dual elasticity and tested its effect early after induced myocardial infarction (MI) in the rat. METHODS: In rats undergoing occlusion of the left anterior descending artery (LAD) with and without cardiac wrapping, pressure-volume (PV) relationships were successively analyzed before, after intravenous volume load (saline 1% of body weight over 30 sec), and 10 to 40 minutes after LAD occlusion. In each situation, end-diastolic and end-systolic PV relationships were defined and LV size and function compared under standardized loading conditions. RESULTS: Ischemic increase in LV end-diastolic and end-systolic volumes was suppressed in a similar magnitude in NET with rats, resulting in preserved stroke volume and ejection fraction early after MI. While the presence of the net yielded a significant hemodynamic difference in response to acute volume load before ischemia, the difference was no longer apparent in the ischemic heart after LAD ligation. CONCLUSION: Static cardiomyoplasty using a synthetic elastic net significantly suppresses ischemic LV dilatation and dysfunction without restriction immediately after MI in the rat. The long-term result is pending. Net material and elasticity needs to be adjusted for optimal girdling effect, or greatest benefits with least functional compromise.     

Myocardial Oxygen Consumption Is Affected by Dynamic Cardiomyoplasty in Dogs with Adriamycin-Induced Cardiomyopathy

The purpose of the study was to investigate a possible myocardial sparing effect by dynamic cardiomyoplasty. We directly measured cardiac work and myocardial oxygen consumption after dynamic cardiomyopathy in dogs with adriamycin-induced cardiomyopathy. Ten dogs with cardiomyopathy induced by 4 weekly intracoronary infusions of adriamycin were studied. Five dogs underwent right latissimus dorsi cardiomyoplasty with progressive myostimulation, and five served as controls. Right heart and coronary sinus catheterizations were performed at 0, 10, and 15 weeks. Four and two dogs, respectively, the cardiomyoplasty and the control group, survived until 15 weeks. Cardiac work was not different between the control and the cardiomyoplasty groups (p = 0.42). Myocardial oxygen consumption was less in the cardiomyoplasty group (185.70 +/- 37.22; 165.75 +/- 25.86; 161.40 +/- 54.14 J/min at 0, 10, and 15 weeks, respectively) compared to the control group (147.80 +/- 70.99; 275.00 +/- 103.24; 263.50 +/- 52.75 J/min at 0, 10, and 15 weeks, respectively, p = 0.019). Mechanical cardiac efficiency was not meaningfully different between the cardiomyoplasty group (16.08% +/- 5.39%; 20.51% +/- 5.89%; 20.67% +/- 11.98% at 0, 10, and 15 weeks, respectively) compared to the control group (15.29% +/- 8.06%; 9.40% +/- 1.22%; 13.40% +/- 2.29% at 0, 10, and 15 weeks, respectively, p = 0.093). Acute changes of the cardiosynchronization ratio (2:1, 1:1, OFF) did not affect myocardial oxygen consumption or cardiac work within the cardiomyoplasty group. Dynamic cardiomyoplasty reduced myocardial oxygen consumption in dogs with adriamycin-induced cardiomyopathy.     

Mechanoenergetics of the Negative Inotropism of Isoflurane in the Canine Left Ventricle: No O sub 2 Wasting Effect

Background: The mechanisms underlying the negative inotropic effects of isoflurane are incompletely understood. One suggested mechanism is that isoflurane may decrease Ca2+ sensitivity of contractile proteins. If so, more free calcium would be needed to activate contractile proteins to the same degree, which would impose a greater requirement for myocardial oxygen consumption used in the cycling of calcium. In this study, the authors use the excised, cross-circulated, canine heart model and the volume servopump technique to measure the effects of isoflurane on Emax (a contractile index) and on the relationship between pressure-volume area (PVA, a measure of total mechanical energy) and myocardial oxygen consumption per beat (VO2).

Methods: Effects of intracoronary isoflurane infused via a precoronary oxygenator on myocardial mechanoenergetics were studied during isovolumic contractions. The authors measured left ventricular (LV) pressure, LV volume, coronary flow, and arteriovenous oxygen content difference and computed Emax, VO2 and PVA at 0, 1.0, 1.5, and 2.0% isoflurane. From these data, the authors obtained oxygen costs of PVA and Emax in control subjects and in those receiving 2.0% isoflurane.

Results: Emax, PVA, and VO2 dose-dependently decreased by similar degrees (P < 0.05). Isoflurane did not change the oxygen costs at 1.5% and 2.0% concentration (P < 0.05).     

Increased myocardial oxygen consumption reduces cardiac efficiency in diabetic mice

Altered cardiac metabolism and function (diabetic cardiomyopathy) has been observed in diabetes. We hypothesize that cardiac efficiency, the ratio of cardiac work (pressure-volume area [PVA]) and myocardial oxygen consumption (MVo(2)), is reduced in diabetic hearts. Experiments used ex vivo working hearts from control db/+, db/db (type 2 diabetes), and db/+ mice given streptozotocin (STZ; type 1 diabetes). PVA and ventricular function were assessed with a 1.4-F pressure-volume catheter at low (0.3 mmol/l) and high (1.4 mmol/l) fatty acid concentrations with simultaneous measurements of MVo(2). Substrate oxidation and mitochondrial respiration were measured in separate experiments. Diabetic hearts showed decreased cardiac efficiency, revealed as an 86 and 57% increase in unloaded MVo(2) in db/db and STZ-administered hearts, respectively. The slope of the PVA-MVo(2) regression line was increased for db/db hearts after elevation of fatty acids, suggesting that contractile inefficiency could also contribute to the overall reduction in cardiac efficiency. The end-diastolic and end-systolic pressure-volume relationships in db/db hearts were shifted to the left with elevated end-diastolic pressure, suggesting left ventricular remodeling and/or myocardial stiffness. Thus, by means of pressure-volume technology, we have for the first time documented decreased cardiac efficiency in diabetic hearts caused by oxygen waste for noncontractile purposes.     

Functional recovery of the native heart after cardiomyoplasty in sheep with heart failure: passive and dynamic effects of volume loading

BACKGROUND: Dynamic cardiomyoplasty (d-CMP) encourages reverse remodeling and improved contractility and stroke work (SW) efficiency of the failing native heart. This contrasts with passive cardiomyoplasty (p-CMP), which provides "passive girdling." To further evaluate pump recovery we assessed native left ventricular performance (without assist) 6 months after dynamic and passive CMP in sheep with heart failure with acute volume loading. METHODS: Heart failure (left ventricular ejection fraction 26%+/-8%) induced by coronary microembolization was followed by CMP in 11 sheep. After 8 weeks of muscle "training," paced cardiac assist was undertaken in the d-CMP group (n = 6). Five sheep with heart failure served as controls. Six months later the pressure-volume relationship was derived before and after volume loading by colloid solution. Latissimus dorsi muscle pacing was previously ceased in the d-CMP group. RESULTS: Volume loading increased left ventricular end-diastolic volume and pressure in all groups. After volume loading in d-CMP, the SW and pressure-volume area were increased, and SW efficiency remained unchanged. In p-CMP neither variable changed, whereas in control heart failure SW efficiency decreased due to a rise in pressure-volume area with stable SW. CONCLUSIONS: Based on response to volume loading, the failing native heart after 6 months of d-CMP showed functional recovery from "active girdling," whereas p-CMP prevented functional deterioration through passive girdling. The failing control heart progressively deteriorated.     

Ventricular remodeling after cardiomyoplasty in heart failure sheep: passive and dynamic effects

Background. Recent reports claim that cardiomyoplasty (CMP) has a girdling effect on the left ventricle, to prevent dilatation and functional deterioration, but the mechanism of its long-term effects on the native heart is not known. We compared the relative role of CMP’s active squeezing and passive girdling in chronically failing hearts.

Methods. After induction of stable heart failure (left ventricular ejection FRACTION = 27% ± 7%) by staged coronary microembolization, CMP was performed in 11 of 18 sheep. After 8 weeks pacing training of the latissimus dorsi muscle (LDM), cardiac assist was begun with 1:2 synchronous bursts in 6 sheep (d-CMP, N = 6), and the LDM in the passive group (p-CMP, N = 5) remained unstimulated. Four (base line) and 30 weeks after induction of heart failure, the pressure-volume relationship was derived.

Results. After 30 weeks in d-CMP the slope (E_max) of the end-systolic pressure-volume relationship increased by 66% ± 55% (p < 0.05) and external work efficiency by 48% ± 41% (p < 0.01). In the passive CMP and control groups, slope and external work efficiency were unchanged. Conversely, left ventricular end-diastolic volume decreased (−14% ± 12%, p < 0.05) in the dynamic CMP group compared with a static course in the passive CMP group (3% ± 10%, p > 0.05) and an increase (18% ± 15%, p < 0.05) in controls.

Conclusions. Dynamic CMP improved native heart’s contractility and external work efficiency. In addition, whereas passive CMP has simply a girdling effect, dynamic CMP also induces reverse left ventricular chamber remodeling.     

Preloading history influences pressure-volume-derived indices of myocardial contractility in the ejecting canine left ventricle

The dependency of indices of myocardial contractility on the immediate preloading protocol was assessed in 14 pentobarbital anesthetized open-chest dogs. An intracavitary micromanometer and epicardially placed ultrasonic dimension transducers allowed acquisition of dynamic left ventricular pressure-volume relationships while varying preload on right heart bypass. A resting cardiac output of 75 ml/kg/min was either increased twofold or reduced to zero flow over a 20-second interval. Linear regression analysis of the mechanical parameters permitted construction of the end-systolic pressure-volume relationship, rate of pressure rise-end-diastolic volume relationship, and the preload recruitable stroke work relationship. The slopes of the end-systolic pressure-volume relationship and rate of pressure rate-end-diastolic volume relationship were significantly higher when measured during volume depletion than during volume expansion (17.2 +/- 1.3 versus 8.5 +/- 0.8 mm Hg/ml and 205 +/- 14 versus 126 +/- 11 mm Hg/sec/ml, p less than 0.001, respectively). This finding was also evident when data analysis was confined to the initial 10 seconds of the loading interval. Nonlinear regression analysis of pooled data from both preloading protocols revealed curvilinear characteristics for each relationship. In contrast, the slope of the preload recruitable stroke work relationship was lower as a result of volume unloading (16.8 +/- 2.0 versus 22.8 +/- 1.7 mJ/beat/100 gm left ventricle/ml, p less than 0.01) and was independent of loading protocol when data analysis was confined to the initial 10-second acquisition period. Furthermore, second-order regression analysis of the pooled data showed no curvilinearity. These findings emphasize the importance of both the timing and method of varying cardiac preload in the determination of intrinsic myocardial contractility and suggest that the preload recruitable stroke work relationship may be a more linear contractile index that is less affected by preloading history over brief intervals.     

Superior myocardial protection with nicorandil cardioplegia.

OBJECTIVE: The ATP-sensitive potassium channel (K(ATP)) activator nicorandil used as cardioplegic agent may protect the left ventricle during cardiac arrest. Nicorandil in cold blood was compared with standard hyperkalemic blood and crystalloid cardioplegia. METHODS: Twenty-one pigs were randomly assigned to three groups: (1) cold hyperkalemic crystalloid (n=7); (2) cold hyperkalemic blood (n=7); and (3) nicorandil as cardioplegia in cold blood (n=7). Left ventricular mechanical performance, pressure-volume area (PVA) and myocardial oxygen consumption (MVO(2)) were measured before and at 1 and at 2 h after 60 min of cold global ischemia on cardiopulmonary bypass using intraventricular pressure-volume conductance catheters, coronary flow probes and O(2)-content difference. RESULTS: The slope (M(w)) of the stroke work end-diastolic volume relationship, the preload recriutable stroke work relationship, was unchanged after ischemia in the nicorandil group, but was reduced to averaged 62.5% (standard deviation 14) of baseline values in both hyperkalemic perfusions (P<0.05). The slope of the MVO(2)-PVA relationship was unchanged after nicorandil cardioplegia while the slope after hyperkalemic blood and crystalloid cardioplegia increased with 33% (P<0.02) and 52% (P<0.02) of baseline values, respectively. CONCLUSIONS: Nicorandil as sole cardioplegic agent in cold blood given intermittently preserves left ventricular contractility and myocardial energetics significantly better than traditional forms of cardioplegia after cardiac arrest.     

Correlation between the linearized Frank-Starling relationship and myocardial energetics in the ejecting heart. Afterload independence and sensitivity to inotropic state

Previous studies suggest that the relationship between end-diastolic volume and stroke work calculated as the area of the pressure-volume work loop is linear, afterload independent, and sensitive to the inotropic state. The correlation of myocardial oxygen consumption with this stroke work could provide an integrated measure of cardiac performance and metabolism to assess perturbations induced by ischemia or pathologic loading conditions. Fourteen canine hearts instrumented for computerized acquisition of instantaneous pressure-volume data and quantitation of myocardial oxygen consumption were studied during progressive volume infusion on right heart bypass (1.5 to 3.5 L/min in 250 ml/min increments). Data acquisition both in the control state and during continuous infusion of calcium chloride (0.03 mEq/kg/min, n = 7) to increase contractility or phenylephrine (2 micrograms/kg/min, n = 7) to alter afterload facilitated the construction of stroke work versus end-diastolic volume and myocardial oxygen consumption versus stroke work relationships by least-squares regression analysis. The cardiac mechanics assessment for this group of dogs confirmed a highly linear (mean r = 0.984) work versus preload relationship that was unaffected by changes in afterload but sensitive to increased contractility (71% increase in slope). The myocardial energetics correlation was also linear (mean r = 0.939) and demonstrated an increased oxygen utilization characteristic of the higher inotropic state produced by calcium chloride infusion (0.047 +/- 0.003 versus 0.070 +/- 0.008 ml oxygen/beat/100 gm left ventricular weight, p = 0.008). Although phenylephrine administration produced variable perturbations of myocardial oxygen consumption, the energetics relationship for this subgroup was not statistically altered by changes in afterload. The features of this cardiac energetics assessment suggest its value as a biological marker to evaluate the postischemic, hypertrophied, or failing heart.     

Increased aortic compliance maintains left ventricular performance at lower energetic cost.

OBJECTIVE: The aim of this study was to investigate left ventricular contractility and energetic cost of cardiac ejection under conditions of acute increase in aortic compliance. METHODS: In six anaesthetized pigs, ascending aortic compliance was increased by adding a volume chamber in parallel to the ascending aorta. Systemic vascular parameters, including characteristic impedance, peripheral resistance, total vascular compliance, and inertance, were estimated with a four-element windkessel model. Arterial elastance was derived from these parameters. Left ventricular systolic function was assessed by end-systolic pressure-volume relationship (end-systolic elastance), and stroke work. Pressure-volume area was used as a measure of myocardial oxygen consumption. Heart rate remained constant during the experimentation. RESULTS: Adding the aortic volume chamber significantly increased vascular compliance from 0. 95+/-0.08 to 1.17+/-0.06 ml/mmHg (P<0.01), while inductance, characteristic impedance, peripheral resistance, and arterial elastance remained statistically at basal values, respectively 0. 0020+/-0.0003 mmHg.s(2)/ml, 0.105+/-0.009 mmHg.s/ml, 1.27+/-0.12 mmHg.s/ml, and 2.43+/-0.21 mmHg/ml. During the same interval, stroke work and pressure-volume area decreased respectively from 2700+/-242 to 2256+/-75 mmHg.ml (P<0.01), and from 3806+/-427 to 3179+/-167 mmHg.ml (P<0.01). Stroke work and pressure-volume area decreased at matched end-diastolic volumes. In contrast, end-systolic elastance, ejection fraction, and stroke volume remained statistically unchanged, respectively at 2.29+/-0.14 mmHg/ml, 48.1+/-2.1 %, and 32. 4+/-1.7 ml. CONCLUSIONS: These data suggest that, when facing an increased aortic compliance, the left ventricle displays unchanged contractility, but the energetic cost of cardiac ejection is significantly decreased. These data may be of clinical importance when choosing an artificial prosthesis for ascending aortic replacement.     

Left ventricular reshaping: effects on the pressure-volume relationship

OBJECTIVE: We tested whether the CardioClasp device (CardioClasp, Inc, Cincinnati, Ohio), a non-blood contact device, would improve left ventricular contractility by acutely reshaping the left ventricle and reducing left ventricular wall stress. METHODS: In dogs (n = 6) 4 weeks of ventricular pacing (210-240 ppm) induced severe heart failure. Left ventricular function was evaluated before and after placement of the CardioClasp device, which uses 2 indenting bars to reshape the left ventricle. Hemodynamics, echocardiography, and Sonometrics crystals dimension (Sonometrics Corporation, London, Ontario, Canada) were measured at steady state and during inferior vena caval occlusion. RESULTS: The CardioClasp device decreased the left ventricular end-diastolic anterior-posterior dimension by 22.8% +/- 1.9%, decreased left ventricular wall stress from 97.3 +/- 22.8 to 67.2 +/- 7.7 g/cm(2) (P =.003), and increased the fractional area of contraction from 21.3% +/- 10.5% to 31.3% +/- 18.1% (P =.002). The clasp did not alter left ventricular end-diastolic pressure, left ventricular pressure, left ventricular dP/dt, or cardiac output. With the CardioClasp device, the slope of the end-systolic pressure-volume relationship was increased from 1.87 +/- 0.47 to 3.22 +/- 1.55 mm Hg/mL (P =.02), the slope of preload recruitable stroke work versus end-diastolic volume was increased from 28.4 +/- 11.0 to 44.1 +/- 23.5 mm Hg (P =.02), and the slope of maximum dP/dt versus end-diastolic volume was increased from 10.6 +/- 4.6 to 18.6 +/- 7.4 mm Hg x s(-1) x mL(-1) (P =.01). The CardioClasp device increased the slope of the end-systolic pressure-volume relationship by 68.0% +/- 21.7%, the slope of preload recruitable stroke work versus end-diastolic volume by 50.7% +/- 18.1%, and the slope of maximum dP/dt versus end-diastolic volume by 85.7% +/- 28.9%. CONCLUSIONS: The CardioClasp device decreased left ventricular wall stress and increased the fractional area of contraction by reshaping the left ventricle. The CardioClasp device was able to maintain cardiac output and arterial pressure. The clasp increased global left ventricular contractility by increasing the slope of the end-systolic pressure-volume relationship, the slope of preload recruitable stroke work versus end-diastolic volume, and the slope of maximum dP/dt versus end-diastolic volume. In patients with heart failure, the CardioClasp device might be effective for clinical application.