Pressure-volume Area Research Articles

Beneficial influence of vasoactive intestinal peptide on ventriculovascular coupling in closed-chest dogs.

The effect of vasoactive intestinal peptide (VIP) on ventriculovascular coupling in the intact cardiovascular system has not been defined. We studied seven dogs chronically instrumented with left ventricular (LV) pressure manometers and three sets of diameter gauges before and after infusions of 0.02, 0.05, and 0.10 microgram.kg-1.min-1 VIP. The dogs were studied after autonomic blockade, anesthesia, and intubation, with a fixed heart rate of 160 beats/min. Contractility was assessed using LV elastance at end systole (Ees) and the slope of the stroke work-end-diastolic volume relation. The vascular influence of VIP was quantified by determining effective arterial elastance (Ea) under steady-state conditions. The overall effect on ventriculovascular coupling was assessed using the transfer of mechanical energy from LV to the arterial system (TransPVA) quantified as the percentage of pressure-volume area (PVA) expressed as stroke work. LV relaxation was measured using the time constant of LV pressure decay. The results showed that VIP increased contractility (Ees increased to 129, 156, and 181% of control; P < 0.01 for all vs. control) and decreased effective arterial elastance (Ea fell to 84, 68, and 64% of control; P < 0.0155 vs. control for the two higher doses). VIP had no consistent effects on LV relaxation. Thus, in addition to its positive ventricular effects (increased contractility), VIP has beneficial vascular effects (reduced Ea). These properties combine to improve ventriculovascular coupling, such that VIP enhances delivery of mechanical energy from the LV to the circulatory bed.

Mechanoenergetic effects of pimobendan in canine left ventricles. Comparison with dobutamine.

We hypothesized that the effect of pimobendan (UD-CG 115 BS) to increase calcium sensitivity of contractile protein might result in less myocardial oxygen consumption (VO2) in comparison with dobutamine when they enhance ventricular contractility to the same extent. To examine this hypothesis, we compared the effects of pimobendan and dobutamine on left ventricular contractility and energetics using the frameworks of Emax (contractility index) and the relation between VO2 and PVA (systolic pressure-volume area, a measure of left ventricular total mechanical energy). We measured VO2, Emax, PVA, and force-time integral (FTI) in excised, cross-circulated, nonfailing dog hearts. The slope of the VO2-PVA relation reciprocally indicates the efficiency from PVA-dependent VO2 to the total mechanical energy (contractile efficiency). The VO2 intercept of the VO2-PVA relation, i.e., PVA-independent VO2, reflects energy utilization for excitation-contraction coupling. The ratio of FTI to PVA-dependent VO2 can be called contractile economy. Both drugs comparably enhanced Emax. Although the contractile economy was greater by 14 +/- 19% (p less than 0.05) for pimobendan than for dobutamine, the contractile efficiency was similar between the two drugs. Oxygen cost of contractility, defined as the slope of the relation between the PVA-independent VO2 and Emax, was the same between the two drugs. Other mechanoenergetic effects of both drugs were similar except for a greater coronary vasodilating effect of pimobendan. Pimobendan has almost the same mechanoenergetic effects as dobutamine but slightly greater contractile economy and coronary vasodilation. The calcium-sensitizing effect of pimobendan did not save the oxygen cost of contractility.

Norepinephrine increases the economy of pressure development in isolated canine hearts.

To test for oxygen wasting by norepinephrine (NE) without relying on normalization by measures of performance such as the pressure-volume area, myocardial oxygen consumption (MVO2) was determined for isovolumic beats at five different left ventricular (LV) end-diastolic volumes (EDV) in nine isolated cross-perfused canine hearts in each of three states: a basal anesthetic state (B); after depression with halothane (H); and after adding NE to increase contractility back to the B state (H+NE). The end-diastolic and peak systolic pressure-volume lines were identical for B and H+NE. The R2 for a linear regression of MVO2 per beat for B vs. H+NE for beats originating at the same EDV and developing similar (within 10%) peak isovolumic pressures for all hearts was 0.85. The slope and intercept were 0.83 and 0.01, which are significantly less than one (P less than 0.001) and greater than zero (P less than 0.001), respectively. These data suggest that NE increases both the economy of pressure development as well as activation energy of an isovolumically contracting LV.

Effect of reduced aortic compliance on cardiac efficiency and contractile function of in situ canine left ventricle.

This study tests the hypothesis that arterial vascular stiffening adversely influences in situ left ventricular contractile function and energetic efficiency. Ten reflex-blocked anesthetized dogs underwent a bypass operation in which a Dacron graft was sewn to the ascending aorta and connected to the infrarenal abdominal aorta via a plastic conduit. Flow was directed through either native aorta or plastic conduit by placement of vascular clamps. Arterial properties were measured from aortic pressure-flow data, and ventricular function was assessed by pressure-volume (PV) relations. Coronary sinus blood was drained via an extracorporeal circuit for direct measurement of myocardial O2 consumption (MVO2). Data at multiple steady-state preload volumes were combined to derive chamber function and energetics relations. Energetic efficiency was assessed by the inverse slope of the MVO2-PV area relation. Directing flow through plastic versus native aorta resulted in a 60-80% reduction in compliance but little change in mean resistance. Arterial pulse pressure rose from 34 to 99 mm Hg (p less than 0.001). Contractile function assessed by the end-systolic PV relation, stroke work-end-diastolic volume relation, and dP/dtmax at matched end-diastolic volume did not significantly change. However, MVO2 increased by 32% (p less than 0.01) and was matched by a rise in PV area, such that the MVO2-PV area relation and efficiency was unaltered. The MVO2 required to sustain a given stroke volume, however, increased from 20% to 40%, depending on the baseline level (p less than 0.001). Thus, whereas the contractile function and efficiency of normal hearts are not altered by ejection into a stiff vascular system, the energetic cost to the heart for maintaining adequate flow is increased. This suggests a mechanism whereby human vascular stiffening may yield little functional decrement at rest but limit reserve capacity under conditions of increased demand.

Epinephrine and calcium have similar oxygen costs of contractility.

We compared the oxygen cost of increasing ventricular contractility using Emax (slope of the ventricular end-systolic pressure-volume relation) as the index of ventricular contractility. Contractility was enhanced by calcium and epinephrine in paired experiments on dog left ventricles. Firstly, we obtained left ventricular oxygen consumption (VO2) and systolic pressure-volume area (PVA, a measure of total mechanical energy) of contractions at different volumes in the control contractile state to determine a reference VO2-PVA relation. PVA was obtained as the area in the pressure-volume (P-V) diagram which was bounded by the end-systolic P-V line, end-diastolic P-V curve and systolic P-V trajectory of individual contractions. Secondly, we gradually enhanced Emax with calcium and epinephrine in two consecutive runs at a fixed ventricular volume. Both VO2 and PVA increased with enhanced Emax. From these VO2-PVA data, we calculated the PVA-independent VO2 values at the respective enhanced Emax levels and determined the oxygen cost of Emax as the slope of the relation between the PVA-independent VO2 and Emax. The cost per beat and per 100 g was 0.00158 ml O2/(mmHg/ml) for calcium and 0.00166 ml O2/(mmHg/ml) for epinephrine on average, values not significantly different from each other (P less than 0.05). We conclude that epinephrine and calcium have similar oxygen costs of contractility over a wide range of Emax despite their different pharmacological mechanisms of positive inotropism.

Myocardial oxygen consumption of fibrillating ventricle in hypothermia

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.

Comparison between the effects of 2–3 dutanedione monoxime (BDM) and calcium chloride on myocardial oxygen consumption

The agent 2,3-butanedione monoxime (BDM) has been reported to reduce the sensitivity of myofilament force development to calcium ions, without affecting the calcium transient in myocardium. One would predict, therefore, that BDM should reduce the contractile state of the heart without reducing the amount of oxygen that is consumed to fuel the process of excitation-contraction coupling. The purpose of the present experiment was to test this hypothesis using isovolumically contracting, isolated, blood perfused canine hearts during β-blockade induced by continuous intra-coronary infusion of propranolol (1 mg/h). Contractile state was increased in seven hearts by CaCl 2 infusion. Subsequently, while the CaCl 2 infusion was continued at the highest rate, contractile state was reduced by BDM infusion. At each contractile state, we measured the left-ventricular end-systolic pressure-volume relation (ESPVR), the relation between myocardial oxygen consumption and its mechanical correlate, pressure-volume area (MVO 2 vs PVA), and the duration of the LV pressure waveform. Contractile state was quantified by interpolated developed pressure at a reference ventricular volume of 25 ml (P 25). BDM infusion (0.5–7 m m) caused a dose-dependent reduction in contractile state (50% reduction in P 25 at 2.4 ± 0.3 m m), and a dose-independent increase in coronary blood flow. Furthermore, BDM significantly reduced the duration of the pressure waveform up to 40% at the highest rate of BDM infusion compared to the pressure waveform duration measured at maximum CaCl 2 infusion. We observed a direct relationship between MVO 2 of the mechanically unloaded heart and contractility; this relation was unaffected by BDM infusion ( P>0.3). The slope of the MVO 2-PVA relation decreased with increases in contractile state, but this decrease was unaffected by BDM ( P≥0.4). We conclude that in the isolated canine heart, BDM does not act energetically as expected for a myofibrillar calcium desensitizing agent.

Obidoxime augments the positive inotropic effect of phosphamidon on the isolated working rat heart.

The present study was designed to determine modulation of the direct inotropic effect of an anticholinesterase organophosphorus compound, phosphamidon, by the reactivator obidoxime. We investigated the effects of phosphamidon (n = 9), obidoxime (n = 5), and their combination (n = 5) on the mechanical and energetic indices of left ventricular function, in the isolated working rat heart model. Phosphamidon at a concentration range of 10(-6)-10(-3) M had a positive inotropic effect. Obidoxime at a concentration range of 10(-6)-10(-3) M had no significant effect on heart rate, but did have a statistically significant positive inotropic effect on end-systolic pressure, cardiac output, mean left ventricular pressure, and maximal time derivative of left ventricular pressure (dP/dtmax) (P less than 0.01). Perfusion with 10(-3) M obidoxime caused a 19% increase in left ventricular stroke work and a 31% increase in total pressure-volume area. Perfusion with phosphamidon and obidoxime at concentrations ranging from 10(-6) to 10(-3) M resulted in a more intense inotropic response than the separate drug effects. At the highest combined concentrations tested, cardiac output increased by 60%, left ventricular stroke work increased by 100%, and left ventricular total pressure volume area increased by 111% of their control values (P less than 0.001). We conclude that obidoxime augments the positive inotropic effect of phosphamidon on the isolated working rat heart.

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.

Relationship between quasi-static pulmonary hysteresis and maximal airway narrowing in humans.

Two groups of subjects were studied: one with (group 1: 5 healthy and 4 mildly asthmatic subjects) and another without (group 2:9 moderately and severely asthmatic subjects) a plateau of response to methacholine (MCh). We determined the effect of deep inhalation by comparing expiratory flows at 40% of forced vital capacity from maximal and partial flow-volume curves (MEF40M/P) and the quasi-static transpulmonary pressure-volume (Ptp-V) area. In group 1, MEF40M/P increased from 1.58 +/- 0.23 (SE) at baseline up to a maximum of 3.91 +/- 0.69 after MCh when forced expiratory volume in 1 s (FEV1) was decreased on plateau by 24 +/- 2%. The plateau of FEV1 was always paralleled by a plateau of MEF40M/P. In group 2, MEF40 M/P increased from 1.58 +/- 0.10 at baseline up to a maximum of 3.48 +/- 0.26 after MCh when FEV1 was decreased by 31 +/- 3% and then decreased to 2.42 +/- 0.24 when FEV1 was decreased by 46 +/- 2%. Ptp-V area was similar in the two groups at baseline yet was increased by 122 +/- 9% in group 2 and unchanged in group 1 at MCh end point. These findings suggest that the increased maximal response to MCh in asthmatic subjects is associated with an involvement of the lung periphery.

Superiority of the University of Wisconsin solution over simple crystalloid for extended heart preservation

To compare the effects of the University of Wisconsin solution with those of an extracellular crystalloid solution, Krebs-Ringer bicarbonate, as cardiac preservation media, we studied 35 adult dogs in an isolated heart preparation. Four groups of seven hearts were preserved in University of Wisconsin solution for 6 or 12 hours or in Krebs-Ringer bicarbonate solution for 6 or 12 hours. An additional group of seven hearts with no ischemia was used for a control group. In the four preservation groups, hearts were arrested by electrolyte solution (Normosol with potassium chloride, 20 mEq/L, added, 4 degrees C), flushed with 200 ml of the preservation solution, and then stored in the same solution at 1 degree to 2 degrees C. The hearts were mounted on an isolated heart preparation equipped with a computer-controlled servo-pump system that used a mock arterial system to modulate the aortic input impedance presented to the left ventricle. Left ventricular pressure-volume loops were measured on-line for 2 hours of reperfusion with autologous warm oxygenated blood. Elastance was derived from the end-systolic pressure-volume relationship, and diastolic compliance was derived from the end-diastolic pressure-volume relationship. The total left ventricular performance was assessed by the preload recruitable stroke work area, the slope, and its x-intercept, all of which derived from the stroke work (pressure-volume area)-end-diastolic volume relationship. Extended global ischemia had more deleterious effects on the end-diastolic than the end-systolic pressure-volume relationship. In confirmation with other studies, elastance did not accurately reflect the level of ventricular contractile dysfunction because of the significant amount of diastolic dysfunction. The preservation of myocardial systolic and diastolic functions, as demonstrated by the preload recruitable stroke work area and diastolic compliance, was better in the University of Wisconsin solution groups than in the Krebs-Ringer bicarbonate solution groups after 6 and 12 hours of preservation. In addition, 6 hours of preservation with University of Wisconsin solution maintained normal systolic and diastolic functions as compared with those of the control group. Preservation with University of Wisconsin solution prevented any myocardial edema formation; by contrast, this was significantly increased after 12 hours in Krebs-Ringer bicarbonate solution. Groups preserved with University of Wisconsin solution had less reperfusion injury as evidenced by the release of coronary sinus creatine kinase during reperfusion; they also had improved oxygen use during reperfusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Energy conversion efficiency in human left ventricle.

Left ventricular mechanical efficiency is one of the most important measures of left ventricular pump performance. Several clinical studies, however, have shown that mechanical efficiency does not fall substantially as the heart fails. To clarify the insensitivity of mechanical efficiency to the change in pump performance, we analyzed human left ventricular mechanical efficiency, applying the concept of left ventricular systolic pressure-volume area (PVA). PVA correlates linearly with myocardial oxygen consumption per beat (MVO2): MVO2 = a.PVA+b, and represents the total mechanical energy of contraction. We determined MVO2-PVA relation and external work in 11 patients with different contractile states. We also calculated the energy transfer from MVO2 to PVA (PVA/MVO2 efficiency), that from PVA to external work (work efficiency), and mechanical efficiency (external work/MVO2). Left ventricular pressure-volume loops were constructed by plotting the instantaneous left ventricular pressure against the left ventricular volume at baseline and during pressure loading. The contractile properties of the ventricle were defined by the slope of the end-systolic pressure-volume relation (Ees). Pressure elevation raised external work by 41.4%, PVA by 71.2%, and MVO2 by 54.5%. These changes were associated with a decrease in work efficiency and an increase in PVA/MVO2 efficiency. The opposite directional changes in these two efficiencies rendered the mechanical efficiency constant. The slope, a, of the relation between MVO2 and PVA was relatively constant (2.46 +/- 0.33) over the range of 0.8-8.8 mm Hg/ml of Ees, but the oxygen axis intercept, b, tended to decrease with the reduction in Ees. PVA/MVO2 efficiency correlated inversely (r = -0.66, p less than 0.05) with Ees, whereas work efficiency correlated linearly with Ees (r = 0.91, p less than 0.01). Mechanical efficiency is not appreciably affected by changes in loading and inotropic conditions as long as the left ventricular contractility is not severely depressed.

Mechanical enhancement and myocardial oxygen saving by synchronized dynamic left ventricular compression

Dynamic cardiomyoplasty with synchronously paced skeletal muscle grafts has recently been developed to augment the performance of impaired myocardium. This method has been reported effective to improve patients' general status and some hemodynamic parameters. It is unknown, however, how a systolic dynamic cardiac compression, as in dynamic cardiomyoplasty, affects left ventricular energetics. The purpose of this study was to characterize the effects of dynamic cardiac compression on the ventricle in terms of the pressure-volume relationship and myocardial oxygen consumption. In an isolated cross-circulated dog heart model, a dynamic cardiac compression device was set to directly compress the ventricle during systole. End-systolic pressure, contractility index (Emax), pressure-volume area, external mechanical work, coronary blood flow, and myocardial oxygen consumption were determined before and during dynamic cardiac compression. Dynamic cardiac compression significantly increased Emax. When end-diastolic and stroke volumes were fixed, end-systolic pressure, pressure-volume area, and external mechanical work significantly increased during dynamic cardiac compression while coronary blood flow and myocardial oxygen consumption remained unchanged. When end-systolic pressure was matched with the pre-dynamic cardiac compression control level by decreasing end-diastolic volume at a constant stroke volume so that external mechanical work under dynamic cardiac compression returned to the control level, both pressure-volume area and myocardial oxygen consumption significantly decreased. In contrast to a marked increase in myocardial oxygen consumption for a given increase in external mechanical work by either volume loading or dobutamine, dynamic cardiac compression did not increase myocardial oxygen consumption for the same increase in external mechanical work. Thus dynamic cardiac compression augments left ventricular pump function without increasing myocardial oxygen demand or compromising coronary blood flow.

Similar oxygen cost of myocardial contractility between DPI 201-106 and epinephrine despite different subcellular mechanisms of action in dog hearts.

The effects of DPI 201-106 (a novel, cyclic AMP-independent positive inotropic agent with Ca(2+)-sensitizing and Na(+)-channel agonistic mechanisms) on myocardial mechanics and energetics were assessed in the excised cross-circulated dog left ventricle. In the first protocol, the relation between left ventricular oxygen consumption (VO2) and systolic pressure-volume area (PVA) was analyzed before and during administration of DPI 201-106. The reciprocal of the slope of the VO2-PVA relation has been shown to reflect the contractile efficiency, and the VO2-intercept consists of the oxygen cost of contractility-dependent excitation-contraction coupling and basal metabolism. DPI 201-106 increased Emax (contractility index) and elevated the VO2-PVA relation in a parallel manner, i.e., the VO2-intercept increased without a change in the slope. In the second protocol, the increase in the VO2-intercept of the VO2-PVA relation for a unit increase in Emax (i.e., oxygen cost of enhanced contractility) was compared between DPI 201-106 and epinephrine in a paired manner in each heart. Epinephrine significantly abbreviated the time to end systole, whereas DPI 201-106 did not, suggesting that the mechanism of inotropic action differed between the two drugs. However, the oxygen cost of enhanced contractility was the same between the two drugs in each heart. Therefore, DPI 201-106 did not alter the contractile efficiency nor spare the oxygen cost of enhanced contractility as compared to epinephrine under the present experimental conditions. This suggests that the Ca(2+)-sensitizing effect of DPI 201-106, if any, is too small to spare the oxygen cost of contractility in the blood-perfused, non-failing dog heart.

Effects of amrinone and isoproterenol on mechanoenergetics of blood-perfused rabbit heart.

To compare the effects of amrinone (AMR) and isoproterenol (Iso) on left ventricular contractility and energetics, we assessed Emax (ventricular contractility index) and the relation between oxygen consumption per beat (VO2) and systolic pressure-volume area (PVA, a measure of left ventricular total mechanical energy) in isolated cross-circulated (blood-perfused) rabbit hearts during infusion of AMR or Iso in either a constant-flow (CF) or constant-pressure (CP) perfusion mode. Both Emax and the VO2 intercept of the linear VO2-PVA relation increased significantly during AMRCP (increase in Emax 15% and increase in VO2 intercept 11%), ISOCF (49 and 43%), and ISOCP (55 and 54%) but not during AMRCF. However, neither drug changed the slope of the VO2-PVA relation (reciprocal of contractile efficiency) in either perfusion mode. Furthermore, with both drugs the relation between increases in Emax and the VO2 intercept fell on a single regression line (r = 0.92). We conclude that 1) although the mechanism of action and inotropic potency of the two drugs differ, their effects on cardiac energetic cost are essentially the same, i.e., both drugs increase the nonmechanical oxygen cost in proportion to the increase in contractility without changing contractile efficiency, and 2) a significant portion of the inotropic effect of AMR in the whole ventricle is likely due to increased coronary blood flow, i.e., Gregg's phenomenon.

Myocardial Energetics and Cardiac Function of Preserved Rat Heart.

We studied mitochondrial function in relation to ATP production and its relationship with myocardial oxygen consumption (VO2) and total mechanical energy using isolated rat hearts after 8, 12, and 24 h of hypothermic preservation. In isovolumic contraction, ventricular contractility and total mechanical energy were respectively assessed by the end-systolic elastance (Ees) and pressure-volume area (PVA). Ees significantly decreased after hypothermic ischemia, although the difference was not significant between 8 and 12 h. In contrast, VO2 measured at each left ventricular volume increased after hypothermic ischemia. PVA and VO2 were found to stay in linear correlation after prolonged hypothermic ischemia, although VO2 at null PVA and VO2 to PVA ratios significantly increased after hypothermic ischemia, especially after 12-h ischemia. Mitochondrial oxidative phosphorylation significantly decreased after hypothermic ischemia for longer than 12 h. These results indicate that mitochondrial oxidative phosphorylation was impaired due to long time hypothermic ischemia especially after 12-h ischemia. We conclude that energy uncoupling between VO2 and PVA in hypothermically preserved heart is attributable to disturbed mitochondrial oxidative phosphorylation and that 8 h is a critical point for efficient conversion of energy from VO2 into PVA in rat heart.

Assessment of left ventricular function using a conductance catheter in the human heart.

To validate the usefulness of the conductance catheter in the clinical setting, we first studied the accuracy of human left ventricular (LV) volume measured by conductance catheter in comparison with LV volume measured by biplane angiography in 19 patients with heart disease. Secondly, we made a comparison of end-systolic pressure volume relation (ESPVR) and preload recruitable stroke work (PRSW) relation in 60 patients with heart disease. Thirdly, we studied the myocardial oxygen consumption (VO2)-pressure volume area (PVA) relation to assess contractile efficiency in 22 patients with heart disease. There was a good correlation between the corrected conductance volume (Vcc) and the angiographic volume (V angio) (Vcc = 0.94 Vangio + 5.4, r = 0.94, P less than 0.001). Two relations, ESPVR and PRSW, were well described by straight lines with high correlation coefficients. However, PRSW was a more linear contractile index than ESPVR. The reciprocal of the slope of the VO2-PVA relation was approximately 40% in the control contractile state. We conclude that the conductance catheter accurately measures LV volumes and facilitates the assessment of ESPVR, PRSW and contractile efficiency in human LV.

External mechanical work during relaxation period does not affect myocardial oxygen consumption

We assessed the effect of external mechanical work (EW) during the relaxation period (RP) on myocardial oxygen consumption (VO2) and clarified the energetic significance of the potential energy (PE) portion of the pressure-volume area (PVA) in the cross-circulated dog left ventricle. We changed the course of the relaxation segment of the pressure-volume (P-V) trajectory by increasing or decreasing EW within a given PVA without changing the end-diastolic volume (EDV) and the systolic segment of the P-V trajectory while measuring VO2. Thus the ventricle underwent ejection or filling during RP. Although the percent fraction of EW in PVA (%EW/PVA) was markedly increased from 32 +/- 12 (SD) to 93 +/- 3% in ejecting contractions (8 hearts) and from 0 to 93 +/- 5% in isovolumic contractions (3 hearts), these marked changes in %EW/PVA did not significantly affect VO2. Moreover, the VO2-PVA data during these procedures fell on the reference VO2-PVA relation line obtained by changing EDV and PVA of isovolumic contractions. We conclude that EW during RP at a constant PVA does not affect VO2 and part of PE can be converted into EW in an energetically equivalent manner.

Equivalent pressure-volume area accounts for oxygen consumption of fibrillating heart

We attempted to find cardiac mechanical parameters to account for myocardial O2 consumption (VO2) during ventricular fibrillation (VF). We fully utilized the concept of pressure-volume (P-V) area (PVA), which is equivalent to the total mechanical energy generated by a ventricular contraction. We also utilized a multicompartment model consisting of multiple asynchronously contracting compartments, which we previously proposed to simulate the mechanics of a fibrillating ventricle. The model analysis had already validated the application of PVA to VF in terms of "equivalent PVA" (ePVA). ePVA is the area surrounded by the end-systolic and end-diastolic P-V relations in beating state and the isobaric P-V line at the VF pressure. ePVA is supposed to represent the total mechanical energy generated by single contractions of each compartment (or myocyte) in a fibrillating ventricle. We determined ePVA and correlated it with measured VO2 per minute (mVO2) at various ventricular volumes in electrically induced fibrillating left ventricles of the excised cross-circulated canine heart preparation. Correlation coefficient (r) of the mVO2-ePVA relation during VF was high (r = 0.95, P less than 0.01). Comparing mVO2 during VF with that in beating state at an unloaded ventricular volume, we calculated equivalent heart rate (eHR) as an estimate of the frequency of contractions of individual compartments (myocytes). With the use of both ePVA and eHR, mVO2 during VF at various ventricular volumes was estimated. The relation between estimated mVO2 and directly measured mVO2 was highly linear (r = 0.88, P less than 0.01), and the regression line almost agreed with the identity line (regression coefficient = 1.05). We conclude that the new ePVA and eHR concepts can reasonably account for VO2 during VF.

Stability of myocardial O2 consumption-pressure-volume area relation in red cell-perfused rabbit heart

We evaluated the mechanical and energetic stability of the isolated rabbit heart perfused with a suspension of bovine red cells in Krebs-Henseleit buffer in terms of the pressure-volume area (PVA) concept. PVA, the area surrounded by the end-systolic and end-diastolic pressure-volume (P-V) relations and the systolic P-V trajectory of the P-V diagram, represents the total mechanical energy generated by each cardiac contraction. Myocardial O2 consumption (VO2) per beat has been reported to be highly linearly correlated with PVA. We used the slope and VO2-axis intercept of the VO2-PVA relation as energetic parameters and the maximum P-V ratio (Emax) as a contractility index of the left ventricle (LV) and compared them every 30 min for 120 min. Emax, the slope, and VO2 intercept of the VO2-PVA relation did not change significantly over 120 min compared with their control values [7.3 +/- 2.9 mmHg.ml-1.100 g LV, (1.67 +/- 0.40) x 10(-5) ml O2.mmHg-1.ml-1, and (3.26 +/- 1.01) x 10(-2) ml O2.beat-1.100 g LV-1, respectively]. However, the goodness of the linear fit of the VO2-PVA relation decreased after 90 min (r = 0.94 control, 0.62 at 90 min, and 0.64 at 120 min). Therefore, we conclude that the isolated bovine red cell-perfused rabbit heart preparation is stable for mechanical and energetic studies for at least 60 min.