Assessment of the end-systolic pressure-volume relationship in human beings with the use of a time-varying elastance model

The analysis of left ventricular end-systolic pressure-volume relationships in human beings has been hindered by the lack of a practical method of serial volume assessment and by an imprecise definition of end-systole. Modifications of the end-systolic relationship that have been used to circumvent these problems have included the use of single-point end-systolic pressure-volume ratios, the use of peak systolic pressure/minimum ventricular volume points for end-systolic points, and the use of end-ejection as a marker for end-systole. To assess the correlation between the parameters generated by these modifications with the slope (Emax) and volume intercept (VO) of the end-systolic line as defined by Sagawa's model of time-varying elastance, simultaneous measurement of left ventricular pressure and gated radionuclide volume was made in 26 patients under various loading conditions and pressure-volume diagrams were constructed for each loading condition from 32 simultaneous pressure-volume coordinates. Two pressure-volume diagrams were recorded in 14 patients and three pressure-volume diagrams were recorded in 12 patients. Emax and VO were determined in all patients from the slope and volume intercept of the isochronic pressure-volume line with the maximum time-varying elastance as described by Sagawa's model and were designated true Emax and true VO, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Time-invariant oxygen cost of mechanical energy in dog left ventricle: consistency and inconsistency of time-varying elastance model with myocardial energetics

We studied whether the oxygen cost of mechanical energy is time-invariant in the excised, cross-circulated canine heart. The total mechanical energy generated by ventricular contraction can be quantified by the total pressure-volume area (PVA) according to the time-varying elastance model. In this model, mechanical energy generated until a specified time (t) during systole can be quantified by the partial pressure-volume area, PVA(t). PVA(t) was obtained by quickly releasing ventricular volume at a varied time during isovolumic contraction. The quick release aborted further development of mechanical energy. We found that PVA(t) at a constant end-diastolic volume linearly correlated with myocardial oxygen consumption (VO2). This indicates that the oxygen cost of mechanical energy is time-invariant. However, we also found that the slope of the VO2-PVA(t) relation decreased with increasing quick-release speed. This indicates a decrease in VO2 by the quick release despite the same PVA(t). The time-invariant oxygen cost of mechanical energy is consistent with the time-varying elastance model of the ventricle, but the decreased VO2 with increasing quick-release speed despite the same PVA(t) is not.     

Responsiveness of the maximum time-varying elastance to alterations in left ventricular contractile state in man

This investigation was designed to establish the relative responsiveness of maximum time-varying elastance (Emax) slope values to alterations in left ventricular contractile state in comparison with isovolumic and ejection phase indices in man. Accordingly, nine patients had a bipolar right atrial pacing catheter and micromanometer left ventricular catheter placed and red blood cells tagged with technetium-99m for radionuclide angiography. Hemodynamic measurements and radionuclide angiograms were acquired simultaneously over a range of loading conditions produced by methoxamine or nitroprusside infusions during both the basal and enhanced contractile states. Enhanced left ventricular contractility was produced by a steady-state dobutamine infusion of 2 to 10 mu/kg/min. The mean (+)dP/dtmax increased from 1510 +/- 460 mm Hg/sec during the basal state to 2537 +/- 546 mm Hg/sec (p less than 0.001) during the dobutamine infusion. The mean Emax slope value also increased from 4.34 +/- 1.40 mm Hg/ml during the basal state to 6.41 +/- 1.90 mm Hg/ml (p less than 0.001) during the dobutamine infusion. The average percent change in the Emax slope value (51 +/- 26%) was less than those for the isovolumic indices (57% to 112%), while it was more than those for the ejection phase indices (11% to 53%). When the variability in the percent changes for each of these contractile indices was incorporated into the analysis, the Emax slope values demonstrated a greater responsiveness to changes in left ventricular contractility than did the isovolumic and ejection phase indices. In conclusion, the Emax slope value calculated by this method is a contractile index, which is less affected by measurement variability and the influences of loading conditions than are the isovolumic and ejection phase indices, and therefore may improve our ability to both detect and quantitate changes in left ventricular contractility in man.     

The relationship of various measures of end-systole to left ventricular maximum time-varying elastance in man

This investigation was designed to calculate left ventricular maximum time-varying elastance (Emax), to define the relationship between Emax and pressure-volume (P-V) relations at other, more easily defined measured of end-systole, and to determine whether these measures of left ventricular contractile function can be normalized in man. Accordingly, we studied 10 subjects with simultaneous high-fidelity micromanometer left ventricular and ascending aortic pressure recordings and biplane contrast cineangiograms at control conditions and during infusion of methoxamine and nitroprusside. Emax was defined as the maximum slope of the linear relation of isochronal, instantaneous P-V data points obtained from each of the three loading conditions. Left ventricular end-systole was also defined for each loading condition as: the time of the maximum P-V ratio (maxPV), minimum ventricular volume (minPV), (-)dP/dtmin [(-)dP/dtPV], and zero systolic flow approximated by the central aortic dicrotic notch (AodiPV). The mean heart rates and LV (+)dP/dtmax were insignificantly altered during the three loading conditions. Isochronal Emax ranged from 3.38 to 6.73 mm Hg/ml (mean 5.48 +/- 1.23 [SD] mm Hg/ml) and the volume-axis intercepts at zero pressure ranged from -2 to 51 ml (mean 18 +/- 16 ml). The isochronal slope calculations were reproducible (r = .97 to .99). The end-systolic P-V slope values for the maxPV, minPV, (-)dP/dtPV, and AodiPV relations correlated with isochronal Emax (r = .90, .88, .69, and .74, respectively). The average slope values for these end-systolic P-V relations, however, underestimated the mean Emax (p less than .01 to p less than .001). The mean extrapolated volume-axis intercepts for these end-systolic P-V relations also underestimated that for Emax. Finally, the isochronal Emax and other end-systolic P-V relation slope values demonstrated inverse linear relationships with left ventricular mass (r = -.68 to -.91, p less than .05 to p less than .001). Only the Emax volume-axis intercepts showed a linear relationship with left ventricular end-diastolic volume (r = .75). Thus we conclude that the time-varying elastic properties of the left ventricle can be calculated in man, that commonly used end-systolic P-V relations significantly underestimate isochronal Emax, and that normalization of isochronal Emax and other end-systolic P-V relation slope values might be performed in man with left ventricular mass; no obvious relationship between volume-axis intercepts and measures of left ventricular or body size was apparent.     

Crossbridge model compatible with the linear relation between left ventricular oxygen consumption and pressure-volume area

Ventricular pressure-volume area (PVA) is a specific area in the pressure-volume diagram, which represents the total mechanical energy generated by each contraction, consisting of stroke work and mechanical potential energy at end-systole. Animal experiments have shown that PVA is correlated linearly with the ventricular oxygen consumption (Vo2) per beat under a variety of loading conditions in a stable contractile state. The slope of the Vo2-PVA line has been shown to remain constant in different contractile states, implying a constant stoichiometry between Vo2 and PVA. As a first step to understand the nature of this Vo2-PVA relation, we devised a new crossbridge (CB) model to theoretically relate PVA with the total enthalpy change associated with the ATP hydrolysis for all CB cycles. One of the most important assumptions on which this model analysis depended was that the time-varying elasticity model could simulate the instantaneous pressure-volume relation. The result of this analysis implied that the empirical linear Vo2-PVA relation could be attributed to the energy balance between energy input and output of the chemomechanical transduction associated with CB cycles during a ventricular contraction.     

Relation between anaerobic threshold and maximal oxygen consumption during graded treadmill exercise

The ratio of anaerobic threshold (AT) to maximal oxygen consumption (Max VO2), which is referred to as relative AT, was evaluated in six athletic students (S), 12 normal male subjects (N) and 39 patients with chronic heart disease (C). Group C was categorized in three subgroups according to the New York Heart Association functional class (CI: 10, CII: 16 and CIII: 13 patients). The symptomatic-maximal graded treadmill exercise test was performed and respiratory parameters were measured by R1500S Autoaerobics. AT was determined as the oxygen consumption (VO2) at which a linear relationship between pulmonary ventilation and VO2 was lost during progressive exercise. All subjects performed maximal exertion until they were limited by either shortness of breath or leg fatigue. AT (ml/min/kg) was 36.4 +/- 6.0, 25.9 +/- 5.7, 21.4 +/- 4.5, 16.3 +/- 4.0 and 11.1 +/- 2.6, and MaxVO2 (ml/min/kg) was 77.3 +/- 6.5, 47.6 +/- 10.2, 29.5 +/- 6.1, 22.5 +/- 5.8 and 15.5 +/- 3.1, respectively, in group S, N, CI, CII and CIII (p less than 0.01 between each group). Relative AT(%) was 46.8 +/- 4.4, 54.9 +/- 7.2, 72.1 +/- 6.4, 73.0 +/- 8.6 and 72.6 +/- 8.7, respectively, in groups S, N, CI, CII and CIII (p less than 0.01 between S and N, between N and CI-CIII, between S and CI-III). The anaerobic threshold appeared at mid-point in the graded symptomatic maximal exercise test. However, the appearance of AT relative to the maximal oxygen consumption varied from 47 to 73% in the study groups tested. AT appeared relatively early in normal subjects compared to cardiac subjects.     

The pancreas and oxygen consumption. 1. Pancreatic oxygen consumption in normo- and hypovolemic dogs

Pancreatic oxygen consumption (VO2) was studied in hypovolemic shock: 4 dogs served as controls and 4 others were kept at 50 mm Hg of mean arterial blood pressure. All 8 were studied for a period of 3 h. Pancreatic VO2 was obtained by adding up VO2 for the head (minus the uncinate process) and tail of the pancreas both equal to the product of regional blood flow times O2 extraction. Regional blood flows were measured electromagnetically on the gastroduodenal (GDA) and the splenic (SA) arteries, whereas O2 extraction was derived from total hemoglobin (THb) and oxygen saturation of hemoglobin (%O2 Hb) determined on the right femoral artery (RFA), the superior pancreaticoduodenal (SPDV), and splenic (SV) veins. A splenectomy was performed in all 8 dogs. Controls showed a significantly elevated pancreatic VO2 from the first hour of observation on (+56% after 1 h, +92% after 3), whereas pancreatic VO2 remained strictly unchanged throughout shock (+2% and +6%, at one and 3 h, respectively), despite significant increases in O2 extraction. These findings give support to the deleterious effects of hypovolemia to the pancreas and that pancreatic O2 extraction indicates metabolic damage to be less severe than observed in experimental bile-trypsin-induced acute pancreatitis.     

Beneficial effect of amrinone on myocardial oxygen consumption during acute left ventricular failure in dogs

In 11 dogs ischemic left ventricular failure characterized by a 30 percent reduction In cardiac output and a left ventricular end-dlastolic pressure of 18 mm Hg or more was produced by proximal occlusion of the left anterior descending coronary artery followed by serial occlusions of the distal left circumflex coronary artery. Administration of amrlnone In an Intravenous bolus injection followed by a constant Infusion produced Improvements in cardiac output (from 1.62 ± 0.50 to 2.19 ± 0.52 Itters/min [mean ± standarddeviation], p <0.05), left ventricular end-dlastolic pressure (from 21.6 ± 3.5 to 11.0 ± 5.4 mm Hg, p <0.05) and peak positive rate of rise of left ventricular pressure [dP/dt](from 1,264 ± 241 to 1,800 ± 458 mm Hg·^?1, p <0.05). These Improvements were maintained throughout the 20 minute period of therapy. No significant alteration in heart rate or arterial pressure was noted. In parallel with the hemodynamic improvement myocardial oxygen consumption improved to 0.094 ± 0.05 and 0.092 ± 0.04 vol·^?1?^?1 after 2 and 20 minutes; respectively, of amrinone compared with 0.124 ± 0.05 during left ventricular failure (both <0.05). The effects of amrinone on left ventricular failure are due to augmented contractility and mild systemic vasodllatation. The reduction in myocardial oxygen consumption during amrlnone-treated left ventricular failure presumably results from a reduction in ventricular wall tension that more than offsets the effect of an Increase in contractility.     

Relation between severity of liver disease and renal oxygen consumption in patients with cirrhosis

BACKGROUND: Worsening cirrhosis may lead to increased renal O2 metabolism caused by activation of neurohumoral antinatriuretic substances. AIMS: To evaluate the relation between the severity of liver disease, sodium excretion, and neurohumoral antinatriuretic substances on the one hand and renal O2 metabolism on the other in patients with cirrhosis. METHODS: Renal O2 consumption and haemodynamics as well as plasma concentrations of noradrenaline, renin, and aldosterone were measured. Investigations were performed in 14 patients with Pugh's grade A, 43 with grade B, and 29 with grade C liver disease. RESULTS: Renal O2 consumption significantly increased with the severity of cirrhosis (grade A, 8.9 (1.6); grade B, 15.5 (1.3); grade C, 18.0 (1.5) ml/min/m2). Plasma concentrations of noradrenaline, renin, and aldosterone significantly increased while mean arterial presssure and systemic vascular resistance significantly decreased with the severity of the disease. A significant inverse correlation was found between renal O2 consumption and sodium excretion. A significant direct correlation was found between plasma levels of noradrenaline and aldosterone on the one hand and renal O2 consumption on the other. Renal blood flow and the glomerular filtration rate did not differ significantly between patients with grade C and grade A or B disease. CONCLUSIONS: This study shows for the first time that, in patients with cirrhosis, worsening of the disease is associated with an increase in renal O2 consumption. The results suggest that increased renal O2 consumption is due to renal tubular sodium retention caused by increased levels of neurohumoral antinatriuretic substances. This neurohumoral activation is related to cirrhosis induced vasodilation.     

Validity of myocardial oxygen consumption parameters

The purpose of this study was to examine any reported indices for estimating myocardial oxygen consumption (MVO2) under uniform experimental conditions at maximal variation of hemodynamics and MVO2. One hundred sixty-two steady states were analyzed in 10 closed-chest dog experiments. Myocardial blood flow was directly measured by a different pressure catheter in the coronary sinus. The indirect values of MVO2 calculated from 24 indices were compared with directly measured MVO2. Throughout a wide range of hemodynamic states, the best correlate with MVO2 was found to be the additive parameter Et (r = 0.96). Any indices that do not incorporate potentially important changes of MVO2 related to both myocardial contractility and ventricular dimensions show unsatisfactory correlations with MVO2 at extreme changes of hemodynamics. Tension-time index (TTI) correlates poorly with MVO2 (r = 0.63). This result is due to the neglect of contractility. Pressure-heart rate product (P X HR) correlates with MVO2 with r = 0.86. Better results for TTI and P X HR, as reported in previous works, are reproducible by dividing our data into two groups of different inotropic states. At normal and moderate inotropic stimulation the correlation for TTI rises to r = 0.96, and for P X HR to r = 0.91. This augmentation is to be referred to the close relationship (r = 0.92) of peak ventricular pressure to maximum rate of pressure rise in this group. The additive parameter E1 is the best, both at moderate (r = 0.97) and at maximal inotropic stimulation (r = 0.87), and is to be preferred for indirect estimation of MVO2. Results are discussed with regard to the clinical application of MVO2 indices.     

The linear relation between oxygen consumption and pressure-volume area can be reconciled with the Fenn effect in dog left ventricle

We studied the Fenn effect in 12 excised cross-circulated dog left ventricles in control contractility and in a contractility enhanced by dobutamine or depressed by propranolol. The additional oxygen consumption (Vo2) in an ejecting contraction compared with that found in an isovolumic contraction at a comparable end-systolic pressure was considered to constitute the cardiac Fenn effect. We examined whether this load-dependent Vo2 could be reconciled with the linear relation between Vo2 and pressure-volume area (PVA) common for both ejecting and isovolumic contractions that has so far been consistently observed and was presently confirmed. PVA is a specific area in the pressure-volume diagram, represents the total mechanical energy generated by each contraction, and consists of external mechanical work (EW) and mechanical potential energy. Because potential energy is common in the isovolumic and ejecting contractions producing the same end-systolic pressure, PVA of the ejecting contraction is greater by EW than that of the isovolumic contraction. Despite this difference in PVA by EW, the Vo2-PVA relation was always linear and load independent regardless of the isovolumic and ejecting contractions in a given heart in any given contractile state. By contrast, the upward convex Vo2-end-systolic pressure relation was higher for ejecting contractions than the downward convex Vo2-end-systolic pressure relation for isovolumic contractions in each contractile state. The difference of Vo2 between the ejecting and isovolumic contractions was proportional to EW at comparable end-systolic pressure. The slope of the additional Vo2 of ejecting contractions plotted against their EW had a slope close to the slope of the Vo2-PVA relation. Thus, the load-independent linear Vo2-PVA relation can be reconciled with the cardiac Fenn effect.     

Comparative influence of ouabain,norepinephrine and heart rate on myocardial oxygen consumption and inotropic state in dogs

The purpose of this study was to compare the myocardial oxygen cost of augmented inotropic state produced by ouabain, norepinephrine, or increased heart rate. This problem was examined in dogs using an isovolumically contracting left ventricular preparation. Inotropic state was measured as the maximum observed contractile element velocity at the lowest common level of wall stress (MAX V). Peak left ventricular wall stress was maintained constant in each dog so that it would not influence changes in myocardial oxygen consumption (MVO₂). Ouabain (4 × 10² μmoles/Kg.) and norepinephrine (2 × 10³ μmoles/Kg./minute) always augmented inotropic state (MAX V) and increased MVO₂. The positive slopes of the regression of MVO₂ on MAX V for ouabain (45.4 ± 12.5 μl/beat/100 Gm./muscle length/sec; mean ± SEM) and norepinephrine (34.5 ± 5.6 μl/beat/100 Gm./muscle length/sec; mean ± SEM) were not significantly different, indicating that for an equal augmentation of inotropic state, ouabain increases myocardial oxygen demands to the same extent as does norepinephrine. When the results with ouabain or norepinephrine were compared to results obtained by altering heart rate, it was found that increasing inotropic state by these pharmacologic agents is more costly in terms of myocardial energy demands than when inotropic state is enhanced by increasing heart rate.     

Myocardial oxygen consumption and the left ventricular pressure-volume area in normal and hypertrophic canine hearts.

BACKGROUND. To assess and compare the energy demands of normal and hypertrophic hearts, we defined the relation between myocardial oxygen consumption (MVO2, an index of the energy consumed by contraction) and the left ventricular pressure-volume area (PVA, an index of the total mechanical energy generated by contraction) in eight normal and eight hypertrophic (aortic band model) dog hearts; MVO2 was also measured in the nonworking (empty beating) and basal (potassium arrest) states. METHODS AND RESULTS. The hearts were studied in an isolated, blood-perfused heart apparatus. The slope of the MVO2-PVA relation (the inverse of which reflects myofibrillar efficiency) was similar in normal and hypertrophic hearts (3.89 +/- 1.91 and 4.19 +/- 1.25 ml O2/mm Hg.ml.10(5), p = NS). The MVO2 in empty beating (0.038 +/- 0.006 and 0.041 +/- 0.015 ml/beat/100 g, p = NS) and potassium-arrested (1.95 +/- 0.06 and 1.98 +/- 0.20 ml/min/100 g, p = NS) hearts was likewise similar in the two groups. CONCLUSIONS. Basal and nonworking energy demands and working efficiencies of hypertrophic hearts are equivalent to those of normal hearts.     

Role of myocardial oxygen consumption in dipyridamole-induced ischemia

The aim of this study was to assess whether myocardial oxygen consumption can be responsible for aminophylline resistance in dipyridamole-induced ischemia. We analyzed 163 consecutive patients who had a positive low-dose (0.56 mg/kg over 4 minutes) dipyridamole-echocardiography test, requiring intravenous aminophylline as an antidote. All patients also performed an exercise stress test. In 141 of these patients, the signs of ischemia were reversed by administration of intravenous aminophylline (group I), while the remaining 22 patients were resistant to aminophylline (240 mg/kg over 3 minutes) and received additional treatment with nitrates to relieve ischemia (group II). The increase in rate-pressure product (RPP = mm Hg x beats/min x 100) measured during the exercise stress test in the patients in group I was significantly greater than that determined during dipyridamole-induced ischemia (204 +/- 41 versus 145 +/- 33, p less than 0.01). However, the increases in RPP under both conditions were similar for the patients in group II (147 +/- 24 versus 150 +/- 20, p = ns). In patients with dipyridamole-induced ischemia who were resistant to aminophylline, the rise in myocardial oxygen consumption--probably linked to reflex sympathetic activation--might maintain ischemia independently from flow maldistribution, which should be reversed by aminophylline.     

Effect of ouabain on the relation between left ventricular oxygen consumption and systolic pressure-volume area (PVA) in dog heart

Summary We studied the effect of ouabain (digitalis) on the relation between left ventricular (LV) O₂ consumption (Vo₂) and pressure-volume (P-V) area (PVA) in 7 excised cross-circulated canine heart preparations. PVA is a measure of the total mechanical energy generated by LV contraction and was obtained as the specific area in the P-V diagram circumscribed by the end-systolic P-V line, end-diastolic P-V curve, and the systolic P-V trajectory. Ouabain (0.11 mg, intracoronary-arterially) increased Emax (LV contractility index) by 58±44% (mean ± SD) from 7.8±3.4 to 12.0±4.8 mmHg/(ml/100 g LV). PVA correlated linearly with LV Vo₂ per beat in either the control (r>0.97) or the ouabain run (r>0.96) in individual hearts. Ouabain increased the Vo₂-axis intercept of the regression line of Vo₂ on PVA from 0.029±0.004 in the control run to 0.036±0.009 ml O₂/beat/100 g LV without significantly changing the slope [(1.53±0.24)·10^–5 ml O₂/(mmHg/ml)] of the regression line. This slope is equivalent to the contractile efficiency value of 44±6% from the excess Vo₂ above unloaded Vo₂ to PVA. The parallel elevation of the Vo₂-PVA relation with ouabain was similar to the results produced by epinephrine and Ca²⁺ in our previous studies. Ouabain, like epinephrine and Ca²⁺, did not change the contractile efficiency from the PVA-dependent fraction of Vo₂ to PVA.