Left Ventricular Diastolic Pressure-volume Relationship Research Articles

Does intravenous milrinone have a direct effect on diastolic function?

Bipyridine derivatives have recently been introduced as a new class of inodilator drugs in the intravenous therapy of heart failure. A member of this class is milrinone, which improves the inotropic state and reduces ventricular afterload, leading to improved hemodynamics. Because systolic and diastolic function are intimately related, it can be expected that the diastolic muscle properties are influenced by changes in systolic function and therefore by milrinone therapy. Since end-diastolic pressure may shift as a result of a change in ventricular volume alone, a complete left ventricular diastolic pressure volume (LVDPV) relationship must always be measured before one can make firm conclusions regarding changes in diastolic function. After a LVDPV relationship is obtained, one should identify the variables that can modify this relationship without directly affecting the intrinsic diastolic muscle properties. These variables can be divided into static effects (coronary vascular bed volume, right ventricular pressure, and pericardial pressure) and dynamic effects (viscoelasticity and myocardial active relaxation). Increments in coronary perfusion pressure of perfusion flow (vascular bed volume) are known to stiffen the cardiac wall (turgor effect). Changes in right ventricular pressure or pericardial pressure are other factors affecting the LVDPV relationship by changing transmural pressure. This effect is more pronounced when the ventricle is already stiff, such as in patients with myocardial hypertrophy. Dynamic effects become important when a LVDPV relationship is measured during isolated cardiac cycles; they include viscoelasticity and abnormal myocardial relaxation. Clinical assessment of diastolic cardiac performance assumes a model in which the heart is considered an elastic body (while in fact it is viscoelastic).(ABSTRACT TRUNCATED AT 250 WORDS)

Load dependence of left ventricular diastolic pressure-volume relations during short-term coronary artery occlusion.

We evaluated the effect of altered loading conditions on left ventricular (LV) diastolic pressure-volume relations during acute coronary artery occlusion that was produced by inflation of an intracoronary balloon. Open-chest anesthetized dogs (n = 18) were instrumented so that LV pressure (micromanometer) and LV volume (conductance) could be measured without disturbing the pericardium. The effects of brief periods of occlusion (1-2 minutes) were assessed under steady-state conditions before and after dextran infusion with the pericardium present and absent and during vena caval occlusion. Under steady-state conditions before dextran infusion with the pericardium removed, at an LV end-diastolic pressure (EDP) of 8.4 +/- 1.4 mm Hg, occlusion resulted in a rightward shift in the diastolic portion of the LV pressure-volume loop (delta LVEDP, 2.7 +/- 2.3 mm Hg; delta LVEDV, 6.3 +/- 4.7 ml, both p less than 0.05 versus control). After dextran infusion (LVEDP, 20.9 +/- 6.0 mm Hg), occlusion resulted in a rightward and upward shift in the diastolic portion of the LV pressure-volume loop (delta LVEDP, 5.8 +/- 4.4 mm Hg; delta LVEDV, 4.2 +/- 3.0 ml, both p less than 0.05 versus control). At low cardiac volumes before dextran infusion, the intact pericardium did not affect the response to occlusion. By contrast, after dextran infusion in the presence of an intact pericardium, LVEDP significantly increased (delta, 6.4 +/- 3.6 mm Hg, p less than 0.05) but LVDEV did not (delta, 0.7 +/- 1.5 ml, p = NS). There was a parallel upward shift in the diastolic portion of the LV pressure-volume loop that was eliminated by removal of the pericardium. Thus, the change in LV diastolic pressure and volume during occlusion varied and depended on the baseline cardiac volume and presence of the pericardium. Before dextran infusion with the pericardium present and absent, coronary artery occlusion did not alter the LV diastolic chamber stiffness parameter, which was calculated from the diastolic interval of an averaged steady-state beat (0.040 +/- 0.019 versus 0.036 +/- 0.015 mm Hg/ml, p = NS). After dextran infusion with the pericardium present and absent, coronary artery occlusion increased the LV diastolic chamber stiffness parameter (0.057 +/- 0.034 and 0.074 +/- 0.034 mm Hg/ml, both p less than 0.05 versus controls, respectively). Vena caval occlusion eliminated the shifts in the diastolic portion of the LV pressure-volume loop with the pericardium present and absent.(ABSTRACT TRUNCATED AT 400 WORDS)

Volume conductance catheter.

HomeCirculationVol. 81, No. 6Volume conductance catheter. Free AccessAbstractPDF/EPUBAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessAbstractPDF/EPUBVolume conductance catheter. S A Glantz, C M BoltwoodJr, R F Appleyard, R J Applegate, C P Cheng and W C Little S A GlantzS A Glantz Search for more papers by this author , C M BoltwoodJrC M BoltwoodJr Search for more papers by this author , R F AppleyardR F Appleyard Search for more papers by this author , R J ApplegateR J Applegate Search for more papers by this author , C P ChengC P Cheng Search for more papers by this author and W C LittleW C Little Search for more papers by this author Originally published21 Mar 2018https://doi.org/10.1161/circ.81.6.2344690Circulation. 1990;81:2028"Volume conductance catheter.." Circulation, 81(6), p. 2028 Previous Back to top Next FiguresReferencesRelatedDetailsCited By Kassab G, Lontis E and Gregersen H (2004) Measurement of Coronary Lumen Area Using an Impedance Catheter: Finite Element Model and in Vitro Validation, Annals of Biomedical Engineering, 10.1007/s10439-004-7817-2, 32:12, (1642-1653), Online publication date: 1-Dec-2004. White P, Brookes C, Ravn H, Hjortdal V, Chaturvedi R and Redington A (2001) Validation and utility of novel volume reduction technique for determination of parallel conductance, American Journal of Physiology-Heart and Circulatory Physiology, 10.1152/ajpheart.2001.280.1.H475, 280:1, (H475-H482), Online publication date: 1-Jan-2001. White P, Brookes C, Ravn H, Stenbøg E, Christensen T, Chaturvedi R, Sorensen K, Hjortdal V and Redington A (1998) The effect of changing excitation frequency on parallel conductance in different sized hearts, Cardiovascular Research, 10.1016/S0008-6363(98)00052-2, 38:3, (668-675), Online publication date: 1-Jun-1998., Online publication date: 1-Jun-1998. (1998) Left ventricular dysfunction after open repair of simple congenital heart defects, The Journal of Thoracic and Cardiovascular Surgery, 10.1016/S0022-5223(98)00433-4, 116:5, (881-883), Online publication date: 1-Nov-1998. Colan S and del Nido P (1998) Editorial: Left ventricular dysfunction after open repair of simple confenital heart defects in infants and children, The Journal of Thoracic and Cardiovascular Surgery, 10.1016/S0022-5223(98)70445-3, 115:1, (74-76), Online publication date: 1-Jan-1998. Kun S and Peura R (1994) Analysis of conductance volumetric measurement error sources, Medical & Biological Engineering & Computing, 10.1007/BF02512486, 32:1, (94-100), Online publication date: 1-Jan-1994. Shintani H and Glantz S (1993) Effect of disrupting the mitral apparatus on left ventricular function in dogs., Circulation, 87:6, (2001-2015), Online publication date: 1-Jun-1993. Herrera M, Valentinuzzi M and Olivera J (1993) Volume profiles obtained by a conductimetric method, Journal of Biomedical Engineering, 10.1016/0141-5425(93)90001-F, 15:4, (267-273), Online publication date: 1-Jul-1993. Kun S and Peura R (1993) Conductance volumetric model of an eccentrically positioned catheter within a three-compartment ellipsoidal ventricle, IEEE Transactions on Biomedical Engineering, 10.1109/10.237679, 40:6, (589-592), Online publication date: 1-Jun-1993. Applegate R (1991) Load dependence of left ventricular diastolic pressure-volume relations during short-term coronary artery occlusion., Circulation, 83:2, (661-673), Online publication date: 1-Feb-1991.Slinker B (1991) Cardiac cycle length modulates cardiovascular regulation that is dependent on previous beat contraction history., Circulation Research, 69:1, (2-11), Online publication date: 1-Jul-1991. Vinten-Johansen J, Julian J, Yokoyama H, Johnston W, Smith T, McGee D and Cordell A (1991) Efficacy of myocardial protection with hypothermic blood cardioplegia depends on oxygen, The Annals of Thoracic Surgery, 10.1016/0003-4975(91)91259-X, 52:4, (939-948), Online publication date: 1-Oct-1991. June 1, 1990Vol 81, Issue 6 Advertisement Article InformationMetrics Copyright © 1990 by American Heart Associationhttps://doi.org/10.1161/circ.81.6.2344690PMID: 2344690 Originally publishedMarch 21, 2018 PDF download Advertisement

Diastolic function and heart failure: an overview

Diastolic dysfunction is being recognized increasingly as a primary cause of congestive heart failure. It may result from physiological abnormalities of myocardial relaxation, or anatomical abnormalities which increase resistance to ventricular inflow. With regard to physiological abnormalities, there is substantial evidence to indicate that myocardial ischaemia and hypertrophy are two conditions characterized by impaired inactivation and relaxation of myocardial cells. These conditions often co-exist in patients with idiopathic hypertrophic subaortic stenosis or calcific valvular aortic stenosis. Recent evidence also suggests a role for calcium overload in the diastolic dysfunction seen in some patients with advanced congestive heart failure. Diastolic dysfunction may be of fundamental importance in the pathophysiology of flash pulmonary oedema in patients with advanced ischaemic heart disease, since myocardial ischaemia in such patients may lead to a decline in relaxation rate, increased resistance to early diastolic filling and further impairment in diastolic coronary blood flow due to intramyocardial compression of capillaries and venules. During the transient ischaemia of angina pectoris, patients with multivessel coronary artery disease often show a striking upward shift in the left ventricular diastolic pressure-volume relationship, signifying a marked decrease in distensibility of the left ventricular chamber. With regard to anatomical abnormalities, diastolic dysfunction in heart failure may result from structural changes within the ventricular wall. Diastolic dysfunction of the left ventricle may result from extrinsic compression by pericardial effusion (tamponade), pericardial constriction, and right ventricular overload. Thus, a variety of physiological and anatomical abnormalities may lead to increased resistance to diastolic filling of one or both ventricles, resulting in diastolic heart failure.

Mechanism of altered pattern of left ventricular filling with aging in subjects without cardiac disease

The mechanism whereby aging, in the absence of cardiac disease, may alter the pattern of left ventricular (LV) diastolic filling is unknown. Accordingly, this study was designed to examine the factors that may be in part responsible for aging's effect on the pattern of LV diastolic filling. The LV enddiastolic pressure-volume relation was analyzed in 11 elderly subjects (68 ± 5 years, mean ± standard deviation) and 15 normal young adults (31 ±7 years) without coronary artery disease, systemic hypertension, LV hypertrophy or abnormality of LV systolic function. After catheterization, the subjects underwent pulsed Doppler analysis of mitral flow. All had normal 2-dimensional echocardiograms without LV or valvular dysfunction. Peak early filling velocity in the elderly subjects was decreased in comparison with that in young adults (61 ± 14 vs 83 ± 8 cm/s, p < 0.001) and the ratio of early and late diastolic filling velocity was reduced (0.81 ± 0.26 vs 1.88 ± 0.40, p < 0.001). The isovolumic relaxation time did not differ between the elderly and young subjects (158 ± 20 vs 146 ± 22 ms, difference not significant). In the elderly, LV end-diastolic pressure was increased (15 ± 7 vs 11 ± 4 mm Hg, p < 0.05) despite a smaller end-diastolic volume index (60 ± 16 vs 74 ± 18 ml/ m 2, p < 0.05), indicating a shift of the passive diastolic pressure-volume relation. It was concluded that early diastolic filling is reduced in normal aged subjects, even in the absence of coronary artery disease and systolic dysfunction. This altered pattern of diastolic filling may result from a shift of the passive LV diastolic pressure-volume relation.

Left ventricular pressure-length relation during exercise-induced ischemia

The pressure-length relation in normal and ischemic segments was analyzed with use of left ventriculography and simultaneous micromanometry during supine exercise in 9 normal subjects and 12 patients with effort angina. Segmental analysis was done in the right anterior oblique projection using a long axis with three perpendicular, equidistant chords. The apical segment in the 12 patients with coronary artery disease represented the ischemic region. In 5 of the 12 patients with coronary artery disease, the basal segment that showed no exercise-induced deterioration in wall motion was used as an intrapatient control (nonischemic segment).In the 12 patients with coronary artery disease, left ventricular ejection fraction decreased (from 65% to 50%, p < 0.001), end-diastolic pressure increased (from 24 to 40 mm Hg, p < 0.001) and the lowest diastolic filling pressure increased (from 9 to 22 mm Hg, p < 0.001) during exercise-induced ischemia. In normal subjects, ejection fraction increased (from 64% to 70%, p < 0.01) with unchanged end-diastolic pressure, whereas the lowest diastolic filling pressure decreased during exercise (from 9 to 3 mm Hg, p < 0.01). Global left ventricular diastolic pressure-volume curves showed an upward and rightward shift during exercise-induced ischemia. Regional pressure-length curves of both nonischemic (n = 5) and ischemic (n = 12) segments were shifted upward in early diastole, but moved to a higher portion of the rest pressure-length curve without an upward shift during mid- to end-diastole. In contrast, the apical segment in normal subjects showed a downward shift during exercise. Regional stiffness increased during exercise-induced ischemia in the ischemic but not in the nonischemic segment.In conclusion, the global left ventricular diastolic pressure-volume relation shows an upward and rightward shift during exercise-induced ischemia, whereas the regional pressure-length curves of the nonischemic and ischemic segments show an upward shift only during early, but not during late, diastole. This early diastolic upward shift of the regional pressure-length curve is more pronounced in the nonischemic segment. Regional stiffness is increased only in the ischemic segment. Thus, there is a time-dependent upward shift of the regional pressure-length curve during exercise-induced ischemia that is probably due to delayed relaxation in the ischemic segment and increased viscous forces in the nonischemic segment.

Left ventricular filling and early diastolic function at rest and during angina in patients with coronary artery disease.

Left ventricular diastolic function was studied in 11 patients with coronary artery disease. Single plane ventriculography (30 degrees right anterior oblique projection) was performed at rest and during an episode of angina immediately after a period of rapid atrial pacing. Left ventricular pressure was recorded simultaneously by a micromanometer tipped catheter. The ventriculograms were digitised frame by frame to derive continuous plots of left ventricular shape, volume, and rate of change of volume. The time constant (tau) of the fall in left ventricular pressure was determined from the exponential portion of pressure decay during isovolumic relaxation. Ventricular pressure-volume loops were constructed to study the left ventricular diastolic pressure-volume relation. The time of minimum left ventricular pressure was used to divide diastole into an early phase and a late phase. Angina was associated with an increase in end systolic volume and a fall in ejection fraction with no significant change in end diastolic volume. Peak left ventricular pressure was unchanged but left ventricular minimum and end diastolic pressures were both increased and the diastolic pressure-volume relation was moved upwards. The time constant of left ventricular pressure fall was prolonged. At rest more than 50% of the stroke volume entered the left ventricle during the period of early diastole. This proportion was significantly reduced during angina and as a consequence a significantly greater proportion of the stroke volume entered the ventricle during late diastole. Despite this, and although the left ventricular diastolic pressure-volume relation was moved upwards with angina, the mean slope of the relation during late diastole--that is, chamber stiffness--was not significantly altered. The upward shift of the left ventricular diastolic pressure-volume relation seen during angina is thus already apparent in early diastole, and its extent does not change during the later phase of diastole, which alone shows the property of passive stiffness. A primary increase in the passive stiffness of the ventricle cannot therefore be the cause of the upward shift of the diastolic pressure-volume relation, and events occurring in early diastole have to be looked to for an explanation. The study findings show that left ventricular function in early diastole is profoundly disturbed during angina pectoris and it is suggested that loss of elastic recoil and dissipation of this restoring force by asynchronous onset of relaxation and abnormal changes in shape are important factors contributing to this disturbance of function.

Comparison of the Effects of Nifedipine and Nitroglycerin on Hemodynamic Determinants of Myocardial Oxygen Consumption and Supply During Exertional Angina

To investigate the antianginal action of nitroglycerin and nifedipine, systemic and right heart pressures, cardiac output, oxygen consumption, and radionuclide left ventricular ejection fraction and volume were measured in 14 men with stable effort angina and a positive exercise electrocardiogram. Exercise tests were performed on a semiupright bicycle ergometer on no therapy and after intravenous nitroglycerin and sublingual nifedipine, which lowered mean arterial pressure by 20 mm Hg. Exercise tolerance improved from 50 +/- 4 to 61 +/- 5 W on nifedipine and to 79 +/- 4 W on nitroglycerin (p less than 0.01, nitroglycerin vs. nifedipine). At submaximal workloads, both drugs decreased arterial pressure and ventricular volumes, but heart rate was higher on nifedipine. At peak exercise on nitroglycerin (79 W), oxygen consumption, cardiac index, heart rate, and rate-pressure product were significantly increased over peak control and nifedipine values, while systolic pressure and end-diastolic volume were unchanged. Nitroglycerin reduced pulmonary wedge pressure more and systemic diastolic pressure less than nifedipine, so the coronary perfusion gradient was reduced by nifedipine and maintained by nitroglycerin. Also, there was less angina and ST-segment depression after nitroglycerin compared to control or nifedipine, and the left ventricular diastolic pressure-volume relationship was improved only by nitroglycerin. This suggests that the action of nitroglycerin in reducing ischemia is not only due to reduced myocardial oxygen demand, but that myocardial oxygen delivery may also be increased.

Right ventricular diastolic pressure-volume relations and regional dimensions during acute alterations in loading conditions.

Acute pharmacologically mediated parallel shifts in the left ventricular diastolic pressure-volume relation may be due to the restraining effect of the pericardium and/or leftward displacement of the interventricular septum. The existence and cause of this phenomenon in the right ventricle has not been studied in animals or in man. Accordingly, we altered right ventricular pressure with intravenous phenylephrine (0.2 to 0.3 mg) and nitroprusside (0.5 to 1.5 micrograms/kg/min) to achieve three disparate peak right ventricular pressures in nine normal subjects after partial autonomic blockade with atropine (1 mg) and propranolol (0.15 mg/kg). Simultaneous high-fidelity right ventricular pressures and biplane cineventriculographic volumes were acquired during the three resultant loading conditions. Right atrial pacing maintained heart rate constant at each pressure level. Peak right ventricular systolic pressure (23 +/- 3 vs 31 +/- 9 vs 45 +/- 6 mm Hg, all p less than .01) and right ventricular end-diastolic pressure (4 +/- 2 vs 8 +/- 4 vs 11 +/- 3 mm Hg, all p less than .01) were significantly different at low, medium, and high loading conditions, respectively. Right ventricular diastolic pressure-volume relations were, in parallel, shifted upward with altered loading in each patient. This was manifest by an unchanged dynamic chamber stiffness constant and a significant increase in the diastolic pressure volume y intercept at each load (1.98 +/- 2.21 vs 5.33 +/- 5.39 vs 8.51 +/- 3.99 mm Hg, p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Passive properties of canine left ventricle: diastolic stiffness and restoring forces.

Left ventricular (LV) diastolic pressure-volume (P-V) relations arise from a complex interplay of active decay of force (i.e., relaxation), passive elastic myocardial properties, and time-varying inflow across the mitral orifice. This study was designed to quantify the passive properties of the intact ventricle and the effects of elastic recoil by separating filling from relaxation with a method of LV volume clamping with a remote-controlled mitral valve. Eleven open-chest fentanyl-anesthetized dogs were instrumented with aortic and mitral flow probes, LV and left atrium micromanometers, and a remote-controlled mitral valve. We prevented complete (end-systolic volume clamping) or partial filling at different times in diastole. The ventricle thus relaxed completely at different volumes, and we generated P-V coordinates for the passive ventricle that included negative, as well as positive, values of pressure. We then estimated ventricular volumes from ventricular weight in eight dogs, using regression equations based on data in the literature, to determine the equilibrium volume (V0), that is, volume at zero transmural pressure, in the working ventricle. We abandoned the traditional exponential approach and characterized by the P-V relation with a logarithmic approach that included maximum LV volume (Vm), minimum volume (Vd), and stiffness parameters (Sp and Sn) for the positive (p) and negative (n) phases: Pp = -Sp In[(Vm - V)/(Vm - V0)] and Pn = Sn In[(V - Vd)/(V0 - Vd)]. With this formulation, the chamber compliance, dP/dV, is normalized by the LV operating volume, and Sp and Sn are size-independent chamber stiffness parameters with the units of stress. In eight ventricles with LV weight = 131 +/- 20 g, Vm = 116 +/- 18 ml, V0 = 37 +/- 6 ml, and Vd = 13 +/- 2 ml, stiffness Sp = 14.6 mm Hg and Sn = 5.1 mm Hg were determined from the slopes of the log-linearized equations. Also, the duration of LV relaxation is increased by the process of ventricular filling (161 +/- 31 msec, filling versus 108 +/- 36 msec, nonfilling, measured from dP/dtmin, p less than 0.0001). We conclude that volume clamping is a useful method of studying restoring forces and that the logarithmic approach is conceptually and quantitatively useful in characterizing the passive properties of the intact ventricle.

Quantification of effect of pericardium on LV diastolic PV relation in dogs

The aim of the present study was to quantify the effect of the pericardium on the left ventricular (LV) diastolic pressure-volume relation. The experiments were done in 10 anesthetized closed-chest dogs. Pericardial and cardiac volumes were determined by computed tomography. Pericardial effusion (n = 5) and volume loading (6% dextran iv; n = 5) were used to increase pericardial volume. Volumes were normalized as multiples of the LV volume measured when LV transmural pressure was 6 mmHg (VLV6). Using the data from the pericardial effusion experiments, we calculated the best-fit exponential equations for the pericardial pressure-volume relations. From these equations we calculated that the changes in pericardial volume necessary to shift the LV diastolic pressure-volume curve upward by 2, 5, 10, and 20 mmHg were 0.6 +/- 0.1, 1.1 +/- 0.2, 1.6 +/- 0.2, and 2.2 +/- 0.3 times VLV6, respectively. Using the data from the volume loading experiments, we also calculated the degree of upward shift of the LV pressure-volume relation caused by volume loading, which increased LV mean diastolic pressure by 12 mmHg. (The upward shift is that increment in pericardial pressure caused by the total increase in volume of the extra-LV contents of the pericardium, i.e., the atria, the right ventricle, and any pericardial effusion.) This volume loading increased the total volume of the right ventricle and the atria by 1.0 +/- 0.1 VLV6, which, in itself, increased pericardial pressure by 3.6 +/- 0.8 mmHg. We conclude that in situations in which heart or pericardial volume increases acutely, the pericardium shifts the diastolic pressure-volume relation of the LV upward by a significant amount.

Effects of verapamil on regional myocardial diastolic function in pacing-induced ischemia in dogs.

The upward shift in the left ventricular diastolic pressure-volume relationship during pacing-induced angina may be related to increased cytosolic calcium availability with persistent contractile element interaction in diastole. To assess the influence of calcium channel blockade on these changes in diastolic function, we studied the effects of verapamil in dogs with 90% stenoses of the left anterior descending and circumflex coronary arteries. Ultrasonic crystals were implanted in the myocardium to monitor anterior wall and lateral wall segment length. Left ventricular pressure was measured with a micromanometer catheter. The left atrium was paced at a rate 1.5 times that of the resting heart rate for 3 min. An upward shift of the left ventricular diastolic pressure-segment length relationship developed after pacing tachycardia, with a rise in the left ventricular end-diastolic pressure (LVEDP) from 4.7 +/- 1.2 to 14.3 +/- 2.2 mmHg (P less than 0.01, n = 13), and pressure was higher at any segment length throughout diastole. Increases in end-diastolic segment length were small (12.3 +/- 1.9 to 12.7 +/- 2.0 mm for the anterior wall, P less than 0.05; 15.1 +/- 1.4 to 16.4 +/- 1.5 mm for the lateral wall, P less than 0.01). Pretreatment with verapamil (0.08 mg/kg iv) did not reduce this upward shift: LVEDP rose from 6 +/- 1 to 16 +/- 1 mmHg (P less than 0.01, n = 7) and there were similar small increases in end-diastolic segment length.(ABSTRACT TRUNCATED AT 250 WORDS)

One versus two MAC halothane anesthesia does not alter the left ventricular diastolic pressure-volume relationship.

Previous studies on halothane's effect on left ventricular diastolic compliance (LVDC) not only have had conflicting results, but are not directly applicable to most intraoperative settings. Therefore, the authors examined in dogs whether the depth of halothane anesthesia alters LVDC under surgical conditions over a wide range of hemodynamic stresses with the cardiovascular reflexes intact. The left ventricular diastolic pressure-volume relation was examined at 1 MAC and 2 MAC halothane in seven dogs over wide ranges of preload and afterload during left thoracotomy. Pulmonary capillary wedge pressure (PCWP), left ventricular end-diastolic pressure (LVEDP), and echocardiographic left ventricular end-diastolic volume (LVEDV) were analyzed with the exponential pressure-volume relation P = AeBV (where P = pressure, V = volume, and A and B are empirically derived coefficients). Multivariate analysis showed no significant differences for diastolic pressure-volume relations, comparing both levels of halothane using either PCWP or LVEDP for pressure. The authors conclude that in the intact cardiovascular system in the healthy open-chest dog: 1) LVDC does not change with the depth of halothane between 1 and 2 MAC (it is still possible LVDC changed between 0 and 1 MAC), and 2) PCWP does reflect the LVEDV during halothane anesthesia (between 1 and 2 MAC) under surgical conditions over a wide range of cardiovascular stresses.

Improvement in indexes of diastolic performance in patients with congestive heart failure treated with milrinone.

To elucidate the mechanisms by which the new bipyridine inotropic agent milrinone improves cardiac function, we examined multiple indexes of left ventricular diastolic function before and after administration of milrinone to patients with advanced (NYHA class III or IV) congestive heart failure. In 13 patients left ventricular pressure measurements were made with a micromanometer to permit assessment of peak negative dP/dt and the time constant of left ventricular isovolumic relaxation, T, before and after milrinone. In nine patients radionuclide ventriculographic studies were performed during left heart catheterization, allowing calculation of left ventricular peak filling rate, volumes, and the diastolic pressure-volume relationship before and after milrinone. After intravenous administration of milrinone, peak negative dP/dt increased (+ 18%; p less than .01) and T decreased (-30%; p less than .01), while heart rate increased by only 8% (87 +/- 12 to 94 +/- 15 beats/min; p less than .01), left ventricular systolic pressure did not change, and mean aortic pressure fell by 11% (p less than .01). Left ventricular peak filling rate increased (1.2 +/- 0.6 to 1.7 +/- 0.7 end-diastolic volumes/sec; p less than or equal to .02) despite a decrease in left ventricular filling pressure (mean pulmonary wedge pressure 27 +/- 7 to 18 +/- 9 mm Hg; p less than .01). There was a fall in left ventricular end-diastolic pressure (28.6 +/- 6 to 19 +/- 7 mm Hg; p less than or equal to .01), with no significant change in left ventricular end-diastolic volume. This was associated with a downward shift in the left ventricular diastolic pressure-volume relationship in most cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of action of nitrates: Role of changes in venous capacitance and in the left ventricular diastolic pressure-volume relation

Nitroglycerin, when administered to patients with heart failure, causes a marked reduction in left ventricular filling pressure but often an increase in stroke volume and stroke work; based on the Frank-Starling principle, such a reduction in “preload” would be expected to result in a decrease in left ventricular end-diastolic volume and, therefore, a decline in stroke volume. Assessment of pressure-volume coordinates, however, has revealed that nitroglycerin produces a downward shift in the pressure-volume relationship. This apparent improvement in left ventricular compliance cannot be attributed to alterations in the elastic properties of the myocardium but rather appear to reflect a reduction in left ventricular external constraint. Recent animal and clinical investigations in our laboratory suggest that nitroglycerin causes venous dilatation (particularly in the mesenteric bed), thereby decreasing venous pressure at any given vascular volume. This decrease in cardiac filling pressure results in a decrease in heart size and, therefore, a reduction in pericardial pressure. Left ventricular transmural (intracavitary minus pericardial) pressure is little changed, however, so that end-diastolic volume and stroke volume are maintained.

Ventricular diastolic pressure-volume shifts during acute ischemic left ventricular failure in dogs

Ischemic left ventricular failure was produced in eight acutely instrumented, anesthetized dogs to study the contribution of changing myocardial compliance and pericardial pressure to shifts in right and left ventricular diastolic pressure-volume relations. Right and left ventricular and pericardial volumes were measured by ungated computed tomography. Cardiac volumes were manipulated by infusion of saline solution, hemorrhage, phenylephrine infusion and, during failure only, nitroglycerin administration. During both control and failure periods, these interventions shifted the left and right ventricular pressure-volume relations by changing pericardial pressure only; that is, these interventions caused no change in the ventricular transmural pressure-volume relation. The induction of failure as such increased pericardial pressure only minimally and did not change the left ventricular or right ventricular transmural pressure-volume relations significantly. Volume loading during the control period caused an apparent pericardial creep which attenuated the pericardial effect on ventricular pressure-volume relations. During failure, volume loading caused an increase of right ventricular volume, but tended to decrease left ventricular volume; this was associated with a leftward displacement of the interventricular septum. In conclusion, in the presence of ischemic left ventricular failure as well as normally, changes in preload, afterload and circulating blood volume shift ventricular diastolic pressure-volume relations by stretching or relaxing the pericardium, thus changing pericardial pressure. In these circumstances, there were no consistent changes in myocardial compliance.

Increased regional myocardial stiffness of the left ventricle during pacing-induced angina in man.

The left ventricular diastolic pressure-volume relationship shifts upward during angina, but why this happens is not known. To assess regional myocardial stiffness, we studied 12 patients who had coronary artery disease using simultaneous left ventricular micromanometer pressure recording and M-mode echocardiography before and during angina induced by pacing tachycardia. All patients had two- or three-vessel coronary artery disease that involved the posterior left ventricular wall circulation and had positive pacing stress tests, i.e., development of angina and a postpacing rise in left ventricular end-diastolic pressure (15 +/- 3 to 31 +/- 6 mm Hg, p less than 0.001). A marked upward shift in the relationship between the diastolic left ventricular pressure and the posterior wall thickness (h) occurred after pacing tachycardia, but the change in left ventricular posterior wall end-diastolic thickness was minimal (8.9 +/- 2.1 to 9.2 +/- 2.1 mm, NS). After pacing, the peak rate of left ventricular posterior wall thinning decreased (82 +/- 37 to 48 +/- 27 mm/sec, p less than 0.005) and the time constant of relaxation derived from the best exponential fit to the isovolumic left ventricular pressure decay increased (49 +/- 5 to 58 +/- 7 msec, p less than 0.001). Diastolic active left ventricular pressure decay, extrapolated from the exponential fit, was subtracted from the measured left ventricular pressure (which is equal in magnitude but opposite in sign to the radial stress at the endocardium) to calculate residual left ventricular pressure (PR) and hence residual stress (sigma R = -PR). A radial stiffness modulus (ER) was determined by the slope of the PR vs log h plots before and after pacing. Over the same range of residual radial stress (sigma R), ER was always higher during pacing-induced angina, indicating increased residual myocardial stiffness. Increased myocardial stiffness in addition to a decreased rate of wall thinning and slow active pressure decay contribute to the upward shift in left ventricular pressure-wall thickness and pressure-volume relationships during pacing-induced angina.

Effect of the undisturbed pericardium on left ventricular size and performance during acute volume loading

Studies in instrumented dogs have suggested that the pericardium alters left ventricular diastolic pressure-volume relations and thus may influence systolic performance. However, the instrumentation used in these studies disrupts the pericardium and may have influenced the results. We therefore studied five conscious dogs by methods not traumatic to the pericardium, before and after pericardiectomy. Although heart rate and left ventricular systolic and end-diastolic pressures were not different before or after pericardiectomy, either at rest or during volume loading, end-diastolic volume measured by biplane two-dimensional echocardiography increased post pericardiectomy at rest from 38 ± 4 (SE) to 61 ± 4 ml ( p < 0.05) and during volume loading from 68 ± 5 to 79 ± 5 ml ( p < 0.005). After pericardiectomy, ejection fraction was unchanged, but the peak value of the first derivative of left ventricular systolic pressure ( dP dt ) increased significantly at rest from 17 ± 2 to 26 ± 4.0 × 10 2 mm Hg/sec. We conclude that pericardiectomy shifts the left ventricular end-diastolic pressure-volume curve to the right and increases the systolic isovolumic index of dP dt in the basal state.

Ventricular diastolic pressure-volume relations after the intra-atrial baffle operation for transposition of the great arteries.

Right and left ventricular diastolic pressure-volume (P-V) relations were assessed in 30 patients approximately 2 years after the Mustard operation. The overall distensibility index (delta V/ delta P), the compliance index at end-diastole (dv/dp), and the modulus of ventricular stiffness (Kp) were calculated in all, as well as the half-time of early diastolic pressure fall (T) in 10 cases. Transducer-tipped catheters were used in 15 patients and biplane cineangiography was employed in all. Values for the above indices equal to 2 standard deviations below the mean, obtained from five postoperative Mustard patients with no residual defects, were used as "normals." Seven patients with pulmonary hypertension (PH) and six with pulmonic stenosis (PS) were found to have impaired P-V relations. The impairment was more profound in the PH group. Delta v/delta p and dv/dp were abnormal in six of seven patients for both ventricles and T was abnormal in two of five. Kp was abnormal for the LV, and the RV ejection fraction was diminished. In the PS group (nine patients) the impairment was milder, affecting more than LV and end-diastole (dv/dp). Compliance studies might be useful in patients with LV afterload problems following the Mustard operation.

Ventricular diastolic pressure-volume relations and the pericardium. Effects of changes in blood volume and pericardial effusion in dogs.

We investigated the role of the pericardium in the mechanism of shifts in the left ventricular (LV) diastolic pressure-volume relation produced by changes in circulating blood volume and by pericardial effusion. Twelve closed-chest anesthetized dogs were instrumented with pericardial and pleural balloons and intracardiac catheters for pressure measurements. We measured the volumes of the pericardium and the left and right ventricles by computed tomography (CT), integrating the area of CT cross-sections measured at 1-cm intervals from the cardiac apex to the aortic arch. The volumes of the pericardium and the cardiac chambers were changed by infusing 40 and 80 ml of dilute contrast medium into the pericardial space, by bleeding, and by rapidly infusing saline intravenously. Pericardial effusions of 80 ml reduced mean right ventricular volumes to 59% of control, whereas LV volumes were less severely compromised (81% of control). Total pericardial volume and pressure increased. Intravenous saline infusions, which raised right atrial pressure 10-15 mm Hg, produced increases of this magnitude in pericardial pressure. This was also the magnitude of the upward displacement in the LV diastolic pressure-volume relation after infusion. However, LV diastolic transmural pressure-volume coordinates fell along a single curve. Similar behavior was observed for the right ventricular diastolic pressure-volume relation. Pericardial transmural pressure-volume curves were described. When cardiac volume was altered by volume load and pericardial effusion, acute shifts in the LV diastolic pressure-volume relation were caused by changes in pericardial pressure, which, in turn, corresponded to changes in pericardial volume.