Left Ventricular Transmural Pressure Research Articles

Esmolol and left ventricular function in the awake dog.

Hypotension has been the most frequently reported adverse reaction associated with infusion of the beta 1-adrenergic receptor antagonist esmolol. In some patients, this hypotension has apparently occurred independent of reduction in heart rate or systemic vascular resistance, suggesting decreased stroke volume. In the present study, the preload recuitable stroke work area (PRSWA) model was used to evaluate the negative inotropic effects of esmolol in nine chronically instrumented awake dogs. Left ventricular (LV) transmural pressure and minor axis diameter were measured by micromanometers and sonomicrometry, respectively. Vena caval occlusions were performed so that an analog of stroke work (area within LV transmural pressure-diameter loop) could be measured over a range of preloading conditions during esmolol infusions of 0, 100, 300, 1000, and 3000 micrograms/kg-1.min-1 (n = 9), and at 15 and 30 min after termination of esmolol (n = 8). The linear relationship between stroke work and end-diastolic diameter was characterized for each caval occlusion by a slope and x-intercept. PRSWA was calculated for each caval occlusion as slope/two times the square of the difference between x-intercept and the largest end diastolic diameter observed in the study of a particular dog. Heart rate was different from control (91 +/- 4) only at the highest esmolol dose (127 +/- 4). LV peak positive dP/dt, minor axis ejection shortening, stroke work, and PRSWA were depressed from control at esmolol doses greater than or equal to 300 micrograms.kg-1.min-1. All parameters except dP/dt recovered within 30 min following termination of esmolol.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Left ventricular external constraint: relationship between pericardial, pleural and esophageal pressures during positive end-expiratory pressure and volume loading in dogs.

Left ventricular (LV) diastolic filling is limited by the constraining effects exerted by the pericardium (PE) and the lung/chest wall. The aim of the present study was to assess the validity of various estimates of external cardiac constraint, compared to pericardial surface pressure (Ppe) measured lateral to the LV myocardium. In nine anesthetized dogs we measured Ppe, pleural surface pressure (Ppt) (lateral to the pericardium) and esophageal pressure (Pes) under conditions of volume loading and positive end-expiratory pressure (PEEP). We measured Ppe and Ppl with flat, liquid-containing silastic rubber balloons and Pes with an air-containing cylindrical balloon. After instrumentation, the chest was resealed and continuous suction (-5 mm Hg, 1 mm Hg = 0.133 kPa) was maintained. Volume loading with incremental intravenous infusions of saline was used to increase LV end-diastolic pressure to 20-25 mm Hg. PEEP of 0, 10 and 20 mm Hg were applied at baseline and after each increment of volume loading. At low volume, increases in PEEP caused simultaneous increases in LV end-diastolic pressure (P less than 0.01) and in Ppe (P less than 0.0001) but a reduction in transmural LV pressure (P less than 0.0005). Ppl and Pes both increased with PEEP (P less than 0.001 and P less than 0.01, respectively). However, Ppe always exceeded Ppl, while Pes remained at only approximately 1/3 Ppl throughout. Volume loading caused a significant increase in Ppe (P less than 0.0001) and a smaller, but significant increase in Ppl (P less than 0.05). Pes remained unchanged during volume loading. Thus external cardiac constraint increased markedly during volume loading and PEEP as evidenced by a marked elevation of Ppe. Both Ppl and Pes markedly underestimated this increase. Therefore, calculation of transmural LV pressure by subtracting pleural or esophageal pressure from intracavitary pressure can lead to overestimation of LV preload. The decrease in cardiac output during PEEP occurs secondary to decreased preload, i.e. decreased transmural pressure and end-diastolic dimension. Analysis of performance using cardiac function curves does not suggest a change in contractility with PEEP.

The effects of pressure-induced right ventricular hypertrophy on left ventricular diastolic properties and dynamic geometry in the conscious dog.

To determine whether chronic pressure overload and hypertrophy of the right ventricle alter the diastolic properties of the left ventricle, six adult dogs underwent banding of the pulmonary artery and were instrumented for studies 8 months later. Fourteen control dogs were also studied. Pressure and dimension data were collected from the dogs while they were awake and unsedated. The anterior-posterior, septal-free wall, and base-apex axis diameters of the left ventricle were measured with ultrasonic dimension transducers. Right and left ventricular pressures were measured with micromanometers. Pulmonary arterial banding resulted in increased right ventricular/body mass ratios (2.70 +/- 0.36 g/kg vs 1.52 +/- 0.15 g/kg control; p less than or equal to .05) and increased left ventricular/body mass ratios (4.84 +/- 0.64 g/kg vs 4.21 +/- 0.49 g/kg control; p less than or equal to .05). Right ventricular peak systolic and end-diastolic pressures were higher among the banded dogs (50 +/- 20/7 +/- 5 mm Hg vs 31 +/- 6/3 +/- 2 mm Hg control; p less than or equal to .05). A rearrangement in the three-dimensional geometry of diastolic filling occurred in the banded dogs. Extension from unstressed diastolic dimension (strain) in the base-apex axis was significantly larger in the banded dogs at left ventricular transmural pressures of 12, 8, and 4 mm Hg; strains in the septal-free wall axis were significantly smaller at transmural pressures of 12 and 8 mm Hg. Normalized diastolic left ventricular pressure-volume data and midwall circumferential stress-strain data were fit to the Kelvin viscoelastic equation. The normalized pressure-volume relationships of the banded dogs lay significantly to the left of those of the controls, indicating a loss of left ventricular chamber compliance. The midwall circumferential stress-strain relationships of the banded dogs were also shifted to the left, indicating a loss of intrinsic myocardial compliance. Thus, during the course of right ventricular hypertrophy caused by right ventricular pressure overload, alterations in the mass, geometry, and material properties of the left ventricle occur. At 8 months the chamber compliance of the left ventricle is compromised by these changes.

Right and left ventricular pressure-volume response to respiratory maneuvers.

With respiration, right ventricular end-diastolic volume fluctuates. We examined the importance of these right ventricular volume changes on left ventricular function. In six mongrel dogs, right and left ventricular volumes and pressures and esophageal pressure were simultaneously measured during normal respiration, Valsalva maneuver, and Mueller maneuver. The right and left ventricular volumes were calculated from cineradiographic positions of endocardial radiopaque markers. Increases in right ventricular volume were associated with changes in the left ventricular (LV) pressure-volume relationship. With normal respiration, right ventricular end-diastolic volume increased 2.3 +/- 0.7 ml during inspiration, LV transmural diastolic pressure was unchanged, and LV diastolic volume decreased slightly. This effect was accentuated by the Mueller maneuver; right ventricular end-diastolic volume increased 10.4 +/- 2.3 ml (P less than 0.05), while left ventricular end-diastolic pressure increased 3.6 mmHg (P less than 0.05) without a significant change in left ventricular end-diastolic volume. Conversely, with a Valsalva maneuver, right ventricular volume decreased 6.5 +/- 1.2 ml (P less than 0.05), and left ventricular end-diastolic pressure decreased 2.2 +/- 0.5 mmHg (P less than 0.05) despite an unchanged left ventricular end-diastolic volume. These changes in the left ventricular pressure-volume relationship, secondary to changes in right ventricular volumes, are probably due to ventricular interdependence. Ventricular interdependence may also be an additional factor for the decrease in left ventricular stroke volume during inspiration.

Pericardial pressure assessed by right atrial pressure: A basis for calculation of left ventricular transmural pressure

Pericardial pressure assessed by right atrial pressure: A basis for calculation of left ventricular transmural pressure

Early mechanical function in the heterotopic heart transplant

The characteristics of left ventricular (LV) function in the nonimmunosuppressed heterotopic heart transplant (TX) with less than 3 hr of cold preservation, were studied in 12 awake chronically instrumented dogs prior to TX (control), 1–12 hr post TX (P 1), 12–24 hr post TX (P 2), and 24–48 hr post TX (P 3). Micromanometers measured LV transmural pressure and ultrasonic transducers measured ventricular dimension in order to allow calculations of myocardial mechanical properties. Immediately after transplant (P 1) there was significant ( P < 0.05) depression noted in both diastolic function and systolic function (peak LV pressure, 137 ± 5 vs 80 ± 10 mm Hg; dp/dt max, 2642 ± 170 vs 1038 ± 98 mm Hg/sec; maximum velocity of minor axis shortening, 4.46 ± 0.50 vs 2.41 ± 0.56; and E max, 6.5 ± 1.2 vs 2.0 ± 1.4 mm Hg/ml). However, the contractility reserve (studied in six dogs) as estimated by postextrasystolic potentiation ratio was maintained (1.41 ± 0.07 vs 1.37 ± 0.15), suggesting reversibility of the depressed function. Over the next 2 days the diastolic function and the systolic function (at P 3: 109 ± 6 mm Hg, 1842 ± 450 mm Hg/sec, 5.54 ± 0.77 cm/sec, and 4.5 ± 1.3 mm Hg/ml, respectively) gradually improved toward control. Microscopic examination of the autopsied hearts did not show significant evidence of rejection. Thus, the early depression of function in the heart TX appeared to be the result of ischemia from preservation and surgical trauma. In spite of the depressed LV function immediately post TX, the contractility reserve of the transplanted heart appeared to be well maintained, and, in this study, recovery of function was observed. It is suggested that measurement of the cardiac contractility reserve may be of value in assessing various methods of long-term cardiac preservation for transplantation.

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.

Volume-dependent effects of positive airway pressure on intracavitary left ventricular end-diastolic pressure.

To test the hypothesis that the effects of positive end-expiratory airway pressure (PEEP) on intracavitary left ventricular end-diastolic pressure (LVEDP) depend on the ventricular filling conditions under which PEEP is applied, the effects of PEEP on pressure in and around the left ventricle were determined before and after stepwise expansion of intravascular blood volume in 10 closed-chest dogs. Over a range of 0 to 20 cm of water, PEEP progressively increased both intrapericardial and intracavitary right ventricular end-diastolic pressures. These increases in pressure around the left ventricle were approximately linear and were relatively unaffected by volume loading. At the same time, PEEP always decreased transmural LVEDP by decreasing ventricular filling. However, transmural LVEDP fell more when ventricular volume was initially large, due to the nonlinear relationship between left ventricular transmural pressure and volume. As a result, intracavitary LVEDP (which reflected the sum of decreased transmural LVEDP and increased external pressure) increased when baseline ventricular volume was small and decreased when baseline ventricular volume was large. At intermediate volumes the fall in transmural pressure equaled the rise in external pressure, and intracavitary LVEDP did not change. These findings demonstrate that changes due to PEEP in intracavitary LVEDP are a complex function of increased intrathoracic pressure, decreased ventricular filling, and the operative level of left ventricular compliance.

Pericardial influences on ventricular filling in the conscious dog. An analysis based on pericardial pressure.

Twenty-five dogs were chronically instrumented to investigate the effects of the normal pericardium on cardiac function. Pulse-transit ultrasonic transducers were implanted to measure multiple ventricular dimensions. The pericardium was incised transversely at the base of the heart and precisely reapproximated, so as to disturb its characteristics minimally. One week later, the dogs were studied in the conscious state, and left ventricular, right ventricular, pericardial, and pleural pressures were measured with matched micromanometers. Data were recorded before and after blood volume expansion. Absolute end-diastolic pericardial pressure varied directly with pleural pressure during the respiratory cycle. Transpericardial pressure (pericardial-pleural pressure) varied little with respiration and was related directly to ventricular diameter during the cardiac cycle with peak transpericardial pressure uniformly occurring at end-diastole. With volume infusion, normalized end-diastolic minor axis diameter and left ventricular transmural pressure (left ventricular-pleural pressure) increased significantly from 0.14 +/- 0.01 and 9.5 mm Hg +/- 1.0 mm Hg, respectively, in the control state to 0.20 +/- 0.01 and 19.3 mm Hg +/- 1.2 mm Hg after volume loading. End-diastolic transpericardial pressure also increased significantly from 2.3 +/- 0.5 mm Hg to 4.1 +/- 0.3 mm Hg, and represented approximately 21% of transmural left ventricular pressure. When measurements were obtained sequentially after implantation, transpericardial pressure was initially high but decreased with time, presumably due to pericardial creep. After volume loading, right ventricular end-diastolic transmural pressure averaged 9.6 mm Hg, and pericardial pressure constituted 42% of right ventricular pressure. Thus, pericardial restraining effects may predominantly influence right ventricular filling and affect the left ventricle through series interaction. In the normal conscious dog, transpericardial pressure remains low over the entire physiological range, and the direct influence of the normal pericardium on diastolic filling of the left ventricle appears to be minimal.

Right and left ventricular pressure-volume response to positive end-expiratory pressure.

Cardiovascular effects of positive end-expiratory pressure (PEEP) at 20 cmH2O were examined in six mongrel dogs (11.3-15.0 kg). The dogs were anesthetized through a combination of intramuscular Innovar and gaseous anesthesia (60% N2O-40% O2). For volume measurements, radiodense tantalum screws were placed on the endocardial surface of the left and right ventricle. Esophageal and left and right ventricular pressures were measured. With the use of this preparation, the effects of positive end-expiratory pressure (PEEP = 20 cmH2O) on cardiovascular function were examined. PEEP caused right ventricular transmural pressures to decrease, 3.4 +/- 1.0 to 2.0 +/- 1.0 mmHg end-diastolic (P less than 0.05) and 29.2 +/- 2.2 to 27.9 + 2.2 mmHg peak systolic; left ventricular transmural pressures decreased, 5.9 +/- 1.6 to 1.2 +/- 1.4 mmHg end-diastolic (P less than 0.05) and 117.2 +/- 8.0 to 76.2 +/- 7.4 mmHg peak systolic (P less than 0.05). After volume loading the animal (500 ml dextran), PEEP caused similar changes in right and left ventricular pressures. Plots of end-diastolic volume versus pressure showed an increase in the apparent diastolic stiffness in both ventricles with decreased end-diastolic volume.

Myocardial depression by anesthetic agents (halothane, enflurane and nitrous oxide): Quantitation based on end-systolic pressure-dimension relations

The end-systolic pressure-diameter relation of the left ventricle was used to examine the effect of halothane, enflurane and nitrous oxide on left ventricular (LV) contractility in 10 dogs chronically instrumented with dimension transducers to measure LV diameter and micromanometers to measure LV transmural pressure. Contractility was assessed by the slope (E ES) of the end-systolic pressure-diameter relation. A new index that identifies the dose of anesthetic necessary to depress the inotropic state by 20% (ID 20) was calculated to be 0.63% for halothane and 1.55% for enflurane, indicating a greater apparent myocardial depressant effect of halothane than enflurane. However, when these agents were compared at equi-anesthetic concentrations by normalizing the ID 20 to the minimal alveolar concentration of each drug, they had comparable degrees of myocardial depressant effects. This measurement technique was used in 7 patients undergoing coronary artery bypass grafting conducted under narcotic anesthesia showing that halothane induced a similar depression of contractility. The use of ID 20 should allow reclassification of anesthetic agents according to their myocardial depressant effects.

Volume loading improves low cardiac output in experimental right ventricular infarction

To evaluate the effect of volume loading in the low output state associated with right ventricular infarction, isolated right ventricular infarction was produced in seven dogs with the pericardium intact. Volume loading and pericardiotomy were then sequentially performed. After the production of right ventricular infarction, right ventricular systolic pressure decreased by 25%, aortic pressure by 36% and cardiac output by 32%. Right ventricular ejection fraction decreased by 57%, but left ventricular ejection fraction did not change significantly. Left ventricular transmural pressure and diastolic size decreased, and right ventricular diastolic size increased. Intrapericardial pressure increased and equalization of diastolic pressures was noted. Volume loading resulted in increased right ventricular systolic pressure and stroke work, increased aortic pressure and cardiac output and increased transmural pressure and diastolic size in both ventricles. Pericardiotomy resulted in further increases in right and left ventricular filling, stroke work and cardiac output, as well as resolution of equalized diastolic pressures. These results indicate that cardiac output in experimental right ventricular infarction increases with volume loading, which enhances left ventricular preload by augmenting right ventricular output. Elevated intrapericardial pressure affects filling of both ventricles and may play a role in the pathophysiology of low cardiac output in right ventricular infarction.

Effects of airway pressure and lung volume on left ventricular transmural pressure-volume relationships in humans

Positive airway pressure, combined with increased lung volume, decreases left ventricular compllance in dogs. To determine whether airway pressure or lung volume influences left ventricular diastolic properties in humans, we examined two consecutive cineanglograms with simultaneous esophageal and left ventricular pressure recordings in 14 patients. Both studies were performed during sustained inspiration, one with atmospheric airway pressure, and one with positive airway pressure (9.1 ± 2.4 mm Hg). Positive pressure caused higher transpulmonary (airway minus esophageal) pressure and therefore greater lung volume in 10 of 14 patients, while four patients had lower transpulmonary pressures due to decreased inspiratory effort. When positive airway pressure and increased lung volume were present together (n = 10), left ventricular transmural (ventricular minus esophageal) pressure-volume curves revealed higher transmural pressures at comparable diastolic ventricular volumes. For example, at end-diastole mean left ventricular transmural pressure was 25.2 ± 12.9 mm Hg (compared to 20.8 ± 12.3 mm Hg during control studies, p < 0.05), while ventricular volume was unchanged (189 ± 87 compared to 185 ± 81 ml, p = NS). When all 14 patients were considered together, this effect was linked more closely to higher transpulmonary pressure than to positive airway pressure. We conclude that human left ventricular transmural pressure-volume relationships are influenced by airway pressure and lung volume. Our findings further suggest that lung volume may be more important than airway pressure in this regard.

The mechanism of halothane-induced myocardial depression: Altered diastolic mechanics versus impaired contractility

Although halothane has been shown to depress left ventricular function, it remains a common alternative to narcotic anesthesia in cardiac operations. To clarify the mechanism by which this functional depression occurs (direct decrease in contractility versus altered diastolic compliance), we studied seven dogs in the closed-chest state following instrumentation with ultrasonic dimension transducers to measure left ventricular anteroposterior diameter and micromanometers to measure transmural left ventricular pressure. Ventricular volumes were varied with transient vena caval occlusions in the awake state and following general anesthesia with halothane at 1% and 2% end-tidal concentrations. Ventricular contractility was assessed by the slope of the end-systolic pressure-diameter relationship (EES). Following normalization of end-diastolic diameters with a Lagrangian strain definition (E), diastolic compliance was assessed by fitting end-diastolic pressure-strain data to the exponential: P = alpha (e beta E -1), where alpha and beta are nonlinear elastic coefficients. Halothane was found to produce a significant, dose-dependent decrease in EES from 10.6 +/- 0.6 control to 6.7 +/- 0.4 at 1% halothane and 4.2 +/- 0.5 at 2% halothane (p less than 0.05, control versus both 1% and 2% halothane). Furthermore, halothane at the concentrations studied did not significantly alter alpha and beta nor significantly shift the exponential end-diastolic pressure-strain curve from control. These data indicate that halothane produces a direct, severe depression of left ventricular contractility without primarily altering the diastolic mechanical properties of the myocardium.

Dynamic ventricular interaction in the conscious dog.

In nine conscious, chronically instrumented dogs, ultrasonic dimension transducers measured left ventricular anterior-posterior and septal-free wall minor axis and major axis diameters. Matched micromanometers measured right and left ventricular transmural and transeptal pressures. Ventricular pressures and volumes were varied by inflation of implanted vena caval and pulmonary artery occluders, and the functional significance of the two types of ventricular interaction, i.e., direct and series, was determined. The left ventricle was represented by a modified ellipsoidal geometry. Left ventricular stroke volume calculated from the dimension data correlated well with that measured directly from ascending aortic electromagnetic flow probes during all interventions (r greater than or equal to 0.96). Partial pulmonary artery occlusion significantly increased right ventricular diastolic and systolic pressures as compared to values obtained during control and venal caval occlusion. During pulmonary artery occlusion, latitudinal septal eccentricity was increased throughout the cardiac cycle compared to control and vena caval occlusion (P less than 0.05), indicating leftward interventricular septal shifting and significant alteration of left ventricular shape. The normalized diastolic pressure-volume curve was shifted to the left with pulmonary artery occlusion compared to control and indicated a decrease in left ventricular chamber compliance. However, when selected cardiac cycles with similar end-diastolic volumes from vena caval and pulmonary artery occlusions were compared, parameters of left ventricular systolic function (stroke volume, percent systolic shortening, peak aortic blood flow, peak left ventricular pressure, and its first derivative) remained relatively constant. These data suggest that mean myocardial fiber length is the major preload determinant of left ventricular systolic function independent of chamber pressure and shape, and that direct ventricular interaction mediated by interventricular septal shifting has minimal effects on systolic myocardial performance in this model. Thus, series ventricular interaction during acute imbalances in biventricular loading, where the output of the right ventricle determines the input of the left, seems to be far more important than direct interaction to the regulation of overall cardiac function.

The role of right ventricular systolic dysfunction and elevated intrapericardial pressure in the genesis of low output in experimental right ventricular infarction.

To elucidate the pathophysiology of severe right ventricular infarction (RVI), isolated RVI was produced in 15 dogs with the pericardium intact or open. After RVI in dogs with the pericardium intact, RV systolic pressure decreased by 27%, aortic pressure by 29% and cardiac output by 34%. RV transmural pressure, RV end-diastolic size and intrapericardial pressure increased, left ventricular transmural pressure and end-diastolic size decreased and the diastolic pressures equalized. Pericardiotomy after RVI resulted in increased ventricular transmural pressures and diastolic size, improved cardiac output and resolution of equalized diastolic pressures. RVI in dogs with the pericardium open resulted in similar changes, but of lesser magnitude and without equalization of diastolic pressures. These results indicate that reduced left ventricular preload due to impaired RV systolic function contributes to low cardiac output in RVI. Elevated intra-pericardial pressure further reduced left ventricular preload and produces equal diastolic pressures.

The deformational characteristics of the left ventricle in the conscious dog.

We studied left ventricular minor and major axis diameters and equatorial wall thickness in eleven conscious dogs with chronically implanted pulse-transit ultrasonic dimension transducers. Left ventricular transmural pressure was measured with micromanometers. Left ventricular volume was varied by inflation of implanted vena caval or aortic occluders. The geometry of the left ventricle was represented as a three-dimensioal ellipsoidal shell. Left ventricular eccentricity was found to be a linear function of ventricular volume during both diastole and ejection. However, the relationship was not the same for diastole and ejection, and during diastole the left ventricle was mre spherical at large volumes and more elliptical at small volumes than during ejection. The rearrangements in geometry observed during isovolumic contraction appeared to be transitional stages from the diastolic to the ejection-phase relationship. Thus, during isovolumic contraction, the left ventricle became more elliptical at large volumes and more spherical at small volumes. These relationships were not altered significantly by increased afterload or inotropic interventions. We also observed that the diastolic deformation of the ventricular chamber occurred in a set and predictable manner that seemed to be determined by the three-dimensional mechanical properties of the myocardium. The geometric inter-relationships of the ventricular wall determined the relationship between diastolic transmural pressure and mural stress. These findings probably reflect basic structural characteristics of the myocardium and provide a convenient method for quantitatively representing the dynamic geometry of the left ventricle.

Effect of negative intrathoracic pressure on left ventricular outflow tract obstruction in muscular subaortic stenosis.

To study the effect of respiration and negative intrathoracic pressure on the left ventricular outflow tract gradient in patients with muscular subaortic stenosis, we studied nine patients using various respiratory maneuvers at the time of cardiac catheterization. Deep inspiration decreased the left ventricular outflow tract gradient from 60 +/- 11 to 34 +/- 6 mm Hg (p less than 0.01) and decreased the left ventricular ejection time (corrected for heart rate) from 0.42 +/- 0.01 to 0.38 +/- 0.01 second (p less than 0.001). The Müller maneuver decreased the left ventricular outflow tract gradient from 69 +/- 13 to 7 +/- 3 mm Hg (p less than 0.001) and decreased the corrected left ventricular ejection time from 0.42 +/- 0.02 to 0.24 +/- 0.01 second (p less than 0.01). In keeping with this amelioration of left ventricular outflow tract obstruction, echocardiography showed a reduction or abolition of the systolic anterior motion of the anterior mitral leaflet, and auscultatory and phonocardiographic studies revealed a decrease or abolition of the apical systolic murmur. These findings indicate that negative intrathoracic pressure reduced the left ventricular outflow tract gradient in muscular subaortic stenosis. We believe that negative intrathoracic pressure produced these changes by increasing left ventricular afterload through an increase in left ventricular transmural pressure, resulting in a decrease in the left ventricular outflow tract obstruction. These observations provide an explanation for the decrease in pressure gradient that occurs on inspiration in patients with muscular subaortic stenosis.

Positive end-expiratory pressure shifts left ventricular diastolic pressure-area curves.

Positive end-expiratory pressure (PEEP) ventilation is frequently associated with reduction in cardiac output despite unchanged transmural left ventricular (LV) end-diastolic pressure. These findings have been interpreted to indicate decreased contractility, but could also be explained by altered LV diastolic pressure-volume characteristics. To study this possibility, radiopaque markers were inserted into a plane of the LV in nine dogs. Transmural pressure (LV-pericardial) was synchronized with LV area during ventilation with zero end-expiratory pressure and with 15 cmH2O PEEP. Mean polynomial curves derived from the diastolic pressure-area data demonstrated that PEEP shifted the curves upward so that a given diastolic area was associated with a higher transmural LV pressure (P less than 0.0001). PEEP decreased end-diastolic area and stroke area, both of which were normalized with dextran volume expansion. Restoration of stroke area by normalizing end-diastolic area with volume expansion suggests the initial changes with PEEP were due to a decrease in preload rather than in contractility.