C E Arentzen

The three-dimensional dynamic geometry of the left ventricle in the conscious dog.

The dynamic geometry of the left ventricle was assessed with the use of chronically implanted pulse-transit ultrasonic dimension transducers. The orientation of the transducers allowed the measurement of left ventricular minor and major axis diameters and equatorial wall thickness in the conscious dog. The left ventricle was modeled as a three-dimensional, prolate ellipsoidal shell. Left ventricular and pleural pressures were measured with high fidelity micTomanometers. Aortic blood flow was obtained with electromagnetic flow probes. To test the assumptions inherent in this technique, left ventricular mass, internal volume, stroke volume, and peak aortic flow were computed from the dimension data and compared to directly measured values. Correlation coefficients of 0.95 or greater were obtained for each of these comparisons. In addition, the calculated left ventricular mass was constant to within ±6% of the mean value throughout the cardiac cycle. We found that the dynamic contraction pattern of the left ventricle was dependent on the physiological state of the dog. Furthermore, in the conscious state, shortening of the minor axis diameter, lengthening of the major axis diameter, and slight thickening or thinning of the wall were noted during isovolumic contraction (isovolumic ellipticalization pattern). In the open-chested, anesthetized state, however, marked rearrangements in geometry were observed during isovolumic contraction manifested by lengthening of the minor axis diameter, shortening of the major axis diameter, and significant thickening of the wall (isovolumic sphericalization pattern). We also observed that left ventricular volume was significantly diminished in the open-chested state. The isovolumic contraction pattern in open-chested dogs could be changed from sphericalization to ellipticalization by increasing end-diastolic volume with the infusion of saline. During a vena caval occlusion in the conscious state, the contraction pattern changed from isovolumic ellipticalization to isovolumic sphericalization as the end-diastolic volume decreased. Thus, the exact pattern of left ventricular contraction was found to be a function of left ventricular volume.

Viscoelastic properties of the diastolic left ventricle in the conscious dog.

The mechanical properties of the normal left ventricular wall during diastole were studied in 15 chronically instrumented, conscious dogs. Left ventricular minor and major axis diameters and equatorial wall thickness were measured with implanted pulse-transit ultrasonic dimension transducers. Left ventricular and pleural pressures were measured with high fidelity micromanometers. Circumferential mural stress was calculated by using an ellipsoidal shell theory; circumferential strain was calculated by using a natural strain definition. The static elastic properties of the myocardium were estimated by fitting the stress-strain values at the points of diastasis during a vena caval occlusion to an exponential function. A modified creep test was used to evaluate the series viscous properties of the myocardium. Acute increases in systolic and diastolic loading were produced by inflating implanted aortic occluders for 15 minutes in five dogs. In these dogs, the static stress-strain curves were not altered significantly after this period of pressure loading, indicating tbat short-term series viscous properties are negligible. Parallel viscous properties were evaluated in 10 dogs by means of the variable rate stretch test of dynamic diastolic filling. A viscoelastic model incorporating a parallel viscous element fit the dynamic stress-strain data better and predicted the static elastic properties more accurately than a simple exponential model. Thus, the mechanical characteristics of the diastolic left ventricle can be represented most precisely by a viscoelastic model that includes a parallel viscous element.

The effects of airway pressure on cardiac function in intact dogs and man.

Ventilation with positive end-expiratory pressure (PEEP) is associated with reduced cardiac output, but the mechanisms involved are controversial. Possible explanations include increased intrathoracic pressure, reflex changes in myocardial inotropism, pulmonary vascular obstruction and abnormal ventricular interaction. Three types of conscious canine preparations were developed to examine simultaneously each of these factors during ventilation with PEEP. In addition, similar measurements were obtained in patients after cardiac surgical procedures and compared with the results of animal experiments. The primary cause of reduced cardiac output during PEEP appeared to be a diminished end-diastolic volume of the left ventricle, and this appeared to be the result of elevated intrathoracic pressure and increased impedance to blood flow through the lungs. Abnormal interventricular septal shifting and reflex autonomic alterations did not appear to be significant in the normal cardiovascular system. These data provide insight into the cardiac effects of PEEP and emphasize the importance of simultaneous quantification of biventricular performance when assessing cardiopulmonary function.

Alterations in left ventricular three-dimensional dynamic geometry and systolic function during acute right ventricular hypertension in the conscious dog.

Fifteen chronically instrumented, conscious dogs were studied to determine whether, in the intact circulation, mechanical interactions dictated by the anatomic contiguity of the two ventricles significantly alter left ventricular (LV) dynamic geometry and systolic function during acute right ventricular (RV) hypertension. The three-dimensional geometry of the left ventricle was monitored with three pairs of ultrasonic dimension transducers; ventricular pressures were measured with micromanometers. Data collected during pulmonary artery constriction (RV pressure 68 ± 8/7 ± 4 mm Hg) were compared with control data collected at matched heart rates (RV pressure 32 ± 8/4 ± 4mm Hg). During pulmonary artery constriction, mean calculated LV end-diastolic volumes decreased from 69.2 ± 20.0 to 56.2 ± 21.3 cm3 (p s 0.05). Mean systolic stroke volume decreased from 20.6 5.5 to 14.0 6.3 cm3 (p % 0.05). These changes were entirely accounted for by alterations in the behavior of the LV septal-free wall minor axis and rearrangements in LVequatorial geometry. When the pulmonary artery was constricted, elongation of the septal-free wall axis occurred during isovolumic systole and was accompanied by a reciprocal decrease in anterior-posterior dimension. Most of the decrease in septal-free wall dimension occurred during relaxation and early diastole rather than during ejection. Mean septal-free wall end-diastolic dimension decreased from 5.45 ± 0.69 to 4.90 ± 0.75 cm (p S 0.05). The mean systolic decrease in septal-free wall dimension fell from 0.36 ± 0.18 to 0.14 ± 0.22 cm (p S 0.05). The end-diastolic dimensions and systolic shortening of the LV anterior-posterior minor axis and base-apex major axis were not significantly altered by pulmonary artery constriction. These findings suggest that during acute RV hypertension, impairment of LV systolic function and rearrangements in LV dynamic geometry are primarily the result of the anatomic contiguity of the two ventricles.

Effects of global ischemia on the diastolic properties of the left ventricle in the conscious dog.

The alterations in regional diastolic mechanics that occur during regional myocardial ischemia (creep and increased myocardial stiffness) may be the result of interactions between the ischemic and surrounding nonischemic myocardium rather than the direct result of ischemia. Thus similar changes may not occur when the entire left ventricle is ischemic. Thus similar changes may not occur when the entire left ventricle is ischemic. To investigate this proposition, left ventricular diastolic mechanics were studied in seven chronically instrumented conscious dogs during global left ventricular ischemia. The anterior-posterior, septal-free wall, and base-apex axes of the left ventricle were measured with ultrasonic dimension transducers. Left and right ventricular pressures were measured with micromanometers. Myocardial blood flows were measured with left atrial injections of 15 microns radioactive microspheres. Global left ventricular ischemia was induced by hydraulic constriction of the left main coronary artery, which resulted in a 54% decrease in mean left ventricular subendocardial blood flow. Left ventricular volume, midwall circumference, and midwall circumferential stress were calculated from ellipsoidal shell theory. To construct pressure-strain and stress-strain relationships from diastolic data collected during vena caval occlusions, all measured and calculated dimensions were normalized to Lagrangian strains (fractional extension from unstressed dimension). During ischemia, creep (elongation of unstressed dimension) occurred in each of the three left ventricular axes. The mean unstressed dimension of the anterior-posterior axis increased from 5.39 +/- 0.53 to 5.85 +/- 0.50 cm ( p less than or equal to .05); the septal-free wall unstressed dimension increased from 5.11 +/- 0.53 to 5.72 +/- 0.80 cm (p less than or equal to .05); and the base-apex unstressed dimension increased from 7.04 +/- 0.61 to 7.25 +/- 0.65 cm (p less than or equal to .05). The relationship between diastolic midwall circumferential stress and strain shifted upward and to the left with ischemia, indicating that an increase in intrinsic myocardial stiffness had occurred. As a result of these mechanical alterations, there was a decrease in left ventricular chamber compliance that was manifested by a leftward shift of the diastolic pressure-volume strain relationship. Neither systolic bulging nor dysynchronous systolic shortening occurred in any of the three left ventricular spatial axes during ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)

Evaluation of the force-frequency relationship as a descriptor of the inotropic state of canine left ventricular myocardium.

The short-term force-frequency characteristics of canine left ventricular myocardium were examined in both isolated and intact preparations by briefly perturbing the frequency of contraction with early extrasystoles. The maximum rate of rise of isometric tension (Fmax) of the isolated trabeculae cameae was potentiated by the introduction of extrasystoles. The ratio of Fmax of potentiated to control beats (force-frequency ratio) was not altered significantly by a change in muscle length. However, exposure of the trabeculae to isoproterenol (10-7 m) significantly changed the force-frequency ratio obtained in response to a constant frequency perturbation. Similar experiments were performed on chronically instrumented conscious dogs. Left ventricular minor axis diameter was measured with implanted pulse-transit ultrasonic dimension transducers, and intracavitary pressure was measured with a high fidelity micromanometer. Atrial pacing was performed so that the end-diastolic diameters of the beats preceding and following the extrasystole could be made identical. Large increases in the maximum rate of rise of pressure (Pmax) were seen in the contraction after the extrasystoie. The ratio of Pmi of the potentiated beat to that of the control beat was not changed by a 9% increase in the end-dlastollc diameter, produced by saline infusion. Conversely, isoproterenol significantly altered this relationship in the same manner as in the isolated muscle. Thus, either in vitro or in situ, left ventricular myocardium exhibits large functional changes in response to brief perturbations in rate. The isoproterenol and length data indicate that the force-frequency ratio reflects frequency-dependent changes in the inotropic state, independent of changes in length.

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.

Force-frequency characteristics of the left ventricle in the conscious dog.

The early and late alterations in left ventricular function which follow a change in contraction frequency were assessed in 10 conscious dogs. Chronically implanted pulse-transit ultrasonic dimension transducers were wed to measure the dynamic geometry of the left ventricle and a high-fidelity micromanometer was employed to measmre left ventricular pressure. The heart was paced from the atrium and, after every 20th regular beat, an extrasystole and a postextrasystole were introduced into the basic pacing rhythm. The ratio of the maximum derivative of left ventricular pressure (Pmax) of the postextrasystolic beat to the Pmax of the control beat was used as a measure of the degree of postextrasystolic potentiation of ventricular function. This postextrasystolic ratio was found to be significantly influenced by the interval preceding the postextrasystolic beat; as this interval was increased, the end-diastolic volume and the Pmax of the postextrasystole also increased. When the end-diastolic geometry of the control and postextrasystolic beats were made identical, the postextrasystolic ratio reflected postextrasystolic potentiation of the inotropic state. The degree of postextrasystolic inotropic potentiation was found to be a direct linear function of the change in contraction frequency induced by the extrasystole (r 2= 0.97). Thus, end-diastolic geometry and the magnitude of the frequency perturbation must be carefully controlled when postextrasystolic potentiation is used to evaluate left ventricular function. In contrast to postextrasystolic potentiation, steady state changes in contraction frequency did not significantly alter Pmax (P > 0.20). However, significant decreases in end-diastolic volume were observed with increasing steady state heart rates (P < 0.0S). This decrease in end-diastolic volume may be partially responsible for the lack of potentiation of steady state Pmax after a sustained increase in contraction frequency.

Carcinoma of the Lung

The effective management of the patient with lung cancer appears to be based on four fundamental issues: diagnosis and histologic classification; staging of the cancer; a decision as to what form of therapy is indicated and whether or not surgery is part of the overall management; and evaluation of the patient’s ability to undergo a thoracic procedure. There are no dramatic new methods for diagnosis or treatment of lung cancer, and the most promising areas appear to be prevention and further understanding of the basic biologic relationship between tumor and host.

Contribution of Atrioventricular Synchrony to Left Ventricular Systolic Function in a Closed‐Chest Canine Model of Complete Heart Block: Implications for Single‐Chamber Rate‐Variable Cardiac Pacing

This study assessed the impact of atrioventricular (AV) synchrony on characteristics of left ventricular (LV) systolic function during ventricular pacing over a wide heart rate range in a conscious closed‐chest canine model of complete AV block. Ten healthy adult dogs underwent thoracotomy during which complete AV block was created by formaldehyde injection, and paired ultrasonic sonomicrometers were positioned on the LV anterior‐posterior minor axis. Following recovery from surgery, peak and end‐diastolic LV transmural pressure, maximum dP/dt, stroke work, end‐diastolic minor axis dimension, and maximum velocity of shortening, were quantitated at heart rates of 80, 100, 120, 140, and 160 beats per minute (bpm) during both ventricular pacing alone and AV sequential pacing with increasing AV intervals (0, 50, 100, 150, 200, 250, and 300 ms). Over the heart rate range tested, parameters of LV systolic function did not differ significantly during ventricular pacing with or without AV synchrony. For example, during ventricular pacing alone maximum LV dP/dt varied from 2110 ± 70 mmHg/s to 2463 ± 567 mmHg/s, a range essentially identical to that observed in the presence of AV synchrony. On the other hand, although the impact on LV performance of varying AV interval from 0 to 300 ms was small, differences tended to become more pronounced at higher pacing rates. At 80 bpm, neither stroke work nor maximum LV dP/dt were affected by change in AV interval, while at heart rates 120 bpm both stroke work and LV dP/dt tended to maximize at AV intervals of 50 and 100 ms and thereafter declined. Thus, findings in this study indicated that LV systolic function in the normal in situ heart is not adversely affected by absence of AV synchrony over a wide heart rate range.