P A McHale

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.

Evaluation of Several Geometric Models for Estimation of Left Ventricular Circumferential Wall Stress

Phasic left ventricular wall force and wall thickness were monitored with appropriate transducers to provide a direct measurement of circumferential wall stress in open-chest dogs. Left ventricular pressure and measurements of chamber geometry were used to estimate the wall stress using several geometric models. During the initial control period, peak and end-ejection measured wall stresses were 207 ± 19 and 104 ± 13 g/cm 2 , respectively. The best estimates of these values were 198 ± 18 and 117 ± 11 g/cm 2 obtained from a modified thin-wall ellipse formula in which the midwall rather than the endocardial radius was used. Wide variations in hemodynamic conditions were produced with intravenous infusions of nitroglycerin, phenylephrine, and isoproterenol. Comparison of directly measured and estimated values during all control periods and during the response to these interventions showed that both the modified thin-wall ellipse and a thick-wall ellipse were generally accurate predictors of the measured wall stress. All other models tended to underestimate measured stress. The sensitivity of the estimated wall stress computed by the models to geometric measurement errors was also evaluated. A thick-wall sphere was the most sensitive to both circumferential length and wall thickness measurement errors, and a thick-wall ellipse was the least sensitive. All models examined were relatively insensitive to base-to-apex length measurement errors.

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 tranemural 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-dimensional 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 more 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.

Evaluation of several methods for computing stroke volume from central aortic pressure.

Six pulse-contour methods for estimating stroke volume from a single central aortic blood pressure were evaluated in 8 dogs and 17 patients. In the dogs, wide variations in stroke volume, measured with an electromagnetic flowmeter, were obtained by pacing the heart at various rates during a control period and during several pharmacologic interventions. Good correlations existed between measured stroke volume and most estimators when the data from each intervention were analyzed separately. However, regression analysis revealed considerable variation in the individual slopes and intercepts, and thus a poor correlation was obtained when all data for one dog were combined in a single analysis. Similar evaluations were carried out in two groups of patients in whom the pressure-gradient technique was used to measure stroke volume. In the group with minimal variations in hemodynamic status, the correlations between estimated and true stroke volume were reasonably good. In the patients having a wide range of hemodynamic conditions, considerable variation in both slopes and intercepts was observed, and the combined correlation coefficients were generally poor. Although pulse contour methods of estimating stroke volume may work reasonably well over a range of stroke volumes when the variation is induced by a single perturbing agent, none of these methods perform adequately when the variation is induced by multiple perturbing agents; thus their clinical usefulness is markedly limited.

An analysis of the pulsatile hemodynamic responses of the pulmonary circulation to acute and chronic pulmonary venous hypertension in the awake dog.

In this study we measured high fidelity pulsatile pressure and flow waveforms at the inlet to the pulmonary vascular bed to assess the differences in adaptation to acute and chronic pulmonary venous hypertension in awake dogs. Acute elevations in left atrial pressure (Pia) were effected by inflation of left atrial balloons, while chronic elevations were accomplished by placement of aorta to left atrial shunts. Pulmonary artery hydraulic impedance was calculated and analysis of these data revealed marked differences between the responses to acute and chronic elevations of left atrial pressure. The acutely stressed dogs (n = 12) had significantly decreased pulmonary vascular resistance (when Pla= 16.9 ± 1.0 mm Hg, PVR = 212 ± 57 dynes sec/cm5; when Pla= 28.6 ± 1.4 mm Hg, PVR = 18 ± 115 dynes sec/cm6; control Pi. = 6.1 ± 1.5 mm Hg, and PVR = 355 ± 69 dynes sec/cm5) and normal characteristic impedances (Zo) (210 ± 36, 227 ± 39, 178 ± 14 dynes sec/cm5, respectively), indicating recruitment of arteriolar-capillary perfusion density and no change in proximal pulmonary arterial physical properties. The chronic pulmonary venous hypertension group (n = 11) retained normal PVR (496 ± 30 dynes sec/cm5) but demonstrated a markedly higher characteristic impedance, Zo = 361 ± 11 dynes sec/cm5(P < 0.001). This indicated a measurably different and extremely potent effect of chronic venous hypertension on the physical properties of the pulmonary vessels with an apparently increased arterial stiffness correlating with a 4-fold increase in Youngs elastic modulus. These changes were not reversed by α-adrenergic blockade or acute lowering of left atrial pressures. Circ Res 47: 902-910, 1980

Pulmonary vascular impedance analysis of adaptation to chronically elevated blood flow in the awake dog.

Pulsatile pulmonary hemodynamics were analyzed in a chronic awake canine high flow model. Standard mean flow and pulsatile flow hemodynamics were measured and alterations in the proximal pulmonary vascular physical properties were quantified by the characteristic impedance (Z«). Pulmonary vascular resistance (PVR), which assesses arteriolar-capillary recruitment of perfusing radius and measures a more distal pulmonary vascular response to changing flows, also was calculated. Twelve control dogs were studied and had mean Qp. (pulmonary blood flow) - 2.02 ± 0.15 liters/min, Z, - 193 ± 20 dyne sec cm−5 and PVR - 416 ± 32 dyne sec cm−5. Ten dogs were studied awake 20 weeks after creation of bilateral arteriovenous fistulae. Five of these shunted dogs, designated group A, developed Qp. = 3-4 liters/min (mean » 3.80 ± 0.09, P < 0.001 different from control group); the other five dogs (group B) developed Qp, - 4-8 liters/min (mean - 5.87 ± 0.16, P< 0.001). In group A, Z, = 143 ± 8 (P< 0.05) and PVR = 249 ± 8 (P< 0.10). In group B, Zo - 90 ± 5 (P< 0.005) and PVR - 126 ± 14 (P < 0.01). The total input power (potential and kinetic) was 125% above the controls for group A (P < 0.001) and 264% for group B (P < 0.001), but the mean energy components increased significantly more than did the pulsatile components. These data demonstrate a lower impedance to pulsatile flow during chronically elevated total flow which effects a reduction in both the work load of the right ventricle and the transmission of energy to the precapillary bed. Analysis of the alterations in characteristic impedance suggests a distinct proximal pulmonary vascular mechanism of decreased vessel stiffness (decreased elastic moduli) for adaptation to chronically elevated flow loads which is in addition to the two geometric alterations of proximal arterial dilation and distal vascular channel recruitment. Circ Res 45: 267-274, 1979

Evidence for myogenic vasomotor activity in the coronary circulation

T HAS BEEN KNOWN for many years that vascular smooth muscle will respond to the application of force by contracting. This myogenie response can be elicited by applying force and stretching an isolated strip of vascular smooth muscle or, in the case of blood vessels, by increasing the intravascular or transmural pressure. The definition of the myogenic response also includes the condition that occurs when vascular smooth muscle relaxes as the result of a decrease in applied force or intravascular pressure. This article will (1) briefly highlight the historical development of the concept of myogenitally mediated autoregulation, (2) describe the salient characteristics of myogenic activity in vascular smooth muscle, and (3) correlate these characteristics with the myogenic activity known to exist in both isolated and in situ vascular beds. The excellent review article by Johnson should be consulted for an in-depth presentation of these important topics.’ Having established the characteristics of myogenic activity, a description of our current studies related to the identification of brief myogenic activity in coronary vascular beds will be presented.

Hyperemic response of the coronary circulation to brief diastolic occlusion in the conscious dog.

This study was undertaken to determine whether coronary blood flow can be regulated in response to coronary arterial occlusions briefer than a single diastole. The possible involvement of metabolic vs. myogenic mechanisms in such regulation was investigated. Eleven conscious dogs with experimentally produced complete heart block, chronically implanted electromagnetic flow probes, and pneumatic occluders on the left circumflex coronary artery were studied. Diastolic coronary occlusions lasting 100 to 400 msec were performed at paced heart rates of 40, 60, and 120 beats/min. At a heart rate of 60 beats/min, a 200-msec occlusion was sufficiently long to produce a significant reactive hyperemic response; 400-msec occlusions resulted in larger responses, while 100-msec occlusions did not generate a discernible response. The onset of reactive hyperemia was delayed from the end of the occlusion until the first post-occlusion systole. The length of this delay could be altered by changing the heart rate or occlusion duration, but no significant response was detected before the first post- occlusion systole. This characteristic of the data is more consistent with a metabolic than with a myogenic mechanism. If the response is metabolic, the data demonstrate that autoregulation of coronary flow by such a mechanism is very rapid, occurring during the first systole in which a flow deficit is detected by the myocardium.