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Biomedical subjects

J W Covell

Publications and source records attributed to J W Covell.

At least 19 recordsLinked to original sources

Transmural distribution of myocardial tissue growth induced by volume-overload hypertrophy in the dog.

BACKGROUND: Although chronic volume overload is thought to induce uniform cardiac enlargement, the stimulus for tissue growth has not been defined. Changes in diastolic and systolic stress or strain have been proposed as mechanical factors that may stimulate hypertrophy. Since there are thought to be transmural variations in these stresses and strains, three-dimensional patterns of myocardial tissue growth may provide insight into the role of these factors. METHODS AND RESULTS: To assess the transmural variation in tissue growth after volume overload, the configurations of three columns of four to six gold beads (1-mm diameter) implanted in the left ventricular anterior free wall were recorded in five dogs before and after cardiac enlargement induced by creating a systemic arteriovenous fistula. Data were obtained with end-diastolic pressures adjusted to the same level in the control and hypertrophic states. End-diastolic wall thickness remained constant, whereas left ventricular diameter increased. Small increases in transmural systolic strain were seen. The volumes defined by four beads (a tetrahedron) at end diastole showed increases in myocardial mass of 20-27% after 3.6 (mean) weeks of hypertrophy and were uniform across the wall of the left ventricle. The edges of single bilinear-quadratic finite elements were fitted to the three columns of the bead set at end diastole in control and at end diastole after hypertrophy at equal end-diastolic pressures. Thus, continuous transmural strain distribution were obtained at the hypertrophic state with respect to the control state. The transmural distributions of these end-diastolic growth strains were uniform and positive for both the circumferential and longitudinal components measured in a cardiac coordinate system, with small radial growth strain indicating that growth was predominantly parallel to the epicardial tangent plane. Moreover, when strains were transformed (rotated) to fiber coordinates, in-plane fiber and cross-fiber growth strains were both positive at all locations across the wall and approximately equal in magnitude, indicating considerable growth in the cross-fiber direction. CONCLUSIONS: These results indicate that the stimulus for volume-overload hypertrophy may be constant across the wall and that substantial cross-fiber growth occurs during volume-overload hypertrophy.

Animals

Transmural myocardial deformation in the ischemic canine left ventricle.

The myocardium is a complex three-dimensional structure consisting of myocytes interconnected by a dense collagen weave that courses in different directions. Regional ischemia can be expected to produce complex changes in ventricular deformation. In the present study, we examined the effects of ischemia on two- and three-dimensional finite strains during acute transmural myocardial ischemia in 13 open-chest anesthetized dogs. In contrast to systolic deformation observed during the control period in which circumferential shortening exceeded longitudinal shortening, our results indicate that after 5 minutes of acute ischemia, end-systolic in-plane lengthening across the left ventricular wall occurs in approximately equal amounts in the circumferential and longitudinal directions. Along with these changes in extensional strains, there were significant negative transverse shearing deformations during ischemia. Myocardial ischemia also resulted in a loss of the normal end-systolic transmural gradients of shortening and thickening. Three-dimensional end-diastolic strains indicate that the left ventricular wall undergoes a significant passive reconfiguration that varies transmurally with lengthening in the epicardial tangent plane and wall thinning increasing from the epicardium toward the endocardium. The large systolic changes in shearing deformations with ischemia could potentially influence collateral blood flow and certainly indicate that uniaxial measurements of deformation in the ischemic myocardium, which do not account for shearing deformation, are incomplete and must be interpreted with caution. Moreover, normal transmural systolic gradients in deformation, which would be anticipated on geometric grounds, are lost during ischemia, implying that the material properties of ischemic tissue or the loading conditions imposed on the ischemic region by partially impaired adjacent myocardium vary transmurally.

Animals

Skeletal muscle deformation in the lateral muscle of the intact rainbow trout Oncorhynchus mykiss during fast start maneuvers.

Although there is an extensive body of information on the kinematics of the fast start response in teleosts, there is little information on the deformation of the skeletal muscle which produces the changes in body position during a fast start. This study presents preliminary information on the determination of skeletal muscle deformation with implanted ultrasonic dimension gauges in the intact fish during startle behavior. Deformation was measured in the lateral epaxial musculature of the rainbow trout Oncorhynchus mykiss during stage one of fast starts. The results show that ultrasound transit time dimension gauges can be implanted in the skeletal muscle of rainbow trout with minimum trauma and used to record local deformation along the length of the fish. Measurements remained stable over 4-8 h of implantation. Preliminary results show that: (1) muscle at different positions along the fish reaches its minimum length (average 9.6% shortening) at approximately the same time and coincident with the end of stage one of the fast start response; (2) the onset of concave curvature of the entire fish precedes the onset of local shortening at more caudal sites; (3) muscle on the convex side of a bend lengthens while muscle on the concave side shortens, and the two deformations follow a similar time course. These results indicate an asynchronous onset of skeletal muscle contraction in fast starts and support the hypothesis that local skeletal muscle deformation is transmitted caudally through skeletal or other structures.

Animals

Fiber orientation in hypertrophied canine left ventricle.

Myocardial fiber orientation was examined in transmural specimens obtained at the maximum diameter of the left ventricle from five dogs with pressure-overload hypertrophy produced by aortic stenosis, six dogs with volume-overload hypertrophy due to an arteriovenous fistula, and six exercise-hypertrophied greyhounds trained for racing. Hearts arrested in diastole were fixed in situ while the operating end-diastolic pressure was maintained. Fiber orientation changed smoothly from about +60 degrees (with respect to the equator) at the endocardium to about -69 degrees at the epicardium. The majority of fibers near the midwall were oriented circumferentially. These findings are quite similar to those previously reported for normal dogs. In comparison to normals, the left ventricles from dogs with pressure-overload had an increase in longitudinally oriented fibers, i.e. fiber angles between -67.5 degrees and -90 degrees and between +67.5 degrees and +90 degrees; these fibers comprised 10.4 +/- 1.8% of the total fibers in dogs with aortic stenosis vs. 2.9 +/- 1.8% of total fibers in normal dogs (P less than 0.001). Neither the dogs with volume-overload hypertrophy nor exercise-trained animals were significantly different from normals.

Animals

Left ventricular function in exercise-induced hypertrophy in dogs.

Indexes of left ventricular function and diastolic compliance were studied in 10 awake exercise-trained greyhounds with left ventricular hypertrophy. Mean left ventricular to body weight ratio and mean myocardial cell diameter were significantly greater than in normal dogs (8.73 +/- 2.7 [standard error of the mean] versus 4.63 +/- 0.24 g/kg, P less than 0.01; and 18.3 +/- 0.67 versus 12.5 +/- 0.71 mu, P less than 0.01, respectively). In awake resting animals, 7 to 50 days after implantation of a high fidelity micromanometer and sonomicrometer crystals, left ventricular contractility indexes were similar to those measured previously in normal dogs (maximal derivative of left ventricular pressure [dP/dt] 3,800 +/- 250 versus 3,810 +/- 330 mm Hg/sec, difference not significant; and mean rate of circumferential fiber shortening 1.54 +/- 0.12 versus 1.43 +/- 0.12 sec-1, difference not significant). During volume loading sufficient to produce a left ventricular end-diastolic pressure of 20 mm Hg, changes in contractility indexes were similar to those in normal dogs; however, heart rate increased significantly (74 percent, P less than 0.005) in the trained greyhounds but not in normal dogs. Left ventricular diastolic stiffness did not differ from normal (51.6 +/- 3.0 versus 45.9 +/- 5.9 mm Hg/cm, P less than 0.01). These findings suggest that left ventricular function in exercise-induced left ventricular hypertrophy is substantially normal.

Animals

Comparison of left ventricular free wall and septal diastolic compliance in the dog.

Septal to free wall dimensions are frequently employed for the analysis of diastolic compliance. However, the diastolic properties of these anatomically distinct regions of left ventricle are not well characterized. Regional compliance was studied in eight open-chest anesthetized dogs. Pairs of 2-mm-diameter piezoelectric crystals were implanted in the left ventricular free wall or septum 1.38 +/- 0.06 cm apart at a midwall location 58% +/- 1.9 of the left ventricular endocardial-epicardial or left ventricular endocardial-right ventricular endocardial distance. Left ventricular end-diastolic pressure was increased from an average of 8.1-21.0 mmHg, with a resulting average maximum end-diastolic strain of 11% (end-diastolic (ED) segment length/control ED length). Regional stiffness was assessed at all sites based on the relationship between left ventricular end-diastolic pressure and regional strain. Neither strain nor calculated stiffness coefficients differed significantly among the three sites. Septal transmural pressure (left ventricular end-diastolic pressure--right ventricular end-diastolic pressure) was nearly constant as left ventricular end-diastolic pressure increased during volume infusion and thus did not account for the observed septal strain.

Animals

Alteration in heart rate response to hemorrhage in conscious dogs with volume overload.

The heart rate response to hemorrhage was studied in conscious dogs before and up to 2 mo after the establishment of volume overload due to systemic arteriovenous (a-v) fistulas. Before a-v fistula, heart rate increased markedly during hemorrhage. When hemorrhage was preceded by dextran infusion, bleeding resulted in a gradual reduction in heart rate. The a-v fistula caused marked increases in resting heart rate, central venous pressure, pulse pressure, and blood volume. During hemorrhage, heart rate initially remained constant, but then declined abruptly from the resting value of 121 +/- 3.7 beats/min to a nadir of 89 +/- 6.5 beats/min (P less than 0.01). Although mean arterial pressure decreased markedly, there was no significant change in pulse pressure, and central venous pressure tended to stabilize with the heart rate decline. The abrupt heart rate decline was prevented by atropine but unaltered by propranolol. The response was observed as early as 5 days after a-v fistula. We conclude that an alteration in the heart rate response to hemorrhage appears early during volume overload. This alteration appears to be reflex in nature and to be mediated by the parasympathetic nervous system.

Animals

Regional myocardial function and dimensions early and late after myocardial infarction in the unanesthetized dog.

Pairs of ultrasonic dimension gauges and a micromanometer implanted in the subendocardium of the left ventricles of unanesthetized dogs were used to analyze serial changes in hemodynamic status and segmental function for up to 4 weeks after permanent circumflex coronary artery occlusion. Regional function was studied in control segments and in segments identified as marginal (hypokinetic) and ischemic. In three dogs, after transient regional dysfunction, no myocardial infarction developed, whereas in five dogs regional dysfunction at 3 hours after occlusion was followed by the development of persistent dysfunction and infarction. Left ventricular end-diastolic segment length (EDL) changes over time; EDL of the control segments increased progressively, but in marginal segments EDL was 12% below control and in the ischemic segments 30% below control by 4 weeks. Progressive increases in percent active shortening occurred in control segments; but holosystolic bulging was replaced by akinesia in ischemic segments, and persistent reduction in shortening was present in marginal segments at 4 weeks. Correlations were found between percent scar and reductions in percent shortening, EDL, and the ratio of change in diastolic length to change in diastolic pressure. These methods have detected hyperfunction in normal regions and variable segmental loss of contractile function, together with reduction of subendocardial dimensions and changes that may reflect decreased diastolic compliance in ischemic regions. We conclude that this model for the conscious animals may be useful for studying the influence of therapy on the extent of myocardial damage after experimental coronary occlusion.

Animals

Effects of heparin in large doses on the extent of myocardial ischemia after acute coronary occlusion in the dog.

Heparin in large doses significantly improved epicardial electrocardiographic findings and preserved myocardial tissue and creatine phosphokinase (CPK) after coronary ligation in the dog. Epicardial S-T segment elevation 15 minutes after occlusion was lowered 84% (from 64.5 + 8.5 [standard error of the mean] to 10.4 +/- 3.0 mv) by heparin infusions of 60,000 units. Myocardial creatine phosphokinase depletion was reduced from 39 to 24% at comparable levels of S-T segment elevation. Histologic evidence of necrosis decreased 32%. It is concluded that heparin can reduce the extent of ischemic injury after acute coronary occlusion in the dog. These results may lend insight into the factors responsible for ischemic injury.

Animals

Effect of intramyocardial pressure on the phasic flow in the intraventricular septal artery.

Phasic flow in the intraventricular septal artery (SA) was measured by an electromagnetic flowmeter in anaesthetized dogs. The ratio of systolic to diastolic flow was less in the intramyocardial artery than in an epicardial (circumflex) artery. The SA systolic to diastolic ratio was further depressed when elevations in intramyocardial pressure were produced. These studies lend insight into the relationships between intramyocardial pressure and coronary arterial flow.

Animals

Regional shortening patterns in canine right ventricle.

The right ventricular outflow tract (OT) is a functionally distinct area of the right ventricle. However, there is little information on the contrdingly, inflow tract (IT) and OT chords and right ventricular free wall segmental changes were measured with implanted ultrasound crystals. The timing and extent of shortening of IT and OT chords and free wall segments were determined both at rest and after stellate ganglion stimulation. At rest, IT chord shortening began 51 ms before OT shortening. OT expansion occurred during this period. IT chord shortening began 51 ms before OT shortening. OT expansion occurred during this period. IT chord shortening was 38% while OT shortening was 34%. In contrast, OT segments did not show systolic expansion. IT segment shortening was 13% while OT shortening was 21%. With stellate stimulation, IT-OT gradients of 15-25 mmHg developed. The lag between IT and OT shortening decreased to 30 ms and segmental shortening increased. We conclude that the OT is a physiologically distinct region which contracts later and remains contracted longer than the IT. Both septal and free wall movements contribute to these changes.

Animals

A comparison of the active stiffness of fetal and adult cardiac muscle.

This report described the in vitro analysis of the series elasticity of ventricular myocardium isolated from five fetal lambs and six adult sheep. Active compliance measurements were obtained by quick releases utilizing a closed loop servosystem and electromagnetic positioning device to control cardiac muscle length or tension. Right ventricular moderator bands were obtained from five fetuses (average 139 days of gestation, term=147 days), and compared with two adult moderator bands and four adult right ventricular trabeculae carneae. After correction for equipment coupling the experimental load extension data were fit to an exponential expression by a least squares technique: strain=1/b ln (1 + stress/a). When fetal and adult data were compared, no age-related differences in the constants were observed (a=0.185 +/- 0.062 SE (fetal) and 0.159 +/- 0.03 g/mm2 (adult); b=40.4 +/- 5.2 (fetal) and 43.1 +/- 5.2 (adult); and ab=7.39 +/-2.34 (fetal) and 5.27 +/- .99 (adult). However, significant variation existed in the histologically determined amount of contractile tissue present in muscle samples from both fetus (57-85%, average=74.0 +/- 4.9) and adult (64-94%, average=82.3 +/- 5.3). Wihtout regard to age, a signficant correlation was found between the b stiffness constant and the amount of contractile mass present in cardiac muscle. Thus, it is concluded that there is no age-related difference in the stiffness of fetal and adult ventricular muscle. However, there is a significant relationship between active compliance and true muscle mass.

Age Factors