Tricuspid valve leaflet strains in the beating ovine heart.

The tricuspid leaflets coapt during systole to facilitate proper valve function and, thus, ensure efficient transport of deoxygenated blood to the lungs. Between their open state and closed state, the leaflets undergo large deformations. Quantification of these deformations is important for our basic scientific understanding of tricuspid valve function and for diagnostic or prognostic purposes. To date, tricuspid valve leaflet strains have never been directly quantified in vivo. To fill this gap in our knowledge, we implanted four sonomicrometry crystals per tricuspid leaflet and six crystals along the tricuspid annulus in a total of five sheep. In the beating ovine hearts, we recorded crystal coordinates alongside hemodynamic data. Once recorded, we used a finite strain kinematic framework to compute the temporal evolutions of area strain, radial strain, and circumferential strain for each leaflet. We found that leaflet strains were larger in the anterior leaflet than the posterior and septal leaflets. Additionally, we found that radial strains were larger than circumferential strains. Area strains were as large as 97% in the anterior leaflet, 31% in the posterior leaflet, and 31% in the septal leaflet. These data suggest that tricuspid valve leaflet strains are significantly larger than those in the mitral valve. Should our findings be confirmed they could suggest either that the mechanobiological equilibrium of tricuspid valve resident cells is different than that of mitral valve resident cells or that the mechanotransductive apparatus between the two varies. Either phenomenon may have important implications for the development of tricuspid valve-specific surgical techniques and medical devices.

Three-dimensional geometric comparison of partial and complete flexible mitral annuloplasty rings.

BACKGROUND: It has previously been shown in sheep that mitral annular physiologic dynamics during the cardiac cycle are abolished by complete ring annuloplasty, but recent clinical studies suggest that flexible partial ring annuloplasty preserves normal mitral annular dynamics. METHODS: Eight radiopaque markers were sutured equidistantly around the mitral anulus in 3 groups of sheep: no-ring control animals (n = 16); animals with a flexible Tailor partial ring annuloplasty (n = 6; St Jude Medical, Inc, St Paul, Minn); and animals with a flexible Duran ring annuloplasty (n = 7; Medtronic, Inc, Minneapolis, Minn). After 7 to 10 days' recovery, 3-dimensional marker coordinates were measured by biplane cinefluoroscopy. Mitral annular area and folding (defined as displacement of the mitral anulus from a least-squares plane) and mitral annular septal-lateral and commissure-commissure dimensions were calculated from the 3-dimensional marker coordinates throughout the cardiac cycle every 17 ms. RESULTS: In the no-ring control group mitral annular area varied from 8.0 +/- 0.2 to 7.2 +/- 0.2 cm(2) (10% +/- 2%), and the septal-lateral and commissure-commissure dimensions varied from 27.7 +/- 0.4 to 25.9 +/- 0.4 mm (7% +/- 1%) and from 38.2 +/- 0.8 to 36.4 +/- 0.8 mm (5% +/- 1%), respectively (mean +/- standard error of the mean, P <.001 for all comparisons). In the Duran ring annuloplasty and Tailor partial ring annuloplasty groups, the anulus was fixed in size throughout the cardiac cycle (area = 4.8 +/- 0.1 and 5.3 +/- 0.3 cm(2), septal-lateral = 21.8 +/- 0.7 and 22.0 +/- 0.8 mm, and commissure-commissure = 27.7 +/- 0.7 and 31.2 +/- 1.7 mm). Mitral annular folding did not differ significantly between the control and Tailor partial ring annuloplasty groups but was dampened in the Duran ring annuloplasty group. CONCLUSIONS: Partial Tailor flexible ring annuloplasty fixed mitral annular area and dimensions throughout the cardiac cycle in sheep; however, it preserved physiologic mitral annular folding dynamics, which might be important in terms of long-term valve function and prevention of left ventricular outflow tract obstruction.

Experimental and clinical assessment of mitral annular area and dynamics: what are we actually measuring?

The mitral annulus is an essential, dynamic, and tightly coupled component of the mitral valve/left atrial/left ventricular complex that aids in effective and efficient valve closure and unimpeded left ventricular filling. Although the dynamic nature of mitral annular motion has been studied carefully for more than 30 years, accurate measurement of mitral annular area and motion continues to be a challenge for physiologists and clinicians alike. Roentgenographic ciné imaging of radiopaque markers, sonomicrometry, magnetic resonance imaging, and two-dimensional echocardiography have all been used to evaluate mitral annular area and dynamics, yet widely disparate measurements abound. Paradoxically, newer three-dimensional transesophageal echocardiographic findings may have added to this miasma. To explore the variability of these measurements, we reviewed our experimental data as well as clinical and experimental observations reported in the literature to clarify what we are actually measuring and perhaps explain the reported disagreement. The objective was to shed some light on the possible reasons for these discordant findings.

Edge-to-edge mitral repair: tension on the approximating suture and leaflet deformation during acute ischemic mitral regurgitation in the ovine heart.

BACKGROUND: Edge-to-edge approximation of the mitral valve leaflets (Alfieri procedure) is a novel surgical treatment for patients with ischemic mitral regurgitation (IMR). Long-term durability may be limited if abnormal mitral leaflet stresses result from this procedure. The aim of the current study was to measure Alfieri stitch tension (F(A)) and to explore its geometric determinants in an ovine model of acute IMR as a reflection of the mitral leaflet stresses imposed by the procedure. METHODS AND RESULTS: Eight sheep were studied immediately after surgical placement of (1) a force transducer interposed between sutures approximating the central leaflet edges and (2) radiopaque markers around the mitral annulus and leaflet edges. Computer-aided analysis of videofluorograms was used to obtained 3D marker coordinates. Simultaneous measurements of F(A), septal-lateral annular dimension (L(S-L)), leaflet edge separation (L(SEP)), anterior (L(AL)) and posterior (L(PL)) leaflet length, and hemodynamic variables were obtained at baseline (CTL) and during acute IMR (circumflex artery occlusion). F(A) was significantly elevated throughout the cardiac cycle during IMR compared with CTL, with maximum F(A) in diastole (0.26+/-0.05 versus 0.46+/-0.08 N, CTL versus IMR; P<0.05). Multivariable analysis revealed L(S-L) as the single independent predictor of maximum F(A) (P<0.001). Positive linear correlations were shown between values of F(A) and L(AL) and L(PL) (dependent variables). CONCLUSIONS: These experimental data demonstrate higher F(A) during IMR and cyclic changes in F(A) closely paralleling changes in L(S-L), eg, being greatest in diastole when the annulus is largest. Increased F(A) during IMR is probably indicative of successful therapeutic intent, but higher diastolic leaflet stresses resulting from persistent or progressive mitral annular dilatation may adversely affect repair durability. This indirectly implies that concomitant mitral ring annuloplasty should be added to the Alfieri repair.

Pathogenesis of mitral regurgitation in tachycardia-induced cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy is often associated with mitral regurgitation (MR), or so-called functional MR, the mechanism of which continues to be debated. We studied the valvular and ventricular 3D geometric perturbations associated with MR in an ovine model of tachycardia-induced cardiomyopathy (TIC). METHODS AND RESULTS: Nine sheep underwent myocardial marker implantation in the left ventricle (LV), mitral annulus, and mitral leaflets. After 5 to 8 days, the animals were studied with biplane videofluoroscopy (baseline), and mitral competence was assessed by transesophageal echocardiography. Rapid ventricular pacing (180 to 230 bpm) was subsequently initiated for 15+/-6 days until the development of TIC and MR, whereupon biplane videofluoroscopy and transesophageal echocardiography studies were repeated. LV volume was calculated from the epicardial marker array. Valve closure time was defined as the time after end diastole when the distance between leaflet edge markers reached its minimal plateau. TIC resulted in increased LV end-diastolic volume (P=0.001) and LV end-systolic volume (P=0.0001) and greater LV sphericity (P=0.02). MR increased significantly (grade 0.2+/-0.3 versus 2.2+/-0.9, P=0.0001), as did mitral annulus area (817+/-146 versus 1100+/-161 mm(2), P=0.0001) and mitral annulus septal-lateral diameter (28.2+/-3.5 versus 35.1+/-2.6 mm, P=0.0001). Time of valve closure (70+/-18 versus 87+/-14 ms, P=0.23) and angular displacement of both the anterior (29+/-5 degrees versus 27+/-3 degrees, P=0.3) and posterior (55+/-15 degrees versus 44+/-11 degrees, P=0.13) leaflet edges relative to the mitral annulus after valve closure did not change, but leaflet edge separation after closure increased (5.2+/-0.9 versus 6.8+/-1.2 mm, P=0.019). CONCLUSIONS: MR in TIC resulted from decreased leaflet coaptation secondary to annular dilatation in the septal-lateral direction. These data support the use of annular reduction procedures, such as rigid, complete ring annuloplasty, to address functional MR in patients with dilated cardiomyopathy.

Influence of anterior mitral leaflet second-order chordae on leaflet dynamics and valve competence.

BACKGROUND: Chordal transposition is used in mitral valve repair, yet the effects of second-order chord transection on valve function have not been extensively studied. We evaluated leaflet coaptation, three-dimensional anterior mitral valve leaflet shape, and valve competence after cutting anterior second-order chordae. METHODS: In 8 sheep radiopaque markers were affixed to the left ventricle, mitral annulus, and leaflets. Animals were studied immediately with biplane videofluoroscopy and echocardiography before (Control) and after (Cut2) severing two anterior second-order "strut" chordae. Leaflet coaptation was assessed as separation between leaflet edge markers in the midleaflet and near each commissure (anterior commissure, posterior commissure). Anterior leaflet geometry was determined 100 milliseconds after end-diastole from three-dimensional coordinates of 13 markers. RESULTS: Anterior leaflet geometry changed only slightly after chordal transection without inducing mitral regurgitation. Leaflet coaptation times were 79+/-17 and 87+/-22 milliseconds at the anterior commissure; 72+/-21, 72+/-19 milliseconds at midleaflet, and 71+/-12 and 75+/-8 milliseconds at the posterior commissure (p = NS) for Control and Cut2, respectively. CONCLUSIONS: Cutting anterior second-order chordae did not cause delayed leaflet coaptation, alter leaflet shape, or create mitral regurgitation. These data indicate that transposition of second-order anterior chordae ("strut" chordae) is not deleterious to anterior leaflet motion per se.

The role of atrial contraction in mitral valve closure.

BACKGROUND AND AIM OF THE STUDY: Ovine mitral valve closure is associated with presystolic mitral annular reduction coincident with atrial contraction, which is abolished with ventricular pacing. Whether lack of properly timed atrial contraction influences mitral valve closure or competence, however, is not known. METHODS: Eight sheep underwent myocardial marker implantation on the left ventricle, mitral annulus (MA), and mitral leaflets. After 7-10 days, the animals were studied with biplane videofluoroscopy at baseline and during ventricular or atrioventricular (AV) sequential pacing. Valve closure was timed from end-diastole (ED) and defined as minimum distance between two leaflet edge markers. ED was defined as peak of ECG R wave, end-systole as peak negative left ventricular (LV) dP/dt, and end-isovolumic contraction (EIVC) as 83.5 ms after ED. Septal-lateral (S-L) annular diameter was defined as distance between two markers at the middle of the anterior and posterior annulus. Regurgitant volume (RV) was calculated as relative volume change between ED and EIVC. RESULTS: V-pacing was associated with delayed leaflet closure (65 +/- 5 versus 29 +/- 10 ms, p = 0.008); moreover, RV (4.1 +/- 0.5 versus 1.4 +/- 0.5 ml, p = 0.02), end-diastolic S-L diameter (2.87 +/- 0.10 versus 2.67 +/- 0.09 cm, p = 0.0005), and MA area (8.12 +/- 0.37 versus 7.26 +/- 0.31 cm2, p = 0.009) all increased. RV and leaflet and annular dynamics during AV-pacing were similar to baseline. CONCLUSION: V-pacing increased S-L MA diameter by only 8 +/- 1%, but this change was associated with delayed leaflet coaptation and a 16 +/- 1% regurgitant fraction. These findings provide direct evidence that a properly timed atrial contraction is functionally important for effective mitral leaflet closure.

Edge-to-edge mitral repair: gradients and three-dimensional annular dynamics in vivo during inotropic stimulation.

OBJECTIVE: The edge-to-edge (Alfieri) mitral repair technique appears to be clinically promising, but the potential for functional mitral stenosis, especially with exercise, remains a concern. We used the myocardial marker method combined with Doppler echocardiography to evaluate mitral annular (MA) three-dimensional (3-D) dynamics and transvalvular gradients after leaflet approximation before and during dobutamine infusion. METHODS: Eight adult sheep underwent implantation of eight myocardial markers around the MA and nine in the left ventricle. Mitral leaflet edges were approximated at the valve center and micromanometers were placed in the left ventricle and atrium. The animals were studied with biplane videofluoroscopy to determine 3-D marker coordinates for computation of precise 3-D MA area and left ventricular (LV) volume. Epicardial Doppler echocardiography measured peak and mean diastolic mitral valve gradients at baseline and during dobutamine infusion (10 microg/kg per min). RESULTS: During dobutamine stimulation, left ventricular dP/dt increased from 1776+/-712 to 3390+/-618 mmHg/s (P=0.002), and cardiac output (CO) increased from 2.7+/-1.1 to 5.1+/-1.2 l/min (P=0.009). Mitral annular area (MAA) at end-diastole (ED) fell from 8.6+/-1.4 to 7.0+/-1.8 cm(2) (P=0.001) with inotropic stimulation, but only a modest increase was observed in mean (1.4+/-0.4 vs. 2.4+/-1.0 mmHg, P=0.046) and peak (2.7+/-0.8 vs. 4.9+/-2.5 mmHg, P=0.03) diastolic mitral valve gradients. MAA changed dynamically throughout the cardiac cycle, reflecting normal physiology, but the magnitude of MAA change was augmented during inotropic stimulation (18+/-5% and 27+/-4% for control and dobutamine, respectively; P=0.004). CONCLUSION: Dobutamine increased CO by 89% and decreased ED annular area by 19% after edge-to-edge repair, yet only a small increase in valve gradient occurred. Marker analysis showed enhanced dynamic motion of the mitral annulus. Thus, the edge-to-edge mitral valve repair was not associated with substantial transvalvular obstruction during high flow conditions and did not perturb normal MA 3-D dynamics in normal ovine hearts.

Three-dimensional in-vivo dimensions of 'He's triangle' during acute left ventricular ischemia.

BACKGROUND AND AIM OF THE STUDY: Changes in the dimensions of 'He's triangle' (formed by mitral leaflet segments subtending two associated chordae tendineae) derived from data obtained in in-vitro mitral valve models have been proposed to provide a mechanistic explanation for mitral leaflet malcoaptation. The in-vivo dynamics of He's triangle, however, have not been hitherto determined. METHODS: Radio-opaque markers were placed in 13 sheep to delineate the mitral annulus and four (of an infinite number of possible) He's triangles formed by: (i) the anterior mitral leaflet (AML), first- (CT1) and second-order (CT2) chordae tendineae emanating from the anterior papillary tip (APT1) as well as from the posterior papillary tip (PPT1), respectively; and (ii) the posterior mitral leaflet (PML), CT1 and CT2 emanating from other loci on the anterior as well as the posterior papillary tips (APT2 and PPT2), respectively. Immediately postoperatively (anesthetized, open-chest), three-dimensional end-systolic marker positions were measured before and during circumflex coronary artery occlusion sufficient to produce mitral regurgitation, as verified by echocardiography. RESULTS: During ischemia, three leaflet segments constituting one side of three He's triangles elongated: The AML attached to APT1 and to PPT1 by 1.5+/-1.2 mm (p <0.001) and 1.3+/-0.8 mm (p <0.001), respectively, and the posterior leaflet attached to APT2 by 1.4+/-1.9 mm (p = 0.02). Apart from a 0.9+/-1.1 mm (p = 0.02) increase in the length of CT2 attached to APT2, the length of the seven other CT1 and CT2 remained relatively unchanged during acute left ventricular ischemia. CONCLUSION: With acute posterolateral ischemia, the lengths of CT1 and CT2 remained relatively constant, but the AML and PML lengths were not constant as the AML and PML 'unfurled' during acute left ventricular ischemia. These geometric changes may provide further insight into the mechanisms of acute ischemic mitral regurgitation, though it is not clear how they will be clinically helpful.

Coordinate-free analysis of mitral valve dynamics in normal and ischemic hearts.

BACKGROUND: The purpose of this investigation was to study mitral valve 3D geometry and dynamics by using a coordinate-free system in normal and ischemic hearts to gain mechanistic insight into normal valve function, valve dysfunction during ischemic mitral regurgitation (IMR), and the treatment effects of ring annuloplasty. METHODS AND RESULTS: Radiopaque markers were implanted in sheep: 9 in the ventricle, 1 on each papillary tip, 8 around the mitral annulus, and 1 on each leaflet edge midpoint. One group served as a control (n=7); all others underwent flexible Tailor partial (n=5) or Duran complete (n=6) ring annuloplasty. After an 8+/-2-day recovery, 3D marker coordinates were measured with biplane videofluoroscopy before and during posterolateral left ventricular ischemia, and MR was assessed by color Doppler echocardiography. Papillary to annular distances remained constant throughout the cardiac cycle in normal hearts, during ischemia, and after ring annuloplasty with either type of ring. Papillary to leaflet edge distances similarly remained constant throughout ejection. During ischemia, however, the absolute distances from the papillary tips to the annulus changed in a manner consistent with leaflet tethering, and IMR was observed. In contrast, during ischemia in either ring group, those distances did not change from preischemia, and no IMR was observed. CONCLUSIONS: This analysis uncovered a simple pattern of relatively constant intracardiac distances that describes the 3D geometry and dynamics of the papillary tips and leaflet edges from the dynamic mitral annulus. Ischemia perturbed the papillary-annular distances, and IMR occurred. Either type of ring annuloplasty prevented such changes, preserved papillary-annular distances, and prevented IMR.

The effects of ring annuloplasty on mitral leaflet geometry during acute left ventricular ischemia.

BACKGROUND: The perturbed mitral leaflet geometry that leads to acute ischemic mitral regurgitation during acute left ventricular ischemia has not been quantified, nor is it known whether annuloplasty rings affect these detrimental changes in leaflet geometry. METHODS: Radiopaque markers were implanted on both mitral leaflets and around the anulus in 3 groups of sheep: one group without rings served as the control group (n = 7); the others underwent Duran (n = 6; Medtronic Heart Valve Division, Minneapolis, Minn) or Carpentier-Edwards Physio (n = 5; Baxter Cardiovascular Division, Santa Ana, Calif) ring annuloplasty. After recovery, 3-dimensional marker coordinates were obtained by means of biplane videofluoroscopy before and during acute posterolateral left ventricular ischemia. Leaflet geometry was defined by measuring distances between annular and leaflet markers and perpendicular distances to the leaflet markers from a best-fit annular plane. RESULTS: In all control animals, left ventricular ischemia was associated with acute ischemic mitral regurgitation and apical displacement (away from the annular plane) of the posterior leaflet edge and base markers by 0.6 +/- 0.4 mm (P =.01) and 0.7 +/- 0.2 mm (P <.001), respectively. The distance between the posterior leaflet markers and the mid-posterior anulus did not change significantly during ischemia. The anterior leaflet edge marker extended 1.0 +/- 0. 5 mm (P =.01) away from the mid-anterior anulus during ischemia, but compared with its nonischemic position, the anterior leaflet was not displaced apically away from the annular plane. In all animals in the Duran and Physio groups, leaflet geometry was unchanged during ischemia, and acute ischemic mitral regurgitation was not detected. CONCLUSION: Acute ischemic mitral regurgitation was associated with restricted motion of the posterior leaflet and extension of the anterior leaflet. Annuloplasty rings prevented these geometric perturbations of the mitral leaflets during acute left ventricular ischemia and preserved valvular competence.

Mitral annular dynamics during rapid atrial pacing.

INTRODUCTION: Ovine mitral annular area (MAA) reduction predominantly occurs before ventricular systole. We used the myocardial marker methods to investigate left atrial and MAA dynamics during rapid atrial pacing. METHODS: Seven sheep underwent implantation of 21 myocardial markers around the mitral annulus, the left ventricle and left atrium. After 7 to 10 days, animals were studied with biplane videofluoroscopy to determine 3-dimensional marker coordinates unpaced and during rapid atrial pacing at 140 minutes(-1). Left ventricle volume, left atrial volume (LAV), and MAA were calculated from marker coordinates. End diastole (ED) was defined at peak of the electrocardiogram R wave; times of minimum MAA and minimum LAV were expressed relative to ED (t = 0). Percent reduction in MAA and LAV were calculated from maximum and minimum values between diastole and early systole. RESULTS: The time of minimum MAA occurred earlier relative to ED during rapid pacing compared with control (-48 +/- 21 vs 19 +/- 14 msec; P <.001), as did the time of minimum LAV (-47 +/- 18 vs 4 +/- 16 msec; P <.001). Minimum MAA and LAV were significantly smaller with rapid pacing (6. 8 +/- 0.6 vs 6.5 +/- 0.5 cm(2); P <.05, respectively; and 15.4 +/- 2. 4 vs 16.5 +/- 2.3 mL; P <.01, respectively), and a relatively greater fractional reduction in MAA and LAV was observed during presystole. CONCLUSIONS: Rapid atrial pacing resulted in greater MAA and LAV reduction, both of which occurred entirely during diastole. This study supports the notion that MAA reduction is closely linked to LA dynamics.

Ring annuloplasty prevents delayed leaflet coaptation and mitral regurgitation during acute left ventricular ischemia.

OBJECTIVE: Incomplete mitral leaflet coaptation during acute left ventricular ischemia is associated with end-diastolic mitral annular dilatation and ischemic mitral regurgitation. Annular rings were implanted in sheep to investigate whether annular reduction alone is sufficient to prevent mitral regurgitation during acute posterolateral left ventricular ischemia. METHODS: Radiopaque markers were inserted around the mitral anulus, on papillary muscle tips, and on the central meridian of both mitral leaflets in three groups of sheep: control (n = 5), Physio ring (n = 5) (Baxter Cardiovascular Div, Santa Ana, Calif), and Duran ring (n = 6) (Medtronic Heart Valve Div, Minneapolis, Minn). After 8 +/- 1 days, animals were studied with biplane videofluoroscopy before and during left ventricular ischemia. Annular area was calculated from 3-dimensional marker coordinates and coaptation defined as minimal distance between leaflet edge markers. RESULTS: Before ischemia, leaflet coaptation occurred just after end-diastole in all groups (control 17 +/- 41, Duran 33 +/- 30, Physio 33 +/- 24 ms, mean +/- SD, P >.2 by analysis of variance). During ischemia, regurgitation was detected in all control animals, and leaflet coaptation was delayed to 88 +/- 8 ms after end-diastole (P =.02 vs preischemia). This was associated with increased end-diastolic annular area (8.0 +/- 0.9 vs 6.7 +/- 0.6 cm(2), P =.004) and septal-lateral annular diameter (2.9 +/- 0.1 vs 2.5 +/- 0.1 cm, P =.02). Mitral regurgitation did not develop in Duran or Physio sheep, time to coaptation was unchanged (Duran 25 +/- 25 ms, Physio 30 +/- 48 ms [both P >.2 vs preischemia]), and annular area remained fixed. CONCLUSION: Mitral annular area reduction and fixation with an annuloplasty ring eliminated delayed leaflet coaptation and prevented mitral regurgitation during acute left ventricular ischemia after ring implantation.

Deformational dynamics of the aortic root: modes and physiologic determinants.

BACKGROUND: Current surgical methods for treating aortic valve and aortic root pathology vary widely, and the basis for selecting one repair or replacement alternative over another continues to evolve. More precise knowledge of the interaction between normal aortic root dynamics and aortic valve mechanics may clarify the implications of various surgical procedures on long-term valve function and durability. METHODS AND RESULTS: To investigate the role of aortic root dynamics on valve function, we studied the deformation modes of the left, right, and noncoronary aortic root regions during isovolumic contraction, ejection, isovolumic relaxation, and diastole. Radiopaque markers were implanted at the top of the 3 commissures (sinotubular ridge) and at the annular base of the 3 sinuses in 6 adult sheep. After a 1-week recovery, ECG and left ventricular and aortic pressures were recorded in conscious, sedated animals, and the 3D marker coordinates were computed from biplane videofluorograms (60 Hz). Left ventricular preload, contractility, and afterload were independently manipulated to assess the effects of changing hemodynamics on aortic root 3D dynamic deformation. The ovine aortic root undergoes complex, asymmetric deformations during the various phases of the cardiac cycle, including aortoventricular and sinotubular junction strain and aortic root elongation, compression, shear, and torsional deformation. These deformations were not homogeneous among the left, right, and noncoronary regions. Furthermore, changes in left ventricular volume, pressure, and contractility affected the degree of deformation in a nonuniform manner in the 3 regions studied, and these effects varied during isovolumic contraction, ejection, isovolumic relaxation, and diastole. CONCLUSIONS: These complex 3D aortic root deformations probably minimize aortic cusp stresses by creating optimal cusp loading conditions and minimizing transvalvular turbulence. Aortic valve repair techniques or methods of replacement using unstented autograft, allograft, or xenograft tissue valves that best preserve this normal pattern of aortic root dynamics should translate into a lower risk of long-term cusp deterioration.

Functional evaluation of the medtronic stentless porcine xenograft mitral valve in sheep.

BACKGROUND: Recently, renewed interest in allograft and stentless "freehand" bileaflet xenograft mitral valve replacement has arisen. The variability of human papillary tip anatomy and scarcity of donors limit allograft availability, making xenograft mitral valves an attractive alternative; however, these valves require new surgical implantation techniques, and assessment of their hemodynamics and functional geometry is lacking. METHODS: Seven sheep underwent implantation of a new stentless, glutaraldehyde-preserved porcine mitral valve (Physiological Mitral Valve [PMV], Medtronic) and were studied acutely under open-chest conditions. A new method of retrograde cardioplegia was developed. Hemodynamic valve function was assessed by epicardial Doppler echocardiography. 3D motion of miniature radiopaque markers sutured to the valve leaflets, annulus, and papillary tips was measured. Six other sheep with implanted markers served as controls. RESULTS: Both papillary muscle tips avulsed in the first animal, leaving 6 other animals. Mitral regurgitation was not observed in any xenograft valve. The peak and mean transvalvular gradients were 4.6+/-1.8 mm Hg and 2.6+/-1.5 mm Hg, respectively. The average mitral valve area was 5.7+/-1.6 cm(2). Valve closure in the xenograft group occurred later (30+/-11 ms, P<0. 015) and at higher left-ventricular pressure (61+/-9 mm Hg, P<0.001) than in the control group; furthermore, leaflet coaptation was displaced more apically (5.6+/-2.2 mm, P<0.001) and septally (5. 8+/-1.5 mm, P<0.001), and the anterolateral papillary tip underwent greater septal-lateral displacement (2.7+/-1.5 mm, P<0.001). Annular contraction during the cardiac cycle was similar in the 2 groups (xenograft 9.2+/-4.5% versus control 10.6+/-4.5% [mean+/-SD; 2-factor ANOVA model]). CONCLUSIONS: Successful freehand stentless porcine mitral valve implantation is feasible in sheep and was associated with excellent early postoperative hemodynamics. Physiological mitral valve annular contraction and functional leaflet closure mechanics were preserved. Long-term valve durability, calcification, and hemodynamic performance remain to be determined in models.

The effect of triiodothyronine on myocardial contractile performance after epinephrine exposure: implications for donor heart management.

BACKGROUND: This study analyzes in the experimental model of isolated human atrial myocardium whether the myocardial contractile depression occurring after high-dose/long-term catecholamine exposure (as typically occurring in brain-dead organ donors) can be reversed by thyroid hormone administration. METHODS: Isolated trabeculae were prepared from atrial myocardium from patients undergoing coronary artery bypass (n = 15). Initial measurements of isometric force were carried out (measurement conditions of 37 degrees C, Krebs Henseleit solution, supramaximal electrical stimulation, 1 Hz, at optimal length). Then the trabeculae were incubated for 6 hours at 26 degrees C in a Krebs Henseleit solution containing epinephrine 10(-7) mol/L and the fluorescent dye FURA-2/AM for calcium measurements. At the end of the incubation period, isometric force, isotonic shortening, and intracellular calcium transient (FURA-2 "ratio method") were measured. After 30 minutes administration of triiodothyronine (5 x 10(-9) mol/L), the measurements were repeated. Control groups included 6 hours incubation in 4 degrees C Krebs Henseleit solution (n = 5); 6 hours incubation in 26 degrees C FURA-2/AM (n = 5); and 6 hours incubation in epinephrine 10(-7) mol/L (n = 5). RESULTS: After 6 hours catecholamine exposure isometric force declined significantly to 56.8% (p < .0001) and isotonic shortening to 54% of its initial value (p < .01). Administration of triiodothyronine was associated with a significant recovery of the isotonic shortening amplitude (p < .005), of isometric force development (p < .01), an increased velocity of force development (p < .0001), and of diastolic force decay (p < .005). At the same time the shape of the intracellular calcium transient became smaller as a result of an accelerated diastolic decay. The amplitude of the calcium transient remained unaltered, whereas the calcium time integral was reduced (p < .05). CONCLUSION: In the model of isolated human myocardium, experimental depression of the contractile performance resulting from long-term catecholamine exposure could be reversed by a 30-minute triiodothyronine incubation. The experimental data showing increased force amplitudes at unaltered amplitudes of the intracellular calcium transient and an even-reduced calcium time integral provide strong evidence for a sensitization of the contractile apparatus for calcium by triiodothyronine. The data provide additional knowledge to explain the successful administration of triiodothyronine in donor heart management.

Length dependence of calcium- and force-transients in normal and failing human myocardium.

UNLABELLED: Two questions were analysed: (1) Is the Frank-Starling mechanism operative in failing human myocardium? (2) Are length-dependent changes in force accompanied by length-dependent changes in intracellular calcium transients in human myocardium? METHODS: (I) in electrically stimulated left-ventricular trabeculae [normal donor heart (NDH), n = 8; end stage dilated cardiomyopathy (DCM), n = 11], isometric force development was analysed as a function of muscle length (37 degrees C, oxygenated Krebs-Henseleit solution, supramaximal electrical stimulation, frequency: 1 Hz). (II) Myocardium from the same patients were loaded with the fluorescent dye FURA-2/AM for simultaneous measurements of intracellular calcium transient (ICT) and force development at different muscle lengths. Muscle length, resting force, developed force and intracellular Calcium ("ratio method") were monitored continuously. RESULTS: (I) developed force increased up to an optimum as a function of muscle length in NDH- and DCM-myocardium. The slope of this increase was flatter in DCM-myocardium (P < 0.01). (II) In NDH- and DCM-myocardium, diastolic and systolic calcium increased significantly with muscle length. With decreasing muscle lengths the ICT became broader, the diastolic decay was retarded and the peak of the ICT was flatter. At Lmax the calcium amplitude was 23% smaller in DCM than in NDH (P < 0.04). CONCLUSION: there is a clear length dependence of active force in DCM-myocardium. The length dependence of force development is associated with length-dependent modulations of the ICT. The flatter slope of the length-force curve in DCM may be partly explained by altered intracellular calcium handling in failing myocardium.

Triiodothyronine reverses depressed contractile performance after excessive catecholamine stimulation.

BACKGROUND: Conflicting results have been reported regarding the acute effects of triiodothyronine (T3) on myocardial contractile performance. The present study analyzes the role of T3 in reversing the depressant effect of excessive catecholamine stimulation in isolated porcine left ventricular myocardium. METHODS: Thirty-six left ventricular trabeculae (0.4 x 6.0 mm) obtained from 6 pigs were used for measurements of isometric force development, isotonic shortening, and intracellular calcium in three experimental series (measurement conditions: 37 degrees C; optimal length; supramaximal electrical stimulation, 1 Hz; calcium measurement, fura-2 ratio method; frequency, 225 Hz). In series 1, isometric force development was measured before and after a 60-minute incubation with 10(-7) mol/L epinephrine in preparations with (n = 6) and without (n = 6) preceding fura-2 loading for calcium measurements. In series 2, the acute effects of a 30-minute administration of T3 (10(-9) mol/L) on isometric force and intracellular calcium were analyzed (n = 6). In series 3, after simultaneous fura-2 loading and a 6-hour 10(-7) mol/L epinephrine exposure the effects of T3 (10(-9) mol/L, 30 minutes) on force development, shortening, and intracellular calcium transient were analyzed. RESULTS: Long-term and high-dose epinephrine exposure induced a severe contractile depression with a significant reduction of isometric force development (p < 0.05) and increased diastolic (p < 0.001) and systolic calcium (p < 0.001). In normal porcine myocardium T3 had no effect on the extent of isometric force generation but accelerated the time course of force development (p < 0.05) and increased the calcium transient (p < 0.001). After induction of myocardial depression by epinephrine exposure T3 accelerated the intracellular calcium transients and reduced diastolic calcium. Triiodothyronine increased the shortening amplitude and the force amplitude (p < 0.01). CONCLUSIONS: Triiodothyronine reverses depressed contractile performance after preceding high-dose epinephrine exposure in isolated porcine myocardium. Increased force amplitudes and unaltered or even reduced intracellular calcium transients argue in favor of a resensitization of the contractile apparatus for calcium by T3. The study supports a potential role for T3 treatment in depressed myocardium after previous excessive catecholamine exposure (eg, brain death, catecholamine treatment, ischemia).

Myocardial length-force relationship in end stage dilated cardiomyopathy and normal human myocardium: analysis of intact and skinned left ventricular trabeculae obtained during 11 heart transplantations.

UNLABELLED: The Frank-Starling-mechanism (FSM) was analyzed in isolated intact and skinned human left ventricular myocardium obtained from 11 heart transplantations (normal donor hearts (NDH), n = 8; dilated cardiomyopathy (DCM), n = 11). The new technique to utilize muscle strips from normal donor hearts which were actually implanted is described in detail. METHODS: I) In electrically stimulated left ventricular trabeculae (37 degrees C, oxygenated Krebs-Henseleit solution, supramaximal electrical stimulation, frequency 1 Hz) force development was analyzed as a function of muscle length (NDH = 8; DCM = 11). II) In an additional series left ventricular myocardium was demembranized ("skinned") by Triton-X-100. At different sarcomere lengths and calcium concentrations corresponding to pCa values of 4.3, 5.5, and 8.0 force development was measured (DCM = 11; NDH = 9). RESULTS: I) Developed force increased up to an optimum as a function of muscle length in intact NDH- and DCM-myocardium. However, the relative increment of developed force after any length step was smaller in DCM than in NDH. Near "Lmax" (muscle length associated with maximum developed force) passive resting tension was considerably elevated in DCM, indicating significantly increased diastolic stiffness. II) In skinned left ventricular DCM- and NDH-myocardium developed force depended on sarcomere length with an optimum near 2.2 microns. However, a reduction of activator calcium concentration from pCa 4.3 to pCa 5.5 produces a smaller percent decline in force at short sarcomere lengths in DCM than it does in NDH. CONCLUSION: The present study shows that except for diastolic stiffness and a smaller relative force increment after any length step in DCM the Frank Starling mechanism is still present in isolated human left ventricular DCM- as in NDH-myocardium. The current study does not allow to decide whether in skinned myocardium the smaller percent decline in force after reduction of activator calcium concentrations in DCM is caused by an increased calcium sensitivity at short sarcomere lengths or decreased sensitivity at long sarcomere lengths.

"Cardioplegia on the contractile apparatus level": evaluation of a new concept for myocardial preservation in perfused pig hearts.

UNLABELLED: The concept of a reversible desensitization of the myocardial contractile apparatus for calcium by 2,3 Butanedione Monoxime (BDM) as a method to improve the myocardium's tolerance to cold ischemia was evaluated in normal pig hearts (n = 14). The results were compared to those obtained after application of Bretschneider's HTK cardioplegic solution. METHODS: Series I) After BDM treatment (concentrations: 0-30 mmol/L) the isometric force output and the intracellular calcium transients (measured using the FURA-2 ratio method) of electrically driven (1 Hz) isolated left-ventricular muscle strips excised from beating pig hearts (n = 14) were recorded simultaneously in order to analyse the mode of action of BDM; Series II) The cardioprotective effects of BDM (30 mmol/L) and Bretschneider's cardioplegic solution (HTK) were compared in a large-animal model: after "in situ perfusion" of pig hearts with either 2000 ml ice-cold BDM solution (30 mmol/L) (n = 7) or 2000 ml HTK (n = 7) the hearts were explanted and stored at 4 degrees C in the same solutions for up to 42 h. The contractile properties of muscle fibres, excised after storage periods of 8, 24, and 42 h from these hearts were analyzed in terms of isometric force development and isotonic shortening. 280 muscle fibres from 14 pigs were used for measurements. RESULTS: Series I) In pig myocardium a dose-dependent reduction of isometric force development was found after BDM application. The shape and the amplitude of the intracellular calcium transient were also affected by BDM. At 30 mmol/L BDM no force development could be elicited despite the presence of an intracellular calcium transient (amplitude < 70% of the control). Series II) Shortening, calcium transient, and force of left-ventricular muscle strips of pig myocardium excised after storage periods for up to 42 h showed complete recovery when BDM was applied. In contrast HTK perfusion allowed complete recovery of these parameters when the storage period did not exceed 6 hours. CONCLUSION: Under the given experimental conditions reversible desensitization of the contractile apparatus for calcium results in a considerable prolongation of the tolerance to cold ischemia in explanted pig hearts. The present study shows that the protective effects of BDM are not only present when isolate muscle fibres were stored (and the extracellular space is large) but also after storage of complete hearts in a solution in a solution containing BDM. Thus BDM may become a useful agent to enlarge the storage period of donor hearts in heart transplatation considerably.