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Biomedical subjects

M Komeda

Publications and source records attributed to M Komeda.

At least 19 recordsLinked to original sources

Comparative histopathology of radial artery versus internal thoracic artery and risk factors for development of intimal hyperplasia and atherosclerosis.

BACKGROUND: In this study, we examined the comparative histopathology, morphometry, and risk factors for the development of intimal hyperplasia and atherosclerosis in the radial artery (RA) and the internal thoracic artery (ITA). METHODS AND RESULTS: Paired specimens of RAs and ITAs, obtained from 150 patients who underwent CABG, were evaluated with histopathology; 110 pairs of arteries were suitable for morphometric analysis. The severity of disease was evaluated on the basis of percentage of luminal narrowing, intimal thickness index, and intima-to-media ratio. Risk factors were determined with stepwise linear regression. Intimal hyperplasia was seen in 141 RAs (94%) and 103 ITAs (69%) (P<0.001). Atherosclerosis was seen in 5% of RAs and 0.7% of ITAs (P=0.04). Medial calcification was found only in RAs (20 of 150, 13.3%) (P<0.001). Morphometric analysis showed that compared with ITAs, RAs had a significantly higher intimal area, medial area, percentage of luminal narrowing, intimal thickness index, and intima-to-media ratio (all P<0.001) Factors found to be significant (P<0.05) predictors of the 3 severity indices of intimal hyperplasia, including atherosclerosis, in RAs were peripheral vascular disease, smoking, age, and diabetes. Risk factors for intimal hyperplasia in ITAs were age and smoking. CONCLUSIONS: The RA is more likely to have atherosclerosis, intimal hyperplasia, and medial calcification than the ITA. Morphometric analysis indices showed marked differences between the RA and the ITA. Care should be taken when selecting the RA as a conduit in CABG, particularly in patients who are elderly, diabetic, smoke, or have peripheral vascular disease.

Adult

Reactive oxygen species play an important role in the activation of heat shock factor 1 in ischemic-reperfused heart.

BACKGROUND: The myocardial protective role of heat shock protein (HSP) has been demonstrated. Recently, we reported that ischemia/reperfusion induced a significant activation of heat shock factor (HSF) 1 and an accumulation of mRNA for HSP70 and HSP90. We examined the role of reactive oxygen species (ROSs) in the induction of stress response in the ischemic-reperfused heart. METHODS AND RESULTS: Rat hearts were isolated and perfused with Krebs-Henseleit buffer by the Langendorff method. Whole-cell extracts were prepared for gel mobility shift assay using oligonucleotides containing the heat shock element. Induction of mRNA for HSP70 and HSP90 was examined by Northern blot analysis. Repetitive ischemia/reperfusion, which causes recurrent bursts of free radical generation, resulted in burst activation of HSF1, and this burst activation was significantly reduced with either allopurinol 1 mmol/L (an inhibitor of xanthine oxidase) or catalase 2x10(5) U/L (a scavenger of H2O2). Significant activation of HSF1 was observed on perfusion with buffer containing H2O2 150 micromol/L or xanthine 1 mmol/L plus xanthine oxidase 5 U/L. The accumulation of mRNA for HSP70 or HSP90 after repetitive ischemia/reperfusion was reduced with either allopurinol or catalase. CONCLUSIONS: Our findings demonstrate that ROSs play an important role in the activation of HSF1 and the accumulation of mRNA for HSP70 and HSP90 in the ischemic-reperfused heart.

Allopurinol

Use of technetium-99m sestamibi ECG-gated single-photon emission tomography for the evaluation of left ventricular function following coronary artery bypass graft: comparison with three-dimensional magnetic resonance imaging.

In patients who had undergone cardiac surgery (coronary artery bypass graft) and whose hearts showed abnormal movement during the cardiac cycle, we studied the accuracy of functional assessment using ECG-gated single-photon emission tomography (SPET) and the automated software developed by Germano et al. by comparing the findings with magnetic resonance (MR) images acquired three-dimensionally. Sixteen patients who had undergone cardiac surgery underwent 99mTc-sestamibi gated SPET (MIBI-g-SPET) and MRI on the same day. Left ventricular end-diastolic and end-systolic volumes (EDV, ESV) and ejection fraction (LVEF) were measured using MIBI-g-SPET and the aforementioned algorithm. Regional wall thickening was assessed using a four-point scale on MIBI-g-SPET and cine MRI. There was a good correlation between MIBI-g-SPET and MRI in respect of EDV (r=0.89), ESV (r=0.93) and LVEF (r=0.89). A high degree of agreement was found between the wall thickening scores obtained by MIBI-g-SPET and MRI in total segments (kappa=0.62) and in septal segments (kappa=0.67). It is concluded that ECG-gated perfusion SPET can provide regional and global functional information, including absolute volumes, in patients following cardiac surgery.

Aged

Should the pericardium be closed routinely after heart operations?

BACKGROUND: Repeat coronary artery bypass grafting is more difficult if the right ventricle is firmly attached to the inner table of the sternum. Closure of the pericardium at the time of the initial procedure may prevent attachment of the right ventricle to the sternum. This study attempts to identify the geometric effects of pericardial closure early after isolated coronary artery bypass grafting. METHODS: Forty-two patients undergoing elective, isolated coronary artery bypass grafting were randomized into two groups: 20 patients underwent closure of the pericardium (Closure group) and the pericardium was left open in 22 patients (Open group). Radiopaque markers were attached to the anterior aspect of the right ventricular epicardium in both groups. RESULTS: Postoperative chest roentgenograms revealed that the distance between the epicardial surface and the posterior table of the sternum was larger in the Closure group compared to the Open group at 1 week and 3 months postoperatively (p < 0.001). Cardiac index and stroke work index in the early postoperative period was lower in the Closure group compared to the Open group (p < 0.001) despite similar filling pressures. CONCLUSIONS: Pericardial closure may reduce the risk of myocardial injury during sternotomy for repeat coronary artery bypass grafting by preventing right ventricular adhesions. However, adverse hemodynamic effects in the early postoperative period may preclude pericardial closure in patients with impaired ventricular function.

Aged

Development of enzyme-linked immunosorbent assay for acidic fibroblast growth factor and its clinical application.

We have developed, for the first time, an enzyme-linked immunosorbent assay (ELISA) system for the measurement of human acidic fibroblast growth factor (aFGF). Anti-bovine aFGF rabbit IgG was conjugated with N-hydroxysuccimidobiotin, and the resulting IgG-biotin conjugate was used as the second antibody. This assay was highly specific and reproducible, enabling us to detect aFGF at a concentration as low as 1 microg/l without any prior processing of samples. With this method, it was possible to determine human aFGF up to 833 x 10(3) ng/l, with the use of anti-bovine aFGF IgG as the first and second antibody. There was no significant cross-reactivity of the antibody with other growth factors, such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). The aFGF concentration in pericardial fluid was significantly higher in patients with unstable angina than in those with other heart diseases, suggesting that the aFGF plays an important role(s) in the course of collateral growth in coronary artery disease. Therefore, our ELISA system may be useful in determining unknown biological function(s) or pathological role(s) of aFGF in various disease entities.

Aged

Mitral annular size and shape in sheep with annuloplasty rings.

BACKGROUND: Mitral annuloplasty is an important element of most mitral repairs, yet the effects of various types of annuloplasty rings on mitral annular dynamics are still debated. Recent studies suggest that flexible rings preserve physiologic mitral annular area change during the cardiac cycle, while rigid rings do not. METHODS: To clarify the effects of mitral ring annuloplasty on mitral annular dynamic geometry, we sutured 8 radiopaque markers equidistantly around the mitral anulus in 3 groups of sheep (n = 7 each: no ring, Carpentier-Edwards semi-rigid Physio-Ring [Baxter Healthcare Corp, Edwards Division, Santa Ana, Calif], and Duran flexible ring [Medtronic, Inc, Minneapolis, Minn]). Ring sizes were selected according to anterior leaflet area and inter-trigonal distance (Physio-Ring 28 mm, n = 7; Duran ring 31 mm, n = 5, and 29 mm, n = 2). After 8 +/- 1 days of recovery, the sheep were sedated and studied by means of biplane videofluoroscopy. Mitral annular area was calculated from 3-dimensional marker coordinates without assuming circular or planar geometry. RESULTS: In the no ring group, mitral annular area varied during the cardiac cycle by 11% +/- 2% (mean +/- SEM; maximum = 7.6 +/- 0.2, minimum = 6.8 +/- 0.2 cm2; P </=.001). Mitral annular area was fixed in the Physio-Ring group (4. 6 +/- 0.1 cm2) and, surprisingly, also static in the Duran ring group (4.8 +/- 0.1 cm2; P =.26 vs Physio-Ring). Furthermore, mitral annular 3-dimensional shape changed in the no-ring group during the cardiac cycle, but not in the Physio-Ring or Duran groups. CONCLUSIONS: Mitral annular area and shape did not change during the cardiac cycle after ring annuloplasty, regardless of ring type. Thus mitral annular area reduction, independent of intrinsic ring flexibility, is the chief mechanism responsible for the salutary effects of mitral ring annuloplasty.

Analysis of Variance

The influence of interleukin-1 receptor antagonist transgene on spiral ganglion neurons.

The cytokine interleukin-1beta (IL-1) has been shown to induce the secretion of NGF and GDNF in several types of neuronal populations. IL-1 has also been shown to mediate immune response following trauma or presence of foreign antigens. We investigated the influence of an IL-1 antagonist on the survival of spiral ganglion neurons in inner ears in which hair cells have been eliminated. We used a replication-deficient adenoviral vector containing the human IL-1 receptor antagonist (IL-1ra) cDNA. Guinea pigs were bilaterally deafened with ototoxic drugs. One week later their left cochleae were inoculated with the IL-1ra vector, designated Ad.IL-1ra. The vector was delivered by injection through the cochlear round window. IL-1ra protein levels within the perilymph of Ad.IL-1ra-injected animals were measured with ELISA and found to be significantly elevated compared to our controls. Spiral ganglion cell counts in experimental ears revealed a lower density of neurons after Ad.IL-1ra inoculation. Taken together, the data suggest that the Ad.IL-1ra-infected cochlear cells synthesized the transgenic human IL-1ra protein, which was then secreted by the cells into the perilymph, resulting in an accelerated neuronal degeneration in hair cell-depleted ears.

Animals

Simultaneous assessment of myocardial free fatty acid utilization and left ventricular function using 123I-BMIPP-gated SPECT.

UNLABELLED: This study was designed to evaluate the methodological feasibility of 123I-labeled beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP)-gated SPECT to assess regional and global left ventricular (LV) function in comparison with 99mTc-sestamibi (methoxyisobutyl isonitrile [MIBI])-gated SPECT and first-pass radionuclide angiography (FPRNA). METHODS: Forty-four patients with stable coronary artery disease underwent rest BMIPP-gated SPECT (111 MBq, 60 s/step) and rest MIBI-gated SPECT (600 MBq, 40 s/step) within a week. From both gated SPECT studies, regional defect scores (DS), wall motion scores (WMS) and wall-thickening scores (WTS) were evaluated visually using 4-point scales for nine segments, and LV ejection fraction (EF) (%) was automatically calculated using Quantitative Gated SPECT (QGS) software. FPRNA was also performed on injection of MIBI. RESULTS: Exact agreement between the two gated SPECT studies was 84.1% (kappa = 0.706, r = 0.907, P < 0.0001) in WMS and 87.1% (kappa = 0.662, r = 0.884, P < 0.0001) in WTS. LVEF obtained from BMIPP-gated SPECT linearly correlated with those from MIBI-gated SPECT (y = -0.27 + 0.944x, r = 0.948, SEE = 5.00, P < 0.0001) and FPRNA (y = -7.32 + 1.042x, r = 0.919, SEE = 6.19, P < 0.0001). Even in 21 patients with mismatch segments (BMIPP DS > MIBI DS), agreement was considered to be acceptable in WMS (81.5%, kappa = 0.707, r = 0.853, P < 0.0001) and in WTS (76.7%, kappa = 0.526, r = 0.754, P < 0.0001), and correlation in LVEF remained good between BMIPP-gated SPECT and MIBI-gated SPECT (y = -1.24 + 0.955x, r = 0.938, SEE = 6.25, P < 0.0001) or FPRNA (y = -6.03 + 1.024x, r = 0.913, SEE = 7.38, P < 0.0001). CONCLUSION: BMIPP-gated SPECT can evaluate regional and global LV function with the QGS software. Therefore, BMIPP-gated SPECT offers the opportunity for simultaneous assessment of myocardial free fatty acid utilization and LV function.

Aged

Bilateral internal thoracic artery grafting may improve outcome of coronary artery surgery. Risk-adjusted survival.

BACKGROUND: Excellent clinical results of the patients with single left internal thoracic artery (ITA) grafting compared with saphenous vein grafting have prompted surgeons to use both ITAs. However, long-term benefits of the bilateral ITA grafting have not been proven. METHODS AND RESULTS: We reviewed our experience of 2826 patients (age 62 +/- 9 years [mean +/- 1 SD], 2350 men, mean follow-up 52 months) who underwent surgery with ITAs, supplemented by saphenous vein grafts when required, between 1985 and 1995. Single ITA grafting (n = 1557) was compared with double (n = 1269), by means of the Cox proportional hazards model. Significant predictors of all-cause mortality were as follows: (1) peripheral vascular disease, rate ratio (RR) = 2.4 (1.7 to 3.4 [95% CI]); (2) prior myocardial infarction, RR = 2.1 (1.5 to 3.1); (3) severe left ventricular dysfunction, RR = 3.9 (2.6 to 5.9) and moderate left ventricular dysfunction, RR = 2.0 (1.5 to 2.6); (4) age > or = 70 years, RR = 3.4 (2.4 to 4.8), and age 60 to 69 years, RR = 1.7 (1.3 to 2.4); (5) diabetes mellitus, RR = 1.7 (1.3 to 2.4); (6) carotid disease, RR = 1.7 (1.2 to 2.4); and (7) single ITA (versus bilateral ITA), RR = 1.4 (1.1 to 1.8). Number of vessels diseased, surgical status (i.e., urgent versus elective), hypertension, and sex were not significant predictors. Unadjusted actuarial survival rates at 10 years were 86 +/- 3% (mean +/- 95% CI) for bilateral ITA group and 71 +/- 5% for single ITA. Single ITA was also a predictor of all-cause mortality, late myocardial infarction, or late reoperation (RR = 1.3 [1.1 to 1.6]). CONCLUSIONS: Bilateral ITA grafting may improve long-term survival and freedom from late myocardial infarction or reoperation after coronary artery surgery. Mathematical modeling may assist in developing a strategy for use of bilateral ITA grafts.

Arteries

Auditory pathway and auditory brainstem response in mice lacking NMDA receptor epsilon 1 and epsilon 4 subunits.

There is considerable evidence that the N-methyl-D-aspartate receptor (NMDAR) is a component of excitatory amino acid synapses in the ascending auditory pathway. The availability of mice that are defective in NMDAR epsilon 1 or NMDAR epsilon 4 subunit paves the way for investigations on the role of this receptor in auditory function. Non-radioactive in situ hybridization was used in the parent C57/6J wild strain to determine if these subunits are normally expressed in cochlear nucleus (CN) and superior olivary complex (SOC) and to confirm their absence in the respective mutant mice. Evoked auditory brainstem response (ABR) to normal acoustic stimulation was investigated to assess function. In situ hybridization revealed the expression of NMDAR epsilon 1 and epsilon 4 subunits mRNAs in major neuronal types in the CN and SOC of the wild type mice while epsilon 1 and epsilon 4 expression were absent in their respective mutant mice. The ABR threshold for the epsilon 1 mutant mice was similar to that of wild type mice however the threshold for the epsilon 4 mutant mice was significantly elevated. These results suggest a role for the NMDAR epsilon 4 in normal auditory functions while the NMDAR epsilon 1 may have a less critical function under normal conditions.

Animals

Early systolic mitral leaflet "loitering" during acute ischemic mitral regurgitation.

BACKGROUND: The mechanism by which incomplete mitral leaflet coaptation develops during ischemic mitral regurgitation is debated, with recent studies suggesting that incomplete mitral leaflet coaptation may be due to apically displaced papillary muscle tips. Yet quantitative in vivo three-dimensional mitral leaflet motion during ischemic mitral regurgitation has never been described. METHODS: Radiopaque markers (sutured around the mitral anulus, to the central free mitral leaflet edges, and to both papillary muscle tips and bases) were imaged with the use of biplane videofluoroscopy in six closed-chest, sedated sheep before (control) and during induction of acute ischemic mitral regurgitation. Leaflet coaptation was defined as the minimum distance measured between edge markers during control conditions. RESULTS: During control, leaflet coaptation occurred 23 +/- 7 msec (mean +/- standard error of the mean) after end-diastole, when left ventricular pressure was 27 +/- 6 mm Hg. During ischemic mitral regurgitation, coaptation was delayed to 115 +/- 19 msec after end-diastole (p < or = 0.01 vs control [n = 4]) when left ventricular pressure was 88 +/- 4 mm Hg. At end-diastole during ischemic mitral regurgitation, the mitral anulus area was 14% +/- 2% larger than control (7.4 +/- 0.3 cm2 vs 6.5 +/- 0.2 cm2, p < or = 0.005) as the result of the lengthening of muscular annular regions (76.0 +/- 2.5 mm vs 70.5 +/- 1.4 mm, p < or = 0.01). Mitral anulus shape (ratio of two diameters) at end-diastole was more circular during ischemic mitral regurgitation (0.79 +/- 0.01 vs 0.71 +/- 0.02, p < 0.01). At end-diastole during ischemic mitral regurgitation, the posterior papillary muscle tip was displaced 1.5 +/- 0.5 mm laterally and 2.0 +/- 0.6 mm posteriorly (p < or = 0.02 vs control), but there was no apical displacement of either papillary muscle tip. CONCLUSIONS: Incomplete mitral leaflet coaptation during acute ischemic mitral regurgitation occurred early in systole, not at end-systole, and was due to "loitering" of the leaflets associated with posterior mitral anulus enlargement and circularization, as well as some posterolateral, but not apical, posterior papillary muscle tip displacement. These data suggest that early systolic mitral anulus dilatation and shape change and altered posterior papillary muscle motion are the primary mechanisms by which incomplete mitral leaflet coaptation occurs during acute ischemic mitral regurgitation.

Acute Disease

Mitral valve opening in the ovine heart.

To study the three-dimensional size, shape, and motion of the mitral leaflets and annulus, we surgically attached radiopaque markers to sites on the mitral annulus and leaflets in seven sheep. After 8 days of recovery, the animals were sedated, and three-dimensional marker positions were measured by computer analysis of biplane videofluorograms (60/s). We found that the oval mitral annulus became most elliptical in middiastole. Both leaflets began to descend into the left ventricle (LV) during the rapid fall of LV pressure (LVP), before leaflet edge separation. The anterior leaflet exhibited a compound curvature in systole and maintained this shape during opening. The central cusp of the posterior leaflet was curved slightly concave to the LV during opening. Markers at the border of the "rough zone" were separated by 10 mm during systole. We conclude that coaptation occurs very near the leaflet edges, that the annulus and leaflets move toward their open positions during the rapid fall of LVP, and that leaflet edge separation, the last event in the opening sequence, occurs near the time of minimum LVP.

Animals

Estimation of regional left ventricular wall stresses in intact canine hearts.

Left ventricular (LV) wall stress is an important element in the assessment of LV systolic function; however, a reproducible technique to determine instantaneous local or regional wall stress has not been developed. Fourteen dogs underwent placement of twenty-six myocardial markers into the ventricle and septum. One week later, marker images were obtained using high-speed biplane videofluoroscopy under awake, sedated, atrially paced baseline conditions and after inotropic stimulation (calcium). With a model taking into account LV pressure, regional wall thickness, and meridional and circumferential regional radii of curvature, we computed average midwall stress for each of nine LV sites. Regional end-systolic and maximal LV wall stress were heterogeneous and dependent on latitude (increasing from apex to base, P < 0.001) and specific wall (anterior > lateral and posterior wall stresses; P = 0. 002). Multivariate ANOVA demonstrated only a trend (P = 0.056) toward increased LV stress after calcium infusion; subsequent univariate analysis isolated significant increases in end-systolic LV wall stress with increased inotropic state at all sites except the equatorial regions. The model used in this analysis incorporates local geometric factors and provides a reasonable estimate of regional LV wall stress compared with previous studies. LV wall stress is heterogeneous and dependent on the particular LV site of interest. Variation in wall stress may be caused by anatomic differences and/or extrinsic interactions between LV sites, i.e., influences of the papillary muscles and the interventricular septum.

Animals

[Coronary stenosis and mechanisms of collateral vessel growth].

The presence or absence of collateral circulation significantly impacts the natural history of coronary artery disease. Collateral growth involves two different mechanism; capillary collaterals develop by sprouting (angiogenesis) and muscular collaterals develop in situ from preexisting arterioles (arteriogenesis). The process is mediated by various angiogenic growth factors such as VEGF, FGFs, IGF-1 and PDGF. Although these growth factors have been studied extensively, controversies still exist as to whether angiogenesis depends on increased supply of these growth factors or their receptors are upregulated by the underlying pathological situation. An increased understanding of the basic biology of collateral vessel development would be instrumental in the establishment of therapeutic angiogenesis.

Angiogenesis Inducing Agents

The road to complete arterial grafting for coronary artery disease.

In 1984, our department moved to the use of single, and subsequently, bilateral internal thoracic artery grafting which, when reviewed after 12 years, suggest the addition of a second internal thoracic artery is beneficial. The 10-year survival using all-cause mortality was 86.9% for bilateral internal thoracic artery grafting compared with 74.2% for the use of a single internal thoracic artery graft. The mortality rate ratio for single versus bilateral internal thoracic artery grafts was 1.4 (P=0.009). In 1995, we entered an era of total arterial grafting using combinations of radial and internal thoracic arteries. There have been no additional early complications in the first 2 years, furthermore the early results show that the postoperative creatinine kinase MB isoenzyme and the myocardial infarction rates were lower in patients receiving at least one radial artery graft compared with those not receiving a radial artery graft. Continued use of internal thoracic and radial arteries to achieve complete arterial revascularisation for patients with coronary artery disease appears justified.

Aged

Most ovine mitral annular three-dimensional size reduction occurs before ventricular systole and is abolished with ventricular pacing.

BACKGROUND: Conventional surgical thinking indicates that mitral annular (MA) size reduction plays a key role in mitral valve closure, and most MA size and shape changes are thought to occur during left ventricular (LV) systole. The influences of left atrial (LA) and LV systole on MA size and shape, however, remain debated. METHODS AND RESULTS: Eight radiopaque markers were placed equidistantly around the MA and imaged using high-speed simultaneous biplane videofluoroscopy in seven closed-chest, sedated sheep before and during asynchronous LV pacing. Marker images were used to compute the three-dimensional coordinates of each marker every 16.7 ms throughout the cardiac cycle, allowing calculation of three-dimensional MA area, septal-lateral (SL) dimension, and commissure-commissure (CC) dimension under control and LV pacing conditions. Maximum MA area occurred in early diastole, and minimum MA area near end-diastole; maximum area reduction was 12+/-1% (P< or =.001). Interestingly, 89+/-3% of area reduction occurred before LV systole. During this "presystolic" period, SL decreased by 8+/-1% and CC by 2+/-1%; the SL/CC ratio fell from 0.73+/-0.02 to 0.69+/-0.01 (P< or =.005), indicating a less circular shape at end-diastole. With LV pacing, total MA area reduction was similar (13+/-2 versus 12+/-1%, P=NS versus control); however, all MA area reduction occurred during LV systole with minimum MA area occurring at end-systole. Presystolic shortening in both SL and CC dimensions was lost, and presystolic ellipticalization disappeared. CONCLUSIONS: Changes in MA size and shape coincident with LA systole included area reduction and shape change prior to the onset of LV contraction. These presystolic changes vanished when LA systole was absent (LV pacing). Thus, LA systole plays a pivotal role in MA size reduction and shape alteration. The unexpected timing of these MA dynamics should be taken into account during mitral valve reparative procedures.

Animals

Geometric determinants of ischemic mitral regurgitation.

BACKGROUND: The precise geometric determinants of ischemic mitral regurgitation (MR) are incompletely understood, although such knowledge is important to improve mitral valve reparative techniques. METHODS AND RESULTS: The three-dimensional geometry of the mitral apparatus was studied using radiopaque markers in eight closed-chest dogs with acute posterior left ventricular wall ischemia either with (MR) or without (no-MR) MR as assessed by using color Doppler. Using a cylindrical coordinate system (origin at the midpoint between the mitral annulus commissures [anterolateral and posteromedial] and z-axis directed toward the left ventricular apex), we measured the distance to the midpoint (z, in millimeters), radial distance from the z-axis (r, in millimeters), and angle from the intercommissural line (theta) of each marker. A multivariate analysis of variance showed the following differences (P < .005) between the MR and the no-MR groups: 1) markedly increased r of the posterior papillary muscle tip (10.3 versus 6.4 mm, MR versus no-MR, at end-systole) and increased r of the anterior papillary muscle tip; 2) dilation (in the septal-lateral direction) of the midpart of the mitral annulus and near the anterolateral region; 3) increased posterior mitral leaflet r near both commissures (eg, 8.3 versus 6.2 mm on the posteromedial side) and increased z (ie, shifted toward the left ventricular apex) of the posterior leaflet on the anterolateral side (eg, 7.0 versus 6.2 mm), which is analogous to restricted (or type III) leaflet motion. CONCLUSIONS: These findings indicate that the geometric determinants of ischemic MR in dogs are complex and involve many parts of the mitral valve apparatus. This complexity suggests that surgical attention to the entire annulus and excursion of the posterior leaflet may be helpful when annuloplasty alone is inadequate.

Animals