Search PubMed⌕ Search

Biomedical subjects

M Komeda

Publications and source records attributed to M Komeda.

At least 55 records · Page 3Linked to original sources
PubMed2000

Myocardial ischemia enhances the expression of acidic fibroblast growth factor in human pericardial fluid.

Acidic fibroblast growth factor (FGF) is a potent mitogen that can induce angiogenesis in vivo. We have recently reported a marked increase of basic FGF in the pericardial fluid of patients with severe coronary stenosis and an increase in vascular endothelial growth factor (VEGF) in the pericardial fluid of patients with severe myocardial ischemia. The purpose of this study was to evaluate whether acidic FGF levels in the pericardial fluid are associated with severe myocardial ischemia. Immediately after incision of the pericardium in 48 patients during open-heart surgery, 3-5ml of pericardial fluid was obtained. Concentrations of basic FGF and VEGF in the pericardial fluid were measured using an enzyme-linked immunosorbent assay (ELISA). The ELISA system for human acidic FGF was newly developed using a rabbit antibovine acidic FGF antibody. The patients were divided into three groups (group A: 13 patients undergoing emergency coronary artery bypass grafting (CABG) for unstable angina; group B: 17 patients undergoing elective CABG for stable angina; group C: 18 patients undergoing nonischemic open-heart surgery). The VEGF level in the pericardial fluid in group A was 68 +/- 59pg/ml, which was significantly higher than 33 +/- 9 pg/ml in group B and 31 +/- 20 pg/ml in group C (P < 0.05). The concentrations of basic FGF in the pericardial fluid in groups A and B were 722 +/- 601 and 773 +/- 763pg/ml, respectively, significantly higher than 263 +/- 349pg/ml in group C. The pericardial acidic FGF level in group A was 4,291 +/- 2,336 pg/ml, which was also significantly higher than 2,386 +/- 1,048 pg/ml in group B and 2,589 +/- 990 pg/ml in group C (P < 0.05). The acidic FGF level correlated well with the level of VEGF (r = 0.61, P < 0.0001). It is concluded that the level of acidic FGF in pericardial fluid is associated with severe myocardial ischemia. This result indicates that the release of acidic FGF from the myocardial tissue into pericardial fluid is closely related to severe myocardial ischemia.

Adult↗
PubMed2000

Basic fibroblast growth factor may improve devascularized sternal healing.

BACKGROUND: We have shown that a gelatin sheet incorporating basic fibroblast growth factor enhanced bone regeneration of the devascularized sternum. The purpose of this study was to determine if topical use of the gelatin sheet accelerated normal sternal regeneration and bone remodeling. METHODS: Thirty Wistar rats had median sternotomy and were divided into 3 groups: 10 had the bilateral internal thoracic arteries removed and basic fibroblast growth factor sheet applied on the sternum (group A), 10 had just the bilateral internal thoracic arteries removed (group B), and 10 had intact bilateral internal thoracic arteries (group C). RESULTS: Four weeks later the peristernal blood flow significantly increased and marked angiogenesis was seen around the sternum in group A. Histologically, the sternum was almost completely healed only in group A. In group A the bone mineral content was highest, but the bone mineral density was similar to that in other groups. The osteoclast index in group A was highest at the border zone of bone formation and remained high in regenerated bone. CONCLUSIONS: The basic fibroblast growth factor sheet offset sternal ischemia and accelerated normal sternal bone regeneration and remodeling, not only by callus formation but also by callus resorption.

Animals↗
PubMed2000

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.

Acute Disease↗
PubMed2000

Pericardial fluid from patients with unstable angina induces vascular endothelial cell apoptosis.

OBJECTIVES: The purpose of this study was to investigate whether pericardial fluid from patients with unstable angina (UA) would modulate vascular endothelial cell survival. BACKGROUND: Apoptosis of vascular endothelial cells promotes the coagulation process, playing an important role in the formation of coronary arterial thrombi. However, little is known about the mechanisms of vascular endothelial cell death in acute coronary syndrome. We hypothesized that factors inducing apoptosis are produced by the ischemic heart and accumulated in high concentrations in pericardial fluid. METHOD: Pericardial fluid was obtained during coronary artery bypass surgery from patients with UA (group A, n = 8) and those with stable angina (group B, n = 23). A survival assay of F2 cells from a mouse vascular endothelial cell line was performed in the presence of 10% pericardial fluid from each patient. RESULTS: Pericardial fluid levels of vascular endothelial growth factor were significantly higher in group A than in group B, indicating that group A had more ischemic insults than group B. Pericardial fluid from group A, but not from group B, markedly induced F2 cell death (cell survival relative to fetal bovine serum; group A: 33 +/- 26% vs. group B: 91 +/- 22%, p < 0.01). Cell death was associated with internucleosomal DNA fragmentation, a hallmark of apoptosis. Fractionation of pericardial fluid using a Centricon C-100 demonstrated that apoptosis-inducible activities exist in the Centricon C-100 retentates but not in the filtrates. CONCLUSIONS: Factors that induce vascular endothelial cell apoptosis are secreted into the pericardial space from the hearts of patients with UA. These factors are large complexes or unknown new proteins larger than 100 kDa.

Aged↗
PubMed2000

Physical model-based indirect measurements of blood pressure and flow using a centrifugal pump.

This article describes a technique offering indirect measurements of pump pressure differential and flow with certain accuracy independent of changes in blood viscosity. This technique is based on noninvasive measurements of the motor current and rotation speed using the physical model equations of the centrifugal pump system. Blood viscosity included in the coefficients of the dynamic equations is first estimated, and then substitution of the estimated viscosity into the steady equations of the model provides pump flow and pressure differential. In vitro tests using a Capiox pump showed a sufficient linear correlation between actual values and their estimates for pressure differential and pump flow. An in vivo test using a 45 kg sheep showed that the proposed algorithm needs robustness for the convergence of estimates of viscosity. An overall evaluation, however, of the developed algorithm/model showed indications of success in terms of efficient computation and modeling.

Algorithms↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗