Anteroapical Myocardial Infarction Research Articles

Frequency of Mitral Regurgitation in Patients with Acute Myocardial Infarction

BACKGROUND: Mechanical complications can occur after acute myocardial infarction. Most commonly mitral regurgitation (MR) occurs after infero-basal myocardial infarction (MI) due to papillary muscles dysfunction. MR may also develop with antero-apical MI. The objective of the study was to determine the frequency of mitral regurgitation in acute MI patients and to risk stratify the patients with MR for anterior and inferior wall MI. AIMS & OBJECTIVE: To assess the frequency of mitral regurgitation in patients with acute myocardial infarction. MATERIAL & METHODS: This was a descriptive case series carried out at the Cardiology department of Jinnah Hospital, Lahore from: 29-10-2013 to 29-04-2014. A total of 340 patients of MI were included. Echocardiography examination was carried out on all subjects on day 3-4 post MI. Frequency of mitral regurgitation in each group was measured by color flow Doppler technique. RESULTS: Out of study population, 153 (45%) were in between 30-50 years and 187 (55%) were in between 51-75 years. The mean of age was calculated as 55.09+11.81 years. In our data 181 (53.24%) were male and 159 (46.76%) were female. Frequency of MR in acute MI patients was recorded in 69 (20.29%) while 271 (79.71%) had no findings of MR. From the total of 69 cases, MR was recorded in 13 (18.84%) as anterior wall MI and 16 (23.19%) as inferior wall MI, p value was calculated as 0.532 which shows insignificant difference. There was a significant difference in hospital stay and mortality between both groups p-value 0.04. CONCLUSION: Mechanical complications develop after acute myocardial infarction and may be associated with serious outcomes. KEYWORDS: Acute MI, mitral regurgitation, anterior and inferior wall MI.

Myocardial injection of a thermoresponsive hydrogel with reactive oxygen species scavenger properties improves border zone contractility.

The decrease in contractility in myocardium adjacent (border zone; BZ) to a myocardial infarction (MI) is correlated with an increase in reactive oxygen species (ROS). We hypothesized that injection of a thermoresponsive hydrogel, with ROS scavenging properties, into the MI would decrease ROS and improve BZ function. Fourteen sheep underwent antero-apical MI. Seven sheep had a comb-like copolymer synthesized from N-isopropyl acrylamide (NIPAAm) and 1500 MW methoxy poly(ethylene glycol) methacrylate, (NIPAAm-PEG1500), injected (20 × 0.5 mL) into the MI zone 40 min after MI (MI + NIPAAm-PEG1500) and seven sheep were MI controls. Cardiac MRI was performed 2 weeks before and 6 weeks after MI + NIPAAm-PEG1500. BZ wall thickness at end systole was significantly higher for MI + NIPAAm-PEG1500 (12.32 ± 0.51 mm/m2 MI + NIPAAm-PEG1500 vs. 9.88 ± 0.30 MI; p = .023). Demembranated muscle force development for BZ myocardium 6 weeks after MI was significantly higher for MI + NIPAAm-PEG1500 (67.67 ± 2.61 mN/m2 MI + NIPAAm-PEG1500 vs. 40.53 ± 1.04 MI; p < .0001) but not significantly different from remote myocardium or BZ or non-operated controls. Levels of ROS in BZ tissue were significantly lower in the MI + NIPAAm-PEG1500 treatment group (hydroxyl p = .0031; superoxide p = .0182). We conclude that infarct injection of the NIPAAm-PEG1500 hydrogel with ROS scavenging properties decreased ROS and improved contractile protein function in the border zone 6 weeks after MI.

Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility.

Decreased contractility in the non-ischemic border zone surrounding a MI is in part due to degradation of cardiomyocyte sarcomeric components by intracellular matrix metalloproteinase-2 (MMP-2). We recently reported that MMP-2 levels were increased in the border zone after a MI and that treatment with doxycycline for two weeks after MI was associated with normalization of MMP-2 levels and improvement in ex-vivo contractile protein developed force in the myocardial border zone. The purpose of the current study was to determine if there is a sustained effect of short term treatment with doxycycline (Dox) on border zone function in a large animal model of antero-apical myocardial infarction (MI). Antero-apical MI was created in 14 sheep. Seven sheep received doxycycline 0.8 mg/kg/hr IV for two weeks. Cardiac MRI was performed two weeks before, and then two and six weeks after MI. Two sheep died prior to MRI at six weeks from surgical/anesthesia-related causes. The remaining 12 sheep completed the protocol. Doxycycline induced a sustained reduction in intracellular MMP-2 by Western blot (3649±643 MI+Dox vs 9236±114 MI relative intensity; p = 0.0009), an improvement in ex-vivo contractility (65.3±2.0 MI+Dox vs 39.7±0.8 MI mN/mm2; p<0.0001) and an increase in ventricular wall thickness at end-systole 1.0 cm from the infarct edge (12.4±0.6 MI+Dox vs 10.0±0.5 MI mm; p = 0.0095). Administration of doxycycline for a limited two week period is associated with a sustained improvement in ex-vivo contractility and an increase in wall thickness at end-systole in the border zone six weeks after MI. These findings were associated with a reduction in intracellular MMP-2 activity.

Parachute-Implantation bei schwerer ischämischer Herzinsuffizienz

Congestive heart failure related to myocardial infarction is characterized by left-ventricular remodeling and moreover it is associated with significant morbidity and mortality with currently limited therapeutic options. The catheter-based left ventricular partitioning device (ParachuteTM, CardioKinetix, Inc., Menlo Park, CA) is a novel therapeutic option available for patients with severe systolic dysfunction following antero-apical myocardial infarction with regional wall motion abnormalities. Preliminary clinical data indicate in addition to the safety the improvement in left ventricular hemodynamics, functional capacity and quality of life.

Transient Dynamic Left Ventricular Outflow Tract Obstruction

Dynamic left ventricular outflow (LVOT) obstruction has been classically described in patients with hypertrophic cardiomyopathy (HCM). The hypertrophy of the basal septum and systolic anterior motion of the mitral valve leaflet (SAM) cause dynamic LVOT obstruction. In addition, HCM also shows speckled appearance of myocardium and LVOT obstruction is persistent, although to a varying degree. Several other conditions cause the echocardiographic finding of dynamic LVOT obstruction like postoperative patients with hypovolemia, post aortic valve replacement (AVR) or mitral valve repair, hyperdynamic left ventricle and acute anteroapical myocardial infarction. We report two patients who had transient dynamic left ventricular outflow obstruction one with hypertension, mitral valve prolapse associated with hypovolemia and anaemia and another with vomiting and hypovolemia.

Myocardial infarction induces structural and functional remodelling of the intrinsic cardiac nervous system.

Intrinsic cardiac (IC) neurons undergo differential morphological and phenotypic remodelling that reflects the site of myocardial infarction (MI). Afferent neural signals from the infarcted region to IC neurons are attenuated, while those from border and remote regions are preserved post-MI, giving rise to a 'neural sensory border zone'. Convergent IC local circuit (processing) neurons have enhanced transduction capacity following MI. Functional network connectivity within the intrinsic cardiac nervous system is reduced post-MI. MI reduces the response and alters the characteristics of IC neurons to ventricular pacing. Autonomic dysregulation following myocardial infarction (MI) is an important pathogenic event. The intrinsic cardiac nervous system (ICNS) is a neural network located on the heart that is critically involved in autonomic regulation. The aims of this study were to characterize structural and functional remodelling of the ICNS post-MI in a porcine model (control (n=16) vs. healed anteroapical MI (n=16)). In vivomicroelectrode recordings of basal activity, as well as responses to afferent and efferent stimuli, were recorded from intrinsic cardiac neurons. From control 118 neurons and from MI animals 102 neurons were functionally classified as afferent, efferent, or convergent (receiving both afferent and efferent inputs). In control and MI, convergent neurons represented the largest subpopulation (47% and 48%, respectively) and had enhanced transduction capacity following MI. Efferent inputs to neurons were maintained post-MI. Afferent inputs were attenuated from the infarcted region (19% in control vs. 7% in MI; P=0.03), creating a 'neural sensory border zone', or heterogeneity in afferent information. MI reduced transduction of changes in preload (54% in control vs. 41% in MI; P=0.05). The overall functional network connectivity, or the ability of neurons to respond to independent pairs of stimuli, within the ICNS was reduced following MI. The neuronal response was differentially decreased to ventricular vs. atrial pacing post-MI (63% in control vs. 44% in MI to ventricular pacing; P<0.01). MI induced morphological and phenotypic changes within the ICNS. The alteration of afferent neural signals, and remodelling of convergent neurons, represents a 'neural signature' of ischaemic heart disease.

Residual Stress Impairs Pump Function After Surgical Ventricular Remodeling: A Finite Element Analysis

Surgical ventricular restoration (Dor procedure) is generally thought to reduce left ventricular (LV) myofiber stress (FS) but to adversely affect pump function. However, the underlying mechanism is unclear. The goal of this study was to determine the effect of residual stress (RS) on LV FS and pump function after the Dor procedure. Previously described finite element models of the LV based on magnetic resonance imaging data obtained in 5 sheep 16 weeks after anteroapical myocardial infarction were used. Simulated polyethylene terephthalate fiber (Dacron) patches that were elliptical and 25% of the infarct opening area were implanted using a virtual suture technique (VIRTUAL-DOR). In each case, diastole and systole were simulated, and RS, FS, LV volumes, systolic and diastolic function, and pump (Starling) function were calculated. VIRTUAL-DOR was associated with significant RS that was tensile (2.89 ± 1.31 kPa) in the remote myocardium and compressive (234.15 ± 65.53 kPa) in the border zone. VIRTUAL-DOR+RS (compared with VIRTUAL-DOR-NO-RS) was associated with further reduction in regional diastolic and systolic FS, with the greatest change in the border zone (43.5-fold and 7.1-fold, respectively; p < 0.0001). VIRTUAL-DOR+RS was also associated with further reduction in systolic and diastolic volumes (7.9%; p = 0.0606, and 10.6%; p = 0.0630, respectively). The resultant effect was a further reduction in pump function after VIRTUAL-DOR+RS. Residual stress that occurs after the Dor procedure is positive (tensile) in the remote myocardium and negative (compressive) in the border zone and associated with reductions in FS and LV volumes. The resultant effect is a further reduction in LV pump (Starling) function.

Handheld echocardiography saves the brain: A serendipitously found left ventricular thrombus

Handheld echocardiography (HHE) is an emerging technology with potential to alter routine clinical practice. Our institution has adopted the use of HHE devices for both teaching and patient care. However, the appropriate clinical scope of HHE continues to be controversial, and the literature is largely devoid of prognosis-altering applications. We report the diagnosis of left ventricular (LV) thrombus with HHE. A 75-year-old man presented with a large anteroapical ST-elevation myocardial infarction (MI). Initial transthoracic echocardiography (TTE) after percutaneous intervention showed no LV thrombus. Before his hospital discharge, HHE was performed and showed LV thrombus. The finding substantially changed the patient's treatment and prognosis; he was discharged with warfarin. This observation will help guide further inquiry into the proper clinical role of HHE.

Patient-specific finite element modeling of the Cardiokinetix Parachute(®) device: effects on left ventricular wall stress and function.

The Parachute(®) (Cardiokinetix, Inc., Menlo Park, California) is a catheter-based device intended to reverse left ventricular (LV) remodeling after antero-apical myocardial infarction. When deployed, the device partitions the LV into upper and lower chambers. To simulate its mechanical effects, we created a finite element LV model based on computed tomography (CT) images from a patient before and 6 months after Parachute(®) implantation. Acute mechanical effects were determined by in silico device implantation (VIRTUAL-Parachute). Chronic effects of the device were determined by adjusting the diastolic and systolic material parameters to better match the 6-month post-implantation CT data and LV pressure data at end-diastole (ED) (POST-OP). Regional myofiber stress and pump function were calculated in each case. The principal finding is that VIRTUAL-Parachute was associated with a 61.2 % reduction in the lower chamber myofiber stress at ED. The POST-OP model was associated with a decrease in LV diastolic stiffness and a larger reduction in myofiber stress at the upper (27.1%) and lower chamber (78.4%) at ED. Myofiber stress at end-systole and stroke volume was little changed in the POST-OP case. These results suggest that the primary mechanism of Parachute(®) is a reduction in ED myofiber stress, which may reverse eccentric post-infarct LV hypertrophy.

Off-pump epicardial ventricular reconstruction restores left ventricular twist and reverses remodeling in an ovine anteroapical aneurysm model

The loss of normal apical rotation is associated with left ventricular (LV) remodeling and systolic dysfunction in patients with congestive heart failure after myocardial infarction. The objective of the present study was to evaluate the effect of epicardial ventricular reconstruction, an off-pump, less-invasive surgical reshaping technique, on myocardial strain, LV twist, and the potential alteration of myocardial fiber orientation in an ovine model of LV anteroapical aneurysm. LV anteroapical myocardial infarction was induced by coil embolization of the left anterior descending artery. Eight weeks after occlusion, epicardial ventricular reconstruction was performed using left thoracotomy under fluoroscopic guidance in 8 sheep to completely exclude the scar. The peak systolic longitudinal/circumferential strains and LV twist were evaluated using speckle tracking echocardiography before (baseline), after device implantation, and at 6 weeks of follow-up. Epicardial ventricular reconstruction was completed in all sheep without any complications. Immediately after device implantation, LV twist significantly increased (4.18 ± 1.40 vs baseline 1.97 ± 1.92; P=.02). The ejection fraction had increased 17% and LV end-systolic volume had decreased 40%. The globallongitudinal strain increased from -5.3% to -9.1% (P<.05). Circumferential strain increased inboth middle and apical LV segments, with the greatest improvement in the inferior lateral wall (from-11.4% to -20.6%, P<.001). These effects were maintained ≥6 weeks after device implantation without redilation. Less invasive than alternative therapies, epicardial ventricular reconstruction on the off-pump beating heart can restore LV twist and systolic strain and reverse LV remodeling in an ovine anteroapical aneurysm model.

Epicardial catheter-based ventricular reconstruction: a novel therapy for ischaemic heart failure with anteroapical aneurysm

Surgical ventricular reconstruction has been used to treat ischaemic cardiomyopathy with large akinetic or dyskinetic areas. However, application of this approach requires a sternotomy, cardiopulmonary bypass and a left ventriculotomy. This study assessed the feasibility and efficacy of minimally invasive, off-pump, epicardial catheter-based ventricular reconstruction (ECVR) in an anteroapical aneurysm ovine model. Left ventricular (LV) anteroapical myocardial infarction was induced percutaneously by coil embolization of the left anterior descending coronary artery. Eight weeks after infarction, via mini left thoracotomy and without cardiopulmonary bypass, ECVR was performed in six sheep. The scar was excluded by placing anchor pairs on the LV epicardial anterior wall and the right ventricular side of the interventricular septum under fluoroscopic guidance. LV performance was evaluated before, immediately after device implantation and after 6 weeks by echocardiography. Terminal histopathology was performed. ECVR was completed expeditiously in all animals without complications. Parameters obtained 6 weeks after device implantation were compared with baseline (pre-device). End-systolic volume was decreased by 38% (25.6 ± 6.1 ml vs baseline 41.2 ± 7.2 ml, P = 0.02) with preservation of stroke volume. Ejection fraction was significantly increased by 13% (48.5 ± 7% vs baseline 35.8 ± 7%, P = 0.02). The circumferential strain in the anterior septum (-7.67 ± 5.12% vs baseline -0.96 ± 2.22%, P = 0.03) and anterior wall (-9.01 ± 3.51% vs baseline -4.15 ± 1.36%, P = 0.01) were significantly improved. The longitudinal strain in apex was reversed (-3.08 ± 1.53% vs baseline 3.09 ± 3.39%, P = 0.01). Histopathology showed full endocardial healing over the anchors with appreciable reduction of the chronic infarct in the LV. ECVR without cardiopulmonary bypass is a less invasive alternative to current standard therapies, reverses LV remodelling and improves cardiac performance in an ovine model of anteroapical aneurysm.

Invited Commentary

Invited Commentary

Left Ventricular Myocardial Contractility Is Depressed in the Borderzone After Posterolateral Myocardial Infarction

Contractility in the borderzone (BZ) after anteroapical myocardial infarction (MI) is depressed. We tested the hypothesis that BZ contractility is also decreased after posterolateral MI. Five sheep underwent posterolateral MI. Magnetic resonance imaging (MRI) was performed 2 weeks before and 16 weeks after MI, and left ventricular (LV) volume and regional strain were measured. Finite element (FE) models were constructed, and the systolic material parameter, Tmax, was calculated in the BZ and remote myocardium by minimizing the difference between experimentally measured and calculated LV strain and volume. Sheep were sacrificed 17 weeks after MI, and myocardial muscle fibers were taken from the BZ and remote myocardium. Fibers were chemically demembranated, and isometric developed force, Fmax, was measured at supramaximal [Ca(2+)]. Routine light microscopy was also performed. There was no difference in Tmax in the remote myocardium before and 16 weeks after MI. However, there was a large decrease (63.3%, p = 0.005) in Tmax in the BZ when compared with the remote myocardium 16 weeks after MI. In addition, there was a significant reduction of BZ Fmax for all samples (18.9%, p = 0.0067). Myocyte cross-sectional area increased by 61% (p = 0.021) in the BZ, but there was no increase in fibrosis. Contractility in the BZ is significantly depressed relative to the remote myocardium after posterolateral MI. The reduction in contractility is due at least in part to a decrease in contractile protein function.

The Benefit of Enhanced Contractility in the Infarct Borderzone: A Virtual Experiment

Objectives: Contractile function in the normally perfused infarct borderzone (BZ) is depressed. However, the impact of reduced BZ contractility on left ventricular (LV) pump function is unknown. As a consequence, there have been no therapies specifically designed to improve BZ contractility. We tested the hypothesis that an improvement in borderzone contractility will improve LV pump function. Methods: From a previously reported study, magnetic resonance imaging (MRI) images with non-invasive tags were used to calculate 3D myocardial strain in five sheep 16 weeks after anteroapical myocardial infarction. Animal-specific finite element (FE) models were created using MRI data and LV pressure obtained at early diastolic filling. Analysis of borderzone function using those FE models has been previously reported. Chamber stiffness, pump function (Starling’s law) and stress in the fiber, cross fiber, and circumferential directions were calculated. Animal-specific FE models were performed for three cases: (a) impaired BZ contractility (INJURED); (b) BZ-contractility fully restored (100% BZ IMPROVEMENT); or (c) BZ-contractility partially restored (50% BZ IMPROVEMENT). Results: 100% BZ IMPROVEMENT and 50% BZ IMPROVEMENT both caused an upward shift in the Starling relationship, resulting in a large (36 and 26%) increase in stroke volume at LVPED = 20 mmHg (8.0 ml, p < 0.001). Moreover, there were a leftward shift in the end-systolic pressure volume relationship, resulting in a 7 and 5% increase in LVPES at 110 mmHg (7.7 ml, p < 0.005). It showed that even 50% BZ IMPROVEMENT was sufficient to drive much of the calculated increase in function. Conclusion: Improved borderzone contractility has a beneficial effect on LV pump function. Partial improvement of borderzone contractility was sufficient to drive much of the calculated increase in function. Therapies specifically designed to improve borderzone contractility should be developed.

Acute non-ST elevation myocardial infarction following paclitaxel administration for ovarian carcinoma: A case report and review of literature

We report a case of an acute non-ST elevation myocardial infarction (AMI) induced by paclitaxel in a patient with ovarian cancer. A 45-year-old premenopausal lady without any co-morbidity was started on the first cycle of neoadjuvant chemotherapy with paclitaxel-based regimen for advanced stage ovarian cancer. The patient developed chest pain 3 h after paclitaxel infusion with characteristic electrocardiographic changes of antero-apical myocardial infarction. The patient recovered on conservative medical management with reversion of electrocardiogram (ECG) changes. Cardiac ischemia and myocardial infarction, possibly due to coronary vasospasm, are rare adverse effects of paclitaxel with reported incidence of 0.26%. We have reported a case of paclitaxel-induced myocardial infarction with reversible cardiac dysfunction. The possibility of myocardial infarction should be considered in patients who develop chest pain or other symptoms after paclitaxel infusion.

Mitral Regurgitation After Anteroapical Myocardial Infarction

Background— Mitral regurgitation (MR) generally accompanies inferobasal myocardial infarction (MI), with leaflet tethering by displaced papillary muscles. Mitral regurgitation is also reported with anteroapical MI without global dilatation or inferior wall motion abnormalities. We hypothesized that anteroapical MI extending to the inferior apex displaces the papillary muscles, tethering the mitral leaflets to cause MR. Methods and Results— In the retrospective part of the study, consecutive anteroapical MI patients were studied. Moderate-severe MR occurred in 9% of 234 patients with only anteroapical MI versus 17% of 242 with inferoapical extension ( P &lt;0.001). Ejection fraction was only mildly different (41±4% versus 46±5%; P &lt;0.01). In the human mechanistic portion of the study, 60 anteroapical MI patients (20 with only 2 apical segments involved and 40 with involvement of all 4 apical segments; 20 with MR and 20 without MR) were compared with 20 normal controls. Those with MR (≥moderate) had higher systolic papillary muscle–to-annulus tethering length ( P &lt;0.01). Mitral regurgitation grade correlated most strongly with tethering length ( r =0.70) and its diminished systolic shortening ( r =−0.65). In the animal study, 9 sheep with left anterior descending coronary artery ligation were analyzed. Four sheep that developed MR had inferoapical MI extension with tethering length increasing over 1.5 months (2.1±0.4 to 2.9±0.4 cm, P &lt;0.001) versus no significant increase in 5 sheep without MR (2.0±0.4 to 2.1±0.3 cm, P not statistically significant). In MR sheep, the normal decrease in tethering length from diastole to systole was eliminated ( P &lt;0.01). Conclusions— Anteroapical MI with inferoapical extension can mechanically displace papillary muscles, causing MR despite the absence of basal and midinferior wall motion abnormalities. This suggests the possibility of repositioning treatments for this condition.

Circulation: Clinical Summaries

Circulation: Clinical Summaries

Novel Ablation Strategy for Treatment of Multiple Ventricular Tachycardias after Anterior Wall Myocardial Infarction: Isolation of the Entire Substrate

Background: Ventricular tachycardia (VT) may occur after anterior wall myocardial infarction. The best ablation strategy is unclear. We report about three patients in whom isolation oft the entire substrate was performed. Methods: Three patients (66±5 years, LVEF 29±14%) underwent catheter ablation for sustained VT after anterior wall myocardial infarction. All patients had recurrent ICD shocks (VT storm in two) despite amiodarone therapy. During electrophysiological-study, 4±2 VTs were induced including the clinical VT. 3D-mapping of the left ventricle (LV) was performed in SR (n=2) or during RV pacing (n=1) and revealed a low-voltage (<1.5 mV) area with fractionated electrograms and late-potentials in the antero-apical LV (mean area of 90±34 cm2). The entire low-voltage area was isolated with a circumferential isolation line along the low-voltage area border-zone. Isolation was defined as absence of all potentials within the isolated area demonstrated by detailed point-by-point mapping. Automaticity was demonstrated in 2/3 pts. Procedure and fluoroscopy time was 155±22 min and 10.3±0.7 min, respectively. At the end oft the procedure, there was no (n=2) or one fast non-clinical VT (n=1) inducible. No complications occurred. No clinical VT occurred during a follow-up of 5±7 months. Conclusions: Isolation of the entire substrate appears to be feasible in patients with antero-apical wall myocardial infarction.

Comparison of the Young-Laplace Law and Finite Element Based Calculation of Ventricular Wall Stress: Implications for Postinfarct and Surgical Ventricular Remodeling

Both the Young-Laplace law and finite element (FE) based methods have been used to calculate left ventricular wall stress. We tested the hypothesis that the Young-Laplace law is able to reproduce results obtained with the FE method. Magnetic resonance imaging scans with noninvasive tags were used to calculate three-dimensional myocardial strain in 5 sheep 16 weeks after anteroapical myocardial infarction, and in 1 of those sheep 6 weeks after a Dor procedure. Animal-specific FE models were created from the remaining 5 animals using magnetic resonance images obtained at early diastolic filling. The FE-based stress in the fiber, cross-fiber, and circumferential directions was calculated and compared to stress calculated with the assumption that wall thickness is very much less than the radius of curvature (Young-Laplace law), and without that assumption (modified Laplace). First, circumferential stress calculated with the modified Laplace law is closer to results obtained with the FE method than stress calculated with the Young-Laplace law. However, there are pronounced regional differences, with the largest difference between modified Laplace and FE occurring in the inner and outer layers of the infarct borderzone. Also, stress calculated with the modified Laplace is very different than stress in the fiber and cross-fiber direction calculated with FE. As a consequence, the modified Laplace law is inaccurate when used to calculate the effect of the Dor procedure on regional ventricular stress. The FE method is necessary to determine stress in the left ventricle with postinfarct and surgical ventricular remodeling.

Regenerative healing following foetal myocardial infarction☆☆☆

The adult response to myocardial infarction results in inflammation, scar formation, left ventricular dilatation, and loss of regional and global function. Regenerative scarless healing has been demonstrated in foetal dermis and tendon and is associated with diminished inflammation. We hypothesised that following foetal myocardial infarction, there would be minimal inflammation, regenerative healing, and preservation of function. Anteroapical myocardial infarction encompassing 20% of the left ventricle was created in adult or early gestation foetal sheep. Myocardial function was serially assessed using quantitative echocardiography. Infarct architecture was examined histologically for evidence of scar formation. Cellular inflammation, cellular proliferation, and apoptosis were assessed using immunohistochemistry. In the adult sheep 4 weeks following myocardial infarction, there was a significant decline in ejection fraction (EF) (41±7.4% to 26±7.4%, p<0.05), and the akinetic myocardial segment increased in size (6.9±0.8 cm to 7.9±1.1 cm, p<0.05). By contrast, there was no decline in the foetal EF (53±8.1% to 55±8.8%) and no akinetic foetal myocardial segment 4 weeks post-infarction. The foetal infarcts lacked an inflammatory cell infiltrate and healed with minimal fibrosis, compared with the adults. Foetal infarcts also demonstrated 5-bromo-2'-deoxyuridine (BrdU)+ proliferating cells, including cardiomyocytes, within the infarct. These data demonstrate that the foetal response to myocardial infarction is dramatically different from the adult and is characterised by minimal inflammation, lack of fibrosis, myocardial proliferation and restoration of cardiac function. Diminished inflammation is associated with foetal regenerative cardiac healing following injury. Understanding the mechanisms involved in foetal myocardial regeneration may lead to applications to alter the adult response following myocardial infarction.