Large Transmural Myocardial Infarction Research Articles

Abstract 10121: Hypoimmunogenic Human Induced Pluripotent Stem Cells Derived Cardiomyocytes for Cardiac Regeneration

Introduction: Post-transplant rejection resulting from human leukocyte antigen (HLA) mismatch is a challenge in allogeneic cell therapy. Human amniotic fluid stem cell-derived iPSCs (hAFSC-iPSCs) are proved to have immune privilege. Hypothesis: hAFSC-iPSC derived cardiomyocytes (hAFSC-iPSC-CMs) are less immunogenic. Methods and Results: hAFSC-iPSCs and hAFSC-iPSC-CMs expressed classical HLA-Ia (HLA-A, -B and -C) and non-classical HLA-Ib but did not have HLA-II expression, indicating that these cells may not be highly immunogenic. We did T Cell Assays to confirm low immunogenicity of hAFSC-iPSC-CMs. We did ischemia-reperfusion surgery of left anterior descending coronary artery to create large transmural myocardial infarction in rats. At post-infarct 4 days, we injected human pluripotent stem cell-derived cardiomyocytes (1.0х10 7 cells/kg), including human embryonic stem cell-derived cardiomyocytes (hESC-CMs), hiPSC-CMs and hAFSC-iPSC-CMs, into the infarcted myocardium. Using very low dose of cyclosporine A (CsA, 2.5 mg/kg/day), only hAFSC-iPSC-CMs transplantation could improve post-infarct cardiac function (left ventricular ejection fraction improvement in hAFSC-iPSC-CMs, hESC-CMs and hiPSC-CMs: 13.1 ± 1.8%, 0.6 ± 1.7% and -1.9 ± 1.6%, respectively). Compared with hESC-CMs and hiPSC-CMs, hAFSC-iPSC-CM transplantation remuscularized the infarcted myocardium with infarct size reduction. Using very low dose CsA, these engrafted hAFSC-iPSC-CMs resulted in a 3-month survival in vivo. hAFSC-iPSC-CMs expressing non-classical HLA-Ib evaded detection and attack by natural killer (NK) cells and cytotoxic T cells because these hAFSC-iPSC-CMs activated the protein tyrosine phosphatase SHP-1/SHP-2 signalling pathway of NK cells and cytotoxic T cells which downregulated signal transducer and activator of transcription 1 (STAT-1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression. Conclusions: We demonstrated the immune privilege of hAFSC-iPSC-CM for cardiac regeneration. HLA-Ib-expressing hiPSCs with reduced HLA-II expression are less immunogenic and may serve as platforms for regenerative medicine.

Abstract 16206: An Atypical Presentation of Spontaneous Coronary Artery Dissection in a Young Male Patient

Background: Spontaneous coronary artery dissection (SCAD) is an important cause of myocardial infarction (MI) in women but rare in young healthy males. We report a case of a young male who presented with left hand tingling/numbness and was ultimately diagnosed with SCAD. Case Presentation: A 24-year-old male with history of asthma developed left hand tingling/numbness while playing basketball. This progressed to cold left upper extremity, prompting him to go to emergency room. Doppler ultrasound showed acute left brachial thrombus and emergent embolectomy of left brachial artery was done. Transesophageal echocardiogram, performed to investigate possible cardiac source of thrombus, showed normal ejection fraction, dyskinetic apex and biventricular thrombus (Figure 1A). Cardiac MRI revealed a large transmural MI in distribution of a wraparound left anterior descending artery (LAD) with associated regional akinesis of the left ventricular apex and an infarct in the right ventricular apex. Subsequent angiography revealed normal coronary arteries (Figure 1B) except a heterogenous linear filling defect in the apical LAD consistent with Type 1 SCAD (Figure 1C). No intervention was performed and the patient was treated conservatively. It was postulated that patient sustained an apical MI after SCAD of LAD, leading to formation of ventricular thrombi which then embolized to cause acute brachial artery thrombosis. Discussion: SCAD in young males is rare and can be a diagnostic challenge. Type 1 “pathognomic” angiographic finding in SCAD, is the classic appearance of multiple radiolucent lumens or arterial wall contrast staining. In case of inconclusive angiography, intravascular ultrasound or optical computed tomography can confirm diagnosis. Interventionalists should be familiar with angiographic appearance of SCAD as advanced imaging might not be available and in many cases, conservative management is preferred to percutaneous coronary intervention.

Chronic Heart Rate Reduction by Ivabradine Does Not Modify the Elastic Fiber Content in Post‐Myocardial Infarction Scar of Middle‐Aged Rats

A large myocardial infarction (MI) triggers progressive cardiac remodeling which results in left ventricular (LV) chamber dilatation and, as a consequence, in greater wall tension, particularly in the area of scar formation. Chronically elevated mechanical stress applied to fibroblasts and myofibroblasts within the scar has been known to stimulate the production of extracellular matrix proteins, predominantly collagen and elastin, that improves the tensile strength of the thinning LV wall. Considering that during a prolonged diastole the end‐diastolic volume and, hence, the force and duration of mechanical signals transduced into the scar become even more augmented it is feasible to assume that any heart rate‐lowering agent would promote further deposition of extracellular proteins by activated fibrogenic cells. Nevertheless, we have previously shown that chronic heart rate reduction (HRR) by ivabradine (IVA), a selective inhibitor of a pacemaker If current, did not alter the content of fibrillar collagen in post‐MI scar of middle‐aged rats. However, whether IVA‐induced HRR affects the content of elastic fibers in the scar remains undetermined. To test this hypothesis a large transmural MI (greater than 50% of the LV free wall) was induced in 12‐month‐old male Sprague‐Dawley rats by ligation of the left coronary artery. Post‐MI rats were then assigned in IVA‐treated (MI+IVA) and corresponding placebo (MI) groups. In MI+IVA groups, rats were treated with IVA i.p. via osmotic pumps in a dose of 10.5 mg/kg/d for 8 and 12 weeks. At the end of each treatment period, the hearts were collected and processed into paraffin‐embedded sections for histological evaluations. Eight‐micron‐thick sections of the left ventricle were stained with picrosirius red and Verhoeff's elastic tissue stains. The entire scar of each heart stained for collagen and elastic fibers were digitally captured on a computer using an Olympus BX53 microscope and the fractional volumes of collagen and elastic fibers were determined by using Image‐Pro Analyzer v.7.0 software. We found that the mean scar size and thickness were comparable among all groups of rats. Furthermore, the spatial distribution of the elastic fibers within the scars demonstrated almost identical pattern with an evident accumulation along the subendocardial and subepicardial regions, in the remnants of coronary vessels, and in isolated areas near the edge or throughout the middle portion of the scar. In addition, IVA‐treated and untreated rats showed a similar tendency in reduction of elastic component of the scars that was directly correlated with scar maturation. The quantitative analysis has revealed that the content of elastic fibers remained relatively analogous in scars of MI and MI+IVA rats 8 weeks (1.88±0.36% vs. 1.21±0.31%, respectively) and 12 weeks (0.99±0.45% vs. 0.89±0.18%, respectively) after MI. Moreover, there was no significant difference in ratio between elastic and collagenous components of the scar in corresponding IVA‐treated and untreated groups of rats. Our data are the first to demonstrate that chronic IVA‐induced HRR does not modify the elastic fiber content in post‐MI scar.

Kidney and Blood Pressure Abnormalities and Cardiac Hypertrophy, Accompany Moderate Coronary Artery Atherosclerosis in Western Diet Fed SR-BI/LDLR Double Knockout Mice

Mice lacking the HDL receptor, SR-BI, are susceptible to spontaneous or diet-inducible occlusive coronary artery (CA) atherosclerosis and myocardial infarction (MI) in the context of absence, or reduced expression of apoE, respectively. Our lab has generated mice lacking both SR-BI and the LDL receptor (dKO mice). When fed diets that are very high in cholesterol, SR-BI/LDL R dKO mice develop rapid CA atherosclerosis and large transmural MIs and exhibit significantly reduced survival. However, when fed a western type diet (WTD) with only moderately high cholesterol (22% fat, 0.125% cholesterol), dKO mice do not appear to exhibit reduced survival, and develop only mild CA atherosclerosis with . However they have significantly larger hearts than LDLR single KO (sKO) controls fed the same diet for the same period of time. We therefore examined additional factors that may account for the cardiac hypertrophy observed in these mice such as blood pressure (BP) and kidney pathology.

Abstract 134: Kidney and Blood Pressure Abnormalities, and Cardiac Enlargement Accompany Moderate Coronary Artery Atherosclerosis in Western Diet Fed SR-BI/LDLR Double Knockout Mice

Mice lacking the HDL receptor, SR-BI, are susceptible to spontaneous or diet-inducible occlusive coronary artery (CA) atherosclerosis and myocardial infarction (MI) in the context of absence, or reduced expression of apoE, respectively. Our lab has generated mice lacking both SR-BI and the LDL receptor (dKO mice). When fed diets that are very high in cholesterol, dKO mice develop rapid CA atherosclerosis and large transmural MIs, and exhibit significantly reduced survival. However, when fed a western type diet (WTD) with only moderately high cholesterol (22% fat, 0.125% cholesterol), dKO mice do not appear to exhibit reduced survival, and develop only mild CA atherosclerosis with little to no cardiac fibrosis. However they have significantly larger hearts than LDLR single KO (sKO) controls fed the same diet for the same period of time. We therefore examined additional factors that may account for the cardiac enlargement observed in these mice such as blood pressure (BP) and kidney pathology. 10 week old dKO mice and sKO controls were fed a WTD for 10 weeks; BP was measured before feeding, and periodically throughout feeding. Mice were euthanized after 10 weeks and blood and tissues were collected for analysis. DKO mice had reduced cholesterol associated with VLDL and LDL sized lipoproteins compared to sKO control mice after 10 weeks of WTD feeding. As expected, heart weights were significantly increased in dKO mice compared to sKO controls. Additionally, dKO mice had significantly lower body weights compared to sKO controls treated equivalently. Before the onset of feeding, there was no significant difference in BP between dKO and sKO mice. After 1 week of WTD feeding, dKO mice had significantly increased BP compared to both pre-diet levels and to sKO controls fed the same diet for the same timeframe. However, BP in dKO mice dropped significantly after 9 weeks of WTD compared to pre-diet measurements, while BP in sKO mice was constant throughout the study. Oil red O staining of kidney sections revealed striking lipid deposition and enlargement of glomeruli in kidneys from dKO mice, this was not observed in sKO control mice.

Improvement of left ventricular remodeling after myocardial infarction with eight weeks L-thyroxine treatment in rats

BackgroundLeft ventricular (LV) remodeling following large transmural myocardial infarction (MI) remains a pivotal clinical issue despite the advance of medical treatment over the past few decades. Identification of new medications to improve the remodeling process and prevent progression to heart failure after MI is critical. Thyroid hormones (THs) have been shown to improve LV function and remodeling in animals post-MI and in the human setting. However, changes in underlying cellular remodeling resulting from TH treatment are not clear.MethodsMI was produced in adult female Sprague–Dawley rats by ligation of the left descending coronary artery. L-thyroxine (T4) pellet (3.3 mg, 60 days sustained release) was used to treat MI rats for 8 weeks. Isolated myocyte shape, arterioles, and collagen deposition in the non-infarcted area were measured at terminal study.ResultsT4 treatment improved LV ±dp/dt, normalized TAU, and increased myocyte cross-sectional area without further increasing myocyte length in MI rats. T4 treatment increased the total LV tissue area by 34%, increased the non-infarcted tissue area by 41%, and increased the thickness of non-infarcted area by 36% in MI rats. However, myocyte volume accounted for only ~1/3 of the increase in myocyte mass in the non-infarct area, indicating the presence of more myocytes with treatment. T4 treatment tended to increase the total length of smaller arterioles (5 to 15 μm) proportional to LV weight increase and also decreased collagen deposition in the LV non-infarcted area. A tendency for increased metalloproteinase-2 (MMP-2) expression and tissue inhibitor of metalloproteinases (TIMPs) -1 to −4 expression was also observed in T4 treated MI rats.ConclusionsThese results suggest that long-term T4 treatment after MI has beneficial effects on myocyte, arteriolar, and collagen matrix remodeling in the non-infarcted area. Most importantly, results suggest improved survival of myocytes in the peri-infarct area.

Regulation of Gene Expression with Thyroid Hormone in Rats with Myocardial Infarction

IntroductionThe expression of hundreds of genes is altered in response to left ventricular (LV) remodeling following large transmural myocardial infarction (MI). Thyroid hormone (TH) improves LV remodeling and cardiac performance after MI. However, the molecular basis is unknown.MethodsMI was produced by ligation of the left anterior descending coronary artery in female SD rats. Rats were divided into the following groups: (1) Sham MI, (2) MI, and (3) MI+T4 treatment (T4 pellet 3.3 mg, 60 days release, implanted subcutaneously immediately following MI). Four weeks after surgery, total RNA was isolated from LV non-infarcted areas for microarray analysis using the Illumina RatRef-12 Expression BeadChip Platform.ResultsSignals were detected in 13,188 genes (out of 22,523), of which the expression of 154 genes were decreased and the expression of 200 genes were increased in MI rats compared with Sham MI rats (false discovery rate (FDR) <0.05). Compared to MI rats, T4 treatment decreased expression of 27 genes and increased expression of 28 genes. In particular, 6 genes down-regulated by MI and 12 genes up-regulated by MI were reversed by T4. Most of the 55 genes altered by T4 treatment are in the category of molecular function under binding (24) and biological processes which includes immune system process (9), multi-organism process (5) and biological regulation (19) nonexclusively.ConclusionsThese results suggest that altered expression of genes for molecular function and biological process may be involved in the beneficial effects of thyroid hormone treatment following MI in rats.

Left Ventricular Pseudoaneurysm Complicating Inferior Myocardial Infarction: A Case Report

Acquired pseudoaneurysm of the left ventricle is a very rare disorder and mostly occurs after large transmural myocardial infarction (MI) with peak creatine phosphokinase-MB levels greater than 150 IU/mL. Patients developing left ventricular (LV) pseudoaneurysm usually present with angina or heart failure symptoms. Although different imaging modalities exist, coronary angiography is the gold standard for diagnosis. Surgery is the treatment of choice for LV pseudoaneurysms detected in the first months after MI. Here we report the case of a 74-year-old woman who presented with a relatively small inferior MI due to right coronary artery occlusion and complicated by LV pseudoaneurysm.

Bioenergetic, Functional and Morphological Consequences of Postinfarct Cardiac Remodeling in the Rat

Despite recent advances in the treatment, severe chronic heart failure (CHF) remains a syndrome associated with high mortality. Therefore, the search for new agents to improve both patient symptoms and survival, as well as the pursuit for detailed knowledge about pathophysiology of the failing heart, will continue to depend on relevant animal models. Large acute myocardial infarction (MI) initiates complex changes in the geometrical, structural, and biochemical architecture of both infarcted and non-infarcted regions of ventricular myocardium, which can profoundly affect left ventricular function and prognosis. In this paper we present a new model for non-invasive cardiac31P MRS in the rat. Volume-selective31P magnetic resonance spectroscopy and echocardiography were used for evaluation of myocardial energy metabolism, cardiac morphology and function in rats 3 days and 3 weeks after induction of large MI. The phosphocreatine:adenosine triphosphate (PCr:ATP) ratio was decreased in rats with MI comparing with controls both at 3 days (1.6±0.06 vs 2.7±0.04; mean±s.e.m.P<0.0001) and 3 weeks (1.6±0.07 v 2.7±0.02 P<0.0001) postinfarct. The results from the study demonstrate that postinfarct cardiac remodeling is a rapid process of changes not only in cardiac geometry, structure and function but also in myocardial energy metabolism after large transmural MI in the rat.

Changes in sarcolemmal PLC isoenzymes in postinfarct congestive heart failure: partial correction by imidapril.

We have examined the changes in quantity and activity of cardiac sarcolemmal (SL) phosphoinositide-phospholipase C (PLC)-beta(1), -gamma(1), and -delta(1) in a model of congestive heart failure (CHF) secondary to large transmural myocardial infarction (MI). We also instituted a late in vivo monotherapy with imidapril, an ANG-converting enzyme (ACE) inhibitor, to test the hypothesis that its therapeutic action is associated with the functional correction of PLC isoenzymes. SL membranes were purified from the surviving left ventricle of rats in a moderate stage of CHF at 8 wk after occlusion of the left anterior descending coronary artery. SL PLC isoenzymes were examined in terms of protein mass and hydrolytic activity. CHF resulted in a striking reduction (to 6-17% of controls) of the mass and activity of gamma(1)- and delta(1)-isoforms in combination with a significant increase of both PLC beta(1) parameters. In vivo treatment with imidapril (1 mg/kg body wt, daily, initiated 4 wk after coronary occlusion) improved the contractile function and induced a partial correction of PLCs. The mass of SL phosphatidylinositol 4,5-bisphosphate and the activities of the enzymes responsible for its synthesis were significantly reduced in post-MI CHF and partially corrected by imidapril. The results indicate that profound changes in the profile of heart SL PLC-beta(1), -gamma(1), and -delta(1) occur in CHF, which could alter the complex second messenger responses of these isoforms, whereas their partial correction by imidapril may be related to the mechanism of action of this ACE inhibitor.

Expression of Gi-2 alpha and Gs alpha in myofibroblasts localized to the infarct scar in heart failure due to myocardial infarction.

Patients surviving large transmural myocardial infarction (MI) are at risk for congestive heart failure with attendant alteration of ventricular geometry and scar remodeling. Altered Gi-2 alpha and Gs alpha protein expression may be involved in cardiac remodeling associated with heart failure, however their expression in scar tissue remains unclear. MI was produced in Sprague-Dawley rats by ligation of the left coronary artery. Gi-2 alpha and Gs alpha protein concentration, localization and mRNA abundance were noted in surviving left ventricle remote to the infarct, in border and in scar tissues from 8 week post-MI hearts with moderate heart failure. We observed a 4.5- and 5.0-fold increase in immunoreactive Gi-2 alpha protein concentration occurs in the border and scar regions vs. control values, respectively, in 8-week post-MI rat hearts. Similarly, immunoreactive Gs alpha protein concentration was increased 3.4- and 8.2-fold, respectively, in these tissues vs. controls. Double-fluorescence labeling and phenotyping studies revealed that both Gi-2 alpha and Gs alpha proteins were localized to myofibroblasts in the infarct scar and to viable myocytes bordering the scar. Northern analysis revealed that the Gi-2 alpha/GAPDH ratio was increased in both viable and scar regions (1.24- and 1.85-fold respectively) from experimental hearts when compared to sham-operated control values when compared to noninfarcted left ventricle, the value of this ratio in scar tissue was elevated approximately 1.5 fold. The Gs alpha/GAPDH ratio was significantly increased (1.28-fold) only in the scar region vs. control. Our results indicate a marked increase in the expression of Gi-2 alpha and Gs alpha from myofibroblasts of the infarct scar as well as remnant myocytes bordering the scar in 8-week post-MI rat hearts. We suggest that these changes may be associated with ongoing remodeling in the infarct scar in chronic post-MI phase of this experimental model.

Angiotensin II, Transforming Growth Factor-β1and Repair in the Infarcted Heart

Tissue repair following myocardial infarction (MI) eventuates in fibrous tissue formation at the site of myocyte necrosis. Following a large transmural MI, fibrosis appears remote to the infarct site. This is associated with extensive tissue remodeling that adversely affects ventricular diastolic function. Substances involved in promoting fibrous tissue formation at MI and remote sites are under investigation. Angiotensin II (AngII), generated at sites of repair, has been implicated. However, its regulatory role on fibrous tissue formation remains uncertain. In the present study we sought to determine whether AngII is correlated to transforming growth factor beta 1 (TGF-β1) expression, a regulator of fibrous tissue formation, at these sites of tissue repair. We studied: (1) localization and expression of angiotensin converting enzyme (ACE), AngII receptors, TGF-β1mRNA and its receptors in the infarcted rat heart; and (2) effect of AngII on TGF-β1synthesis by chronic blockade of AT1receptors began at the time of surgery by losartan in rats with MI. Hearts were studied at 4 weeks post-MI. We found: (1) low-density ACE, AngII and TGF-β1receptor binding and low mRNA for type I collagen and TGF-β1in the normal heart; (2) fibrosis at sites of MI and remote to it, including endocardium and fibrosis of intraventricular septum, interstitial fibrosis of non-infarcted myocardium and fibrosis of visceral pericardium; (3) markedly increased (P<0.01) and colocalized ACE, AngII and TGF-β1receptor binding, type I collagen and TGF-β1mRNA at MI and remote sites of repair; (4) increased TGF-β1concentration (P<0.01) at these sites; and (5) attenuated TGF-β1and type I collagen gene expression (P<0.01) at these sites in rats receiving losartan. These observations suggest locally generated AngII via ATireceptor binding is correlated to TGF-β1expression and synthesis at sites of repair and remote sites in the infarcted rat heart. The mechanism responsible for the role of AngII in TGF-β1remains to be elucidated.

Cytokine gene expression after myocardial infarction in rat hearts: possible implication in left ventricular remodeling.

A large transmural myocardial infarction may initiate structural and geometric changes in the left ventricle that are commonly referred to as remodeling. Progressive, adverse remodeling of the myocardium may lead to ventricular dilatation and congestive heart failure. Recent studies have highlighted the effects of some cytokines on immune-mediated myocyte injury, postischemic myocardial inflammation, and cardiac function. However, studies of the involvement of cytokines in remodeling of the heart are few. In a rat model of myocardial infarction, progressive dilatation of the left ventricular cavity and lack of appropriate hypertrophy of the surviving myocardium were confirmed by transthoracic echocardiography. The relative expression of mRNA for tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 in the infarcted and noninfarcted myocardium of these rats, as well as in a group of sham-operated animals, was assessed by the technique of quantitative polymerase chain reaction amplification. In the infarcted region, TNF-alpha, IL-1beta, and IL-6 gene expression peaked at 1 week after infarction and decreased rapidly thereafter. In contrast, at 20 weeks after infarction, the gene expression levels of these cytokines remained significantly higher in the noninfarcted than in the infarcted zone or in the myocardium of sham-operated animals. Furthermore, the levels of these cytokines in the noninfarcted region correlated with the left ventricular end-diastolic diameter measured at 8 and 20 weeks after infarction. Among these cytokines, IL-1beta expression was highest, and its level correlated well with collagen deposition in the noninfarcted myocardium at 8 and 20 weeks after surgery. At 20 weeks after infarction, immunohistochemical analysis revealed the presence of IL-1beta in macrophages, endothelial cells, and vascular smooth muscle cells in the noninfarcted region, whereas no such immunoreactivity was found in the myocardium of sham-operated animals. These findings suggest the possible involvement of cytokines during the remodeling process of the noninfarcted left ventricular myocardium.

Expression of Gq alpha and PLC-beta in scar and border tissue in heart failure due to myocardial infarction.

Large transmural myocardial infarction (MI) leads to maladaptive cardiac remodeling and places patients at increased risk of congestive heart failure. Angiotensin II, endothelin, and alpha1-adrenergic receptor agonists are implicated in the development of cardiac hypertrophy, interstitial fibrosis, and heart failure after MI. Because these agonists are coupled to and activate Gq alpha protein in the heart, the aim of the present study was to investigate Gq alpha expression and function in cardiac remodeling and heart failure after MI. MI was produced in rats by ligation of the left coronary artery, and Gq alpha protein concentration, localization, and mRNA abundance were noted in surviving left ventricle remote from the infarct and in border and scar tissues from 8-week post-MI hearts with moderate heart failure. Immunohistochemical staining localized elevated Gq alpha expression in the scar and border tissues. Western analysis confirmed significant upregulation of Gq alpha proteins in these regions versus controls. Furthermore, Northern analysis revealed that the ratios of Gq alpha/GAPDH mRNA abundance in both scar and viable tissues from experimental hearts were significantly increased versus controls. Increased expression of phospholipase C (PLC)-beta1 and PLC-beta3 proteins was apparent in the scar and viable tissues after MI versus controls and is associated with increased PLC-beta1 activity in experimental hearts. Furthermore, inositol 1,4,5-tris-phosphate is significantly increased in the border and scar tissues compared with control values. Upregulation of the Gq alpha/PLC-beta pathway was observed in the viable, border, and scar tissues in post-MI hearts. Gq alpha and PLC-beta may play important roles in scar remodeling as well as cardiac hypertrophy and fibrosis of the surviving tissue in post-MI rat heart. It is suggested that the Gq alpha/PLC-beta pathway may provide a possible novel target for altering postinfarct remodeling.

Use of the Abiomed BVS 5000 Ventricular Assist Device for Myocardial Support Following Left Ventricular Aneurysmectomy: Case Report

Left ventricular aneurysms (LVA) are most commonly the result of a large transmural myocardial infarction, usually in the distribution of an occluded left anterior descending coronary artery. We investigated a case at Allegheny University Hospitals, Hahnemann Division, Philadelphia, PA, involving the use of the Abiomed BVS 5000 ventricular assist device (VAD) for LVA repair. The patient was successfully weaned from cardiopulmonary bypass using the Abiomed BVS Left Ventricular Assist Device (LVAD). The LVAD was successfully removed on the fourth postoperative day. In summary, we report the successful support of the myocardium with the Abiomed BVS 5000 Ventricular Assist Device after left ventricular aneurysmectomy. We favor mechanical over high dose inotropic support of the myocardium with a V AD in postcardiotomy patients with severe ventricular dysfunction.

Sinus rhythm mapping in healed experimental myocardial infarction: contrasting activation patterns for inducing ventricular tachycardia versus fibrillation

The inducibility of ventricular tachycardia (VT) and fibrillation (VF) is variable in healed myocardial infarction (MI) in the dog. To better understand the electrophysiologic basis for these arrhythmias, MI was produced in dogs by ligating the left anterior descending artery. One week later, epicardial mapping was performed with the dog in sinus rhythm using a hand-held bipolar electrode. Transmural mapping was performed with the dog in sinus rhythm with 4 pairs of bipolar electrodes mounted on a #14 needle. Ventricular arrhythmias were induced by the S 1S 2S 3 technique or 3- to 5-beat burst pacing at twice diastolic threshold. Only VF could be induced in 11 dogs, while sustained VT was induced in 6 dogs. Significantly more marked and more extensive delay in activation was seen both in the epicardium and transmurally in dogs with VT than in dogs with VF. In addition, dogs with VT had morphologic evidence of a large transmural MI, whereas dogs with VF had only a subendocardial MI. It is concluded that inducible sustained VT in the dog is usually associated with a large transmural MI and an activation sequence in sinus rhythm characterized by an extensive area of marked delay in activation. This activation pattern in sinus rhythm presumably is necessary to provide the underlying electrophysiologic milieu for sustained reentry.