Survival and reoperation after valve-sparing root replacement and root repair in acute type A dissection.

OBJECTIVE: Optimal treatment of the dissected root in type A dissection is still controversial. Valve-sparing techniques offer the advantage of better valve performance compared with mechanical valves or bioprostheses. The role of the different valve-preserving methods-root repair and replacement-needs further evaluation. METHODS: Follow-up data (median follow-up, 11.4 years; 95% confidence interval [CI], 10.1-12.7; range, 0-22.1 years) of 179 patients with acute type A dissection and root involvement, who underwent a valve-sparing root replacement using reimplantation (n = 44) or remodeling (n = 39) or a valve-sparing root repair (n = 96) between 1993 and 2017 were analyzed with respect to survival and reoperation. RESULTS: Median age of patients with reimplantation was 56.9 (range, 20.2-78), with remodeling 62.6 (range, 31-79.1), and with valve-sparing root repair 64.5 (range, 31-89.6) years. Thirty-day mortality for these groups was 15.9%, 15.4%, and 12.5% (P = .829), late mortality at 15 years was 43.2% (95% CI, 28.1-66.5), 36.7% (95% CI, 19.7-68.1), and 36.5% (95% CI, 23.0-57.9; P = .504). Risk factors for overall mortality were age, connective tissue disease, total arch replacement, surgical time, cross-clamp time, circulatory arrest, and the reimplantation technique. Cumulative incidence of reoperation at 15 years was 13.4% (95% CI, 2.1-24.7), 20% (95% CI, 6.3-33.6), and 13.3% (95% CI, 4.8-21.7; P = .565), respectively. CONCLUSIONS: With the different conditions in each group in this study on patients with acute type A dissection the valve-preserving root repair technique has similar long-term rates of survival and reoperation compared with root replacement techniques, underlining its usefulness as a less complex and even faster surgical technique if individually indicated.

Presence of reduced regional left ventricular function even in the absence of left ventricular wall scar tissue in the long term after repair of an anomalous left coronary artery from the pulmonary artery.

BACKGROUND: We sought to assess left ventricular regional function in patients with and without left ventricular wall scar tissue in the long term after repair of an anomalous origin of the left coronary artery from the pulmonary artery. METHODS: A total of 20 patients aged 12.8±7.4 years were assessed 10 (0.5-17) years after the repair of an anomalous origin of the left coronary artery from the pulmonary artery; of them, 10 (50%) patients showed left ventricular wall scar tissue on current cardiac MRI. Left ventricular regional function was assessed by two-dimensional speckle-tracking echocardiography in 10 patients with scar tissue and 10 patients without scar tissue and in 10 age-matched controls. RESULTS: In patients with scar tissue, MRI-derived left ventricular ejection fraction was significantly reduced compared with that in patients without scar tissue (51 versus 61%, p<0.05), and echocardiography-derived longitudinal strain was significantly reduced in five of six left ventricular areas compared with that in healthy controls (average relative reduction, 46%; p<0.05). In patients without scar tissue, longitudinal strain was significantly reduced in two of six left ventricular areas (average relative reduction, 23%; p<0.05) and circumferential strain was reduced in one of six left ventricular areas (relative reduction, 56%; p<0.05) compared with that in healthy controls. CONCLUSIONS: Regional left ventricular function is reduced even in patients without left ventricular wall scar tissue late after successful repair of an anomalous origin of the left coronary artery from the pulmonary artery. This highlights the need for meticulous lifelong follow-up in all patients with a repaired anomalous origin of the left coronary artery from the pulmonary artery.

Myocardial perfusion, scarring, and function in anomalous left coronary artery from the pulmonary artery syndrome: a long-term analysis using magnetic resonance imaging.

BACKGROUND: Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital heart defect. We aimed to examine the role of cardiac magnetic resonance imaging (MRI) in the long-term surveillance of repaired ALCAPA with regard to myocardial scarring, wall motion abnormalities, perfusion deficits, and myocardial function. METHODS: Twenty-one patients after direct reimplantation of ALCAPA (median age at operation, 2.8 years) were examined after a median 10.6 years by MRI at rest and under dobutamine stress conditions, echocardiography, and ergometry. Results were compared with preoperative, immediately postoperative (5 days), and intermediate-term (5.8 years) echocardiography. RESULTS: No early or late deaths occurred. Improvements in indexed left ventricular end-diastolic dimension, ejection fraction, and mitral valve function were observed in all patients. However, MRI at rest showed wall motion abnormalities in 67% and perfusion deficits in 28%. Myocardial scars were seen in 67%. Dobutamine stress MRI detected wall motion abnormalities in 19% and perfusion deficits in 14%, which were not seen on MRI at rest. Exercise testing did not reflect cardiac dysfunction. CONCLUSIONS: Although long-term follow-up showed global left ventricular function had improved after ALCAPA repair, MRI showed left ventricular wall motion abnormalities, perfusion deficits, and myocardial scarring were seen in many patients. Dobutamine stress MRI identified deficits that were not evident on MRI at rest, and can therefore be considered a valuable surveillance tool. These results suggest the need for lifelong surveillance of repaired ALCAPA.

Autologous CD133+ bone marrow cells and bypass grafting for regeneration of ischaemic myocardium: the Cardio133 trial.

AIMS: Intra-myocardial transplantation of CD133(+) bone marrow stem cells (BMC) yielded promising results in clinical pilot trials. We now performed the double-blinded, randomized, placebo-controlled CARDIO133 trial to determine its impact on left ventricular (LV) function and clinical symptoms. METHODS AND RESULTS: Sixty patients with chronic ischaemic heart disease and impaired LV function (left ventricular ejection fraction, LVEF <35%) were randomized to undergo either coronary artery bypass grafting (CABG) and injection of CD133(+) BMC in the non-transmural, hypokinetic infarct border zone (CD133), or CABG and placebo injection (placebo). Pre-operative LVEF was 27 ± 6% in CD133 patients and 26 ± 6% in placebo patients. Outcome was assessed after 6 months, and the primary endpoint was LVEF measured by cardiac magnetic resonance imaging (MRI) at rest. The incidence of adverse events was similar in both groups. There was no difference in 6-min walking distance, Minnesota Living with Heart Failure score, or Canadian Cardiovascular Society (CCS) class between groups at follow-up, and New York Heart Association class improved more in the placebo group (P = 0.004). By cardiac MRI, LVEF at 6 months was 33 ± 8% in the placebo group and 31 ± 7% in verum patients (P = 0.3), with an average inter-group difference of -2.1% (95% CI -6.3 to 2.1). Systolic or diastolic LV dimensions at 6 months were not different, either. In the CD133 group, myocardial perfusion at rest recovered in more LV segments than in the placebo group (9 vs. 2%, P < 0.001). Scar mass decreased by 2.2 ± 5 g in CD133(+) patients (P = 0.05), but was unchanged in the placebo group (0.3 ± 4 g, P = 0.7; inter-group difference in change = 2 g (95% CI -1.1 to 5)). By speckle-tracking echocardiography, cell-treated patients showed a better recovery of regional wall motion when the target area was posterior. CONCLUSION: Although there may be some improvements in scar size and regional perfusion, intra-myocardial injection of CD133(+) BMC has no effect on global LV function and clinical symptoms. Improvements in regional myocardial function are only detectable in patients with posterior infarction, probably because the interventricular septum after anterior infarction is not accessible by trans-epicardial injection. CLINICAL TRIAL REGISTRATION: This trial was registered at http://www.clinicaltrials.gov under NCT00462774.

Hemodynamic outcomes of geometric ring annuloplasty for aortic valve repair: a 4-center pilot trial.

OBJECTIVES: A geometric annuloplasty ring could improve efficacy and stability of aortic valve repair. Toward this goal, a 1-piece 3-dimensional titanium annuloplasty ring with Dacron covering was developed and tested successfully in animals. The purpose of this study was to define hemodynamic outcomes with this device used as the annuloplasty component of human aortic valve repair. METHODS: In a 4-center pilot trial with informed consent, 16 patients underwent aortic valve repair for aortic insufficiency, with the annuloplasty device sutured into the annulus beneath the leaflets. Preoperative annular diameter averaged 26.5 ± 2.0 (mean ± standard deviation) mm, and average ring size was 22.3 ± 1.2 mm. After annuloplasty, leaflet defects were easy to identify, and 14 of 16 patients (88%) required leaflet plication and/or autologous pericardial reconstruction for leaflet defects. Three patients had ascending aortic replacement, and 2 had remodeling root replacement. One had ultrasonic leaflet decalcification and another tricuspid valve annuloplasty. Follow-up data were from site-specific studies at the 6-month postoperative time point. RESULTS: There were no in-hospital mortalities or major complications. Preoperative aortic insufficiency grade (0-4 scale) was 3.6 ± 1.0 and fell to 1.0 ± 0.8 at 6 months (P < .0001). New York Heart Association class fell from 2.5 ± 0.5 to 1.1 ± 0.3 (P < .0001). Postrepair valve area was 2.7 ± 0.2 cm(2), and 6-month mean systolic gradient was 11.3 ± 3.3 mm Hg. Left ventricular end-diastolic diameter and ejection fraction both normalized (both P < .0001). CONCLUSIONS: Geometric ring annuloplasty facilitated aortic valve repair, allowing more precise reconstruction of leaflet defects. Aortic insufficiency reduction and systolic gradients were excellent, and expansion of valve reconstruction into broader categories of aortic valve disease seems indicated.

Cardiac cell therapy and bypass surgery.

More than 10 years ago, the first clinical application of cardiac cell therapy was performed in a patient undergoing coronary bypass grafting (CABG). Ever since, catheter-based cell delivery approaches have dominated the field, but surgical cell therapy continues to provide important information on safety and efficacy of various cell therapy strategies. The open chest offers unrivalled simplicity and precision of intramyocardial cell injection, and the cardiac surgical patient population includes those with very advanced heart disease who are in greatest need of innovative regeneration concepts. In this review, the clinical experience with cardiac surgical cell therapy is summarized and critically appraised.

Repair of anomalous origin of the left coronary artery from the pulmonary artery in infants and children.

OBJECTIVE: Although mortality after direct aortic reimplantation for anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) has significantly decreased, many questions remain unanswered. METHODS: Between 1986 and June 2010, we operated on 27 consecutive pediatric patients with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). All patients underwent reestablishment of a dual coronary system with direct aortic reimplantation of the left coronary artery into the aorta. Postoperative extracorporeal mechanical circulatory support was necessary in 7 cases. In all 7 patients, hemodynamic stability was achieved after 4 to 10 days of support. Mitral valve repair was performed in 9 patients with severe mitral valve incompetence and resulted in stable mitral valve function during follow-up as long as 19 years. RESULTS: There were no early or late deaths. During follow-up (3 months-17.5 years), both early and late improvement of myocardial function was observed in all patients. Reduced left ventricular regional function late after successful surgical correction of ALCAPA was related to the presence of left ventricular myocardial scar tissue, as detected by magnetic resonance imaging. CONCLUSIONS: Despite the absence of early and late mortality, the long-term prognosis for patients after reimplantation of ALCAPA into the aorta is not clear. Scars and perfusion deficits of the left ventricle may not be detected by standard echocardiographic evaluation of global left ventricular function and therefore may be underestimated. We therefore recommend lifelong surveillance of these patients, including magnetic resonance imaging.

Combined anterior mitral valve leaflet retention plasty and septal myectomy in patients with hypertrophic obstructive cardiomyopathy.

OBJECTIVES: Septal myectomy is the treatment of choice for patients with hypertrophic obstructive cardiomyopathy (HOCM) with significant left-ventricular outflow tract (LVOT) obstruction. In some HOCM patients, however, systolic anterior motion (SAM) of the anterior mitral leaflet significantly contributes to LVOT obstruction, resulting in mitral regurgitation and insufficient release of the obstruction after myectomy. We, therefore, developed a strategy of combined myectomy and anterior leaflet retention plasty (ALRP), and investigated its results in adult HOCM patients with manifest SAM. METHODS: Subaortic septal myectomy and ALRP were performed in 25 adult HOCM patients with significant SAM, as assessed by echocardiography (mean age = 48.5 ± 15 years). All patients received cardiac catheterization and echocardiography evaluation prior to the operation, before discharge, and at follow-up. Follow-up ranged between 0.8 and 14 years (median = 2.5 years). RESULTS: All patients survived the operation, and the Kaplan-Meier estimated survival was 100% at 1 year and 82 ± 6% at 5 years. Freedom from re-operation at 5 years was 83 ± 8%. The mean LVOT pressure gradient decreased from 84 ± 32 to 19 ± 11 mm Hg postoperatively (p < 0.001), and only two patients had mild residual or recurrent SAM at follow-up. Mitral regurgitation and New York Heart Association classification were also markedly improved at follow-up. CONCLUSIONS: Combined subaortic septal myectomy and ALRP is a safe and effective therapy in HOCM patients with significant SAM. ALRP can help prevent residual or recurrent LVOT obstruction and improves mitral regurgitation.

Cardiac cell therapies: the next generation.

Although significant advances have been made in terms of pharmacological, catheter-based, and surgical palliation, heart failure remains a fatal disease. As a curative concept, regenerative medicine aims at the restoration of the physiologic cellular composition of diseased organs. So far, clinical cardiac regeneration attempts have only been moderately successful, but a better understanding of myocardial cell homeostasis and somatic as well as embryonic stem cell biology has opened the door for the development of more potent therapeutic cardiac regeneration strategies. Accumulating evidence indicates that the postnatal mammalian heart retains a pool of tissue-specific progenitor cells and is also repopulated by cells from extracardiac sources. However, this intrinsic myocardial regeneration potential clearly needs to be augmented by either manipulation of the cell cycle of differentiated cells, activation of resident cardiac progenitor cells, and/or the transplantation of exogenous cells. This review summarizes the recent developments in cardiac regenerative medicine, many of which may find their way into the clinical setting in the foreseeable future.

Predictors for the use of left ventricular assist devices in infants with anomalous left coronary artery from the pulmonary artery.

BACKGROUND: Left ventricular (LV) mechanical circulatory support (MCS) may be necessary after repair of anomalous left coronary artery from the pulmonary artery. We evaluated LV function parameters for their ability to predict postoperative need for MCS. METHODS: Fourteen infants (median age, 3.6; range, 2.3 to 12 months) underwent direct aortic reimplantation of the left coronary artery. We compared preoperative LV end-diastolic diameter, end-diastolic pressure, ejection fraction, and fraction of shortening of 8 patients with successful weaning from cardiopulmonary bypass (group 1) and 6 patients with unsuccessful weaning from cardiopulmonary bypass and temporary MCS support (group 2). RESULTS: No perioperative or late deaths occurred. All patients at follow-up were free of reoperation (median follow-up, 10.4 years [range, 1.4 to 17 years]). Median preoperative LV end-diastolic diameter (47 [range, 41 to 60 mm] vs 32 mm [range, 21 to 36 mm]) and LV end-diastolic pressure (20 [range, 18 to 25 mm Hg] vs 12 mm Hg [range, 7 to 20 mm Hg]) were significantly higher in group 2 than in group 1 (p = 0.002 and p = 0.048). LV ejection fraction (0.28 [range, 0.19 to 0.37] vs 0.43 [range, 0.23 to 0.76]) and LV fraction of shortening (9% [range, 7% to 15%] vs 22% [range 13% to 30%]) were significantly lower in group 2 than in group 1 (p = 0.035 and p = 0.002). MCS support duration ranged from 4 to 12 days. There were no significant differences in LV function parameters at discharge or during follow-up between the groups. CONCLUSIONS: A preoperative LV end-diastolic diameter above 40 mm is the strongest predictor for postoperative temporary MCS after anomalous left coronary artery from the pulmonary artery repair in infancy. However, even with temporary MCS, direct aortic reimplantation for anomalous left coronary artery from the pulmonary artery can be performed with no mortality and excellent LV recovery.

Two-dimensional speckle tracking strain analysis for efficacy assessment of myocardial cell therapy.

The subtle effects of transplanted bone marrow cells (BMC) on regional myocardial behavior in patients with ischemic heart disease are difficult to assess. Novel echocardiographic techniques can quantify regional myocardial deformation (strain) and distinguish between passive and active wall motion. We hypothesized that this technique may help delineate cell therapy-induced changes in regional LV contractility that escape clinical routine studies. Twelve patients with coronary artery disease and impaired LV function (LVEF &<35%) underwent CABG surgery plus intramyocardial injection of autologous bone marrow mononuclear cells. Between two and five predefined segments of ischemic myocardium per patient received BMCs, and untreated ischemic segments served as internal controls. Segmental echocardiographic analysis of peak systolic strain by speckle tracking was performed before and 1 year after surgery and compared with standard wall motion analysis. Two patients died during the follow-up period. In the remaining 10 patients, mean LVEF increased from 24.5 +/- 10% to 32.1 +/- 11% (p = 0.02). A moderate improvement of systolic function was noted in ischemic control segments by both wall motion score (WMS) and 2D strain echocardiography (2DSE). In BMC-treated segments, WMS improved slightly, but the data failed to reach statistical significance. As assessed by 2DSE, however, systolic function of BMC-treated segments improved by nearly 100%. 2DSE proved to detect BMC-induced change with 30-fold higher sensitivity than WMS, and the Receiver Operating Characteristic curve (ROC) confirmed the diagnostic precision of 2DSE (area-under-the-ROC = 0.87). We conclude that echocardiographic speckle tracking two-dimensional strain analysis can detect cell therapy-induced changes in regional contractile function that may escape detection by standard wall motion assessment. Thus, 2DSE may be a useful tool for the further development of clinical cardiac cell therapy.

A heart full of stem cells: the spectrum of myocardial progenitor cells in the postnatal heart.

Influencing cellular regeneration processes in the heart has been a long-standing goal in cardiovascular medicine. To some extent, this has been successful in terms of vascular regeneration as well as intercellular connective tissue remodeling processes. Several components of today's routine heart failure medication influence endothelial progenitor cell behavior and support collateral vessel growth in the heart, or have been shown to prevent or reverse fibrosis processes. Cardiomyocyte regeneration, however, has so far escaped therapeutic manipulation strategies. Delivery of exogenous cells of bone marrow origin to the human myocardium may improve heart function, but is not associated with relevant neomyogenesis. However, accumulating evidence indicates that the myocardium contains resident cardiac progenitor cells (CPC) that may be therapeutically useful. This notion indeed represents a paradigm shift but is still controversial. The purpose of this review is to summarize the rapidly expanding current knowledge on CPC, and to assess whether it may be translated into solid therapeutic concepts.

The feasibility of speckle tracking for intraoperative assessment of regional myocardial function by transesophageal echocardiography.

OBJECTIVES: The authors aimed to examine the feasibility of intraoperative transesophageal echocardiography (TEE) acquisition of a non-Doppler-based, speckle tracking-derived myocardial deformation parameter (strain) immediately before and after coronary artery bypass graft (CABG) surgery in patients with reduced left ventricular (LV) function. DESIGN: A clinical study. SETTING: The cardiac surgery operating room of a tertiary referral institution. PATIENTS: Ten patients with reduced LV function (ejection fraction lower than 35%) undergoing coronary revascularization were studied before and immediately after the procedure. INTERVENTIONS: Perioperative TEE. MEASUREMENTS AND RESULTS: A total of 120 myocardial segments were analyzed before and after CABG surgery. In visually obtained wall motion scoring (WMS), there were 29 normokinetic (N), 69 hypokinetic (H), 19 akinetic (A), and 3 dyskinetic (D) segments preoperatively and 26 N, 65 H, 21 A, and 8 D segments after CABG surgery. Preoperative radial strain correlated well with WMS (R = 0.82, p < 0.0001), whereas longitudinal strain showed only a weak correlation (R = 0.36, p < 0.0001). Postoperatively, correlations were similar. Interobserver variability as analyzed by kappa-statistics showed better agreement for radial (kappa = 0.82 +/- 0.05, p = 0.001) and longitudinal strain (kappa = 0.73 +/- 0.06, p = 0.004) than for WMS (kappa = 0.65 +/- 0.06). Preoperatively, strain was markedly greater in normally perfused segments than in ischemic segments, whereas the mean WMS revealed only minor differences. CONCLUSIONS: Strain calculation from TEE images is feasible during cardiac surgery and correlates well with WMS but has better interobserver agreement. Strain analysis, but not WMS, detected wall motion differences between normally perfused and ischemic segments. This simple method allows objective intraoperative quantification of myocardial segment function and may become an important monitoring tool in the future.

Cell therapy for heart disease: great expectations, as yet unmet.

Regenerative medicine is often touted as an achievement of the new millennium, but many approaches to improve health by stimulating the organism's own capacity for healing have existed for a long time. Some components of today's regenerative medicine, however, are indeed fundamentally new developments, and one of those is the concept of increasing the number of contractile cells in the heart to cure heart failure, either by stimulating intrinsic regeneration processes or by transplanting exogenous cells. The aim of this paper is to review the current status of some key aspects of cell therapy and obstacles to clinical translation.

Cardiac cell therapy: a realistic concept for elderly patients?

Established therapeutic concepts for heart failure in elderly patients aim at long-term medical and/or surgical palliation. Heart transplantation is limited to younger individuals, and permanent mechanical assist devices are not yet widely used. In this situation, myocardial cell therapy offers fascinating new perspectives, the ultimate goal being the complete regeneration of heart muscle and blood vessel cells. In small animal models, myocardial cell therapy often leads to a striking improvement of heart function, but the success in man has so far been modest. A possible explanation for the problems with bench-to-bedside translation of cardiac cell therapy is that mainly autologous cell products from aged patients with chronic diseases have been used so far. The aim of this paper is to summarize the current state of development of clinical cardiac cell therapy, to outline how autologous regenerative cells are subject to ageing processes, and to discuss whether the cardiac cell therapy in its present form is a realistic concept for elderly patients.

Intramyocardial delivery of bone marrow mononuclear cells and mechanical assist device implantation in patients with end-stage cardiomyopathy.

In end-stage heart failure, mechanical ventricular assist devices (VAD) are being used as bridge-to-transplantation, as a bridge-to-recovery, or as the definitive therapy. We tested the hypothesis that myocardial implantation of autologous bone marrow mononuclear cells (BMNC) increases the likelihood of successful weaning from left VAD (LVAD) support. Ten patients (aged 14-60 years) with deteriorating heart function underwent LVAD implantation and concomitant implantation of autologous BMNC. Bone marrow was harvested prior to VAD implantation and BMNC were prepared by density centrifugation. Two patients received a pulsatile, extracorporeal LVAD and eight a nonpulsatile implantable device. Between 52 and 164 x 10(7) BMNC containing between 1 and 12 x 10(6) CD34+ cells were injected into the LV myocardium. There was one early and one late death. The median time on LVAD support was 243 days (range 24-498 days). Repeated echocardiographic examinations under increased hemodynamic load revealed a significant improvement of LV function in one patient. Three patients underwent heart transplantation, and four patients remain on LVAD support >1 year without evidence of recovery. Only one patient was successfully weaned from LVAD support after 4 months, and LV function has remained stable ever since. In patients with endstage cardiomyopathy, intramyocardial injection of BMNC at the time of LVAD implantation does not seem to increase the likelihood of successful weaning from VAD support. Other cell-based strategies should be pursued to harness the potential of cell therapy in LVAD patients.

Postnatal myocardial augmentation with skeletal myoblast-based fetal tissue engineering.

BACKGROUND: Cardiac anomalies constitute the most common birth defects, many of which involve variable myocardial deficiencies. Therapeutic options for structural myocardial repair remain limited in the neonatal population. This study was aimed at determining whether engineered fetal muscle constructs undergo milieu-dependent transdifferentiation after cardiac implantation, thus becoming a potential means to increase/support myocardial mass after birth. METHODS: Myoblasts were isolated from skeletal muscle specimens harvested from fetal lambs, labeled by transduction with a retrovirus-expressing green fluorescent protein, expanded in vitro, and then seeded onto collagen hydrogels. After birth, animals underwent autologous implantation of the engineered constructs (n = 8) onto the myocardium as an onlay patch. Between 4 and 30 weeks postoperatively, implants were harvested for multiple analyses. RESULTS: Fetal and postnatal survival rates were 89% and 100%, respectively. Labeled cells were identified within the implants at all time points by immunohistochemical staining for green fluorescent protein. At 24 and 30 weeks postimplantation, donor cells double-stained for green fluorescent protein and Troponin I, while losing skeletal (type II) myosin expression. CONCLUSIONS: Fetal skeletal myoblasts engraft in native myocardium up to 30 weeks after postnatal, autologous implantation as components of engineered onlay patches. These cells also display evidence of time-dependent transdifferentiation toward a cardiomyocyte-like lineage. Further analysis of fetal skeletal myoblast-based constructs for the repair of congenital myocardial defects is warranted.

Rosuvastatin reduces experimental left ventricular infarct size after ischemia-reperfusion injury but not total coronary occlusion.

This study compared the effects of rosuvastatin on left ventricular infarct size in mice after permanent coronary occlusion vs. 60 min of ischemia followed by 24 h of reperfusion. Statins can inhibit neutrophil adhesion, increase nitric oxide synthase (NOS) expression, and mobilize progenitor stem cells after ischemic injury. Mice received blinded and randomized administration of rosuvastatin (20 mg.kg(-1).day(-1)) or saline from 2 days before surgery until death. After 60 min of ischemia with reperfusion, infarct size was reduced by 18% (P = 0.03) in mice randomized to receive rosuvastatin (n = 18) vs. saline (n = 22) but was similar after permanent occlusion in rosuvastatin (n = 17) and saline (n = 20) groups (P = not significant). Myocardial infarct size after permanent left anterior descending coronary artery occlusion (n = 6) tended to be greater in NOS3-deficient mice than in the wild-type saline group (33 +/- 4 vs. 23 +/- 2%, P = 0.08). Infarct size in NOS3-deficient mice was not modified by treatment with rosuvastatin (34 +/- 5%, n = 6, P = not significant vs. NOS3-deficient saline group). After 60 min of ischemia-reperfusion, neutrophil infiltration was similar in rosuvastatin and saline groups as was the percentage of CD34(+), Sca-1(+), and c-Kit(+) cells. Left ventricular NOS3 mRNA and protein levels were unchanged by rosuvastatin. Rosuvastatin reduces infarct size after 60 min of ischemia-reperfusion but not after permanent coronary occlusion, suggesting a potential anti-inflammatory effect. Although we were unable to demonstrate that the myocardial protection was due to an effect on neutrophil infiltration, stem cell mobilization, or induction of NOS3, these data suggest that rosuvastatin may be particularly beneficial in myocardial protection after ischemia-reperfusion injury.