Unusual indication for extracorporeal membrane oxygenation immediately after successful sequential bilateral lung transplantation: a case report.

BACKGROUND: Ischemia-reperfusion injury-induced primary graft dysfunction after lung transplantation is a major cause of early morbidity and mortality. CASE REPORT: We report an unusual case of primary graft dysfunction grade III following uneventful off-pump bilateral sequential lung transplantation caused by paradoxical left ventricular failure due to systolic anterior motion of the mitral valve-induced left ventricular outflow tract obstruction. Cardiac failure was precipitated by profound dehydration and administration of high doses of vasopressin and norepinephrine. Immediate connection to extracorporeal membrane oxygenation treated the graft failure-associated respiratory-pulmonary hypoxia and reversed the cardiogenic shock syndrome. CONCLUSIONS: Hypovolemia together with a hyperdynamic state resulting from catecholamine administration may result in the development of dynamic left ventricular outflow tract obstruction even if baseline cardiac evaluation is unremarkable. Early detection and intensive efforts to reverse the underlying conditions including cessation of catecholamine therapy and correction of hypovolemia are essential.

Fate of patients with extracorporeal lung assist as a bridge to lung transplantation versus patients without--a single-center experience.

OBJECTIVES: Mechanical lung assist (MLA; extracorporeal membrane oxygenation (ECMO) or extracorporeal lung assist (ECLA)) is increasingly used as a temporary bridge to lung transplantation (LTx). This study was designed to evaluate the impact of preoperative MLA on the operative outcome, including longer-term survival, in comparison to patients undergoing LTx without preoperative MLA. METHODS: A total of 143 patients underwent LTx at our institution from 2002 to 2011. Forty-three percent (n=62) of patients presented with idiopathic pulmonary fibrosis and 71% (n=102) presented with severely elevated pulmonary artery pressure. RESULTS: Thirteen patients (9.1%) required pre-LTx MLA support (age 44 ±13 years, double LTx 73.3%, female gender 53%) whereas 130 patients did not (age 52 ±11 years, double LTx 41.5%, female gender 36.9%). In one patient, MLA was successfully weaned and the patient underwent subsequent LTx. All patients in the MLA group were intraoperatively supported with continuous ECMO. One patient had to be supported with MLA after LTx for a period of 8 days. The short-term and mid-term postoperative survival of the MLA patient group was not significantly different from the non-MLA group (LogRank p=0.28). The 30-day, 90-day and 1-year survivals were 95%, 90% and 71%, respectively, in the patients without MLA compared to 85%, 77% and 68% in the MLA group. CONCLUSIONS: MLA has no impact on long-term survival rate in LTx patients, but has an influence in postoperative survival. MLA support is a valuable tool to bridge unstable patients to LTx.

Immunological monitoring of extracorporeal photopheresis after heart transplantation.

Extracorporeal photopheresis (ECP) has been used as a prophylactic and therapeutic option to avoid and treat rejection after heart transplantation (HTx). Tolerance-inducing effects of ECP such as up-regulation of regulatory T cells (T(regs)) are known, but specific effects of ECP on regulatory T cell (T(reg)) subsets and dendritic cells (DCs) are lacking. We analysed different subsets of T(regs) and DCs as well as the immune balance status during ECP treatment after HTx. Blood samples were collected from HTx patients treated with ECP for prophylaxis (n = 9) or from patients with histologically proven acute cellular rejection (ACR) of grade ≥ 1B (n = 9), as well as from control HTx patients without ECP (HTxC; n = 7). Subsets of T(regs) and DCs as well as different cytokine levels were analysed. Almost 80% of the HTx patients showed an effect to ECP treatment with an increase of T(regs) and plasmacytoid DCs (pDCs). The percentage of pDCs before ECP treatment was significantly higher in patients with no ECP effect (26·3% ± 5·6%) compared to patients who showed an effect to ECP (9·8% ± 10·2%; P = 0·011). Analysis of functional subsets of CD4⁺CD25(high)CD127(low) T(regs) showed that CD62L-, CD120b- and CD147-positive T(regs) did not differ between the groups. CD39-positive T(regs) increased during ECP treatment compared to HTxC. ECP-treated patients showed higher levels for T helper type 1 (Th1), Th2 and Th17 cytokines. Cytokine levels were higher in HTx patients with rejection before ECP treatment compared to patients with prophylactic ECP treatment. We recommend a monitoring strategy that includes the quantification and analysis of T(regs), pDCs and the immune balance status before and up to 12 months after starting ECP.

Aprotinin-associated risks in off-pump coronary artery bypass grafting.

BACKGROUND: Little data is available regarding the safety of using the serine protease inhibitor aprotinin in off-pump cardiac surgery. We retrospectively assessed the risks of administering the drug to adult patients undergoing off-pump coronary artery bypass grafting (OPCABG). METHODS: Aprotinin was administered as a bolus of 1 or 2 million kallikrein inhibiting units to 391 patients following median sternotomy; 370 control patients underwent surgery during the same time period without receiving aprotinin. No other antifibrinolytic agents were administered. RESULTS: Preoperative characteristics, length of ICU and hospital stay were similar between the mostly medium-risk aprotinin and the control patients. Postoperative cardiac, renal, neurological, and respiratory complications and hospital mortality occurred with comparable frequencies in both groups. Levels of myocardial enzymes during the first 72 h after surgery also did not differ significantly. CONCLUSION: Use of aprotinin in OPCABG was not associated with a higher incidence of hospital mortality, cardiovascular, renal, or other complications. Given the good safety profile in this large patient population we suggest that aprotinin could still be a valid antifibrinolytic treatment option in OPCABG.

Reducing ischemia-reperfusion injury in clinical lung transplantation.

OBJECTIVE: Acute graft dysfunction secondary to ischemia-reperfusion injury (IRI) continues to be the most common cause of early mortality after lung transplantation. The perioperative management with aprotinin could decrease the incidence of severe IRI. METHODS: A retrospective analysis was conducted of the data from 180 patients who underwent either single lung (56%) or bilateral sequential lung transplantation for similar end-stage lung disease between 1997 and 2005. The most recent 68 patients were managed perioperatively with the high-dose aprotinin infusion regimen (aprotinin group). The ISHLT grade III injury score was used for the diagnosis of severe IRI, which is based on a Pao(2)-FIo(2) ratio of less than 200 mmHg. RESULTS: Grade III injury was observed in 18% of the patients who were not managed with aprotinin (control group, 152 grafts, 64% single transplants, 68% male, 54 +/- 8 years of age). Early ECMO support was required in 25% of these patients. The associated mortality rate was 40%. Despite significantly longer cold ischemic times (290 +/- 14 minutes vs 231 +/- 14 minutes), older donors (42 +/- 12 years of age), and more frequently observed severely elevated systolic PAP of greater than 60 mmHg (60% vs 48%) as well as more frequently required extracorporeal circulatory support (24%* vs 12%) in the aprotinin group, the incidence of severe IRI (8%) and associated mortality (9%) was markedly reduced. CONCLUSIONS: The use of aprotinin in LTX surgery, which had strong beneficial effects on patient outcomes, significantly decreased the incidence of severe posttransplant IRI.

Pharmacodynamics of T-cell function for monitoring immunosuppression.

OBJECTIVES: Recent studies show that measuring pharmacodynamic (PD) effects offers a unique possibility to predict immunosuppression. Thus, in this study we have monitored the PD properties of immunosuppressants on diverse T-cell functions in heart transplant (HTx) recipients. MATERIALS: PDs and blood concentrations (PK) of three different basis-immunosuppressive drugs were studied: cyclosporin A (CsA); tacrolimus (TRL) and sirolimus (SRL). T-cell function was analysed by expression of proliferating cell nuclear antigen (PCNA) labelling, expression of cytokines (IL-2, IFN-gamma) and surface antigen (for example, CD25) by FACS analysis. RESULTS: In group I, at time points C0 and C2, increased CsA-PK significantly inhibited expression of IL-2, IFN-gamma, PCNA and CD25 (P < 0.05). Correlations (r(2)) at C2 between inhibition of T-cell functions (PD) with PK and with drug doses were: CsA-PK: 0.71-0.91 and CsA-dose: 0.73-0.87. In group II, increased TRL-PK over time did not further inhibit expression of CD25, but inhibited PCNA expression more on day 3, and IL-2 and IFN-gamma expression was significantly higher on days 2 and 3 compared to PD effects of CsA (P < 0.05). Blood SRL concentrations in C0 group III, increased on day 1 and remained stable at days 3 and 4. Expression of PCNA was not altered in the SRL-PK category, whereas expression of CD25 was higher and expression of cytokines was lower than PD effects of CsA. CONCLUSIONS: Our results show that PD effects on T-cell function can be used to monitor immunosuppression bringing potential to increase the efficacy and safety of immunosuppressive therapy after HTx.

C0h/C2h monitoring of the pharmacodynamics of cyclosporin plus mycophenolate mofetil in human heart transplant recipients.

UNLABELLED: Pharmacokinetic (PK) parameters like C2h have improved efficacy of immunosuppressive therapy. However, drug interactions, toxicities, and individual differences to drug effects still remain challenging. Therefore, this study was designed to assess pharmacodynamic (PD) effects of the combination cyclosporin (CsA) plus mycophenolate mofetil (MMF) on lymphocyte functions in peripheral blood of stable heart transplant recipients (HTx) using our established FACS assays. METHODS: Blood from 25 HTx patients was drawn before (C0h) and 2 hours after dosing (C2h). CsA and mycophenolic acid (MPA) concentrations were measured by EMIT. FACS assessed expression of cytokine production (IL-2, TNF-alpha), lymphocyte proliferation (PCNA), and T-cell activation (CD25, CD95). RESULTS: Evening doses of CsA (25/50/75 or 100 mg) and MMF (250/500 or 1000 mg) produced C0h levels as follows: CsA, 162 +/- 12 ng/mL; MPA, 1.7 +/- 0.2 mg/L. Morning doses of CsA (50/75 or 100 mg) and MMF (250/500/1000 or 1500 mg) produced C2h-levels as follows: CsA, 589 +/- 56 ng/mL and MPA, 7.4 +/- 1.3 mg/L. PD effects at C0h/C2h (% expression +/- SEM, all P < .05) were IL-2, 18 +/- 3/10 +/- 2; TNF-alpha, 12 +/- 2/7 +/- 1; PCNA, 8 +/- 1/5 +/- 1; CD25, 26 +/- 4/13 +/- 2; CD95, 23 +/- 4/11 +/- 2). Correlations (r2) at time point C2h between inhibition of lymphocyte functions (PD) with drug concentrations (PK) and with drug doses were CsA-PK, 0.71 to 0.91; MMF-PK, 0.55 to 0.76; CsA-dose, 0.73 to 0.87; MMF-dose, 0.61 to 0.80. CONCLUSION: For the first time, the immunosuppressive effects of the combination CsA plus MMF were quantified in whole blood of human HTx at different time points. PD assays may offer the opportunity to optimize clinical immunosuppressive drug therapy.

Pharmacodynamic monitoring of the conversion of cyclosporine to tacrolimus in heart and lung transplant recipients.

OBJECTIVE: Conversion from cyclosporine (CsA) to tacrolimus (TRL) remains challenging in the daily routine due to individual variations in blood concentrations (pharmacokinetics, PK), pharmacodynamics (PD) and in interactions on plasma mycophenolic acid (MPA) concentrations. Therefore, we used our PD assays of lymphocyte function to monitor the conversion of CsA to TRL in heart (HTx) and lung (LTx) transplant recipients. METHODS: Patients (six HTx, two LTx) were converted from CsA to TRL because of gingival hyperplasia. All patients were treated with 6 mg BID TRL 24 hours after the last CsA dose and received mycophenolate mofetil BID cotherapy. PK measurements of CsA, TRL, and MPA were done by EMIT. Expression of cytokine production (IL-2, TNF-alpha), lymphocyte proliferation (PCNA), and activation (CD25) was assessed by FACS. RESULTS: TRL concentrations increased from day 1 to 3, but did not alter MPA concentrations, which were comparably high to MPA concentrations in combination with CsA (day 0). Compared to CsA therapy, increased TRL concentrations did not further inhibit PCNA expression, inhibited CD25 expression less on days 1 and 2 and equally high on day 3, but inhibited expression of IL-2 and TNF-alpha significantly higher on days 2 and 3 (P < .05). CONCLUSION: This study shows that monitoring PD of lymphocyte functions after conversion from CsA to TRL in HTx and LTx recipients revealed differences of inhibition of lymphocyte functions. Monitoring PD of lymphocyte function may provide insights in drug interactions of immunosuppressive combination therapy and may help to tailor immunosuppression to avoid toxicity and to enhance efficacy.

Off-pump coronary artery revascularization: ideal indication for patients with porcelain aorta and calcification of great vessels.

Patients with porcelain aorta and severe calcification of the great vessels are a challenging dilemma for the cardiovascular surgeon regarding bypass technique, choice of conduit, and selection of proximal anastomotic sites due to the high incidence of devastating thromboembolization and aortic injury. No currently proposed surgical approach avoids manipulation of the heavily calcified ascending aorta. Three patients presented with unstable angina and decreased ventricular function secondary to significant left main coronary artery stenosis and 3-vessel coronary artery disease. In addition to the coronary artery disease, severely calcified ascending aorta and great vessels were discovered. One patient presented with near total distal abdominal aortic occlusion, severe peripheral vascular disease, history of stroke, and carotid endarterectomy. Surgical coronary revascularization was indicated. Coronary artery bypass grafting using internal thoracic artery and greater saphenous vein composite arterial inflow grafts in combination with off-pump beating heart surgery was successfully used. Cardiopulmonary bypass and clamping of the aorta was avoided. No new neurologic deficit was observed. Coronary revascularization with internal thoracic artery composite grafts and avoiding cardiopulmonary bypass and clamping the calcified aorta is an effective method to prevent clamp injury and thromboembolization. Off-pump coronary artery bypass grafting seems to be an ideal indication in patients with porcelain aorta because the surgical techniques of "no-touch" and "no-cannulation" can be applied.

Off-pump coronary artery bypass grafting in a patient with AIDS, acute myocardial infarction, and severe left main coronary artery disease.

A 48-year-old male patient with AIDS presented with postinfarct unstable angina, decreased left ventricular function (EF 35%), significant left main coronary artery disease, and total occlusion of the proximal left anterior descending and right coronary arteries. In order to avoid the potential immunosuppressive effect of cardiopulmonary bypass (CPB) in an already compromised host with an already low CD4+ helper/inducer T cell count (180/microL) and high retroviral load (165,000 copies/mL), the application of beating-heart technology and off-pump coronary bypass grafting was an ideal indication. The patient underwent successfully off-pump/CPB coronary revascularization. The triple drug combination of highly active antiretroviral therapy (HAART) was resumed postoperatively. The patient was discharged from the hospital on the 7(th) postoperative day. The CD4+ count was 142/microL and the viral load decreased to 450 copies/mL. Seven months post-operatively the patient was free of angina and without shortness of breath. The CD4+ count was 160/(m)L and the viral load undetectable. Improved survival of HIV positive patients has resulted in a shift from caring for terminally ill patients to caring for patients with chronic illness. While protease inhibitors have positively affected survival, they may also cause plasma lipid abnormalities, which can lead to severe premature coronary artery disease. Therefore, an increasing population of AIDS and HIV positive patients with coronary artery disease may require cardiac interventions in the near future. Coronary revascularization without CPB and its potential immunocompromising effect may play an important role in patients with severe coronary artery disease and AIDS.

Management of porcelain aorta and calcified great vessels in coronary artery bypass grafting with off-pump and no-touch technology.

A 69-year-old woman presented with postinfarct unstable angina and decreased ventricular function secondary to significant left main coronary artery stenosis in combination with total right coronary artery occlusion. We did successful off-pump coronary revascularization in this patient with severely calcified ascending aorta and great vessels, subtotal aortobiiliac stenoses, a history of previous stroke, and right carotid endarterectomy.

Off-pump coronary artery bypass grafting. Excellent results in a group of selected high-risk patients.

BACKGROUND: Off-pump coronary artery bypass grafting (OPCABG) has assumed an increasing role in many surgical practices. The ideal candidate has not been defined, but high-risk patients seem to benefit most when cardiopulmonary bypass (CPB), aortic cross clamping and cardioplegic arrest are avoided. METHODS: Fourteen high-risk patients (age 52 to 81 years, 1 female, EF 44%+/-8, Parsonnet score 23+/-4) were studied. They presented with acute coronary syndroms on platelet glycoprotein IIb/IIIa antagonists, acute myocardial infarction, worsening renal failure, decompensating ischemic cardiomyopathy, religious beliefs and denial of blood transfusion, and severe peripheral/cerebrovascular disease (total bilateral internal carotid artery occlusion and/or >90% stenosis). These patients underwent OPCABG via sternotomy with the intention of complete coronary revascularization. RESULTS: An average of 2.3 grafts/patient were performed and the posterior descending artery (PDA) and marginal branches of the circumflex artery (LCX) were grafted in 79% of the patients. There were 3 events of intraoperative cardiac arrest precipitated by occlusion of right coronary artery (RCA) or positioning a cardiomegaly heart leading to immediate intravascular shunting (2) and/or conversion to CPB (1). One patient was converted to CPB and graft revision (intraoperative ultrasound and probing). The mortality rate was 0% and one stroke was observed on post-operative day 1. Coronary angiography (n=6) showed no significant stenosis. CONCLUSIONS: OPCABG complete revascularization is feasible in high-risk patients with low morbidity and mortality and excellent early RESULTS: OPCABG may be indicated in patients on platelet receptor antagonists preventing bleeding complications. Cardiomegaly can cause difficult off-pump LCX and PDA exposure and stabilization. RCA grafting off-pump is less tolerated and PDA grafting is preferred. High-risk patients for CPB are the ones who may benefit the most from OPCABG.

Myocardial function in hearts with transgenic overexpression of the G protein-coupled receptor kinase 5.

BACKGROUND: Chronic heart failure is associated with impairment of the myocardial beta-adrenergic receptor (beta-AR) system. In this study, the effects of G protein-coupled receptor kinase 5 (GRK5) overexpression on myocardial performance were directly assessed in the hearts of transgenic mice using an isolated work-performing murine heart preparation and computerized analysis of functional data. METHODS: A controlled experimental study was performed to evaluate cardiac function in both transgenic mice with a 30-fold overexpression of GRK5 (n = 9, 23 to 29 g) and littermate controls (n = 10, 22 to 29 g). Preload-dependent cardiac output, contractility, stroke work, stroke volume, and heart rate were compared between the two groups. RESULTS: Significant decreases in preload-dependent cardiac output and contractility were observed in the mice with GRK5 overexpression when compared with control group mice and occurred in association with significant decreases in stroke work and stroke volume. There was no significant difference in the average heart rate between the two groups. CONCLUSIONS: These data suggest that GRK5 upregulation may be partially responsible for alterations in myocardial function in chronic heart failure.

Hyperacute rejection in single lung transplantation--case report of successful management by means of plasmapheresis and antithymocyte globulin treatment.

We describe the third case and first successful treatment of hyperacute rejection in a pulmonary allograft recipient and detail the immediate clinical findings. The patient underwent single right lung transplantation for severe emphysema and chronic obstructive pulmonary disease. Three hours after completion of the vascular anatomoses oxygen desaturation and increased airway pressure was noted in combination with graft edema, frothy, pink fluid draining from the bronchial orifice, hemodynamic instability, thrombocytopenia, and coagulopathy. The retrospective cross-match result was reported to be positive. The clinical diagnosis of hyperacute rejection was made. A donor-specific IgG HLA antibody to A2 was identified. The standard immune suppression regimen was immediately modified and a hyperacute rejection protocol applied including plasmapheresis and antithymocyte globulin treatment as well as cyclophosphamide to decrease antibody existence and production. A remarkable clinical recovery was observed after the fifth postoperative day and completion of plasmapheresis when a repeated retrospective cross-match showed significantly decreasing anti-donor reactivity.

Surgical resection of an intracardiac rhabdomyoma.

There are only a few previous reports of intracardiac rhabdomyomas causing ventricular arrhythmias and near syncope. In this report we describe the successful surgical resection of an intracardiac rhabdomyoma using cardiopulmonary bypass, blood cardioplegia, and hypothermia. Preoperative evaluation consisting of echocardiography, computed tomography (CT), magnet resonance imaging (MRI), and positron emission tomography (PET) strongly suggested the presence of a symptomatic primary cardiac tumor projecting from the interventricular septum into the right ventricle.

Right ventricular dysfunction after cardiac transplantation: primarily related to status of donor heart.

BACKGROUND: It is unclear whether right ventricular dysfunction after transplantation is due to donor brain death-related myocardial injury or recipient pulmonary hypertension. METHODS: A canine donor model of brain death and a monocrotaline pyrrole-induced chronic pulmonary hypertension recipient model were established, and used for 30 orthotopic bicaval cardiac transplantations divided into three groups: Controls (group A, normal donor/recipient), group B (brain-dead donors/normal recipient), and group C (normal donor/recipients with pulmonary hypertension). Right ventricular function was measured before transplant and brain death, 4 hours after brain death, and after transplant (1 hour off bypass) by load-independent means plotting stroke work versus end-diastolic volume during caval occlusion. Right ventricular total power and pulmonary vascular impedance were determined by Fourier analysis. RESULTS: In comparison to the control group right ventricular preload-recruitable stroke work and total power decreased significantly after brain death and transplant in group B (from 22.7 x 10(3) erg (+/-1.2) at baseline to 15.6 x 10(3) (+/-0.9) after brain death and to 11.3 x 10(3) (+/-0.9) after transplant). In group C there was a significant increase in pulmonary artery pressure, impedance, right ventricular preload-recruitable stroke work, total power after transplant. CONCLUSIONS: Normal donor hearts adapt acutely to the recipient's elevated pulmonary vascular resistance by increasing right ventricular power output and contractility. Brain death caused significant right ventricular dysfunction and power loss, which further deteriorated after graft preservation and transplantation. The effects of donor brain death on myocardial function contribute to right ventricular dysfunction after cardiac transplantation.

Molecular and functional mechanisms of right ventricular adaptation in chronic pulmonary hypertension.

BACKGROUND: Chronic pulmonary hypertension can lead to compensatory changes in the right ventricle. In this study, the adaptive mechanisms of the right ventricle in the setting of pulmonary hypertension were assessed at the molecular and functional level using a canine model of monocrotaline pyrrole-induced pulmonary hypertension. METHODS: Animals underwent pulmonary artery catheterization to measure pulmonary hemodynamics before and 8 weeks after an injection of monocrotaline pyrrole, 3 mg/kg (n = 8) or placebo (n = 8) (controls). Systolic function was assessed with load-insensitive means (preload-recruitable stroke work). Myocardial biopsy specimens were collected to analyze membrane alpha1- and beta-adrenergic receptor density and adenylate cyclase activity. RESULTS: Eight weeks after injection, significant increases in pulmonary hemodynamic indices were noted in monocrotaline-injected dogs. Significant increases in right ventricular preload-recruitable stroke work were also observed in these animals compared with controls and occurred in association with significant increases in right ventricular alpha1- and beta-adrenergic receptor density and isoproterenol hydrochloride-stimulated adenylate cyclase activity. No significant differences in basal adenylate cyclase activity in the right ventricle were noted between the two groups. CONCLUSIONS: These data suggest that alterations in right ventricular function in the setting of chronic pulmonary hypertension may partially be due to changes in myocardial adrenergic receptor signaling.

Myocardial recovery after ischemia and reperfusion injury is significantly impaired in hearts with transgenic overexpression of beta-adrenergic receptor kinase.

BACKGROUND: beta-Adrenergic receptor kinase 1 (beta ARK1) mediates beta-adrenergic receptor signaling via receptor phosphorylation, which results in functional uncoupling. The physiological importance of beta ARK1 on cardiac performance in the setting of ischemia and reperfusion injury, however, has not been clearly established. In this study, the effects of beta ARK1 overexpression on myocardial recovery after ischemia and reperfusion injury were evaluated in transgenic mice with the use of an isolated work-performing murine heart preparation and computerized analysis of functional data. METHODS AND RESULTS: A controlled, experimental study was performed to compare cardiac function in the hearts of both transgenic mice with a 3-fold overexpression of beta ARK1 (n = 6; weight, 25 to 29 g) and littermate controls (n = 9; weight, 25 to 28 g). Preload-dependent cardiac output, contractility, heart rate, stroke work, and stroke volume were evaluated in the 2 groups before and after a 6-minute period of normothermic ischemia. Before ischemia, significant decreases were observed in all parameters of myocardial performance in beta ARK1 mice compared with control mice. After ischemia and reperfusion, significant decreases in cardiac function were observed in both experimental groups; however, significantly lower percentages of myocardial recovery occurred in beta ARK1 hearts compared with control hearts. CONCLUSIONS: After global normothermic ischemia, significant decreases in cardiac function were observed in both beta ARK1 and control mice; however, significantly lower percentages of myocardial recovery occurred in beta ARK1 mice. These data suggest that myocardial beta ARK1 overexpression significantly impairs cardiac function in the setting of ischemia and reperfusion injury.