A Lost Bullet in the Coronary Sinus: A Cautionary Tale.

We present a case of venous bullet embolism to the right atrium following a gunshot wound (GSW) to the abdomen. A 53-year-old male presented after a GSW to the abdomen. His workup included a computed tomography (CT) scan demonstrating an aortic injury with aortocaval fistula. A radio-opaque object consistent with a bullet was visualized in the right atrium. First, this case details an important decision, choice of surgery versus an interventional approach. After repair of the aortocaval fistula, the patient underwent a planned attempt to extract the bullet through a right lateral thoracotomy approach utilizing cardiopulmonary bypass to facilitate a right atriotomy. Intraoperatively, the team was not able to localize the bullet in the right atrium despite fluoroscopic evaluation. A postoperative CT scan demonstrated that the bullet had migrated into the coronary sinus. Lastly, this case demonstrates successful positioning maneuvers to dislodge the bullet out of the heart and into the inferior vena cava, allowing for the endovascular extraction of the bullet.

Type 1 Diabetes Impairs Endothelium-Dependent Relaxation Via Increasing Endothelial Cell Glycolysis Through Advanced Glycation End Products, PFKFB3, and Nox1-Mediated Mechanisms.

BACKGROUND: Type 1 diabetes (T1D) is a major cause of endothelial dysfunction. Although cellular bioenergetics has been identified as a new regulator of vascular function, whether glycolysis, the primary bioenergetic pathway in endothelial cells (EC), regulates vascular tone and contributes to impaired endothelium-dependent relaxation (EDR) in T1D remains unknown. METHODS: Experiments were conducted in Akita mice with intact or selective deficiency in EC PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3), the main regulator of glycolysis. Seahorse analyzer and myography were employed to measure glycolysis and mitochondrial respiration, and EDR, respectively, in aortic explants. EC PFKFB3 (Ad-PFKFB3) and glycolysis (Ad-GlycoHi) were increased in situ via adenoviral transduction. RESULTS: T1D increased EC glycolysis and elevated EC expression of PFKFB3 and NADPH oxidase Nox1 (NADPH oxidase homolog 1). Functionally, pharmacological and genetic inhibition of PFKFB3 restored EDR in T1D, while in situ aorta EC transduction with Ad-PFKFB3 or Ad-GlycoHi reproduced the impaired EDR associated with T1D. Nox1 inhibition restored EDR in aortic rings from Akita mice, as well as in Ad-PFKFB3-transduced aorta EC and lactate-treated wild-type aortas. T1D increased the expression of the advanced glycation end product precursor methylglyoxal in the aortas. Exposure of the aortas to methylglyoxal impaired EDR, which was prevented by PFKFB3 inhibition. T1D and exposure to methylglyoxal increased EC expression of HIF1α (hypoxia-inducible factor 1α), whose inhibition blunted methylglyoxal-mediated EC PFKFB3 upregulation. CONCLUSIONS: EC bioenergetics, namely glycolysis, is a new regulator of vasomotion and excess glycolysis, a novel mechanism of endothelial dysfunction in T1D. We introduce excess methylglyoxal, HIF1α, and PFKFB3 as major effectors in T1D-mediated increased EC glycolysis.

Role of Caveolae in the Development of Microvascular Dysfunction and Hyperglycemia in Type 2 Diabetes.

In type 2 diabetes (T2D) microvascular dysfunction can interfere with tissue glucose uptake thereby contributing to the development of hyperglycemia. The cell membrane caveolae orchestrate signaling pathways that include microvascular control of tissue perfusion. In this study, we examined the role of caveolae in the regulation of microvascular vasomotor function under the condition of hyperglycemia in T2D patients and rodent models. Human coronary arterioles were obtained during cardiac surgery from T2D patients, with higher perioperative glucose levels, and from normoglycemic, non-diabetic controls. The coronary arteriole responses to pharmacological agonists bradykinin and acetylcholine were similar in T2D and non-diabetic patients, however, exposure of the isolated arteries to methyl-ß-cyclodextrin (mßCD), an agent known to disrupt caveolae, reduced vasodilation to bradykinin selectively in T2D subjects and converted acetylcholine-induced vasoconstriction to dilation similarly in the two groups. Dilation to the vascular smooth muscle acting nitric oxide donor, sodium nitroprusside, was not affected by mßCD in either group. Moreover, mßCD reduced endothelium-dependent arteriolar dilation to a greater extent in hyperglycemic and obese db/db mice than in the non-diabetic controls. Mechanistically, when fed a high-fat diet (HFD), caveolin-1 knockout mice, lacking caveolae, exhibited a significantly reduced endothelium-dependent arteriolar dilation, both ex vivo and in vivo, which was accompanied by significantly higher serum glucose levels, when compared to HFD fed wild type controls. Thus, in T2D arterioles the role of caveolae in regulating endothelium-dependent arteriole dilation is altered, which appears to maintain vasodilation and mitigate the extent of hyperglycemia. While caveolae play a unique role in microvascular vasomotor regulation, under the condition of hyperglycemia arterioles from T2D subjects appear to be more susceptible for caveolae disruption-associated vasomotor dysfunction and impaired glycemic control.

Adenosine kinase is critical for neointima formation after vascular injury by inducing aberrant DNA hypermethylation.

AIMS: Adenosine receptors and extracellular adenosine have been demonstrated to modulate vascular smooth muscle cell (VSMC) proliferation and neointima formation. Adenosine kinase (ADK) is a major enzyme regulating intracellular adenosine levels but is function in VSMC remains unclear. Here, we investigated the role of ADK in vascular injury-induced smooth muscle proliferation and delineated the mechanisms underlying its action. METHODS AND RESULTS: We found that ADK expression was higher in the neointima of injured vessels and in platelet-derived growth factor-treated VSMCs. Genetic and pharmacological inhibition of ADK was enough to attenuate arterial injury-induced neointima formation due to inhibition of VSMC proliferation. Mechanistically, using infinium methylation assays and bisulfite sequencing, we showed that ADK metabolized the intracellular adenosine and potentiated the transmethylation pathway, then induced the aberrant DNA hypermethylation. Pharmacological inhibition of aberrant DNA hypermethylation increased KLF4 expression and suppressed VSMC proliferation as well as the neointima formation. Importantly, in human femoral arteries, we observed increased ADK expression and DNA hypermethylation as well as decreased KLF4 expression in neointimal VSMCs of stenotic vessels suggesting that our findings in mice are relevant for human disease and may hold translational significance. CONCLUSION: Our study unravels a novel mechanism by which ADK promotes VSMC proliferation via inducing aberrant DNA hypermethylation, thereby down-regulating KLF4 expression and promoting neointima formation. These findings advance the possibility of targeting ADK as an epigenetic modulator to combat vascular injury.

Leptin Restores Endothelial Function via Endothelial PPARγ-Nox1-Mediated Mechanisms in a Mouse Model of Congenital Generalized Lipodystrophy.

Leptin is the current treatment for metabolic disorders associated with acquired and congenital generalized lipodystrophy (CGL). Although excess leptin levels have been associated with vascular inflammation and cardiovascular disease in the context of obesity, the effects of chronic leptin treatment on vascular function remain unknown in CGL. Here, we hypothesized that leptin treatment will improve endothelial function via direct vascular mechanisms. We investigated the cardiovascular consequences of leptin deficiency and supplementation in male gBscl2-/- (Berardinelli-Seip 2 gene-deficient) mice-a mouse model of CGL. CGL mice exhibited reduced adipose mass and leptin levels, as well as impaired endothelium-dependent relaxation. Blood vessels from CGL mice had increased NADPH Oxidase 1 (Nox1) expression and reactive oxygen species production, and selective Nox1 inhibition restored endothelial function. Remarkably, chronic and acute leptin supplementation restored endothelial function via a PPARγ-dependent mechanism that decreased Nox1 expression and reactive oxygen species production. Selective ablation of leptin receptors in endothelial cells promoted endothelial dysfunction, which was restored by Nox1 inhibition. Lastly, we confirmed in aortic tissue from older patients undergoing cardiac bypass surgery that acute leptin can promote signaling in human blood vessels. In conclusion, in gBscl2-/- mice, leptin restores endothelial function via peroxisome proliferator activated receptor gamma-dependent decreases in Nox1. Furthermore, we provide the first evidence that vessels from aged patients remain leptin sensitive. These data reveal a new direct role of leptin receptors in the control of vascular homeostasis and present leptin as a potential therapy for the treatment of vascular disease associated with low leptin levels.

Progesterone Predisposes Females to Obesity-Associated Leptin-Mediated Endothelial Dysfunction via Upregulating Endothelial MR (Mineralocorticoid Receptor) Expression.

Compelling clinical evidence indicates that obesity and its associated metabolic abnormalities supersede the protective effects of female sex-hormones and predisposes premenopausal women to cardiovascular disease. The underlying mechanisms remain poorly defined; however, recent studies have implicated overactivation of the aldosterone-MR (mineralocorticoid receptor) axis as a cause of sex-specific cardiovascular risk in obese females. Experimental evidence indicates that the MR on endothelial cells contributes to obesity-associated, leptin-induced endothelial dysfunction in female experimental models, however, the vascular-specific mechanisms via which females are predisposed to heightened endothelial MR activation remain unknown. Therefore, we hypothesized that endogenous expression of endothelial MR is higher in females than males, which predisposes them to obesity-associated, leptin-mediated endothelial dysfunction. We found that endothelial MR expression is higher in blood vessels from female mice and humans compared with those of males, and further, that PrR (progesterone receptor) activation in endothelial cells is the driving mechanism for sex-dependent increases in endothelial MR expression in females. In addition, we show that genetic deletion of either the endothelial MR or PrR in female mice prevents leptin-induced endothelial dysfunction, providing direct evidence that interaction between the PrR and MR mediates obesity-associated endothelial impairment in females. Collectively, these novel findings suggest that progesterone drives sex-differences in endothelial MR expression and predisposes female mice to leptin-induced endothelial dysfunction, which indicates that MR antagonists may be a promising sex-specific therapy to reduce the risk of cardiovascular diseases in obese premenopausal women.

Akt2 (Protein Kinase B Beta) Stabilizes ATP7A, a Copper Transporter for Extracellular Superoxide Dismutase, in Vascular Smooth Muscle: Novel Mechanism to Limit Endothelial Dysfunction in Type 2 Diabetes Mellitus.

OBJECTIVE: Copper transporter ATP7A (copper-transporting/ATPase) is required for full activation of SOD3 (extracellular superoxide dismutase), which is secreted from vascular smooth muscle cells (VSMCs) and anchors to endothelial cell surface to preserve endothelial function by scavenging extracellular superoxide. We reported that ATP7A protein expression and SOD3 activity are decreased in insulin-deficient type 1 diabetes mellitus vessels, thereby, inducing superoxide-mediated endothelial dysfunction, which are rescued by insulin treatment. However, it is unknown regarding the mechanism by which insulin increases ATP7A expression in VSMCs and whether ATP7A downregulation is observed in T2DM (type2 diabetes mellitus) mice and human in which insulin-Akt (protein kinase B) pathway is selectively impaired. APPROACH AND RESULTS: Here we show that ATP7A protein is markedly downregulated in vessels isolated from T2DM patients, as well as those from high-fat diet-induced or db/db T2DM mice. Akt2 (protein kinase B beta) activated by insulin promotes ATP7A stabilization via preventing ubiquitination/degradation as well as translocation to plasma membrane in VSMCs, which contributes to activation of SOD3 that protects against T2DM-induced endothelial dysfunction. Downregulation of ATP7A in T2DM vessels is restored by constitutive active Akt or PTP1B-/- (protein-tyrosine phosphatase 1B-deficient) T2DM mice, which enhance insulin-Akt signaling. Immunoprecipitation, in vitro kinase assay, and mass spectrometry analysis reveal that insulin stimulates Akt2 binding to ATP7A to induce phosphorylation at Ser1424/1463/1466. Furthermore, SOD3 activity is reduced in Akt2-/- vessels or VSMCs, which is rescued by ATP7A overexpression. CONCLUSION: Akt2 plays a critical role in ATP7A protein stabilization and translocation to plasma membrane in VSMCs, which contributes to full activation of vascular SOD3 that protects against endothelial dysfunction in T2DM.

Role of Adipose Tissue Endothelial ADAM17 in Age-Related Coronary Microvascular Dysfunction.

OBJECTIVE: A disintegrin and metalloproteinase ADAM17 (tumor necrosis factor-α [TNF]-converting enzyme) regulates soluble TNF levels. We tested the hypothesis that aging-induced activation in adipose tissue (AT)-expressed ADAM17 contributes to the development of remote coronary microvascular dysfunction in obesity. APPROACH AND RESULTS: Coronary arterioles (CAs, ≈90 µm) from right atrial appendages and mediastinal AT were examined in patients (aged: 69±11 years, BMI: 30.2±5.6 kg/m2) who underwent open heart surgery. CA and AT were also studied in 6-month and 24-month lean and obese mice fed a normal or high-fat diet. We found that obesity elicited impaired endothelium-dependent CA dilations only in older patients and in aged high-fat diet mice. Transplantation of AT from aged obese, but not from young or aged, mice increased serum cytokine levels, including TNF, and impaired CA dilation in the young recipient mice. In patients and mice, obesity was accompanied by age-related activation of ADAM17, which was attributed to vascular endothelium-expressed ADAM17. Excess, ADAM17-shed TNF from AT arteries in older obese patients was sufficient to impair CA dilation in a bioassay in which the AT artery was serially connected to a CA. Moreover, we found that the increased activity of endothelial ADAM17 is mediated by a diminished inhibitory interaction with caveolin-1, owing to age-related decline in caveolin-1 expression in obese patients and mice or to genetic deletion of caveolin-1. CONCLUSIONS: The present study indicates that aging and obesity cooperatively reduce caveolin-1 expression and increase vascular endothelial ADAM17 activity and soluble TNF release in AT, which may contribute to the development of remote coronary microvascular dysfunction in older obese patients.

Altered energy state reversibly controls smooth muscle contractile function in human saphenous vein during acute hypoxia-reoxygenation: Role of glycogen, AMP-activated protein kinase, and insulin-independent glucose uptake.

Hypoxia is known to promote vasodilation of coronary vessels through several mediators including cardiac-derived adenosine and endothelium-derived prostanoids and nitric oxide. To date, the impact of endogenous glycogen depletion in vascular smooth muscle and the resultant alterations in cellular energy state (e.g., AMP-activated protein kinase, AMPK) on the contractile response to G protein-coupled receptor agonists (e.g., serotonin, 5-HT) has not yet been studied. In the present study, ex vivo exposure of endothelium-denuded human saphenous vein rings to hypoxic and glucose-deprived conditions during KCl-induced contractions for 30 min resulted in a marked depletion of endogenous glycogen by ∼80% (from ∼1.78 µmol/g under normoxia to ∼0.36 µmol/g under hypoxia). Importantly, glycogen-depleted HSV rings, which were maintained under hypoxia/reoxygenation and glucose-deprived conditions, exhibited significant increases in basal AMPK phosphorylation (∼6-fold ↑) and 5-HT-induced AMPK phosphorylation (∼19-fold ↑) with an accompanying suppression of 5-HT-induced maximal contractile response (∼68% ↓), compared with respective controls. Exposure of glycogen-depleted HSV rings to exogenous D-glucose, but not the inactive glucose analogs, prevented the exaggerated increase in 5-HT-induced AMPK phosphorylation and restored 5-HT-induced maximal contractile response. In addition, the ability of exogenous D-glucose to rescue cellular stress and impaired contractile function occurred through GLUT1-mediated but insulin/GLUT4-independent mechanisms. Together, the present findings from clinically-relevant human saphenous vein suggest that the loss of endogenous glycogen in vascular smooth muscle and the resultant accentuation of AMPK phosphorylation by GPCR agonists may constitute a yet another mechanism of metabolic vasodilation of coronary vessels in ischemic heart disease.

Peroxynitrite disrupts endothelial caveolae leading to eNOS uncoupling and diminished flow-mediated dilation in coronary arterioles of diabetic patients.

Peroxynitrite (ONOO(-)) contributes to coronary microvascular dysfunction in diabetes mellitus (DM). We hypothesized that in DM, ONOO(-) interferes with the function of coronary endothelial caveolae, which plays an important role in nitric oxide (NO)-dependent vasomotor regulation. Flow-mediated dilation (FMD) of coronary arterioles was investigated in DM (n = 41) and non-DM (n = 37) patients undergoing heart surgery. NO-mediated coronary FMD was significantly reduced in DM patients, which was restored by ONOO(-) scavenger, iron-(III)-tetrakis(N-methyl-4'pyridyl)porphyrin-pentachloride, or uric acid, whereas exogenous ONOO(-) reduced FMD in non-DM subjects. Immunoelectron microscopy demonstrated an increased 3-nitrotyrosine formation (ONOO(-)-specific protein nitration) in endothelial plasma membrane in DM, which colocalized with caveolin-1 (Cav-1), the key structural protein of caveolae. The membrane-localized Cav-1 was significantly reduced in DM and also in high glucose-exposed coronary endothelial cells. We also found that DM patients exhibited a decreased number of endothelial caveolae, whereas exogenous ONOO(-) reduced caveolae number. Correspondingly, pharmacological (methyl-ß-cyclodextrin) or genetic disruption of caveolae (Cav-1 knockout mice) abolished coronary FMD, which was rescued by sepiapterin, the stable precursor of NO synthase (NOS) cofactor, tetrahydrobiopterin. Sepiapterin also restored coronary FMD in DM patients. Thus, we propose that ONOO(-) selectively targets and disrupts endothelial caveolae, which contributes to NOS uncoupling, and, hence, reduced NO-mediated coronary vasodilation in DM patients.

Obesity and statins are both independent predictors of enhanced coronary arteriolar dilation in patients undergoing heart surgery.

BACKGROUND: A paradoxical inverse relationship between body mass index, morbidity and mortality in patients with ischemic heart disease has been noted; but the underlying mechanisms remain unclear. Given that coronary resistance arteries are the primary regulators of myocardial blood flow, we examined the effects of obesity and medication on dilator function in coronary microvessels. METHODS: Bradykinin-induced coronary dilation was assessed by videomicroscopy in ex vivo coronary arterioles obtained from 64 consecutive patients undergoing heart surgery. Multi-variable linear regression and logistic regression were used to investigate the effects of obesity (BMI ≥ 30 kg/M2) and the influences of medications on vessel responses. RESULTS: In isolated, pressurized (80 mmHg) coronary arterioles of obese and non-obese patient the active (73±4 vs. 79±13 µm) and passive (111 ± 5.5 vs. 118 ± 5.0 µm) diameters were similar. Bradykinin elicited substantial dilation in coronary arterioles, with a similar magnitude in obese and non-obese patients (to 10-8 M: 55 ± 5% vs. 46 ± 5%, P = 0.20), but with significantly enhanced sensitivity in obesity (EC50: 8.2x10-9 M vs. 1.9x10-8 M, respectively, P = 0.03). When adjusted for other risk factors and medications, obesity and statins were determined to be the only positive predictors of enhanced dilation, as assessed with multiple regression analysis. Moreover, obese patients with or without statin exhibited significantly increased coronary dilation to bradykinin, when compared to non-obese patients without statin therapy. CONCLUSIONS: Obesity and statin therapy are independently associated with an enhanced dilator function of coronary arterioles in patients undergoing heart surgery, which may offer a potential mechanism for the better cardiovascular outcome described earlier as the obesity paradox.

Identification of distant metastases with PET-CT in patients with suspected recurrent head and neck cancer.

OBJECTIVES: To investigate the utility of positron-emission tomography/computed tomography (PET-CT) in identifying distant metastatic disease in patients with suspected recurrent head and neck squamous cell cancer (HNSCC). STUDY DESIGN: Retrospective analysis. METHODS: Retrospective analysis of 64 consecutive patients with suspected recurrent HNSCC following definitive treatment who underwent PET-CT imaging were eligible for inclusion. Patients with previous known distant metastatic disease were excluded. RESULTS: The majority of patients (81%) had TNM stage III or IV disease. PET-CT was suspicious for pulmonary malignancy in 14 patients (22%) and indeterminate in 6 patients (9%). Pulmonary metastases or a new lung primary were present in 10 patients (16%): 7 of 14 patients with positive PET-CT scans (50%) and 3 of 50 patients with negative or indeterminate PET-CT scans (6%). Including nonpulmonary sites, the overall incidence of distant disease was 23% (15/64) with 20% (13/64) unsuspected prior to PET-CT. The sensitivity and specificity of PET-CT in predicting distant malignancy was 86% and 84%, respectively, with a positive predictive value of 60% and a negative predictive value of 95%. There was a significant correlation between standardized uptake value (SUV) on PET-CT and positive histology, with a mean SUV of 8.5 (range, 4.7-16.2) in patients with distant metastases compared with a mean SUV of 2.9 (range, 1.9-4.2) in patients with benign pathology (r = 0.87, P < .0001). CONCLUSIONS: A significant number of patients with recurrent HNSCC have distant metastases at the time of recurrence. These data suggest that PET-CT improves detection of metastatic disease in the high-risk patient and should be performed as part of the routine evaluation of patients with suspected recurrence prior to salvage surgery.

Identification of distant metastases with positron-emission tomography-computed tomography in patients with previously untreated head and neck cancer.

OBJECTIVES: To investigate the utility of positron-emission tomography-computed tomography (PET-CT) in identifying distant metastatic disease in patients with previously untreated head and neck squamous cell cancer (HNSCC) prior to definitive treatment. MATERIALS AND METHODS: Retrospective analysis of 27 consecutive patients with previously untreated HNSCC who underwent PET-CT imaging in addition to chest radiography (CXR) as part of their metastatic workup. RESULTS: The majority of patients (89%) had TNM stage III or IV disease. PET-CT was suspicious for pulmonary malignancy in four (15%) patients and indeterminate in one (4%) patient. CXR was suspicious for pulmonary malignancy in two (7%) patients. Pulmonary metastases or a new lung primary was present in 3 (11%) patients: 3 of 4 (75%) patients with positive PET-CT scans and 0 of 23 (0%) patients with negative or indeterminate PET-CT scans compared with 2 of 2 (100%) patients with positive CXR and 1 of 25 (4%) patients with negative CXR. The sensitivity and specificity of PET-CT in predicting pulmonary malignancy was 100% and 96%, respectively, with a positive predictive value of 75% and a negative predictive value of 100%. The sensitivity and specificity of CXR in predicting pulmonary malignancy was 67% and 100%, respectively, with a positive predictive value of 100% and a negative predictive value of 96%. Including nonpulmonary sites, the overall incidence of distant metastatic disease was 19% (5/27) with 11% (3/27) unsuspected prior to PET-CT. CONCLUSIONS: PET-CT improves detection of metastatic disease in the high-risk patient and should be performed as part of the routine pretreatment evaluation of patients with advanced stage HNSCC.

Percutaneous tracheostomy after mechanical ventricular assist device implantation.

BACKGROUND: Several studies have shown that percutaneous dilational tracheostomy (PDT) is safe and cost-effective for patients recovering from surgery that requires a median sternotomy. We report our experience with PDT in patients receiving mechanical cardiac assistance. METHODS: We reviewed the medical records of all patients who underwent ventricular assist device implantation at our institution between July 2000 and July 2003, and who subsequently required long-term ventilatory support during the same hospital admission. Data obtained from the records included demographic and biometric information, primary diagnosis, early (< or =30days) and late (>30days) complications, date and cause of death, type of anti-coagulation used at the time of tracheostomy, and various coagulation measures. RESULTS: Thirty-one consecutive patients (29 men, 2 women; mean age, 56 years) had PDT after ventricular assist device implantation. Four minor complications occurred among 3 of the patients (10%), including 3 early complications (2 peristomal oozing and 1 peristomal cellulitis) and 1 late complication (recurrent peristomal cellulitis), none of which affected long-term outcome. No major adverse events, long-term complications, or deaths resulted from the PDT procedure. CONCLUSIONS: PDT is feasible for patients with mechanical support devices who require long-term ventilatory support. Although some of these patients are coagulopathic, our results indicate that PDT is safe and effective in this challenging patient population.

BVS5000 support after cardiac transplantation.

OBJECTIVE: This study examines short-term mechanical assist device support for cardiac transplant patients and compares their outcomes with nontransplant patients requiring similar support. METHODS: Of 350 cardiac transplant patients at our institution, 7 patients required mechanical ventricular assistance with the Abiomed BVS5000 assist device (Abiomed, Inc, Danvers, Mass) after transplant secondary to severe acute rejection with cardiogenic shock (n = 4) or primary graft failure (n = 3). Recovery of ventricular function, survival to discharge, and complications were determined for the transplant group and compared with a second group comprising all other patients supported with the BVS5000 at our institution (n = 15). Additionally, the results of prior series reporting mechanical ventricular support of the failing transplant heart are reviewed. RESULTS: Demographics and duration of support were similar between the groups. The transplant group had a higher wean rate from device relative to the nontransplant group (100% versus 13%; P < 0.01). Five of 7 in the transplant group achieved survival to discharge (71%), relative to 5 of 15 in the nontransplant group (33%). Complications between the two groups were similar, although the transplant group experienced a higher rate of renal insufficiency (57% versus 13%, P = 0.05). CONCLUSION: Severe acute rejection with cardiogenic shock and primary graft failure are two conditions that may warrant mechanical ventricular support in the cardiac transplant patient. Transplant patients with these conditions have a high rate of ventricular functional recovery, greater than nontransplant patients supported with the same device and for a similar period of time. Although the incidence of renal insufficiency was higher, the majority of transplant patients who were supported with the BVS5000 achieved survival to discharge.