Rituximab-Induced Acute ST Elevation Myocardial Infarction.

BACKGROUND: Rituximab has rarely been associated with acute coronary syndrome (ACS). We report the case of a patient in whom rituximab, a monoclonal antibody used to treat lymphomas of B-cell origin, induced ST elevation myocardial infarction. CASE REPORT: A 46-year-old male patient diagnosed with stage II non-Hodgkin lymphoma presented to the emergency department with acute crushing, substernal chest pain that radiated to his back 1 day after a chemotherapy infusion with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. An electrocardiogram revealed normal sinus rhythm with ST elevations in the inferior leads. The patient underwent primary percutaneous coronary intervention (PCI) of his right coronary artery and first diagonal artery with placement of drug-eluting stents. He did well postprocedure and resumed therapy with rituximab under close monitoring by the cardiology and oncology departments without any further cardiac events. CONCLUSION: In patients with ACS because of chemotherapy, complete revascularization during PCI should be considered.

Anomalous right coronary artery: a case report.

BACKGROUND: Anomalous coronary arteries (ACAs) are rare but potentially life-threatening abnormalities of coronary circulation. Most variations are benign; however, some may lead to myocardial ischemia and/or sudden cardiac arrest. CASE REPORT: We present the case of a patient with a significant medical history of hypertension, hyperlipidemia, type 2 diabetes, obesity, and gastroesophageal reflux disease who presented to the emergency department with atypical chest pain. She underwent a cardiac catheterization that showed an anomalous right coronary artery originating near the anterior left coronary artery sinus and coursing between the pulmonary artery and aorta. The patient was deemed a poor surgical candidate, was discharged home on medical management with beta blocker therapy, and was instructed to restrict her physical activity. CONCLUSION: Treatment of significant anomalies should be guided by the nature of the anomalous vessel. Symptomatic patients with ACAs have 3 treatment options: medical management, coronary angioplasty and stent deployment, or surgical correction. These treatment options remain controversial. Some clinicians advocate revascularization, but the long-term benefits of revascularization therapies have not yet been demonstrated.

The impact of peripheral arterial disease on patients with congestive heart failure.

Congestive heart failure (CHF) is a prevalent disease with many comorbidities and is associated with high health care expenditures. Peripheral arterial disease (PAD) is a known comorbidity of CHF and is associated with worse morbidity and mortality. CHF and PAD share risk factors, pathophysiology, treatment strategies, and prognostic features. We review the impact of PAD on patients with CHF using several studies to support PAD's influence on outcomes in CHF. Based on the evidence and current guidelines, patients with heart failure who are smokers, and those who have known coronary artery disease and/or diabetes should be screened for PAD.

The cyclic GMP modulators YC-1 and zaprinast reduce vessel remodeling through antiproliferative and proapoptotic effects.

Guanosine-specific cyclic nucleotide signaling is suggested to serve protective actions in the vasculature; however, the influence of selective pharmacologic modulation of cyclic guanosine monophosphate- synthesizing soluble guanylate cyclase or cyclic guanosine monophosphate-degrading phosphodiesterase on vessel remodeling has not been thoroughly examined. In this study, rat carotid artery balloon injury was performed and the growth-modulating effects of the soluble guanylate cyclase stimulator YC-1 or the cyclic guanosine monophosphate-dependent phosphodiesterase-V inhibitor zaprinast were examined. YC-1 or zaprinast elevated vessel cyclic guanosine monophosphate content, reduced medial wall and neointimal cell proliferation, stimulated medial and neointimal cellular apoptosis, and markedly attenuated neointimal remodeling in comparable fashion. Interestingly, soluble guanylate cyclase inhibition by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one failed to noticeably alter neointimal growth, and concomitant zaprinast with YC-1 did not modify any parameter compared to individual treatments. These results provide novel in vivo evidence that YC-1 and zaprinast inhibit injury-induced vascular remodeling through antimitogenic and proapoptotic actions and may offer promising therapeutic approaches against vasoproliferative disorders.

Arginase promotes neointima formation in rat injured carotid arteries.

OBJECTIVE: Arginase stimulates the proliferation of cultured vascular smooth muscle cells (VSMCs); however, the influence of arginase on VSMC growth in vivo is not known. This study investigated the impact of arginase on cell cycle progression and neointima formation after experimental arterial injury. METHODS AND RESULTS: Balloon injury of rat carotid arteries resulted in a sustained increase in arginase activity in the vessel wall and the induction of arginase I protein in both the media and neointima of injured vessels. Furthermore, local perivascular application of the potent and selective arginase inhibitors S-(2-boronoethyl)-L-cysteine (BEC) or N(G)-hydroxy-nor-L-arginine (L-OHNA) immediately after injury markedly attenuated medial and neointimal DNA synthesis and neointima formation. Substantial arginase I protein and arginase activity was also detected in rat cultured aortic VSMCs. Moreover, treatment of VSMCs with BEC or L-OHNA, or knockdown of arginase I protein, arrested cells in the G(0)/G(1) phase of the cell cycle and induced the expression of the cyclin-dependent protein kinase inhibitor, p21. CONCLUSIONS: This study demonstrates that arginase is essential for VSMCs to enter the cell cycle and that arginase I contributes to the remodeling response after arterial injury. Arginase I represents a potentially new therapeutic target for the treatment of vasculoproliferative disorders.

Butylated hydroxyanisole stimulates heme oxygenase-1 gene expression and inhibits neointima formation in rat arteries.

OBJECTIVE: Butylated hydroxyanisole (BHA) is a synthetic phenolic compound that is a potent inducer of phase II genes. Since heme oxygenase-1 (HO-1) is a vasoprotective protein that is upregulated by phase II inducers, the present study examined the effects of BHA on HO-1 gene expression and vascular smooth muscle cell proliferation. METHODS: The regulation of HO-1 gene expression and vascular cell growth by BHA was studied in cultured rat aortic smooth muscle cells and in balloon injured rat carotid arteries. RESULTS: Treatment of cultured smooth muscle cells with BHA stimulated the expression of HO-1 protein, mRNA and promoter activity in a time- and concentration-dependent manner. BHA-mediated HO-1 expression was dependent on the activation of NF-E2-related factor-2 by p38 mitogen-activated protein kinase. BHA also inhibited cell cycle progression and DNA synthesis in an HO-1-dependent manner. In addition, the local perivascular delivery of BHA immediately after arterial injury of rat carotid arteries induced HO-1 protein expression and markedly attenuated neointima formation. CONCLUSIONS: These studies demonstrate that BHA stimulates HO-1 gene expression in vascular smooth muscle cells, and that the induction of HO-1 contributes to the antiproliferative actions of this phenolic antioxidant. BHA represents a potentially novel therapeutic agent in treating or preventing vasculoproliferative disease.

Single perivascular delivery of mitomycin C stimulates p21 expression and inhibits neointima formation in rat arteries.

OBJECTIVE: Mitomycin C (MMc) is an antibiotic that exerts a potent antiproliferative effect in tumor cells. Because the proliferation of vascular smooth muscle cells (VSMCs) plays a prominent role in the development of restenosis after percutaneous coronary interventions, the present study examined the effect of MMc on VSMC proliferation and on neointima formation after arterial balloon injury. METHODS AND RESULTS: Treatment of cultured rat aortic VSMCs with MMc (1 nmol to 30 micromol/L) inhibited VSMC proliferation in a concentration-dependent manner. Whereas high concentrations of MMc (1 to 30 micromol/L) induced VSMC apoptosis, as reflected by DNA laddering and caspase-3 activation, lower concentrations of MMc (1 to 300 nmol/L) directly inhibited VSMC growth by arresting cells in the G2/M phase of the cell cycle. The antiproliferative action of MMc was associated with a selective increase in the expression of the cyclin-dependent kinase inhibitor p21, and with a decrease in cyclin B1-cyclin-dependent kinase-1 complex activity. Finally, the local perivascular delivery of MMc immediately after balloon injury of rat carotid arteries induced p21 expression and markedly attenuated neointima formation. CONCLUSIONS: These studies demonstrate that MMc exerts a potent inhibitory effect on VSMC proliferation and neointima formation after arterial injury. MMc represents a potentially new therapeutic agent in treating and preventing vasculoproliferative disease.