Chronic venous disease (CVD) has a range of clinical presentations, including tortuous, distended veins in lower extremities, increasing skin pigmentation, and in severe cases ulceration of the affected skin. Venous insufficiency, a precursor to CVD characterized by improper return of blood from the lower extremities to the heart, must be studied in its earliest stages at a time when preventative measures could be applied in man. This underscores the need for basic research into biomarkers and genetic predisposing factors affecting the progression of venous disease. Investigation over the past decade has yielded insight into these specific genetic, cellular and molecular mechanisms underlying the development of venous disease. Among the many advances include the elucidation of an increasing role for matrix metalloproteinases as important mediators of the degenerative process involved with venous insufficiency. This may be preceded by an inflammatory process which further contributes to venular degeneration and endothelial dysfunction seen in advanced presentation of disease. Furthermore, genomic analyses have shed light upon temporal expression patterns of matrix remodeling proteins in diseased tissue samples. In this review we examine some of the current findings surrounding cellular, molecular and genetic advances in delineating the etiology of chronic venous disease.
Background: Matrix metalloproteinases (MMP) and VEGFR2 often coexist in many settings, but their interactions are unknown. Results: MMP-1 stimulates VEGFR2 up-regulation in endothelial cells. Conclusion: MMP-1-stimulated cells have elevated intracellular signaling and proliferate at a faster rate than unstimulated cells. Significance: A novel mechanism is uncovered whereby MMP-1 is able to sensitize endothelial cell functions.
In patients with previous acute type I aortic dissection repair, hemiarch and total arch operations have respectable morbidity and survival rates. Congestive heart failure predicts operative death, long-term mortality, and our adverse event endpoint. Cardiopulmonary bypass time predicts operative mortality, and female sex and circulatory arrest time predict long-term mortality.
Venous hypertension is associated with microvascular inflammation, restructuring, and apoptosis, but the cellular and molecular mechanisms underlying these events remain uncertain. In the present study we tested the hypothesis that elevated venous pressure and reduction of shear stress induces elevated enzymatic activity. This activity in turn may affect endothelial surface receptors and promote their dysfunction. Using a rodent model for venous hypertension using acute venular occlusion, microzymographic techniques for enzyme detection, and immunohistochemistry for receptor labeling, we found increased activity of the matrix metalloproteases (MMPs) -1, -8 and -9 and tissue inhibitors of metalloproteases (TIMPs) -1,-2 in both high and low-pressure regions. In this short time frame we also observed that elevated venule pressure led to two different fates for the vascular endothelial growth factor receptor-2 (VEGFR2); in higher-pressure upstream regions some animals exhibited higher VEGFR2 expression, while others displayed lower levels upstream compared to their downstream counterparts with lower pressure. VEGFR2 expression was, on average, more pronounced upon application of MMP inhibitor, suggesting possible cleavage of the receptor by activated enzymes in this model. We conclude that venous pressure elevation increases enzymatic activity which may contribute to inflammation and endothelial dysfunction associated with this disease by influencing critical surface receptors.
Coronary abnormalities, including the anomalous aortic origin of a coronary artery, coronary fistula and myocardial bridge, are among the most common congenital cardiovascular anomalies. A left coronary artery arising from the right cusp is less common than the right coronary artery arising from the left cusp but is more often found in autopsy series of sudden cardiac deaths. A slit-like/fish-mouth-shaped orifice, acute angle take-off, intramural course, interarterial course and hypoplasia of the proximal coronary artery have all been proposed as reasons for symptoms, ischaemia and sudden cardiac death. Surgical intervention is recommended for those patients with signs or symptoms of myocardial ischaemia. Intervention in asymptomatic patients with an interarterial/intramural left coronary artery from the right sinus of Valsalva is recommended due to the higher calculated risk of sudden cardiac death. In asymptomatic patients with an intramural right coronary artery from the left sinus of Valsalva, provocative testing is recommended. The slit-like orifice is more commonly seen in an anomalous right coronary artery arising from the left sinus, and we believe it is the major factor responsible for myocardial ischaemia. Our unroofing technique focuses on: (i) transecting the endothelial tissue flap to create a neo-ostium; (ii) limiting the flap resection to the intramural portion to avoid extra-aortic incision; and (iii) marsupialization of a neo-ostium with interrupted sutures to reapproximate the endothelium and prevent aortic dissection.
INTRODUCTION:Two young adults with COVID-19 associated myocarditis and refractory cardiogenic shock, without respiratory failure were successfully treated with venoarterial extracorporeal membrane oxygenation (VA ECMO) and percutaneous left ventricular assist device (pLVAD), or "ECPELLA, " and glucocorticoids.DESCRIPTION: Case 1: A previously healthy 23-year-old female presented four days after a COVID-19 diagnosis with fevers, lethargy and hypotension. Labs were notable for Pro-BNP 16,000 pg/mL, lactate 15 mg/dL, troponin 1.4 ng/mL. Transthoracic echocardiography (TTE) showed biventricular failure with ejection fraction (EF) 20% and an intra-aortic balloon pump (IABP) was placed for COVID-19 associated myocarditis prior to a tertiary care facility transfer. On arrival, she was on four vasopressors despite IABP. Renal replacement therapy was initiated for acute kidney injury and she was cannulated for ECPELLA. Shortly after cannulation vasopressor doses decreased. Intravenous (IV) methylprednisolone was given for three days and tapered. She was decannulated on ECPD 10 with recovery of cardiac and renal function. She was discharged home on HD 21. Case 2: A previously healthy 22-year-old male presented three days after COVID-19 diagnosis for fever, worsening dyspnea, and chest pain. He deteriorated, requiring intubation and three vasopressors. Labs notable for troponin 2.9 ng/ mL, pro-BNP 33200 pg/mL, creatinine 6.9 mg/dL, lactate 14 mg/dL. TTE revealed biventricular failure, EF 20-25%, consistent with COVID-19 associated myocarditis. He was cannulated for ECPELLA on HD 1 and started on five days of IV methylprednisolone. Hemodynamics improved, he was decannulated on ECPD 7 and extubated on HD 8. TTE on HD 14 showed cardiac recovery, with EF 55-60%. He was discharged home on HD 20. DISCUSSION:This highlights the success of ECPELLA and glucocorticoids in COVID-19 associated myocarditis in two young patients. ECPELLA has been previously described in myocarditis and may be important in early treatment of COVID-19 myocarditis in young patients. Glucocorticoids are increasingly used in patients with severe respiratory COVID-19 and its role in myocarditis remains to be seen. Clinicians should be aware of this presentation of COVID-19 and quickly request consultation from an ECMO center. Further investigation is paramount.
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