Introduction: This study seeks to evaluate the incidence and associated risk factors for

No abstract

Small cell carcinoma is an aggressive malignancy often associated with dismal prognosis due to the presence of advanced disease. Small cell malignancies, initially described in the lung (small cell carcinoma of the lung), can occur in extrapulmonary sites, such as prostate (small cell carcinoma of the prostate) and bladder (small cell carcinoma of the bladder), with similar clinicopathologic outcomes. There has been a paradigm shift in the management of small cell carcinoma of the lung from initial surgical treatment to use of chemotherapy followed by local therapies. Such treatment modalities have been applied to small cell carcinoma of the prostate and the bladder, with promise in improving patient survival. Use of platinum-based combination chemotherapy followed by surgical resection and/or radiation offers the most benefit. Further investigation at the molecular level may offer targeted therapies earlier in the course of the disease.

Previous studies have demonstrated a key role for voltage‐dependent K (KV) channels in the regulation of coronary metabolic and ischemic vasodilation. However, the KV channel subtypes responsible for the control of coronary blood flow have not been clearly defined. This investigation examined the hypothesis that KV7 channels are present in coronary vascular smooth muscle and regulate perfusion of the myocardium at rest and during pacing‐induced increases in metabolism. In anesthetized, open‐chest swine, we found that intracoronary administration of the KV7 agonist flupirtine (1 nM‐10 μM) or the KV7 antagonist linopiridine (1–100 μM) did not significantly affect baseline coronary blood flow (Δ = −0.002 ± 0.005 vs. −0.010 ± 0.004 ml/min/g, respectively). H2O2 increased coronary flow ~2‐fold and this response was unaffected by linopiridine. Whole‐cell recording of isolated coronary smooth muscle cells revealed that flupirtine and linopirdine both inhibited KV current by ~25 ± 3% (P < 0.05). Cardiac pacing (57 + 5 to 102 + 12 bpm) increased myocardial oxygen consumption (~35%) and coronary blood flow (~38%). However, linopridine (10 μM) did not significantly alter this increase in coronary flow or the slope of the relationship between coronary blood flow and myocardial oxygen consumption (P = 0.61). These data do not support a prominent role for KV7 channels in the regulation of coronary blood flow. (Support: HL092245)