Additive effects of nicorandil on coronary blood flow during continuous administration of nitroglycerin.

OBJECTIVES: We examined whether patients with ischemic heart disease (IHD) should be treated with nicorandil, an adenosine triphosphate-sensitive potassium channel opener, in addition to the regular use of nitrates. BACKGROUND: It has been reported that nicorandil possibly has additive effects on nitroglycerin (NTG) treatment for angina, but the mechanism is not clear. METHODS: We directly measured anterograde coronary blood flow (CBF) with a Doppler guide wire to examine the effects of intravenous administration of NTG (0.3 mg) and nicorandil (6 mg) during continuous administration of NTG at a sufficient dose (25 microg/min) in subjects with normal and stenotic coronary arteries. RESULTS: Additional systemic administration of NTG decreased anterograde CBF (normal -19.7%; stenotic -21.2%). In contrast, nicorandil increased anterograde CBF in both normal (54.6%) and stenotic (89.6%) coronary arteries, without the coronary steal phenomenon. There was a tendency toward nicorandil-dilated diameters in the patients with stenotic arteries (p = 0.06). There were no effects of additional administration on pulmonary artery wedge pressure. There was no difference in changes in heart rate and mean aortic blood pressure between NTG and nicorandil therapy. CONCLUSIONS: These results suggest that in patients treated with nitrates, additional administration of nicorandil is more useful, in terms of increasing CBF, than additional administration of nitrates. Adjunctive use of nicorandil with nitrates may provide the further benefit of myocardial protection and may improve the prognosis of patients with IHD.

Effect of iC3b binding to immune complexes upon the phagocytic response of human neutrophils: synergistic functions between Fc gamma R and CR3.

We compared the phagocytosis of immune complexes (IC) and iC3b-opsonized derivatives (iC3b-IC) by human neutrophils. The phagocytosis of iC3b-IC via Fc gamma R and CR3 was much greater than that of IC via Fc gamma R alone. Adding ethanol to the cells decreased iC3b-IC phagocytosis to that of IC, which was not affected by these reagents, suggesting that the enhanced phagocytosis is attributable to CR3-mediated phospholipase D activation. The IC phagocytosis was inhibited more effectively by anti-Fc gamma IIIB, whereas the iC3b-IC phagocytosis was partly inhibited only by anti-Fc gamma RII. The main Fc gamma R might differ in IC and iC3b-IC phagocytosis.

Effect of C1q on the processing of immune complexes by human neutrophils.

We prepared immune complexes (IC) composed of human anti-tetanus toxoid IgG and tetanus toxoid, and examined the effect of C1q on the processing of IC by human neutrophils. Treating IC with increasing amounts of C1q enhanced the binding and phagocytosis of IC by neutrophils, unless the amounts of C1q added were less than those required to saturate the C1q binding sites of IC. With the increase of unbound excess C1q, the IC processing by neutrophils decreased. Superoxide anions generated during the processing of IC-C1q were entrapped in phagosomes and were not released from neutrophils. The C1q-dependent inhibition of IC processing by neutrophils was not observed when C1q-treated neutrophils were washed and allowed to react with IC, suggesting that the inhibition by excess C1q is due to the hindrance of IC-C1q binding to neutrophils by loosely bound C1q on neutrophils. The C1q-treated, washed neutrophils still showed enhanced responses to IC, suggesting that free C1q as well as the IC-C1q complex can prime neutrophils to enhance Fc receptor (FcR)-mediated cellular responses. Thus, C1q may have two effects on the processing of IC by neutrophils; firstly, it enhances FcR-mediated cellular responses, and secondly, it prevents superoxide anion-induced tissue damage by trapping superoxide anions in phagosomes.