The effects of the GPIIb-IIIa antagonists abciximab and MK-852 on platelet-leukocyte interactions in vitro were studied and the results compared with those obtained with a combination of aspirin, dipyridamole and AR-C69931 (Asp/Dip/AR-C). Platelet-monocyte (P/M) and platelet-neutrophil (P/N) conjugate formation increased when blood was stirred or a platelet agonist was added. Leukocyte activation also occurred as judged by expression of surface tissue factor antigen and CD11b. Abciximab and MK-852 potentiated P/M, especially when collagen was used. They also increased the amount of tissue factor on the monocytes, but not CD11b. The Asp/Dip/AR-C did not enhance P/M or tissue factor exposure. Augmented tissue factor expression on monocytes in the presence of a GPIIb-IIIa antagonist may be relevant to the increased mortality associated with trials of such antagonists when given orally in patients with vascular disease. The Asp/Dip/AR-C was superior to abciximab and MK-852 in inhibiting platelet and leukocyte function.

To determine if the addition of preload reduction with nitrates would potentiate the acute vasodilator actions of nifedipine, we titered intravenous nitroglycerin in seven patients with severe congestive heart failure after they received a single oral dose of nifedipine. The peak hemodynamic effect of nifedipine occurred at 30 minutes, with large reductions of systemic vascular resistance (1831 ± 128 to 1132 ± 154 dynes · sec · cm−5; p < 0.001) and mean arterial pressure (87 ± 7 to 71 ± 7 mm Hg; p < 0.01). This was associated with an increase of stroke volume index from 22 ± 3 to 27 ± 3 ml/m2 (p < 0.01) but no significant changes in heart rate, right atrial pressure, or pulmonary wedge pressure. These hemodynamic changes were attenuated over a 2-hour observation period. At 2 hours, the addition of intravenous nitroglycerin resulted in large reductions in right atrial pressure (9 ± 2 to 6 ± 1; p < 0.01) and pulmonary wedge pressure (23 ± 2 to 17 ± 2; p < 0.001). This was associated with further increases in cardiac index (from 1.99 ± .15 to 2.25 ± .14 L/min/m2; p < 0.001) and stroke volume index (26 ± 3 to 29 ± 3 ml/m2; p < 0.01). Thus, the addition of nitroglycerin to nifedipine will optimize preload reduction and enhance the vasodilator action of nifedipine. Further controlled studies are necessary to determine the long-term hemodynamic effects and the clinical role of nifedipine and its combination with nitrates in patients with severe congestive heart failure.