Cocaine-induced coronary vasoconstriction is potentiated by beta-adrenergic blockade. Beta-adrenergic blocking agents probably should be avoided in patients with cocaine-associated myocardial ischemia or infarction.

Cocaine increases myocardial oxygen demand and paradoxically decreases oxygen supply by reducing coronary blood flow. Such "inappropriate" vasoconstriction also occurs with exercise, which causes intense vasoconstriction of coronary artery segments narrowed by atherosclerosis. This study was done to assess the cocaine-induced change in vasomotor tone of diseased and nondiseased coronary artery segments. In 18 patients (15 men, 3 women, aged 35 to 67 years), coronary artery areas in diseased and nondiseased segments were quantitated before and 15 min after administration of intranasal saline solution (6 patients) or cocaine (2 mg/kg body weight) (12 patients). No variables changed after intake of the saline solution. In response to cocaine, the luminal areas of diseased and nondiseased segments decreased, but the magnitude of vasoconstriction was greater in the diseased segments (mean +/- SD 29 +/- 23% versus 13 +/- 8%, p less than 0.05). Thus, cocaine causes vasoconstriction of diseased and nondiseased coronary artery segments, but its effect is particularly marked in the former.

Blood oxygenators provide crucial life support for patients suffering from respiratory failure, but their use is severely limited by the complex nature of the blood circuit and by complications including bleeding and clotting. We have fabricated and tested a multilayer microfluidic blood oxygenation prototype designed to have a lower blood prime volume and improved blood circulation relative to current hollow fiber cartridge oxygenators. Here we address processes for scaling the device toward clinically relevant oxygen transfer rates while maintaining a low prime volume of blood in the device, which is required for clinical applications in cardiopulmonary support and ultimately for chronic use. Approaches for scaling the device toward clinically relevant gas transfer rates, both by expanding the active surface area of the network of blood microchannels in a planar layer and by increasing the number of microfluidic layers stacked together in a three-dimensional device are addressed. In addition to reducing prime volume and enhancing gas transfer efficiency, the geometric properties of the microchannel networks are designed to increase device safety by providing a biomimetic and physiologically realistic flow path for the blood. Safety and hemocompatibility are also influenced by blood-surface interactions within the device. In order to further enhance device safety and hemocompatibility, we have demonstrated successful coating of the blood flow pathways with human endothelial cells, in order to confer the ability of the endothelium to inhibit coagulation and thrombus formation. Blood testing results provide confirmation of fibrin clot formation in non-endothelialized devices, while negligible clot formation was documented in cell-coated devices. Gas transfer testing demonstrates that the endothelial lining does not reduce the transfer efficiency relative to acellular devices. This process of scaling the microfluidic architecture and utilizing autologous cells to line the channels and mitigate coagulation represents a promising avenue for therapy for patients suffering from a range of acute and chronic lung diseases.