Oxygen Transport in Peripheral Vascular Disease: A Novel Approach to the Search for Effective Agents

Abstract

Peripheral vascular disease (PVD) is one of several types of disturbances that can interfere with the transport of oxygen from atmospheric air in the alveoli to the ATPasecontaining inner surface of the inner mitochondria1 membrane. The consequences can include functional and structural tissue degeneration. The preferred therapeutic approach to PVD, as with any disease, is to identify and remove the cause. When this approach is not feasible, the therapist seeks to influence any aspect of the mechanism that may alleviate the damage to function and structure.The rational classical approaches to the ischemia of PVD include widening vascular channels by the surgical or medical removal of obstructing materials, vasodilation, and neovascularization. More recently, effective therapeutic agents have been developed on the basis of pathophysiologic mechanisms that do not involve an increase in the total cross-sectional area of the lumen of the vessels involved. These include drug-enhanced red cell deformability (35) and hemodilution (12) to reduce blood viscosity as a means of increasing blood flow without widening narrowed vascular channels, the trapping of free radicals that form on reperfusion of ischemic tissue (13), and better survival of injured cells by controlling the intracellular calcium ion concentration with drugs that act on calcium channel receptors (31). This discussion will deal with still another hypothesis not directly concerned with vascular channel caliber, i.e., oxygen diffusion. Impaired oxygen diffusion as a possible contributing factor to the inadequate delivery of oxygen from alveolus to mitochondria has received little attention even though limitations to oxygen diffusion are recognized (25). While good experimental data support the commonly accepted thesis that the rate of diffusion is not a limiting factor in the normal chain of oxygen transport (4), recent observations suggest the possibility that limitations of oxygen diffusion may in fact contribute significantly to the consequences of PVD,

Concepts of “Tissue PO2” In Relation to O2Delivery

“…While the rapid establishment of equilibrium between alveolus gases and lung capillary blood in n o d subjects is well documented [6], there are data which suggest that capillary pathology may result in fkilure to reach p02 equilibrium [7].…”

Oxygen Transport in Peripheral Arterial Occlusive Disease: Effects of Calf Blood Dialysate

“…More likely, a capillary disturbance associated with chronic ischemia&dquo; may be favorably modified by calf blood dialysate, leading to improved oxygen diffusion both from alveoli to blood and peripherally from red cells in capillaries to tissue myocytes . 2 This postulate takes into account the following considerations: the circulatory system is a closed loop, and total blood flow through each of its segments in series (heart, arteries, capillary bed, and veins), is essentially the same. However, the velocity of movement through each unit varies considerably, depending on the total cross-sectional area.…”