D. K. Harrison

Regulation of capillary blood flow and oxygen supply in skeletal muscle in dogs during hypoxaemia.

1. Multiwire surface electrodes were used to measure local hydrogen clearance curves and tissue PO2 in vivo. Evaluation of the initial slopes of the hydrogen clearance curves enabled the measurement of capillary blood flow and its distribution. 2. Capillary blood flow and tissue PO2 frequency distribution histograms were measured in the m. sartorius of anaesthetized, relaxed mongrel dogs under conditions of normoxic (Fi, O2 = 0.3) and hypoxic (Fi, O2 = 0.15 and 0.1) artificial ventilation. 3. Stepwise hypoxaemia (hypoxic hypoxia) induced an increasing discrepancy between capillary blood flow and arterial blood flow. The former decreased by 6% whereas the latter increased by 86%. 4. PO2 histograms provided no evidence of cellular anoxia even at Fi,O2 = 0.1. Capillary blood flow histograms suggested a redistribution of the local pattern of flow. 5. A 34.7% reduction of O2 consumption was observed as the result of severe hypoxaemia. 6. The concept of heterogeneity of capillary blood flow as a functional O2 reserve is presented, together with evidence for oxygen‐dependent regulation of capillary blood flow and oxygen consumption.

Local oxygen supply and blood flow regulation in contracting muscle in dogs and rabbits.

1. Multiwire surface electrodes were used to measure local hydrogen clearance curves and tissues PO2 in the sartorius muscle in dogs under resting conditions and during stimulation of the muscle at 1, 2, 4, 8 and 20 Hz via the femoral nerve. Tissue oxygen supply was assessed by means of PO2 histograms; evaluation of the initial slopes of the hydrogen clearance curves enabled the measurement of capillary blood flow. 2. In a further model, the analysis of hydrogen clearance curves measured in the femoral vein using intravascular needle electrodes in rabbits enabled the distribution of blood flow to be evaluated both under resting conditions and during direct 2 Hz stimulation of the vastus medialis muscle. 3. Increased oxygen consumption, induced by stimulation, caused increases in capillary flow which were not necessarily accompanied by augmentation of femoral artery flow. 4. PO2 histograms provided no evidence of cellular anoxia even at the maximum level of oxygen consumption. 5. A two‐compartment distribution of flow was measured under resting conditions, whereas only one compartment could be resolved during 2 Hz stimulation of the vastus medialis muscle in the rabbit experiments. A clear redistribution of flow was observed in the absence of any increase in total flow. 6. A model for oxygen‐dependent regulation of capillary blood flow involving high‐flow and normal‐flow compartments is proposed.

Tissue O2 Supply Under Normal and Pathological Conditions

Systematic investigations of a variety of local parameters which form part of the complex functional chain responsible for delivery of oxygen to tissues revealed that most relevant information can be obtained by direct measurements of the oxygen tension field (Po2 histogram) by means of Clark-type and Po2 needle electrodes.

Regulation of Capillary Blood Flow: A New Concept

Last year we presented preliminary data which indicated a considerable inhomogeneity of capillary blood flow in skeletal muscle as measured both in the sartorius muscle of dogs and in the vastus medialis muscle in rabbits (Harrison et al., 1988). Measurements of capillary blood flow with particular emphasis on its distribution at rest, using hydrogen clearance techniques, during hypoxaemia and in contracting muscle led us to propose a two compartment model for the distribution of capillary blood flow in skeletal muscle.

Local Oxygen Supply and Regional Wall Motion of the Dog’s Heart During Critical Stenosis of the Lad

When open heart surgery is performed in order to bypass stenosed coronary arteries by a vein graft, the heart surgeon often discovers hypokinetic zones in the poorly perfused area of the myocardium.

The role of high flow capillary channels in the local oxygen supply to skeletal muscle.

Investigations over the years into the local oxygen supply in various organs have revealed (with the exception of the heart and kidneys) an interesting discrepancy between the mean tissue and venous pO2 values. The latter values were found to be higher than might be expected (Kessler et al., 1976) indicating a heterogeneity of capillary flow through the organ. More specifically, studies of the spatial distribution of local pO2 at the surface of skeletal muscle have revealed considerable differences in mean tissue pO2 values between different capillary supply units (Fig. 1) confirming that a large degree of heterogeneity in flow probably exists.

Microcirculation and Po2 in Skeletal Muscle During Respiratory Hypoxia and Stimulation

The regulation of blood flow to skeletal muscle has, for many years, been the subject of much research (Hudlicka, 1973) with the result that nowadays many phenomena can be explained by the presence of local oxygen sensors which serve to regulate the flow in order to maintain an adequate oxygen supply to the tissue (Granger and Shepherd, 1973). For example, the vasodilation which occurs during hypoxia almost certainly takes place as a result of signals from such sensors, and there is strong evidence to suggest that the majority of these sensors may be located in the tissue cells (Kessler et al., 1983).

Oxygen Supply and Microcirculation of the Beating Dog Heart after Haemodilution with Fluosol DA20

Previous studies on local tissue oxygen supply after haemodilution with the colloidal perfluorocarbon Fluosol DA20% (FDA20%) carried out in the liver (Hoper et al., 1982), pancreas, kidney and skeletal muscle (Kessler et al., 1982), and the heart (Vogel et al., 1983; Kessler et al., 1983) have demonstrated that an improvement in local tissue oxygen supply was observed which was greater than could be explained simply in terms of the increased quantity of oxygen delivered by the fluo-rocarbon. It was evident that changes in flow occured (Hoper et al., 1982), probably at the microcirculation 1evel.

Redistribution of microcirculation in skeletal muscle during hypoxaemia.

Previous studies of tissue pO2 in the sartorius muscle in dogs revealed that hypoxaemia induced a redistribution of local pO2 in such a way that a lower mean value, but a very much narrower range of values was observed, without the appearance of partial pressures in the 0–5 mmHg range (Harrison et al., 1984). Preliminary measurements of capillary blood flow using the hydrogen clearance technique indicated that under these conditions a redistribution of microflow may occur.

Measurement of Local Po2 and Intracapillary Hemoglobin Oxygenation in Lung Tissue of Rabbits

To date investigations of the mechanisms involved in the ventilation and perfusion of the lung have only been carried out by indirect methods. The disadvantage of such methods is that the local distribution of these parameters within the lung, particularly in the alveolar-capillary area, cannot be adequately determined.