Diabetes mellitus is a chronic syndrome affecting carbohydrate, protein, and fat metabolism. It is characterized primarily by relative or absolute insufficiency of insulin secretion (type I diabetes or IDDM) or concomitant insensitivity / resistance to the metabolic action of insulin on target tissues (Type II diabetes or NIDDM), both resulting in hyperglycaemia. Diabetes mellitus is known to induce microvascular changes and alterations to neuronal functions. The neurovascular system comprising of unmyelinated primary afferent sensory neurones and the microvasculature innervated by these nerves play a major role in modulating inflammatory and tissue repair processes. Sensory nerve terminals respond to injury via the release of sensory neuropeptides which mediate inflammation and tissue repair. These processes are known to be altered in diabetes. This thesis is concerned with the role of diabetes in modulating microvascular blood flow directly and indirectly via modulating sensory nerve activity and the effect of these changes on repair processes in skin of 4 weeks streptozotocin (STZ)-induced diabetic rats. The following hypotheses were examined: 1. That factors implicated in long-term diabetic vascular damage play a role in altering skin microvascular function in early diabetes. 2. That preventing the deleterious effects of these factors could improve skin microvascular blood flow and skin repair processes in early diabetes. (For complete abstract open document)

We assessed potential mechanisms that may jeopardize skeletal muscle perfusion during surgery leading to adverse outcomes including muscle injury and flap hypoxia. In craniotomy patients, we observed an increase in serum lactate and creatine kinase and urine myoglobin; indicative of muscle damage. The early rise in lactate correlated with elevated BMI, suggesting that obesity caused tissue compression and muscle ischemia. In our rodent model, we investigated the effects of flap preparation and phenylephrine on muscle perfusion by assessing microvascular blood flow and tissue PO2. Phenylephrine reduced muscle blood flow by ~20%, yet increased PO2 by ~10% suggestive of decreased O2 metabolism. At baseline, muscle flap blood flow was reduced by ~50% while PO2 was severely reduced ~80% (~5 torr) suggesting that flap perfusion was attenuated and O2 metabolism was increased. Phenylephrine infusion further reduced muscle flap perfusion. These data demonstrate multiple mechanisms by which muscle perfusion is jeopardized during surgery.

We assessed potential mechanisms that may jeopardize skeletal muscle perfusion during surgery leading to adverse outcomes including muscle injury and flap hypoxia. In craniotomy patients, we observed an increase in serum lactate and creatine kinase and urine myoglobin; indicative of muscle damage. The early rise in lactate correlated with elevated BMI, suggesting that obesity caused tissue compression and muscle ischemia. In our rodent model, we investigated the effects of flap preparation and phenylephrine on muscle perfusion by assessing microvascular blood flow and tissue PO2. Phenylephrine reduced muscle blood flow by ~20%, yet increased PO2 by ~10% suggestive of decreased O2 metabolism. At baseline, muscle flap blood flow was reduced by ~50% while PO2 was severely reduced ~80% (~5 torr) suggesting that flap perfusion was attenuated and O2 metabolism was increased. Phenylephrine infusion further reduced muscle flap perfusion. These data demonstrate multiple mechanisms by which muscle perfusion is jeopardized during surgery.