Resistance to ischemic conduction block of the peripheral nerve in hyperglycemic rats: An electrophysiological study

Abstract

Resistance to ischemic conduction block (RICB) was studied in rats with streptozotocin (STZ) induced hyperglycemia, hyperglycemia by glucose injection, and glycerin-induced hyperosmolarity. Ischemia was produced by tight ligation at the base of the tail. The time required for nerve action potentials (NAP) to disappear was defined as the disappearance time of NAP (DT-NAP). Both STZ and glucose rats showed a marked prolongation of DT-NAP at 2 hours after injection of STZ (up to 120 minutes) or glucose (up to 95 minutes), as compared with the control rats (less than 45 minutes). Hyperosmolar rats showed no prolongation of DT-NAP. The amplitude of NAP remained at the initial level for at least 2 hours after ligation of the sciatic nerve, whereas NAP disappeared within 45 minutes after ligation of the abdominal aorta. These findings indicate that the RICB can be produced by means of hyperglycemia without the presence of diabetic neuropathy and is the most sensitive indicator of hyperglycemia.

The paradox between resistance to hypoxia and liability to hypoxic damage in hyperglycemic peripheral nerves. Evidence for glycolysis involvement

“…Another possibility underlying the abnormal sensitivity to hypoxia of hyperglycemic nerves is enhanced glycolysis, as suggested previously (8)(9)(10)(11)(12). The possible importance of this mechanism is strongly supported by the effects of D-mannose seen in this study.…”

“…However, the precise mechanisms underlying these alterations are not yet clear. Resistance to ischemia was first described by Steiness (3), and several hypotheses have attempted to explain this phenomenon (4): 1) a decrease in the accumulation of extracellular K + during ischemia caused by a change of a nodal diffusion barrier (5) or an enlarged interstitial endoneurial space (6); 2) changes in the internodal length of myelinated axons (7); 3) increased availability of energy sources for anaerobic glycolysis in diabetic nerve (8)(9)(10)(11)(12); 4) other alterations in neuronal metabolism such as inhibition of inositol uptake, accumulation of polyols, and/or reduced activity of the Na"7K + -ATPase (13), and 5) adaptation to chronic hypoxemia (14)(15)(16).…”

Is resistance to ischaemia of motor axons in diabetic subjects due to membrane depolarization?

“…The correlation coefficients for the actual blood glucose concentration or the HbA lc values were lower. In rats made hyperglycaemic with streptozotocin or glucose injections, resistance to ischaemia has been seen as early as 2 h (Shirabe et al 1988). A pressure cuff can be applied for 5 min as often as every 15 min to obtain consistent measurements of ischaemic sensitivity by threshold tracking, so this method should allow the time relationship between blood glucose and ischaemic resistance to be precisely defined.…”

“…It was first described by Steiness (1959Steiness ( , 1961a and later confirmed by many other investigators (Gregersen 1968;Horowitz and Ginsberg-Fellner 1979: reviews by Ludin and Tackmann 1984;Low 1987;Thomas and Brown 1987). Recent publications have provided good evidence that resistance to ischaemia is due to a marked increase in energy substrate stores (Jaramillo et al 1985;Low et al 1985;Low 1987;Shirabe et al 1988;Parry and Kohzu 1989). An alternative hypothesis was put forward by Ritchie (1985), that membrane depolarization is responsible for the change in sensitivity to ischaemia.…”

Association between clinical condition and F-waves changes in the acute phase of stroke

“…Hyperglycemia in the acute phase of stroke may play a role in ischemic neuronal damage 24 and, additionally, hyperglycemia is associated with a poorer long-term prognosis 25,26,27 . Hyperglycemia has been reported to alter nerve conduction in some preclinical studies 28,29 . In clinical studies, acute hyperglycemia did not alter nerve conduction velocities and amplitudes…”