Effect of aldose reductase inhibition on resistance to ischemic conduction block in diabetic subjects

Diabetes Care. 1991 May;14(5):411-3. doi: 10.2337/diacare.14.5.411.

Abstract

Objective: To study the effect of aldose reductase inhibition with ponalrestat on resistance to ischemic conduction block (RICB) in diabetic subjects.

Research design and methods: Twenty-one healthy diabetic subjects without neuropathy were studied. Subjects were randomized to take either a double-blind trial of 600 mg ponalrestat or placebo once daily for 6 wk. The median nerve action potential (MNAP) and conduction velocity (NCV), before and after 20 min of forearm ischemia, were measured at the start and finish of the study.

Results: RICB (MNAP remaining after ischemia) decreased from 39.5 to 29.4% in the ponalrestat-treated group (P less than 0.05) and increased from 48.1 +/- 10.2 to 49.5 +/- 6.5% in the placebo-treated group. MNAP and NCV were unchanged in both groups.

Conclusions: Aldose reductase inhibition with ponalrestat partly reverses RICB in diabetes, perhaps by improving nerve hypoxia or reducing nerve energy substrates.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Aldehyde Reductase / antagonists & inhibitors*
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / physiopathology*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diabetes Mellitus, Type 2 / physiopathology
  • Double-Blind Method
  • Female
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Ischemia / physiopathology*
  • Male
  • Median Nerve / blood supply
  • Median Nerve / drug effects
  • Median Nerve / physiopathology*
  • Middle Aged
  • Neural Conduction / drug effects*
  • Phthalazines / pharmacology
  • Phthalazines / therapeutic use*
  • Reference Values

Substances

  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Phthalazines
  • ponalrestat
  • Aldehyde Reductase