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


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.
Price
D E
DE
Department of Medicine, General Infirmary, Leeds, United Kingdom.
Alani
S M
SM
Wales
J K
JK
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D008475:Median Nerve / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D008875:Middle Aged; D009431:Neural Conduction / Q000187:drug effects*; D010793:Phthalazines / Q000494:pharmacology / Q000627:therapeutic use*; D012016:Reference Values
D000449:Aldehyde Reductase; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010793:Phthalazines; C042829:ponalrestat