Niacin protects the isolated heart from ischemia-reperfusion injury

Nicotinic acid (niacin) has been shown to decrease myocyte injury. Because interventions that lower the cytosolic NADH/NAD(+) ratio improve glycolysis and limit infarct size, we hypothesized that 1) niacin, as a precursor of NAD(+), would lower the NADH/NAD(+) ratio, increase glycolysis, and limit i schemic injury and 2) these cardioprotective benefits of niacin would be li mited in conditions that block lactate removal. Isolated rat hearts were pe rfused without (Ctl) or with 1 mu M niacin (Nia) and subjected to 30 min of low-flow ischemia (10% of baseline flow, LF) and reperfusion. To examine t he effects of limiting lactate efflux, experiments were performed with 1) C tl and Nia groups subjected to zero-flow ischemia and 2) the Nia group trea ted with the lactate-H+ cotransport inhibitor alpha-cyano-4-hydroxycinnamat e under LF conditions. Measured variables included ATP, pH, cardiac functio n, tissue lactate-to-pyruvate ratio (reflecting NADH/NAD(+)), lactate efflu x rate, and creatine kinase release. The lactate-to-pyruvate ratio was redu ced by more than twofold in Nia-LF hearts during baseline and ischemic cond itions (P < 0.001 and P < 0.01, respectively), with concurrent lower creati ne kinase release than Ctl hearts (P < 0.05). Nia-LF hearts had significant ly greater lactate release during ischemia (P < 0.05 vs. Ctl hearts) as wel l as higher functional recovery and a relative preservation of high-energy phosphates. Inhibiting lactate efflux with alpha-cyano-4-hydroxycinnamate a nd blocking lactate washout with zero flow negated some of the beneficial e ffects of niacin. During LF, niacin lowered the cytosolic redox state and i ncreased lactate efflux, consistent with redox regulation of glycolysis. Ni acin significantly improved functional and metabolic parameters under these conditions, providing additional rationale for use of niacin as a therapeu tic agent in patients with ischemic heart disease.