INCREASED INDUCIBLE NITRIC-OXIDE SYNTHASE IN SKELETAL-MUSCLE BIOPSIESFROM PATIENTS WITH CHRONIC HEART-FAILURE

In addition to left ventricular pump failure and low cardiac output, s tructural and metabolic alterations of skeletal muscle are thought to contribute to exercise intolerance seen in patients with CHF. Studies using cardiac myocytes have implicated nitric oxide elaborated by indu cible nitric oxide synthase (iNOS) as a potential agent associated wit h the genesis of dilated cardiomyopathy. The present study was designe d to locate iNOS in the working skeletal muscle of patients with conge stive heart failure. Specific antibodies were used to detect iNOS by i mmunohistochemistry in skeletal muscle biopsies (m. vastus lateralis) of 37 patients with left ventricular pump failure and 8 normal control s. The expression was restricted to skeletal muscle myocytes and was i ncreased five-to ninefold in patients with chronic heart failure. Ther e was no statistically significant difference in iNOS expression betwe en patients with dilated cardiomyopathy and those with ischemic cardio myopathy. The finding of a locally increased expression of iNOS and th e experimental evidence that NO attenuates the contractile performance of the skeletal muscle suggest that the expression of iNOS may be res ponsible for the exercise intolerance seen in patients with chronic he art failure. (C) 1997 Academic Press.