Manipulation of papillary muscle cyclic nucleotides during anoxia-reoxygenation: Effects on contractility

Upton J.J. ; Huisamen B. ; Lochner A. (2002)


Endogenous nitric oxide and the accompanying cGMP formation has been postulated to play a role in the pathophysiology of myocardial anoxia-reoxygenation. A direct relationship between cGMP and the alterations observed in contractility under these conditions has never been demonstrated. In this study, cGMP in rat papillary muscles during anoxia and reoxygenation was correlated with mechanical function. Isolated papillary muscles were stimulated continuously and made anoxic for 40 min after a 2-hour stabilisation period. Anoxia caused an abbreviated contraction curve by decreasing the maximum contraction strength, time to peak contraction and relaxation time, accompanied by a significant decrease in tissue cGMP and cAMP levels (controls: 29.09 ± 1.62 and 568.8 ± 35.65; anoxia: 16.62 ± 1.51 and 403.3 ± 30.19 pmoles/gww), which partially returned to pre-anoxic values upon reoxygenation. cGMP levels were significantly elevated by addition of 8-Br-cGMP (a cGMP analogue), but this elevation (154.4 ± 20.89 pmoles/gww), had no effects on the contractility pattern of muscles during normoxia, anoxia or reoxygenation, suggesting that in isolated ventricular muscle, cGMP levels play a minor role in regulating muscle contractility.

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