Adenosine and cardioprotection: what can we learn from nature's genetic polymorphism?

Adenosine is an endogenous nucleoside that has been shown to be beneficial for the myocardium in different settings by a large number of experimental studies. In this article, we 1) outline adenosine's metabolic pathways, 2) address cardioprotective properties of adenosine, and 3) discuss possible implications of the two recently published clinical studies disclosing a positive effect of adenosine monophosphate deaminase 1 (AMPD1) gene mutation on cardiovascular survival in heart failure and ischemic heart disease. (Fig. 2, Ref. 84.)

Norepinephrine concentrations in the epicardial transudate reflect early changes in adrenergic activity in the isolated perfused heart.

The aim of this study was to establish whether epicardial transudates could be used to uncover small, but physiologically important changes in interstitial NE concentrations under normal and pathological conditions. Norepinephrine (NE) concentrations measured in epicardial transudate fluid were compared to NE levels in the coronary effluent in normal and pressure overload hypertrophied (POH) rat hearts. Hearts were isolated together with the stellate ganglion and perfused in the inverted position. Epicardial surface transudates, representative fluid of the interstitial myocardial compartment, and coronary effluents were collected for determination of NE levels in the presence and absence of stellate ganglion stimulation. The same protocol was repeated in the presence and absence of nisoxetine, a NE uptake blocker. NE concentrations in epicardial transudates were 16- and 19-fold higher than in the coronary effluent in both sham and POH groups, respectively. NE concentrations in the transudates but not in the coronary effluents were significantly higher (1.6-fold) in hearts with POH when compared to normal hearts. Likewise, nisoxetine (10(-5)m) increased (1.3-fold) NE concentrations in the transudates but not in the effluents of sham animals. As expected, stellate ganglion stimulation increased NE concentrations in both transudates and effluents in sham and POH hearts. In conclusion, determination of NE concentrations in epicardial transudates represents a simple, rapid and sensitive method to detect increases in adrenergic activity in normal and abnormal hearts.