Abstract
We examined myocardial 5′-adenosine monophosphate (5′-AMP) catabolism, adenosine salvage and adenosine responses in perfused guinea pig, rat and mouse heart. M V o 2 increased from 71±8 μl O 2/min per g in guinea pig to 138±17 and 221±15 μl O 2/min per g in rat and mouse. V o 2/beat was 0.42±0.03, 0.50±0.03 and 0.55±0.04 μl O 2/g in guinea pig, rat and mouse, respectively. Resting and peak coronary flows were highest in mouse vs. rat and guinea pig, and peak ventricular pressures and Ca 2+ sensitivity declined as heart mass increased. Net myocardial 5′-AMP dephosphorylation increased significantly as mass declined (3.8±0.5, 9.0±1.4 and 11.0±1.6 nmol/min per g in guinea pig, rat and mouse, respectively). Despite increased 5′-AMP catabolism, coronary venous [adenosine] was similar in guinea pig, rat and mouse (45±8, 69±10 and 57±14 nM, respectively). Comparable venous [adenosine] was achieved by increased salvage vs. deamination: 64%, 41% and 39% of adenosine formed was rephosphorylated while 23%, 46%, and 50% was deaminated in mouse, rat and guinea pig, respectively. Moreover, only 35–45% of inosine and its catabolites derive from 5′-AMP (vs. IMP) dephosphorylation in all species. Although post-ischemic purine loss was low in mouse (due to these adaptations), functional tolerance to ischemia decreased with heart mass. Cardiovascular sensitivity to adenosine also differed between species, with A 1 receptor sensitivity being greatest in mouse while A 2 sensitivity was greatest in guinea pig. In summary: (i) cardiac 5′-AMP dephosphorylation, V o 2, contractility and Ca 2+ sensitivity all increase as heart mass falls; (ii) adaptations in adenosine salvage vs. deamination limit purine loss and yield similar adenosine levels across species; (iii) ischemic tolerance declines with heart mass; and (iv) cardiovascular sensitivity to adenosine varies, with increasing A 2 sensitivity relative to A 1 sensitivity in larger hearts.
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