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Adenosine-induced hyperemia attenuates myocardial ischemia in coronary microembolization in dogs
1First Department of Medicine, Osaka University School of Medicine, Japan.
Insights
Adenosine released during myocardial ischemia improves blood flow and reduces damage. Blocking adenosine release or its receptors worsens ischemia, confirming adenosine
Area of Science:
- Cardiovascular Physiology
- Myocardial Ischemia Research
- Pharmacology of Adenosine
Background:
- Coronary microembolization causes myocardial ischemia and adenosine release.
- Adenosine release triggers a hyperemic response in coronary blood flow (CBF).
Purpose of the Study:
- To test if adenosine-induced hyperemic flow improves myocardial ischemia.
- To elucidate the role of adenosine in microembolization-induced ischemia.
Main Methods:
- Used a canine model of coronary microembolization.
- Administered prazosin to inhibit adenosine release and theophylline to block adenosine receptors.
- Monitored coronary blood flow (CBF), fractional shortening, and lactate extraction ratio (LER).
Main Results:
- Control group showed a hyperemic CBF response to microembolization.
- Prazosin and theophylline significantly attenuated the hyperemic response and worsened myocardial function (fractional shortening, LER).
- Reversal of drug effects improved ischemic parameters, confirming adenosine's beneficial role.
Conclusions:
- Adenosine released from ischemic myocardium improves myocardial ischemia.
- The beneficial effect is mediated through the hyperemic coronary blood flow response.
- Targeting adenosine pathways may offer therapeutic potential for ischemic conditions.
Abstract:
We have recently reported that coronary microembolization sustains myocardial ischemia with hyperemic response of coronary blood flow (CBF) induced by massive release of adenosine from the ischemic myocardium. In this study, we tested the hypothesis that this hyperemic flow caused by released adenosine improves myocardial ischemia. In eight dogs (control), microspheres (5.0 X 10(4)/ml of base-line CBF) were repetitively injected until CBF decreased toward zero, and the changes in CBF, fractional shortening, lactate extraction ratio (LER), and adenosine release were studied. In 15 other dogs, an identical procedure was done with an intracoronary infusion of prazosin (4 micrograms.kg-1.min-1, n = 8) or theophylline (0.1 mg.kg-1.min, n = 7) to elucidate the effect of adenosine, since prazosin inhibits release of adenosine from ischemic myocardium and theophylline blocks adenosine receptors. In 16 other dogs, hemodynamic and metabolic parameters were examined with and without these drugs after a single injection of microspheres (1.0 X 10(5)/ml of base-line CBF). In the control group, CBF increased to 170 +/- (SE) 14% of the base-line CBF at 16-30% of maximal embolization. In contrast, intracoronary infusion of prazosin markedly attenuated adenosine release and hyperemic response and significantly deteriorated both fractional shortening and LER. Theophylline also significantly attenuated the hyperemic response and tended to decrease both fractional shortening and LER. A salutary effect of adenosine release was further confirmed by the improvement of ischemic changes in the same dog after withdrawal of prazosin and theophylline associated with an increase in CBF. Thus we conclude that adenosine released from ischemic myocardium improves ischemia in microembolization through the hyperemic response.