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Microembolization in pigs: effects on coronary blood flow and myocardial ischemic tolerance
F Grund1, H T Sommerschild, T Lyberg
1Institute for Experimental Medical Research, University of Oslo, Ullevâl Hospital, N-0407 Oslo, Norway. frank.grund@ioks.uio.no
Abstract:
Coronary microembolization has been reported to increase coronary blood flow (CBF) through adenosine release. Because adenosine may increase ischemic tolerance against infarction, we tested the hypothesis that myocardial microembolization, a common finding in patients with ischemic heart disease, induces cardioprotection. Additionally, because the use of microspheres is a common tool to measure tissue perfusion, the effects of small amounts of microspheres on CBF were examined. Using anesthetized pigs, we measured CBF with a transit time flow probe on the left anterior descending coronary artery (LAD). In six pigs the relationship between the amount of injected microspheres (0-40 x 10(6), 15 micrometer in diameter, left atrial injections) and the effect on CBF was examined. Coronary hyperemia occurred, which was linearly related to the amount of microspheres injected: maximal increase in CBF (%) = 2.8 +/- 1.5 (SE) + (5.8 +/- 0.7 x 10(-7) x number of injected microspheres). Because injection of 40 x 10(6) microspheres induced a long-lasting hyperemic response, which could be blocked by 8-p-sulfophenyl theophylline, ischemic tolerance was examined in five other pigs after two injections, each of 40 x 10(6) microspheres, at a 30-min interval. Six control pigs had no injections. Ischemic tolerance was evaluated by measuring infarct size (tetrazolium stain) as the percentage of area at risk (fluorescent particles) after 45 min of LAD occlusion followed by 2 h of reperfusion. Pretreatment by microspheres increased infarct size from 60 +/- 3% of area at risk in control animals to 84 +/- 6% (P < 0.05). The injection of microspheres induced a significant hyperemic flow response without causing necrosis by itself. We conclude that microembolization, evoking coronary hyperemia, does not improve but reduces myocardial ischemic tolerance against infarction in pigs.
Insights
Myocardial microembolization, which increases coronary blood flow, paradoxically reduces protection against infarction. This study found that microembolization worsens ischemic tolerance in pigs, contrary to expectations.
Area of Science:
- Cardiovascular Physiology
- Ischemic Heart Disease Research
- Myocardial Infarction Studies
Background:
- Coronary microembolization is known to increase coronary blood flow (CBF) via adenosine release.
- Adenosine may offer cardioprotection by increasing ischemic tolerance against infarction.
- Microembolization is a common finding in patients with ischemic heart disease.
Purpose of the Study:
- To test the hypothesis that myocardial microembolization induces cardioprotection.
- To examine the effects of microspheres on coronary blood flow.
- To evaluate if microembolization improves or reduces myocardial ischemic tolerance.
Main Methods:
- Anesthetized pigs were used to measure coronary blood flow (CBF) in the left anterior descending coronary artery (LAD).
- The relationship between injected microsphere amount and CBF was assessed.
- Ischemic tolerance was evaluated by measuring infarct size after LAD occlusion and reperfusion in microsphere-injected pigs versus controls.
Main Results:
- Injection of microspheres caused coronary hyperemia, linearly related to the amount injected.
- Pretreatment with microspheres significantly increased infarct size (84% vs. 60% of area at risk) compared to controls.
- Microsphere injection induced hyperemia but did not cause necrosis itself.
Conclusions:
- Myocardial microembolization, despite inducing coronary hyperemia, does not improve but reduces myocardial ischemic tolerance against infarction in pigs.
- The findings challenge the assumption that adenosine-mediated hyperemia from microembolization confers cardioprotection.
- Further research is needed to understand the mechanisms behind reduced ischemic tolerance post-microembolization.