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Coronary endothelial dysfunction after ischemia and reperfusion in the dog: a functional and morphological
P A Martorana1, B Goebel, H Ruetten
1Hoechst Marion Roussel, Disease Group Cardiovascular Agents, Frankfurt/Main.
Insights
Coronary endothelial dysfunction after ischemia-reperfusion impairs blood vessel response to acetylcholine and serotonin. Scanning electron microscopy revealed arteriolar damage, confirming impaired vasoreactivity.
Area of Science:
- Cardiovascular Physiology
- Endothelial Function
- Ischemia-Reperfusion Injury
Background:
- Coronary endothelial dysfunction is a key feature of cardiovascular disease.
- It manifests as reduced responsiveness to endothelium-dependent vasodilators like acetylcholine (ACh) and serotonin (5-HT).
- Endothelium-independent vasodilators like nitroglycerin (NTG) typically remain effective.
Purpose of the Study:
- To investigate coronary vasoreactivity in vivo following ischemia and reperfusion (I/R).
- To assess the morphological changes in coronary arterioles and capillaries using scanning electron microscopy (SEM).
Main Methods:
- Anesthetized dogs underwent 60 minutes of left circumflex coronary artery ischemia followed by 180 minutes of reperfusion (I/R group, N=27) or a sham procedure (N=8).
- Intracoronary administration of ACh, 5-HT, and NTG was performed before and after I/R.
- Myocardial biopsies were analyzed using SEM to evaluate arteriolar and capillary morphology.
Main Results:
- The I/R group exhibited a significant reduction in basal coronary flow (35%) compared to sham-operated dogs.
- Vasoreactivity to ACh and 5-HT was significantly blunted in the I/R group, while the response to NTG remained unaltered.
- SEM revealed leukocyte adhesion and endothelial surface damage in arterioles of I/R dogs, whereas capillaries were unaffected.
Conclusions:
- Ischemia-reperfusion induces coronary endothelial dysfunction, evidenced by impaired vasoreactivity to endothelium-dependent vasodilators in vivo.
- Preserved response to NTG suggests intact smooth muscle cell function.
- SEM findings highlight arteriolar damage as a potential mechanism underlying endothelial dysfunction post-I/R.
Abstract:
Coronary endothelial dysfunction is characterized by a lower response to endothelium-dependent vasodilators such as acetylcholine (ACh) and serotonin (5HT), but by an unaltered response to endothelium-independent vasodilators such as nitroglycerin (NTG). In the present study, we investigated the vasoreactivity of the coronary bed in vivo, in a dog model of ischemia and reperfusion (I/R). We also assessed the morphology of the subepicardial arterioles and capillary bed by means of scanning electron microscopy (SEM). Anesthetized, instrumented dogs were divided in two groups. One group (N = 27) was submitted to ischemia (60 min) and reperfusion (180 min) of the left circumflex coronary artery, the second group (N = 8) was sham-operated. Prior to and following I/R, ACh, 5-HT, and NTG were given intracoronarily. At the end of the experiment a 1 cm3 myocardial biopsy was processed for SEM. The sham-operated dogs showed a reduction of basal coronary flow of 11%, but the vasoreactivity to ACh and 5-HT remained constant. In the I/R group, basal coronary flow was reduced by 35% (p < 0.05), and the vasoreactivity to ACh and 5-HT, but not to NTG, was significantly blunted. At SEM the arterioles of the dogs submitted to I/R showed a marked adhesion of leukocytes associated with holes on the endothelial surface, while the capillary bed was free of changes and patient. Thus, following I/R, coronary endothelial dysfunction could be demonstrated in vivo by the blunting of the vasoreactive responses to two different endothelium-dependent vasodilators. The responses to NTG were not affected, probably because the function of the smooth muscle cell was preserved, and the capillary bed was patent.