Key result
Simultaneous treatment with 5-HT2A and 5-HT1B receptor antagonists completely suppressed 5-HT-induced vasocontraction in the human internal thoracic artery, suggesting utility in preventing perioperative vasospasm, especially in patients with diabetes mellitus.
Why the study?
Does simultaneous treatment with 5-HT2A and 5-HT1B receptor antagonists prevent 5-HT-induced vasospasm in the internal thoracic artery of patients with diabetes mellitus?
Does simultaneous treatment with 5-HT2A and 5-HT1B receptor antagonists prevent 5-HT-induced vasospasm in the internal thoracic artery of patients with diabetes mellitus?
Simultaneous antagonism of 5-HT2A and 5-HT1B receptors may be useful to prevent perioperative vasospasm of internal thoracic artery grafts, particularly in patients with diabetes mellitus who exhibit enhanced 5-HT responsiveness.
May support dual 5-HT2A/1B antagonism to prevent internal thoracic artery graft spasm in diabetes; leaves open prospective trials before clinical adoption.
In ischemic heart diseases, the use of the internal thoracic artery (ITA) as an arterial graft has been associated with longer survival and better quality of life. However, it has been reported that vasospasm of the ITA graft frequently occurs and increases perioperative and postoperative morbidity. Serotonin (5-HT) plays an important role in the occurrence of vasospasm. We examined 5-HT receptor subtypes responsible for the 5-HT-induced vasocontraction in the human ITA. The contractile response caused by 5-HT was mediated by activation of not only 5-HT(2A) receptors but also 5-HT(1B) receptors. We also examined the relationship between 5-HT-induced vasocontraction of the rabbit femoral artery and arteriosclerosis using the arteriosclerosis model of repeated balloon-injury. The contractile response caused by 5-HT in the femoral artery with arteriosclerosis was significantly greater than that in the normal artery. Additionally, we demonstrated that insulin induced internalization of 5-HT(2A) receptors from the plasma membrane in HEK293 cells. Diabetes mellitus (DM) is a risk factor for ischemic heart diseases. We evaluated the 5-HT-induced vasocontraction, mediated by activation of 5-HT(2A) and 5-HT(1B) receptors, in the ITA obtained from patients with DM or without DM undergoing coronary bypass surgery. The contractile response caused by 5-HT in the ITA from patients with DM was significantly greater than that from patients without DM. Our findings suggest that when the ITA is used as an arterial graft, simultaneous treatment with 5-HT(2A) and 5-HT(1B) receptor antagonists is useful to prevent 5-HT-induced vasospasm, especially in patients with DM.
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Naoko Tanaka (2009) conducted a review in Coronary artery bypass graft vasospasm. 5-HT2A and 5-HT1B receptor antagonists was evaluated on 5-HT-induced vasocontraction. Simultaneous treatment with 5-HT2A and 5-HT1B receptor antagonists completely suppressed 5-HT-induced vasocontraction in the human internal thoracic artery, suggesting utility in preventing perioperative vasospasm, especially in patients with diabetes mellitus.
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