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Decreased coronary microvascular reactivity after cardioplegic arrest in patients with uncontrolled diabetes mellitus
Jun Feng1, Louis M Chu, Nikola Dobrilovic
1Division of Cardiothoracic Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA.
Insights
Uncontrolled diabetes impairs coronary arteriolar function and worsens recovery after heart surgery. This vascular dysfunction is linked to increased protein kinase C and oxidative stress.
Area of Science:
- Cardiovascular Science
- Diabetology
- Vascular Biology
Background:
- Coronary artery bypass graft surgery involves cardioplegic arrest and reperfusion.
- Diabetes mellitus, particularly uncontrolled diabetes, can affect vascular health.
- The impact of diabetes on coronary arteriolar function post-surgery requires further investigation.
Purpose of the Study:
- To investigate the effects of cardioplegic arrest and reperfusion on coronary arteriolar responses in diabetic and non-diabetic patients.
- To assess associated signaling pathways, including protein kinase C and oxidative stress.
Main Methods:
- Coronary arterioles were dissected from atrial tissues of uncontrolled diabetic, well-controlled diabetic, and non-diabetic patients.
- Vascular responses to vasodilators were measured pre- and post-cardioplegic arrest and reperfusion.
- Protein expression (PKC-α, PKC-β) and protein oxidation were analyzed.
Main Results:
- Baseline microvascular responses were reduced in uncontrolled diabetics compared to other groups.
- Cardioplegic arrest and reperfusion decreased vasodilatory responses in all groups, more so in uncontrolled diabetics.
- Uncontrolled diabetes showed increased expression of PKC-α, PKC-β, and protein oxidation.
Conclusions:
- Uncontrolled diabetes causes significant endothelial-dependent and -independent coronary arteriolar dysfunction.
- Diabetes exacerbates the negative impact of cardioplegic arrest and reperfusion on coronary arterioles.
- Increased PKC activation and oxidative stress contribute to vascular dysfunction in uncontrolled diabetes.
Background:
We investigated the effects of cardioplegic arrest and reperfusion on coronary arteriolar responses to endothelium-dependent and -independent vasodilators and associated signaling pathways in uncontrolled diabetic, well controlled diabetic, and case-matched nondiabetic patients undergoing coronary artery bypass graft surgery.
Methods:
Coronary arterioles from harvested right atrial tissues were dissected pre- and post-cardioplegic arrest and reperfusion from uncontrolled diabetic (n = 10; hemoglobin A1c = 9.3 ± 0.3), well controlled diabetic (n = 10; hemoglobin A1c = 6.2 ± 0.2), and nondiabetic patients (n = 10; hemoglobin A1c = 5.1 ± 0.1) undergoing coronary artery bypass graft surgery.
Results:
The baseline microvascular response to adenosine 5'-diphosphate, substance P, and sodium nitroprusside of arterioles from uncontrolled diabetic patients were decreased compared to the respective response from nondiabetic or well controlled diabetic patients (P < .05). The vasodilatory responses to adenosine 5'-diphosphate and substance P after cardioplegic arrest and reperfusion were significantly decreased in all 3 groups compared to pre-cardioplegic arrest and reperfusion responses (P < .05). However, these decreases were more pronounced in the uncontrolled diabetic group (P < .05). The expression of protein kinase C-α, protein kinase C-β, and protein oxidation in atrial tissues was significantly increased in the uncontrolled diabetic group compared to the nondiabetic or controlled diabetes groups.
Conclusion:
Uncontrolled diabetes is associated with endothelium-dependent and -independent vascular dysfunction of coronary arterioles. In addition, uncontrolled diabetes worsens the recovery of coronary arteriolar function after cardioplegic arrest and reperfusion. These alterations are associated with an increased expression/activation of protein kinase C-α and protein kinase C-β and enhanced oxidative stress.
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