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Published on: August 6, 2015
Impaired coronary contraction to phenylephrine after cardioplegic arrest in diabetic patients
Nicholas Sellke1, Caroline Gordon1, Isabella Lawandy1
1Division of Cardiothoracic Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island.
Insights
Diabetes impairs coronary arteriolar response to phenylephrine after cardiopulmonary bypass (CP/CPB). This effect is more pronounced in diabetic patients, potentially contributing to microcirculatory dysfunction.
Area of Science:
- Cardiovascular Physiology
- Vascular Biology
- Diabetic Complications
Background:
- Cardiopulmonary bypass (CP/CPB) with cardioplegic arrest affects coronary arteriolar response in non-diabetic patients.
- The impact of diabetes on coronary arteriolar response to alpha-1 adrenergic agonists during CP/CPB remains unclear.
Purpose of the Study:
- To investigate the effect of diabetes on coronary arteriolar response to phenylephrine during cardiac surgery with CP/CPB.
- To compare the microvascular reactivity between diabetic and non-diabetic patients post-CP/CPB.
Main Methods:
- Harvested coronary arterioles (90-150 μm) from diabetic (DM) and non-diabetic (ND) patients pre- and post-CP/CPB.
- Assessed in-vitro microvascular reactivity to phenylephrine.
- Measured alpha-1 adrenergic receptor expression in atrial myocardium via Western blotting and immunohistochemistry.
Main Results:
- Phenylephrine induced dose-dependent contractions in both groups pre- and post-CP/CPB.
- Post-CP/CPB contractile response was diminished in both ND and DM groups compared to pre-CP/CPB.
- The diminished contractile response to phenylephrine was significantly more pronounced in diabetic patients compared to non-diabetic patients post-CP/CPB.
- No significant differences in alpha-1A and alpha-1B adrenergic receptor expression were found between groups or time points.
Conclusions:
- Diabetes is associated with a reduced contractile response of coronary arterioles to phenylephrine following CP/CPB.
- This altered vascular response in diabetic patients may contribute to early coronary microcirculation vasomotor dysfunction after CP/CPB.
Background:
We have previously found that hyperkalemic cardioplegic arrest in the setting of cardiopulmonary bypass (CP/CPB) is associated with impairment of the coronary arteriolar response to phenylephrine in nondiabetic (ND) patients. We hypothesized that diabetes may alter coronary arteriolar response to alpha-1 adrenergic agonist in the setting of CP/CPB. In this study, we further investigated the effects of diabetes on the altered coronary arteriolar response to phenylephrine in patients undergoing cardiac surgery.
Methods:
Coronary arterioles (90-150 μm in diameter) were harvested pre- and post-CP/CPB from the ND and diabetic mellitus (DM) patients (n = 8/group) undergoing cardiac surgery. In-vitro microvascular reactivity was examined in response to phenylephrine. The protein expression/localization of the alpha-1 adrenergic receptors in the atrial myocardium was measured by Western blotting and immunohistochemistry.
Results:
Phenylephrine (10-9 to 10-4 M) induced a dose-dependent contractile response in both ND and DM vessels pre- and post-CP/CPB. There was no significant difference in the pre-CP/CPB contractile responses to phenylephrine between ND and DM groups. The post-CP/CPB contractile response was significantly diminished in both ND and DM groups compared with the respective pre-CP/CPB response (P < 0.05 versus pre-CP/CPB). This diminished contractile response was more pronounced in vessels from DM patients compared with vessels from ND patients (P < 0.05 versus ND). There were no significant differences in the protein expression of alpha-1A and alpha-1B receptors in the atrial myocardium between the ND and DM groups or tissue harvested pre- or post-CP/CPB.
Conclusions:
Diabetes is associated with a decreased contractile response of coronary arterioles to phenylephrine in the setting of CP/CPB versus that observed in ND patients. This alteration may contribute to the vasomotor dysfunction of coronary microcirculation seen early after CP/CPB in patients with diabetes.
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