Plasma hydrogen sulfide as a promising predictor of collateral cerebral circulation in acute ischemic stroke

Abstract

Objectives: To investigate the relationship between plasma hydrogen sulfide (H₂S) levels and collateral circulation in patients with acute ischemic stroke (AIS), and to explore the effects of vascular endothelial growth factor (VEGF), homocysteine (Hcy), folic acid (FA), vitamin B₁₂ (VB₁₂), and vitamin B₆ (VB₆).

Methods: A total of 68 AIS patients were enrolled and classified into two groups based on collateral vessel grading: the Good Collateral Circulation (GCC) group (n = 37) and the Poor Collateral Circulation (PCC) group (n = 31). Plasma levels of H₂S, VEGF, Hcy, FA, VB₁₂, and VB₆ were measured on the 2^nd and 7^th days after admission using microassays and ELISA.

Results: Compared to the PCC group, patients in the GCC group had significantly lower National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale scores (mRS) scores at both admission and discharge (all P < 0.05). On both the 2^nd and 7^th days, plasma levels of H₂S, VEGF, FA, VB₁₂, and VB₆ were significantly higher in the GCC group, while Hcy levels were significantly lower (all P < 0.05). Within group comparisons between the two time points also showed significant changes (all P < 0.001). Correlation analysis revealed that plasma H₂S levels were positively correlated with collateral circulation, VEGF, FA, VB₁₂, and VB₆, and negatively correlated with Hcy levels (all P < 0.001). Plasma H₂S levels demonstrated high predictive value for collateral circulation (area under the curve, AUC = 0.943). An interaction between time and collateral circulation on H₂S levels was also observed.

Conclusions: Plasma H₂S levels may serve as a valuable biomarker for predicting good collateral circulation in patients with acute ischemic stroke.

Keywords: Plasma hydrogen sulfide; acute ischemic stroke; collateral circulation; homocysteine; vascular endothelial growth factor.

Figure 1

DSA results of different collateral circulation states. Panels (A-D) show the DSA results on the day after admission for a patient in the PCC group. Panels (A and C): Right middle cerebral artery occlusion (anteroposterior and lateral views). Panels (B and D): The right anterior cerebral artery leptomeningeal vessels compensating for the pericortical blood supply to the ipsilateral middle cerebral artery, with sparse and slow blood flow, and a collateral circulation score of 1 (anteroposterior and lateral views). Panels (E-H) show the DSA results on the day after admission for a patient in the GCC group. Panels (E and G): Right middle cerebral artery occlusion (anteroposterior and lateral views). Panels (F and H): Formation of leptomeningeal vessels and capillary networks from the right external carotid artery and right anterior cerebral artery, compensating for the blood supply to the entire region of the ipsilateral middle cerebral artery, with a collateral circulation score of 4 (anteroposterior and lateral views). DSA, digital subtraction angiography; PCC, poor collateral circulation; GCC, good collateral circulation.

Figure 2

Levels of H₂S in peripheral blood in different collateral circulation. Note: Paired t test ###P < 0.001; independent t test, &&&P < 0.001. Plasma hydrogen sulfide (H₂S).

Figure 3

Peripheral blood VEGF levels in different collateral circulation. Note: Paired t test ###P < 0.001; independent t test &&&P < 0.001. VEGF, vascular endothelial growth factor.

Figure 4

Levels of Hcy, FA, VB₆ and VB₁₂ in peripheral blood in different collateral circulation. Note: Paired t test ###P < 0.001; independent t test &&&P < 0.001. Hcy, homocysteine; VB₆, vitamin B₆; FA, folic acid; VB₁₂, vitamin B₁₂.

Figure 5

ROC curve of H₂S expression on collateral circulation. ROC, receiver operator characteristic curve; AUC, Area Under The Curve. Plasma hydrogen sulfide (H₂S).

Figure 6

Interaction of time and collateral circulation on H₂S change. Plasma hydrogen sulfide (H₂S).