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Laith R Sultan

Publications and source records attributed to Laith R Sultan.

2 recordsLinked to original sources
PubMed2026

Evaluation of muscle microvascular perfusion in primary mitochondrial disease by contrast-enhanced ultrasound: Feasibility study.

BACKGROUND: Primary mitochondrial disease (PMD) are genetic disorders characterized by impaired oxidative metabolism and microvascular abnormalities that contribute to the myopathy. OBJECTIVES: This study evaluates the feasibility and utility of contrast-enhanced ultrasound (CEUS) for quantifying skeletal muscle perfusion in patients with PMD. In addition, we assessed exercise-induced changes following cardiopulmonary exercise testing (CPET) to characterize dynamic vascular responses. DESIGN: Prospective pilot feasibility study. METHODS: We enrolled genetically confirmed PMD and healthy control participants with ability to complete the CPET protocol. CEUS of the vastus lateralis muscle was performed at rest and following CPET. Imaging parameters were standardized across all CEUS scans, with a fixed mechanical index of 0.13. Perfusion parameters, including perfusion index (PI), peak enhancement (PE), and area under the curve (AUC) were quantified using delta projection analysis, and compared between PMD and control participants, and within each group, pre- and post-exercise. RESULTS: A total of 5 PMD and 5 control participants were evaluated. At rest, CEUS demonstrated a trend in higher muscle perfusion in PMD as compared to control participants on comparing PI (13.7 ± 2.7 vs. 10.7 ± 3.2; p = 0.42), PE (24.9 ± 11.5 vs. 14.3 ± 6.8; p = 0.22), and AUC (95,253.4 ± 35,072.8 vs. 73,591.2 ± 32,820.6; p = 0.31), which did not reach statistical significance, likely in part due to the small cohort size. Following CPET, PMD participants demonstrated exaggerated percentage increases in PI (+21.1% vs. +16.0%), PE (+11.2% vs. +7.6%), and AUC (+20.2% vs. +12.5%) as compared to control participants. Within group analysis revealed a significant post-exercise increase in AUC among PMD participants (p = 0.01) but did not reach significance in control participants. CONCLUSION: This is the first study to demonstrate the feasibility and utility of conducting CEUS to assess skeletal muscle perfusion in ambulatory PMD patients. The distinct perfusion patterns and exaggerated exercise-induced responses observed in PMD as compared to control participants suggest that reactive hyperemia occurs in PMD at rest and is further exaggerated by exercise. CEUS may serve as a sensitive tool for detecting microvascular alterations in PMD.

cardiopulmonary exercise testing (CPET)↗
PubMed2026

Endothelial-mitochondrial coupling in mitochondrial disease: A systematic review and quantitative synthesis of vascular, biochemical, and oxidative bioenergetic dysfunction.

INTRODUCTION: Mitochondrial diseases are multisystem disorders in which defects in oxidative phosphorylation disrupt cellular bioenergetics and redox signaling across the vasculature and heart. Because mitochondrial function is closely linked to endothelial nitric oxide (NO) production, we hypothesized that mitochondrial diseases manifest as a NO-deficiency endotheliopathy affecting conduit and microvascular function. To evaluate this, we performed a systematic review with quantitative synthesis of human studies reporting vascular reactivity, biochemical NO production, or myocardial metabolic imaging, aiming to define the magnitude of impairment and responsiveness to NO-precursor therapy (l-arginine or l-citrulline). METHODS: Following PRISMA 2020 guidelines, we conducted a comprehensive search (inception-October 2025) identifying clinical studies of genetically or clinically confirmed mitochondrial disease with quantitative endothelial or bioenergetic endpoints. Eligible measures included flow-mediated dilation (FMD), reactive hyperemia index (RHI), passive-leg-movement (PLM) hyperemia, absolute synthesis rate of NO metabolites (ASR NOm), and positron emission tomography (PET)-derived myocardial oxidative indices (k mono , DP/k mono ). Quantitative synthesis used Hedges g for between-group comparisons and standardized mean change (SMC) for within-subject responses. Risk of bias was evaluated using ROBINS-I and a modified Newcastle-Ottawa Scale. RESULTS: Seven studies met these inclusion criteria, comprising 76 mitochondrial-disease subjects and 81 controls (ages 8-63 years). Across all vascular and metabolic domains, mitochondrial disease was associated with marked endothelial and bioenergetic impairment. Macro- and microvascular dysfunction, reflected by reduced FMD, RHI, and PLM hyperemia, demonstrated severe endothelium-specific abnormalities. Biochemical assays showed diminished NO synthesis. Myocardial PET imaging revealed reduced oxidative rate constants and increased energetic inefficiency despite preserved perfusion. Nitric oxide synthesis-precursor therapy was associated with improved endothelial reactivity (increased FMD, RHI, and ASR NOm) and significant, modest improvements in myocardial oxidative metabolism, consistent with partial restoration of endothelial NO signaling. Effect sizes collectively supported a reversible NO-deficiency endotheliopathy. The risk-of-bias assessment indicated moderate-to-good methodological quality, with limitations primarily related to small sample sizes and nonrandomized designs. CONCLUSIONS: Mitochondrial disease is characterized by significant impairments in vascular reactivity, NO signaling, and myocardial bioenergetics. Improvements in endothelial function and NO synthesis following l-arginine or l-citrulline supplementation are consistent with a role for impaired endothelial NO signaling in the vascular manifestations of mitochondrial disease. These findings highlight the vascular endothelium as a potential therapeutic target and underscore the need for future clinical intervention trials that use standardized vascular and bioenergetic endpoints.

and stroke-like episodes (MELAS)↗