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Kuopio, Finland – New research from Kuopio University Hospital and the University of Eastern Finland reveals a surprising potential cause of chronic limb-threatening ischemia (CLTI): persistent over-dilation of small blood vessels in muscles. This finding could lead to new screening methods and treatments for the debilitating condition.
CLTI, often caused by peripheral arterial disease, occurs when blocked arteries restrict blood and oxygen flow to the legs. While it’s understood that reduced blood flow is a key factor, this new study suggests an unexpected complication: the body’s attempt to compensate for reduced flow can actually worsen the problem.
“Muscle microvasculature responds to hypoxia by dilating in an attempt to increase the flow of blood and oxygen to the tissues. However, microvascular over-dilation seems to also cause adverse changes,” explains Associate Professor Petra Korpisalo of the University of Eastern Finland.
Using advanced imaging techniques, Korpisalo’s team discovered that in patients with CLTI, blood flow to muscles was often not reduced despite arterial blockages. In some cases, it was even increased due to this persistent over-dilation of the microvasculature. Surprisingly, over half of the capillaries in examined muscle samples had transformed to resemble arterioles, further damaging the affected tissues.
The researchers demonstrated that these dilation-induced changes in the capillary walls impede the transfer of oxygen from the blood to the surrounding tissues. “Microvascular over-dilation causes hypoxia and cell shrinkage even in healthy muscle,” Korpisalo stated.
The study, published in the European Heart Journal, also found a strong link between microvascular over-dilation and negative outcomes for CLTI patients. Those with increased capillary flow associated with their ischemia experienced over three times as many adverse events, including hospitalizations, amputations, and deaths, compared to control groups.
“Patients with chronic limb-threatening ischemia often die of heart and brain diseases,” Korpisalo noted. “Prolonged microvascular over-dilation may also be linked to this, as changes in muscle blood flow affect the function of the whole circulatory system.”
Because CLTI can remain asymptomatic for extended periods, early diagnosis is challenging. This new research suggests that imaging microvascular over-dilation could offer a potential future screening method. Developing treatments that target these vascular transformations could also significantly improve the prognosis for many patients.
The research highlights the complex interplay of factors contributing to CLTI and opens new avenues for research and treatment. The study, titled “Microvascular blood flow disturbances predict poor outcome of revascularization in CLTI patients,” can be found in the European Heart Journal (DOI: 10.1093/eurheartj/ehae666.2275).
