Vasoplegia, where “vaso” refers to blood vessels and “plegia” stands for paralysis, is a condition where the patient exhibits a low blood pressure, even in the presence of normal or increased output of blood from the heart. When this occurs as a complication of cardiopulmonary bypass surgery, there is a chance that it can lead to multiple organ failure and even death. Now, a diverse group of researchers including clinicians, computational biologists and biotechnologists have come together to study how this may be predicted early on based on clinical observations, so that effective treatment may be given.
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In a pilot study involving 19 patients who underwent elective cardiac surgery, the researchers measured the circulating counts of endothelial progenitor cells and hematopoietic stem cells at different points in time starting from when the patient was being anaesthetised to until 24 hours after the surgery. They find that in a statistically significant number of people in the group that showed clinically significant vasoplegia, there was a blunting of the endothelial progenitor cell response. Also, in the group that did not show clinically significant vasoplegia, they observed that there was no such blunting.
“We can say there appears to be a pattern, which is well worth exploring in a larger cohort of patients and further delineating this particular response as a biomarker in predicting a potentially devastating complication following cardiac surgeries,” says Dr. Paul Ramesh Thangaraj, from the department of cardiothoracic surgery, Apollo Hospitals, Chennai, who is one of the PIs of the study. This research is published in the journal
Hematopoietic and endothelial progenitor cells play an important role in repair of damaged tissues and inner lining of the blood vessels called the endothelium, respectively. “Usually, these cells reside in the bone marrow; however, in response to injury to a tissue or a blood vessel, they come out into the circulation from the bone marrow and home into the site of injury for tissue repair,” says Madhulika Dixit from the Department of Biotechnology, Indian Institute of Technology Madras, in an email to
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Prof Dixit describes using flow cytometry to measure the counts during the surgery and afterwards. “The cells were identified by means of expression of specialised cell surface receptors. For this, at regular intervals the blood withdrawn from the patient was subjected to flow cytometry. We checked for time-dependent changes in circulating counts of progenitor cells during the course of cardiopulmonary bypass in patients.”
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Key challenge
One of the key challenges was to get significant patterns in this small dataset, according to Rahul Siddharthan, from The Institute of Mathematical Sciences, Chennai, who was one of the people involved in formal analysis. “In this case, we have two data sets, with two-valued outcomes [non-vasoplegic or vasoplegic], and the goal is to see how other measured parameters can predict them,” he says. There are very sophisticated machine-learning algorithms available these days for such tasks. “In this case the most basic algorithm, ‘logistic regression’, is good enough,” says Prof. Siddharthan.
Striking trends
As he explains, in both cases, the idea is to look at a single value (change in circulating progenitor cells at two timepoints) and in seeing its predictive power for the output. “The trend is clear, that for non-vasoplegic patients, the level of circulating progenitor cells increases, while for vasoplegic patients, it stays flat or decreases. There are exceptions but the finding is statistically significant even on this small study,” says Prof. Siddharthan.
With a larger study, Dr.. Paul Ramesh envisages even developing a risk score for predicting vasoplegia as a complication following surgery.