Contrast-enhanced ultrasound detects changes in microvascular blood flow in adults with sickle cell disease

Abstract

In patients with sickle cell disease (SCD), poor outcome measures compromise the potential success of clinical trials. Contrast-enhanced ultrasound (CEUS) is a technique that can non-invasively quantify deep tissue microvascular blood flow. We tested the hypothesis that CEUS of forearm skeletal muscle could be used to: 1) assess microvascular abnormalities that occur during vaso-occlusive crisis; and 2) test new therapies for SCD that are targeted to improving the status of the microcirculation. We performed a prospective study, CEUS perfusion imaging of resting forearm muscle was performed in adults with SCD: 1) during and after a pain episode, and 2) before, during, and after a 24-hour infusion of the investigative agent, regadenoson, an adenosine A 2A agonist. CEUS destruction-replenishment time-intensity data were analyzed to measure microvascular blood flow, as well as its components, microvascular blood volume and flux rate. Serial CEUS measurements were obtained in 32 adults with SCD. For the studies during crisis, there was a 30% reduction in microvascular blood flow compared to steady-state (p = 0.031), a reduction that was largely due to microvascular flux rate. For the regadenoson group, a non-significant 25% increase in flux rate and 9% increase in microvascular blood flow compared to baseline were detected during infusion. In a study of adults with SCD, CEUS detected changes in microvascular blood flow associated with vaso-occlusive crises. No changes were found during an infusion of the adenosine A 2A agonist, regadenoson. This study provides preliminary evidence that CEUS could detect blood flow changes consistent with SCD physiology.

Adenosine A2A receptor agonist (regadenoson) in human lung transplantation

“…In a separate study, the effects of regadenoson on skeletal muscle microvascular flow produced a 9% improvement in blood flow during regadenoson infusion, which was encouraging, but not statistically significant (p = 0.13). 32 Because activated iNKT cells are known to synthesize and release proinflammatory cytokines such as interferon gamma and tumor necrosis factor-a (TNF-a) within 2 hours of their activation, 33 we suspect that the efficacy of regadenoson to reduce iNKT cell−mediated inflammation will be reduced as the time between the initiation of acute inflammatory insult and the infusion of regadenoson is increased. In the case of lung transplantation, regadenoson infusion is initiated before transplantation, so the drug is on board at the time that the recipient iNKT cells are activated, presumably resulting in a greater efficacy.…”

Safety of Ultrasound Contrast Agents in Pediatric Patients With Sickle Cell Disease and Trait

“…Recently, three reports observed an unexpectedly high rate of pain-related adverse events in adults with sickle cell disease following IV administration of the UCA Definity. [16][17][18] Back pain was the most commonly reported symptom in these studies, with additional reports of hip pain, chest pain, diffuse pain, and headache. In one study, it was theorized that phospholipid components in the shell of Definity may trigger molecular pathways similar to those involved in vaso-occlusion, thus leading to pain.…”

Effect of high‐flow oxygen therapy on regional oxygen saturation during vaso‐occlusive pain crisis: An observational study

“…6 Another study evidenced a 30% reduction in microvascular blood flow during pain crisis as compared to steady state. 7 However, no comparison between most painful and less painful limbs was performed in these studies. Values of rSO 2 we observed in less painful limbs are T A B L E 1 Effects of high-flow nasal oxygen on regional oxygen saturation, vital parameters and pain score.…”