Microvascular oxygen consumption during sickle cell pain crisis

Abstract

• Patients with sickle cell disease have greater microvascular oxygen consumption rates than healthy individuals.• During sickle cell pain crisis, microvascular oxygen consumption increases further.Sickle cell disease is an inherited blood disorder characterized by chronic hemolytic anemia and episodic vaso-occlusive pain crises. Vaso-occlusion occurs when deoxygenated hemoglobin S polymerizes and erythrocytes sickle and adhere in the microvasculature, a process dependent on the concentration of hemoglobin S and the rate of deoxygenation, among other factors. We measured oxygen consumption in the thenar eminence during brachial artery occlusion in sickle cell patients and healthy individuals. IntroductionSickle cell disease is a blood disorder caused by homozygous or compound-heterozygous inheritance of abnormal hemoglobin-b chains that form hemoglobin S. Patients with sickle cell disease endure pain crises that may last days and occur multiple times each year.1,2 The etiology of painful crises is unknown but may involve blockage of vessels by sickled and adherent blood cells, 3 followed by ischemia reperfusion injury 4 and local inflammatory responses. Inflammation, in addition to increasing pain, can increase oxygen consumption 6,7 and might have adverse effects on hemoglobin oxygenation and sickling when oxygen delivery is limiting. We hypothesized that sickle cell patients would have increased rates of oxygen consumption during acute pain crisis. We measured microvascular oxygen consumption and systemic biomarkers of inflammation in healthy African American volunteers, in patients with sickle cell disease in clinical steady state, and in patients both during pain crisis and after recovery. Study design PatientsThe Institutional Review Board of the National Heart, Lung and Blood Institute approved clinical protocol 12-H-0101 specifically for this study. All participants provided written informed consent in accordance with the Declaration of Helsinki. See http://www.clinicaltrials.gov/ct2/show/ NCT01568710 and supplemental Table 1 (available on the Blood Web site) for enrollment criteria. Pain crisis was defined as acute pain occurring in a typical distribution requiring hospital admission and parenteral analgesia. Acute crisis studies were performed within 36 hours of admission, after patients had received intravenous fluids and pain medications. Follow-up studies were performed more than 3 weeks after resolution of acute pain symptoms. Near-infrared spectroscopy and oxygen consumption calculationNear-infrared spectroscopy has been validated against magnetic resonance spectroscopy as a measure of local oxygen consumption in muscle. 8 We used the Inspectra 650 (Hutchinson Technology, Hutchinson, MN) to record tissue hemoglobin oxygen saturation 9 (StO 2 ) and tissue hemoglobin index 10 (THI; a measure of hemoglobin signal strength) every 2 seconds during a 5-minute brachial artery occlusion. Oxygen consumption (VO 2 ) was calculated as the sum of each change in StO 2 over each 2-second interval, weighted by t...

Bayesian analyses demonstrate tissue blood volume is not decreased during acute sickle cell pain episodes: A preliminary study

“…While blood volume was not explicitly measured by their device, microvascular oxygen consumption was elevated in SCD and further elevated during painful crisis. This is consistent with our finding of a trend towards increased blood volume and oxygen delivery in subcutaneous tissue at painful sites (opposite to our a priori hypothesis) [22]. Blood flow has been explored in SCD using other modalities.…”

“…Certain rheological parameters associated with vaso-occlusion have been found to fluctuate throughout the steady state, with no significant difference in the level of fluctuation between steady state and crisis [21]. Recently, tissue oximetry measurements at the thenar eminence demonstrated that microvascular oxygen consumption is elevated in SCD compared to controls, and further elevated during painful episodes [22]. While some patients demonstrate vaso-occlusion (as shown by an increased percentage of dense cells in the blood) concurrently with the onset of pain, others show similar blood characteristics with no pain [1].…”

“…The melanin fitting parameters were key in extracting accurate hemodynamic parameters, which were one-or-more orders of magnitude weaker than melanin absorption [7, 12]. Similar methods have been used in SCD, however most measured cerebral or thenar eminence oxygenation, rather than sites of acute pain [2, 19, 20, 22, 25, 28]. …”

Antisickling Effects of Quercetin may be Associated with Modulation of Deoxyhaemoglobin, 2, 3-bisphosphoglycerate mutase, Redox Homeostasis and Alteration of Functional Chemistry in Human Sickle Erythrocytes.

“…In silico studies carried out with quercetin on deoxy-haemoglobin and 2, 3bisphophoglycerate mutase, showed a strong interaction, which was found to effectually bind with the receptors by fully inhabiting their catalytic sites. Higher levels of deoxy-haemoglobin and 2,3-bisphophoglycerate mutase have been reported in SCD (Ngozi, 2013;Poillon et al, 1995;Rowley et al, 2014). Consequently, targeting these proteins via sequestration as 46| This journal is © The Nigerian Young Academy 2019…”

“…The symptoms associated with the condition are attributed to a distinct nucleotide alteration in the beta globin gene, which predisposes hemoglobin with the altered amino acid sequence to increased polymerization, microscopically evidenced by red blood cells (RBC) taking a sickle shape (Adewoyin, 2015). This alteration to RBC shape alters not only the structure but also the function of this important protein, resulting in decreased blood flow and lower oxygen supply to tissues and organs (Rowley et al, 2014). Low oxygen levels further cause increased red cell deformation and polymerization which also cause damage to vascular endothelial cells (Sedrak and Kondamudi, 2018).…”