The link between carotid artery stenosis and outcomes in patients with refractory out-of-hospital cardiac arrest.

BACKGROUND: Mortality of out-of-hospital cardiac arrest (OHCA) remains high. Extracorporeal cardiopulmonary resuscitation (ECPR) has revolutionized OHCA treatment, but our understanding of the ECPR responder's clinical profile is incomplete. Carotid artery stenosis (CAS) is a well-established cardiovascular disease risk factor. The impact of CAS on OHCA outcomes remains unelucidated. OBJECTIVE: To assess whether CAS burden affects the outcomes of OHCA patients treated with ECPR. METHODS: This study included patients with OHCA admitted for ECPR consideration, who had carotid ultrasonography performed. A numeric scale was applied to the plaque to create a CAS burden numeric scale. The primary outcome of the study was survival at discharge, compared among the different degrees of CAS. Neurologically intact survival and surrogate markers of neurologic injury were the secondary study endpoints. To assess the independent effect of CAS burden on survival to hospital discharge, we conducted a logistic regression analysis. RESULTS: Between 2019 and 2023, carotid ultrasonography was performed on 163 patients who were admitted for refractory OHCA. CAS burden was equally distributed between the right and left carotid arteries. Logistic regression analysis indicated that the CAS burden was significantly associated with both overall and neurologically intact survival at discharge (p = 0.004). A linear relationship between the CAS burden and neuron-specific and S-100 levels was identified. Patients with normal carotids were significantly less likely to have encephalopathy on electroencephalograms. CONCLUSION: CAS burden independently predicts the risk for worse survival and neurologic outcomes in patients suffering refractory OHCA who are treated with ECPR.

Reviewing data reduction methods for ektacytometry.

Ektacytometry quantifies erythrocyte deformability by measuring the elongation of suspended red blood cells subjected to a range of shear stresses. Raw shear stress-elongation index plots are difficult to interpret and thus data reduction methods characterizing the relationship using few parameters without loss of information and good reproducibility are essential, especially for the clinician. Two such curve fitting formulas, used widely in the literature for this purpose, are reviewed herein. The Lineweaver-Burke method overestimates maximal deformability if shear stresses below 1 Pa are applied. A modified version of the formula estimates maximal deformation more accurately but gives little weight to data at low shear stresses. Neither method is accurate if negative elongation indices are present (artifact phenomenon when measurement is performed from high to low shear stresses). The Streekstra-Bronkhorst method provides efficient data reduction though the theoretical background of the formula is incorrect. The parameters have expressive meaning; however, both maximal and minimal deformations are slightly underestimated. Moreover, parameters are biased according to the range of measured shear stresses.

Sickle cell disease: selected aspects of pathophysiology.

Sickle cell disease (SCD), a genetically-determined pathology due to an amino acid substitution (i.e., valine for glutamic acid) on the beta-chain of hemoglobin, is characterized by abnormal blood rheology and periods of painful vascular occlusive crises. Sickle cell trait (SCT) is a typically benign variant in which only one beta chain is affected by the mutation. Although both SCD and SCT have been the subject of numerous studies, information related to neurological function and transfusion therapy is still incomplete: an overview of these areas is presented. An initial section provides pertinent background information on the pathology and clinical significance of these diseases. The roles of three factors in the clinical manifestations of the diseases are then discussed: hypoxia, autonomic nervous system regulation and blood rheology. The possibility of a causal relationship between these three factors and sudden death is also examined. It is concluded that further studies in these specific areas are warranted. It is anticipated that the outcome of such research is likely to provide valuable insights into the pathophysiology of SCD and SCT and will lead to improved clinical management and enhanced quality of life.

Inter-species differences in hematocrit to blood viscosity ratio.

Hematocrit (Hct) is the major determinant of whole blood viscosity and of its oxygen binding capacity: with increasing Hct, viscosity increases exponentially and oxygen capacity increases linearly. Thus, the theoretical oxygen transport potential of blood, as indexed by the ratio of Hct to viscosity (Hct/viscosity), generally yields a curve concave to the Hct axis with a maximum at an "optimal hematocrit" value. This study analyzed relations between Hct, blood viscosity and shear rate for rats and dogs to explore whether different optima exist for Hct or Hct/viscosity. Our results reveal differences depending on both shear rate and species: at equal Hct, rats had higher blood viscosity and thus lower Hct/viscosity levels. Optimum values for Hct/viscosity were markedly different between the two species at shear rates of 90 and 200 s-1. Conversely, Hct/viscosity data at 10 s-1 did not exhibit an optimum but rather a linear decrease of the ratio with increasing hematocrit. Relations between Hct and blood viscosity thus differ among animal species. Inasmuch as animal studies are often utilized as an aid to understanding hemorheological aspects of clinical conditions and/or therapy, evaluating Hct/viscosity ratios may be a useful supplementary tool for research focused on various physiological and patho-physiological processes.

An automated tube-type blood viscometer: validation studies.

The technical complexity of previous rheometers has tended to limit the availability of blood viscosity data obtained over a wide range of shear rates. However, an automated tube-type viscometer, the Rheolog, has been developed; it employs a disposable flow assembly and less than five minutes are required to obtain blood viscosity results over a shear rate range of 1-1500 s(-1). We have carried out validation studies of the Rheolog using normal human blood and have compared these results with those obtained by cone-plate and Couette viscometers; storage time and temperature effects were also evaluated. Replicate measurements indicated mean CV levels less than 5%, and were independent of hematocrit and shear rate. Rheolog blood viscosity data agreed closely with those from other viscometers: average Rheolog differences from mean cone-plate and Couette values were -0.3% at 28% hematocrit, -1.4% at 41% hematocrit (i.e., native), and 1.0% at 56% hematocrit. Storage at room temperature up to 8 hours and at 4 degrees C up to 4 days had minimal effects whereas notable changes were observed when stored for 3 hours at 37 degrees C. Our results indicate that, within the hematocrit and shear rate limits employed herein, the Rheolog provides rapid, accurate and reproducible blood viscosity data, and suggest its usefulness for both basic science and clinical studies.

Hemorheological disturbances in patients with chronic cerebrovascular diseases.

Hemorheological disturbances may occur in more than 40% of patients with ischemic cerebrovascular diseases. In this study the changes of rheological factors--hematocrit, plasma fibrinogen concentration, whole blood and plasma viscosity, red blood cell aggregation and deformability were investigated in 297 patients (173 males, 124 females, mean age 60 +/- 11 years) with transient ischemic attack or chronic phase (> 3 months after onset) ischemic stroke, and in 73 healthy volunteers (35 males, 38 females, mean age 38 +/- 7 years). Hematocrit, plasma and whole blood viscosity were significantly (p < 0.0001) elevated in cerebrovascular patients compared to controls. Plasma fibrinogen concentration (p < 0.001), red blood cell aggregation (p < 0.05) and deformability (p < 0.01) were also impaired in stroke patients. Hemorheological disturbances were dominant in stroke patients with diabetes, hyperlipidemia and smoking habits. Hematocrit, plasma viscosity and red blood cell aggregation showed a significant (p < 0.025-0.001) correlation with the severity of carotid artery stenosis. We could not find any characteristic distribution of rheological parameters among the three subtypes of brain ischemia. Our results show that all of the measured rheological parameters are significantly impaired in chronic ischemic cerebrovascular disorders, especially in diabetic, smoking and alcoholic patients. They correlate with the severity of the carotid artery stenosis, but there is no association with the type of ischemic stroke.

Follow-up of hemorheological parameters and platelet aggregation in patients with acute coronary syndromes.

Pathologic hemorheological parameters and increased platelet aggregation in association with other risk factors significantly increase the possibility of the development of myocardial ischemia. Hemorheological parameters and platelet aggregation were investigated in 157 patients (mean age: 65+/-12 years) with acute coronary syndromes and in 68 healthy subjects (mean age: 36+/-6 years). Plasma fibrinogen, plasma and whole blood viscosity, red blood cell aggregation and filterability and platelet aggregation were measured in the hospital phase (after admission, on 2nd and 6th days) and monitored after discharge (at 1, 6 and 12 months). After admission all these parameters were significantly higher in patients than in control subjects (p<0.01) and almost all of them remained in the pathologic range at discharge. Some of the rheologic parameters showed a slight improvement after 1 month, but hematocrit and whole blood viscosity were higher than those after admission and of control subjects (p<0.05). After 6 and 12 months these parameters showed a small, but significant increase. Pathologically altered hemorheological parameters could be observed in patients with classical cardiovascular risk factors and significant improvement was found after elimination of them. Antiplatelet therapy was efficient in about half of the treated patients after admission; and despite a significant improvement, the proportion of ineffectively treated patients was still considerable during the follow-up. Our results support the role of abnormal hemorheological parameters in the development of myocardial ischemia and draw attention to the rheologic risk of these patients. The results of platelet aggregation measurements show the insufficiency of antiplatelet therapy at some cases and confirm the importance of guided secondary prevention.

Scavenger effect of experimental and clinically used cardiovascular drugs.

Oxygen free radicals play an important role in several physiologic and pathophysiologic processes. In pathophysiologic circumstances they can modify and damage biologic systems. Their functional properties (exposed to high oxygen tension) place red blood cells among the most susceptible cells to the harmful effect of free radicals. Because oxygen free radicals are involved in a wide range of diseases, scavenging these radicals should be an important therapeutic approach. In this study the antioxidant capacities of experimental and clinically used cardiovascular drugs were investigated. Phenazine methosulfate was used to generate free radicals and thus harden red blood cells. Filtration technique and potassium leaking were used to detect the scavenging effect of the examined drugs. The experimental drug H-2545 provided 43% protection against phenazine methosulfate-induced changes in red blood cell filterability (p < 0.001). Although some of the examined, clinically used cardiovascular drugs (carvedilol, metoprolol, verapamil, trimetazidine) also showed significant (p < 0.05) antioxidant effect, they were less efficient than H-2545. The scavenger effect of this novel drug exceeded the antioxidant properties of vitamin E. Modification of mexiletine with a pyrroline ring significantly improved its antioxidant capacity, suggesting that this molecular segment is responsible for the antioxidant effect.