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  • 1.
    Boivie, Patrik
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Hedberg, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Engström, Karl Gunnar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Size distribution of embolic material produced at aortic cross-clamp manipulation2010In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 44, no 6, p. 367-372Article in journal (Refereed)
    Abstract [en]

    Objectives: The association between aortic atherosclerosis and neurological damage during cardiac surgery is well recognized. The purpose was here to analyze the size distribution of particles produced at cross-clamp manipulation of the ascending aorta.

    Design: A human cadaveric aortic perfusion model of retrograde design was applied (n 27). With this model, washout samples were collected from the pressurized ascending aorta during cross clamp manipulation. Before the experiment, the aorta was flushed to remove debris and with a baseline sample collected. The cross-clamp was opened to collect ten repeated aliquots with dislodged particles. Collected washout samples were evaluated by digital image analysis and microscopy.

    Results: Cross-clamping produced a significant output of particles, which was seen for size intervals of 1 mm and smaller (p 0.002 to p 0.022). In all size intervals the particle output correlated with the degree of overall aortic calcification(p 0.002 to p 0.025). The model generated substantially more small-size particles than large debris (p 0.010).

    Conclusions: Aortic clamping was here verified to dislodge aortic debris which correlated with the degree of observed calcification. Macroscopic particles were few. In contrast, cross-clamping produced substantial numbers of small-size particles. These findings emphasize microembolic risks associated with cross-clamping of atherosclerotic vessels.

  • 2.
    Hedberg, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Stroke during cardiac surgery: risk factors, mechanisms and survival effects2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Introduction: Neurological complications and stroke in association with cardiac surgery is a serious problem. The stroke event can occur during surgery (early stroke) or in the postoperative period with a symptom free interval (delayed stroke). Particle embolization due to aortic manipulation during surgery has been suspected as a mechanism for early stroke. The present thesis address mechanisms and survival effects of stroke both clinically (I-III) and experimentally (IV-V).

    Methods: Study I) Within a cohort of 2641 consecutive cases, a group of cardiac surgery patients with stroke and evaluated by computed tomography (CT) were studied (n=77). CT-findings were analyzed in relation to stroke symptoms. Study II) Data from 9122 patients undergoing coronary surgery were analyzed. Records of patients with any signs of neurological complications were reviewed to extract 149 subjects with stroke at extubation (early, 1.6%) versus 99 patients having a free interval (delayed, 1.1%). Early and delayed stroke were evaluated separately. Independent risk factors for stroke were analyzed by logistic regression and survival by Cox regression (9.3 years median follow-up). Study III) Patients with early (n=223) and delayed stroke (n=116) were identified among 10809 patients undergoing cardiac and aortic surgery, both groups exposed to cardiopulmonary bypass. Stroke patients were subdivided by the hemispheric location of lesions. Subgroups were compared and their associated pre- and peroperative variables and survival were analyzed. Study IV) Aortic cross-clamp manipulation was studied in a human cadaveric perfusion model. The pressurized aorta was repeatedly cross-clamped and washout samples were collected before and after clamp maneuvers. Particles in the washout samples were evaluated by microscopy and by digital image analysis. Study V) Pig aortas were pressurized and cannulated. Washout samples were collected before and after cannulation (n = 40). Particles were deposited onto a 10-μm filter to be evaluated by microscopy and digital image analysis.

    Results: Study I) In the group of patients exposed to routine cardiac surgery (i.e., clamping and cannulation) and with early stroke, right-hemispheric lesions were more frequent than of the contra-lateral side (P=0.005). Patients with aortic dissections had a strong dominance of bilateral findings, which was different from the unilateral pattern in the routine-surgery group (P<0.001). Study II) Early and delayed stroke did not share any risk factors. Both early and delayed stroke explained mortality in the early postoperative period (P<0.001, P<0.001 respectively) but also at long term follow-up (P=0.008, P<0.001 respectively). For patients surviving their first postoperative year, delayed but not early stroke influenced long-term mortality (P=0.001 and P=0.695, respectively). Study III) Stroke lesions in association to cardiac surgery were near exclusively ischemic. Early stroke had a preponderance for right-hemispheric lesions (P=0.009). In contrast, patients with early stroke that had undergone surgery of the aorta with circulatory arrest showed a pattern with more bilateral lesions compared to ‘cardiac-type’ operations (P<0.001). Patients with bilateral lesions had a dramatically impaired survival compared to those with unilateral lesions (P<0.001). Study IV) In the cadaveric perfusion model, cross-clamping produced a significant output of particles, which was seen for size intervals of 1 mm and smaller (P=0.002 to P=0.022). In all size intervals the particle output correlated with the degree of overall aortic calcification (P =0.002 to P=0.025). Study V) At cannulation of the pig aorta, more particles were noted after cannulation compared to before the maneuver (P<0.001). This increase included small (<0.1 mm, P<0.001) and intermediate-size particles (0.1-0.5 mm, P< 0.001). Particles above 0.5 mm were few and were not associated with cannulation.

    Conclusions: The influence of stroke on mortality was devastating, for both early and delayed stroke. These two stroke groups had obvious differences in both their risk factors and their hemispheric distribution. It is here emphasized that early and delayed stroke should be considered as two separate entities with suggested mechanistic differences. Ischemic lesions accounted for near all stroke events seen in association to cardiac surgery. For early stroke, these were mostly located within the right hemisphere. Results from the experimental studies underscore microembolic risks associated with aortic manipulation.

  • 3.
    Hedberg, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Boivie, Patrik
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Edström, Cecilia
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Engström, Karl Gunnar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Cerebrovascular accidents after cardiac surgery: an analysis of CT scans in relation to clinical symptoms2005In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 39, no 5, p. 299-305Article in journal (Refereed)
    Abstract [en]

    There is a link between aortic manipulation, particle embolization, and cerebrovascular accidents (CVA) in cardiac surgery. The present aim was to study hemispheric side differences of CVA. Cardiac-surgery patients with CVA and with computer tomography (CT) performed (n = 77) were analyzed within a total group of 2641 consecutive cases. CT data were reviewed for hemispheric and vascular distribution, and compared with CVA-symptom data of immediate and delayed type. Of the included patients, 66% had positive CT. In the group of 'cardiac-type' operations (e.g., routine clamping and cannulation) and having immediate CVA, right-hemispheric lesions were more frequent than of the contra-lateral side (p = 0.005). Patients with aortic dissections had strong dominance of bilateral findings, which was different from the unilateral pattern of 'cardiac-type' operations (p = 0.001). The middle-cerebral artery territory dominated, and when involved showed a significant (p = 0.022) right-sided distribution. Both CT and clinical symptoms confirmed that CVA after cardiac surgery has a right-hemispheric predominance. These observations may imply that aortic manipulation directs embolic material towards the brachiocephalic trunk.

  • 4.
    Hedberg, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Boivie, Patrik
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Engström, Karl Gunnar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Early and delayed stroke after coronary surgery: an analysis of risk factors and the impact on short- and long-term survival2011In: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734X, Vol. 40, no 2, p. 379-387Article in journal (Refereed)
    Abstract [en]

    Objective: Stroke is a serious complication to cardiac surgery, and is generally considered as a uniform disease regardless of its temporal relationship to surgery. Our hypothesis suggests that stroke, in association with surgery, reflects other characteristics than stroke occurring with a free interval. This issue was here explored for risk factors and survival effects.

    Methods: Data were collected from 7839 procedures of isolated coronary artery bypass grafting (CABG), 297 off-pump CABG, and 986 combined CABG and valve procedures. Records of patients with any signs of neurological complications were reviewed to extract 149 subjects with stroke at extubation (early, 1.6%) versus 99 patients having a free interval (delayed, 1.1%). Survival data were complete, with a median follow-up time of 9.3 years (maximum 16.3 years). Independent risk factors were analyzed by logistic regression and survival by Cox regression.

    Results: Risk factors for early stroke were advanced age, high preoperative creatinine level, extent of aortic atherosclerosis, and long cardiopulmonary bypass time (all P<0.001). Factors associated with delayed stroke were female gender (P<0.001), unstable angina (P=0.003), previous cerebrovascular disease (P=0.009), inotropic support requirement (P<0.001), and postoperative atrial fibrillation (P<0.001). Stroke explained mortality not only in the early postoperative period (P<0.001), but also at long-term follow-up (P<0.001). Early and delayed stroke were associated with mortality hazard ratios (HRs) of 1.44 and 1.85 (P=0.008, P<0.001), respectively. However, for patients surviving their first postoperative year, early stroke did not influence long-term mortality (HR 1.07, P=0.695). This was in contrast to delayed stroke (HR 1.71, P=0.001).

    Conclusions: Early and delayed stroke differed in their related risk factors. The influence of stroke on short-term mortality was obvious and devastating. Mortality in association with early stroke mainly presented itself in the acute period, whereas for delayed stroke survival continued to be impaired also in the long-term perspective. Our report emphasizes that early and delayed stroke should be considered as two separate entities.

  • 5.
    Hedberg, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Boivie, Patrik
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Engström, Karl Gunnar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Early and delayed stroke after coronary surgery: an analysis of risk factors and the impact on short and long-term survivalManuscript (preprint) (Other academic)
  • 6.
    Hedberg, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Engström, Karl Gunnar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Hemispheric distribution of stroke after cardiac surgery: patient characteristics and survival impactManuscript (preprint) (Other academic)
  • 7.
    Hedberg, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Engström, Karl Gunnar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Stroke after cardiac surgery - hemispheric distribution and survival2013In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 47, no 3, p. 136-144Article in journal (Refereed)
    Abstract [en]

    Objectives. Stroke following cardiac surgery may occur either in association with surgery (early) or occur postoperatively (delayed). The hemispheric distribution of lesions may provide information about embolic routes, which was analyzed here. Design. In 10,809 patients undergoing cardiac surgery, early (n = 223) and delayed stroke (n = 116) were explored. Symptoms and computed tomography findings were evaluated to categorize hemispheric distributions. This was compared with pre- and intra-operative characteristics and survival, using logistic regression and Kaplan-Meier statistics. Results. Early stroke had preponderance for the right rather than the left hemisphere (P = 0.009), whereas delayed stroke had a uniform distribution. Several intraoperative variables predicted the development of bilateral stroke compared with its unilateral counterpart. At multivariable analysis, the use of tranexamic acid was associated with bilateral stroke (P = 0.017), but was also associated with right rather than left-hemispheric stroke (P = 0.001). Bilateral lesions dramatically impaired survival versus those with unilateral lesions (P < 0.001). There was no survival difference between left and right-hemispheric stroke. Conclusions. When stroke, after cardiac surgery, is subdivided into early and delayed forms, it becomes evident that early, but not delayed stroke, demonstrates a hemispheric side difference. The preponderance for right-hemispheric lesions may indicate embolic mechanisms routed via the brachiocephalic trunk.

  • 8.
    Hedberg, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Funck, Bertil
    Swedish National Food Administration, Food Control Department, Meat Inspection Division, Luleå, Sweden.
    Engström, Karl Gunnar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Cannulation of the noncalcified aorta generates particles of microembolic nature: an experimental study using pig aorta2008In: Journal of cardiac surgery, ISSN 0886-0440, E-ISSN 1540-8191, Vol. 23, no 1, p. 39-43Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIM OF THE STUDY: Aortic cannulation during cardiac surgery is a potential etiological factor for perioperative stroke. Cannulae may dislodge aortic-wall calcifications. In addition, the sharp edge of the cannula-tip may shear off vessel-wall tissue, which can be expelled into the lumen. This hypothesis concerning source of emboli was tested in a noncalcified aortic perfusion model.

    METHODS: Pig aortas were pressurized and cannulated. Washout samples were collected before and after cannulation (n = 40). Particles were deposited onto a 10-microm filter and evaluated by microscopy and digital image analysis.

    RESULTS: A higher incidence of particles generated by cannulation was noted as compared to before the maneuver (p < 0.001). This increase included small (<0.1 mm, p < 0.001) and intermediate-size particles (0.1-0.5 mm, p < 0.001). Particles above 0.5 mm were few and were not associated with cannulation.

    CONCLUSIONS: Cannulation was a source of embolic material in the noncalcified aortic model. However, these particles were less than 0.5 mm in diameter and may contribute to neurocognitive decline after cardiac surgery.

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