Association of preoperative plasma suPAR levels with intraoperative sublingual microvascular perfusion in patients undergoing major non-cardiac surgery

Introduction: The plasma suPAR level has previously been associated with postoperative complications and has been shown to be an independent predictor of coronary microvascular function and flow reserve. We investigated the association between preoperative suPAR levels and intraoperative sublingual microvascular perfusion in patients undergoing elective major non-cardiac surgery. Methods: This study included 100 patients undergoing major non-cardiac surgery between February 2019 and September 2020. The primary objective was to investigate the association between preoperative suPAR and intraoperative sublingual De Backer score, Consensus Proportion of Perfused Vessels (Consensus PPV), and Consensus PPV (small). Secondary objectives were to investigate the associations between these sublingual microcirculatory variables and (1) complications and (2) mean arterial pressure. EDTA blood was collected before induction of anesthesia and plasma suPAR levels were determined using the suPARnostic quick triage lateral flow assay. Sublingual microcirculation was monitored with Sidestream DarkField (SDF+) imaging technique at 20 minutes after induction of anesthesia before surgical incision (baseline) and then every 30 minutes until emergence from anesthesia. Results: A decrease of 0.7 mm-1 in the De Backer score, 2.5% in the Consensus PPV, and 2.8% in the Consensus PPV (small) from baseline measurement was observed for every 1 ng/ml increase of suPAR or 1 additional minute of intraoperative time. De Baker score did not change significantly from baseline (p=0.404), while Consensus PPV and Consensus PPV (small) decreased significantly from baseline (p<0.001 in both cases). The De Backer score, the Consensus PPV, and the Consensus PPV (small) correlated with postoperative complications. Mean arterial pressure correlated with De Backer score (p=0.487) but not with Consensus PPV (p=0.506) or Consensus PPV (small) (p=0.697) during the intraoperative period. Conclusion: Preoperative suPAR levels and prolonged operative duration were associated with intraoperative impairment of sublingual microvascular perfusion in patients undergoing elective major non-cardiac surgery.

Συσχέτιση των μεταβολών του ενδοθηλιακού γλυκοκάλυκα με τη στεφανιαία εφεδρεία ροής την αρτηριακή σκληρία (arterial stiffness) και τα ανακλώμενα κύματα της αορτής σε νεοδιαγνωσθέντες υπερτασικούς ασθενείς

Σκοπός: Διερευνήσαμε τη συσχέτιση της βλάβης του ενδοθηλιακού γλυκοκάλυκα με την αρτηριακή σκληρία, τη δυσλειτουργία της στεφανιαίας μικροκυκλοφορίας και την εξασθένιση της μυοκαρδιακής παραμόρφωσης, σε νεοδιαγνωσθέντες υπερτασικούς ασθενείς χωρίς φαρμακευτική αγωγή.Μέθοδοι και αποτελέσματα: Σε 320 νεοδιαγνωσθέντες υπερτασικούς ασθενείς χωρίς φαρμακευτική αγωγή και σε 160 φυσιολογικά άτομα της ομάδας ελέγχου, μετρήσαμε: α) το perfused boundary region (PBR) στην υπογλώσσια αρτηριακή μικροκυκλοφορία, β) το δείκτη του πάχους του γλυκοκάλυκα, χρησιμοποιώντας Sidestream Darkfield Imaging, γ) τη στεφανιαία εφεδρεία ροής (CFR) με τη ηχωκαρδιογραφία Doppler, δ) τη συνολική επιμήκης παραμόρφωση (GLS) και το ρυθμό συνολικούς επιμήκους παραμόρφωσης (GLSr) με την ηχωκαρδιογραφική μέθοδο speckle tracking, ε) την καρωτιδική και μηριαία ταχύτητα παλμικού κύματος (PWV) και τη συστολική κεντρική αρτηριακή πίεση (cSBP. Συγκριτικά με τα φυσιολογικά άτομα, οι υπερτασικοί είχαν υψηλότερες τιμές του PBR, του PWV, της cSPB και χαμηλότερες τιμές του GLS και GLSr (p<0.05). Στους υπερτασικούς ασθενείς υπήρξε στενή συσχέτιση στο μειωμένο πάχος του ενδοθηλιακού γλυκοκάλυκα όπως εκτιμήθηκε με το αυξημένο PBR, την αυξημένη κεντρική συστολική αρτηριακή πίεση και την αυξημένη ταχύτητα παλμικού κύματος όπως και στη μείωση της στεφανιαίας εφεδρείας ροής (CFR) (p<0,05), την οριακή σχέση του PBR με τη συστολική αρτηριακή πίεση του ιατρείου (p=0,06) μετά από προσαρμογή της ηλικίας, του φύλλου, του δείκτη μάζας σώματος, του καπνίσματος, της μάζας της αριστερής κοιλίας, της καρδιακής συχνότητας ,της δυσλιπιδαιμίας και της συστολικής αρτηριακής πίεσης του ιατρείου.Το PBR είχε μία επιπρόσθετη αξία του πολυπαραγοντικού μοντέλου που περιλάμβανε το PWV, τη CFR και τη συστολική αρτηριακή πίεση του ιατρείου στην πρόβλεψη του παθολογικού GLS (x2=2.4 έναντι 3.8 μετά από την προσθήκη του PBR 5-25, p για αλλαγή=0,03). Συμπεράσματα: Ο ενδοθηλιακός γλυκοκάλυκας είναι παθολογικός στους νεοδιαγνωσθέντες υπερτασικούς ασθενείς. Αυτή η βλάβη σχετίζεται με την ανωμαλία των ελαστικών ιδιοτήτων της αορτής και την παθολογική λειτουργία της στεφανιαίας μικροκυκλοφορίας, που συμβάλλει στην εξασθένηση της επιμήκους παραμόρφωσης της αριστερής κοιλίας.

Systemic microvascular shunting through hyperdynamic capillaries after acute physiological disturbances following cardiopulmonary bypass

Previously we showed that cardiopulmonary bypass (CPB) during cardiac surgery is associated with reduced sublingual microcirculatory perfusion and oxygenation. It has been suggested that impaired microcirculatory perfusion may be paralleled by increased heterogeneity of flow in the microvascular bed, possibly leading to arteriovenous shunting. Here we investigated our hypothesis that acute hemodynamic disturbances during extracorporeal circulation indeed lead to microcirculatory heterogeneity with hyperdynamic capillary perfusion and reduced systemic oxygen extraction. In this single-center prospective observational study, patients undergoing cardiac surgery with ( n = 18) or without ( n = 13) CPB were included. Perioperative microcirculatory perfusion was assessed sublingually with sidestream darkfield imaging, and recordings were quantified for microcirculatory heterogeneity and hyperdynamic capillary perfusion. The relationship with hemodynamic and oxygenation parameters was analyzed. Microcirculatory heterogeneity index increased substantially after onset of CPB [0.5 (0.0–0.9) to 1.0 (0.3–1.3); P = 0.031] but not during off-pump surgery. Median capillary red blood cell (RBC) velocity increased intraoperatively in the CPB group only [1,600 (913–2,500 μm/s) vs. 380 (190–480 μm/s); P < 0.001], with 31% of capillaries supporting high RBC velocities (>2,000 μm/s). Hyperdynamic microcirculatory perfusion was associated with reduced arteriovenous oxygen difference and systemic oxygen consumption during and after CPB. The current study provides the first direct human evidence for a microvascular shunting phenomenon through hyperdynamic capillaries following acute physiological disturbances after onset of CPB. The hypothesis of impaired systemic oxygen offloading caused by hyperdynamic capillaries was supported by reduced blood arteriovenous oxygen difference and low systemic oxygen extraction associated with CPB.

Acute ischemic injury to the renal microvasculature in human kidney transplantation

Increased understanding of the pathophysiology of ischemic acute kidney injury in renal transplantation may lead to novel therapies that improve early graft function. Therefore, we studied the renal microcirculation in ischemically injured kidneys from donors after cardiac death (DCD) and in living donor kidneys with minimal ischemia. During transplant surgery, peritubular capillaries were visualized by sidestream darkfield imaging. Despite a profound reduction in creatinine clearance, total renovascular resistance of DCD kidneys was similar to that of living donor kidneys. In contrast, renal microvascular perfusion in the early reperfusion period was 42% lower in DCD kidneys compared with living donor kidneys, which was accounted for by smaller blood vessel diameters in DCD kidneys. Furthermore, DCD kidneys were characterized by smaller red blood cell exclusion zones in peritubular capillaries and by greater production of syndecan-1 and heparan sulfate (main constituents of the endothelial glycocalyx) compared with living donor kidneys, providing strong evidence for glycocalyx degradation in these kidneys. We conclude that renal ischemia and reperfusion is associated with reduced capillary blood flow and loss of glycocalyx integrity. These findings form the basis for development of novel interventions to prevent ischemic acute kidney injury.