Cerebral protection in aortic arch surgery with a special reference to Acute Type A Aortic Dissection

Abstract Acute Stanford Type A Aortic Dissection (ATAAD) is one of the most life-threatening acute pathologies in the human body; without treatment mortality nears 100%. One third of ATAAD patients suffer from cerebral malperfusion, and permanent ischaemic brain injury occurs in approximately 10% of patients. ATAAD is treated with open aortic arch surgery that involves cardiopulmonary bypass (CPB) and deep or profound (18–24 °C) hypothermic circulatory arrest (HCA); they can provide sufficient cerebral protection for up to 20–30 minutes by lowering the glucose and oxygen consumption of the brain. However, additional strategies on cerebral protection are still needed. ATAAD patients often present with shock, cardiac tamponade, malperfusion, or they could be still resuscitated while they are brought to the operation room. The rapid institution of antegrade cerebral blood flow through the CPB circuit is particularly vital for these patients and a new aortic cannulation strategy of direct true lumen cannulation after venous exsanguination (DTLC) was developed accordingly. However, associated normothermic circulatory arrest carries an inherent risk for neurologic sequalae. Our research group has studied the field of cerebral protection in aortic arch surgery extensively for the last 20 years through the use of a porcine model that closely simulates the clinical situation. One of the most promising neuroprotective strategies that has emerged from this research has been remote ischaemic preconditioning (RIPC), which is based on the notion that applying short ischaemia-reperfusion periods to a skeletal muscle increases ischaemic tolerance in other organs including the brain. Therefore, the present thesis studied whether DTLC with a 5-minute normothermic circulatory arrest was safe in terms of cerebral ischaemia (I), if RIPC would prolong the permissible period of HCA (II), and if it would improve the neurologic outcome combined with moderate hypothermia (III). The first study suggested that DTLC would not impair the neurologic outcome, even with a prolonged cannulation process. The second study proposed that RIPC would prolong the permissible period of HCA to up to nine minutes at 18 °C. The third study suggested that RIPC at 24 °C would provide five additional minutes of permissible HCA as compared to HCA alone at 18 °C. It also proposed that moderate HCA at 24 °C combined with RIPC would provide a superior neurologic outcome as compared to deep HCA alone at 18 °C.Tiivistelmä Tyypin A akuutti aortan dissekoituma (ATAAD) on edelleen yksi ihmiskehon hengenvaarallisimmista akuuteista sairaustiloista. Kolmanneksella potilaista aivojen verenkierto häiriintyy ja noin 10 prosenttia potilaista saa pysyvän aivovaurion joko itse sairaustilasta tai operaatiosta johtuen. ATAAD hoidetaan sydän-keuhkokoneen avulla syvässä (18–24°C) hypotermiassa eli alilämpöisyydessä tapahtuvan verenkierron seisautuksen (HCA) aikana. HCA vähentää sekä aivojen sokeriaineenvaihduntaa että hapen käyttöä, jolloin saadaan aikaa 20–30 minuuttia kirurgiselle toimenpiteelle riippuen lämpötilasta. ATAAD-potilaat ovat usein kriittisessä tilassa saapuessaan leikkaussaliin. Heillä voi olla verenkiertoshokki, verenkierto pääte-elimiin voi olla estynyt, tai heitä voidaan elvyttää. Erityisesti näiden potilaiden kohdalla on tärkeää edetä nopeasti kehonulkoiseen verenkiertoon sydän-keuhkokoneen avulla. Tätä varten kehitettiin uusi nousevan aortan kanylaatiomenetelmä. Potilaan verenkierto pysäytetään valuttamalla veri sydän-keuhkokoneeseen, nouseva aortta avataan ja aorttakanyyli asetetaan aorttaan näkökontrollissa (DTLC). Normaalissa kehon lämpötilassa tapahtuva verenkierron seisautus kuitenkin altistaa nopeasti neurologisille vaurioille. Tutkimusryhmämme on tutkinut aivojen suojaamista aortan kaaren kirurgian aikana jo 20 vuoden ajan kliinisesti merkittävän kokeellisen porsasmallin avulla. Etäinen iskeeminen esialtistus (RIPC) on osoittautunut lupaavaksi aivojen suojausmenetelmäksi. Siinä raajan lihaskudokseen kohdistetaan lyhyitä verenkierron pysäytyksiä ja palautuksia tavallisella verenpainemansetilla, minkä on osoitettu lisäävän aivojen sietokykyä hapenpuutteelta. Tässä väitöskirjassa tutkittiin, onko DTLC-kanylointimenetelmä aivojen kannalta turvallista, jos oletetaan sen kestävän viisi minuuttia (I). Lisäksi tutkimme, pidentääkö RIPC turvallista HCA:n kestoa (II) ja parantaako RIPC maltilliseen (24 °C) hypotermiaan yhdistettynä neurologista toipumista (III). Ensimmäinen tutkimus näytti, että DTLC ei vaikuta huonontavan neurologista lopputulosta. Toisen tutkimuksen perusteella RIPC pidentää turvallista HCA:n kestoa yhdeksällä minuutilla 18 asteen lämpötilassa. Kolmannen tutkimuksen mukaan RIPC pidentää turvallista HCA:n kestoa kymmenellä minuutilla 24 asteen lämpötilassa ja RIPC yhdessä maltillisen hypotermian kanssa parantaa neurologista lopputulosta

Spinal cord injury during selective cerebral perfusion and segmental artery occlusion:an experimental study

Abstract Objectives: Since selective cerebral perfusion (SCP) has been used in aortic arch surgical procedures, the core temperature during lower body circulatory arrest (LBCA) has been steadily rising. Simultaneously, the use of a frozen elephant trunk (FET) graft has been increasing. The safe period of LBCA in relation to spinal cord ischaemic tolerance in combination with segmental artery occlusion by the FET procedure has not been defined. Methods: Sixteen pigs were assigned to undergo 65 (n = 10) or 90 min (n  = 6) of SCP at 28°C with LBCA in combination with occlusion of the 8 uppermost segmental arteries in the thoracic (Th) aorta (15–20 cm FET, Th8-level). The follow-up period consisted of a 6-h intensive period and a 5-day observation period. Near-infrared spectroscopy of the collateral network was used to determine spinal cord oxygenation. The neurological status of the patients was evaluated daily, and the brain and the spinal cord were harvested for a histopathological analysis. Results: Five out of 6 pigs after 90 min and 1 out of 10 pigs after 65 min of LBCA died within 48 h of multiorgan failure. Of the survivors in the 65-min group, 6 out of 9 had paraparesis/paraplegia; the remaining 3 reached normal function. The lone survivor after 90 min of LBCA was paraplegic. Nadir near-infrared spectroscopy of the collateral network values at Th8 and Th10 were 34 (±5) and 39 (±4), and they were reached within 35 min of SCP in both groups. Conclusions: An extended FET graft with LBCA and SCP durations >65 min at 28°C results in a poor outcome

Impact of high-risk features on outcome of acute type B aortic dissection

Abstract Background: Acute type B aortic dissection (TBAD) is a severe condition associated with significant morbidity and mortality. The optimal classification and treatment strategy of TBAD remain controversial and inconsistent. Methods: This analysis includes patients treated for acute TBAD at the Helsinki University Hospital, Finland between 2007 and 2019. The endpoints were early and late mortality, intervention of the aorta, and a composite of death and aortic intervention in uncomplicated patients and high-risk patients. Results: This study included 162 consecutive TBAD patients (27.8% females), 114 in the high-risk group and 48 in the uncomplicated group, with a mean age of 67.6 ± 13.9 years. Intramural hematoma was reported in 63 cases (38.9%). The mean follow-up was 5.1 ± 3.9 years. In-hospital/30-day mortality (n = 4; 3.5%) occurred solely in the high-risk group (P = 0.32). Additionally, TBAD-related adverse events (n = 23; 20.2%) were observed only in the high-risk group (P < 0.001). The cumulative incidences of the composite TBAD outcome with non–TBAD-related death as a competing risk were 6.6% (95% CI, 1.7%–16.5%) in the uncomplicated group and 29.5% (95% CI, 21.1%–38.3%) in the high-risk group at 5 years and 6.6% (95% CI, 1.7%–16.5%) and 33.0% (95% CI, 23.7%–42.6%) at 10 years (P = 0.001, Gray test). Extracardiac arteriopathy (subdistribution hazard ratio [SHR], 2.61; 95% CI, 1.08–6.27) and coronary artery disease (SHR, 2.24; 95% CI, 1.07–4.71) were risk factors for adverse aortic-related events in univariable competing-risk regression analysis. Conclusions: Recognition of risk factors underlying adverse events related to TBAD is essential because the disease progression impacts both early and late outcomes. Early aortic repair in high-risk TBAD may reduce long-term morbidity and mortality

Remote ischemic preconditioning and hypoxia-induced biomarkers in acute myocardial infarction:study on a porcine model

Abstract Objectives: Remote ischemic preconditioning (RIPC) mitigates acute myocardial infarction (AMI). We hypothesized that RIPC reduces the size and severity of AMI and explored molecular mechanisms behind this phenomenon. Design: In two series of experiments, piglets underwent 60 min of the circumflex coronary artery occlusion, resulting in AMI. Piglets were randomly assigned into the RIPC groups (n = 7 + 7) and the control groups (n = 7 + 7). The RIPC groups underwent four 5-min hind limb ischemia-reperfusion cycles before AMI. In series I, the protective efficacy of RIPC was investigated by using biomarkers and echocardiography with a follow-up of 24 h. In series II, the heart of each piglet was harvested for TTC-staining to measure infarct size. Muscle biopsies were collected from the hind limb to explore molecular mechanisms of RIPC using qPCR and Western blot analysis. Results: The levels of CK-MBm (p = 0.032) and TnI (p = 0.007) were lower in the RIPC group. Left ventricular ejection fraction in the RIPC group was greater at the end of the follow-up. The myocardial infarct size in the RIPC group was smaller (p = 0.033). Western blot indicated HIF1α stabilization in the skeletal muscle of the RIPC group. PCR analyses showed upregulation of the HIF target mRNAs for glucose transporter (GLUT1), glucose transporter 4 (GLUT4), phosphofructokinase 1 (PFK1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), enolase 1 (ENO1), lactate dehydrogenase (LDHA) and endothelial nitric oxidate synthase (eNOS). Conclusions. Biochemical, physiologic, and histologic evidence confirms that RIPC decreases the size of AMI. The HIF pathway is likely involved in the mechanism of the RIPC