Etäinen iskeeminen esialtistus - laboratoriosta kliiniseen käyttöön?

English summaryPeer reviewe

Sepelvaltimoiden ohitusleikkaus 2020-luvulla

Vertaisarvioitu. English summary.• Sepelvaltimoiden ohitusleikkauksella voidaan helpottaa oireita ja vähentää kuoleman riskiä iskeemistä sepelvaltimotautia sairastavilla potilailla. • Ohitusleikkauksella saavutetaan erinomaiset pitkäaikaistulokset. Se on suositeltava revaskularisaatiomuoto varsinkin pitkälle edenneen ja vasenta päärunkoa ahtauttavan sepelvaltimotaudin hoidossa. • Diabeetikoilla ohitusleikkauksella saavutetaan pitkäaikaisempi hoitotulos kuin perkutaanisella ¬pallolaajennus- ja verkkoputkihoidolla. • Suomessa on merkittäviä alueellisia eroja sepelvaltimotaudin revaskularisaatiomuotojen käytössä.Peer reviewe

Sepelvaltimoiden ohitusleikkaus 2020-luvulla

• Sepelvaltimoiden ohitusleikkauksella voidaan helpottaa oireita ja vähentää kuoleman riskiä iskeemistä sepelvaltimotautia sairastavilla potilailla.• Ohitusleikkauksella saavutetaan erinomaiset pitkäaikaistulokset. Se on suositeltava revaskularisaatiomuoto varsinkin pitkälle edenneen ja vasenta päärunkoa ahtauttavan sepelvaltimotaudin hoidossa.• Diabeetikoilla ohitusleikkauksella saavutetaan pitkäaikaisempi hoitotulos kuin perkutaanisella ­pallolaajennus- ja verkkoputkihoidolla.• Suomessa on merkittäviä alueellisia eroja sepelvaltimotaudin revaskularisaatiomuotojen käytössä.</p

Pharmacological Preconditioning with Diazoxide in the Experimental Hypothermic Circulatory Arrest Model

Background: Hypothermic circulatory arrest includes a remarkable risk for neurological injury. Diazoxide, a mitochondrial adenosine triphosphate-dependent potassium ion (K+ATP) channel opener, is known to have cardioprotective effects. We assessed its efficacy in preventing ischemic injury in a clinically relevant animal model. Methods: Eighteen piglets were randomized into a diazoxide group (n = 9) and a control group (n = 9). Animals underwent 60 minutes of hypothermic circulatory arrest at 18 degrees C. Diazoxide (5 mg/kg + 10 mL NaOH + 40 mL NaCl) was infused during the cooling phase. Metabolic and hemodynamic data were collected throughout the experiment. After 24-hour follow-up, whole brain, heart, and kidney biopsy specimens were collected for analysis. Results: Cerebellar Cytochrome-C and caspase-3 activation was higher in the control group (P = .02 and P = .016, respectively). Antioxidant activity tended to be higher in the diazoxide group (P = .099). Throughout the experiment, the oxygen consumption ratio was higher in the control animals (P-g = .04), as were the lactate levels (P-g = .02). Cardiac function tended to be better in diazoxide-treated animals. Conclusion: Diazoxide might confer neuroprotective effect as implied by the immunohistochemical analysis of the brain. Additionally, the circulatory effects of diazoxide were beneficial, supporting its neuroprotective effect.Peer reviewe

The N-methyl-D -aspartate antagonist memantine has no neuroprotective effect during hypothermic circulatory arrest: A study in the chronic porcine model

AbstractBackground: Glutamate excitotoxicity has an important role in the development of brain injury after prolonged hypothermic circulatory arrest. The goal of the present study was to determine the potential efficacy of memantine, an N -methyl-D -aspartate receptor antagonist, to mitigate cerebral injury after hypothermic circulatory arrest. Methods: Twenty pigs (23-33 kg) were randomly assigned to receive memantine (5 mg/kg) or placebo in a blinded fashion before a 75-minute period of hypothermic circulatory arrest at 20°C. Hemodynamic, electroencephalographic, and metabolic monitoring were carried out. The intracerebral concentrations of glucose, lactate, glutamate, and glycerol were measured by means of enzymatic methods on a microdialysis analyzer. Daily behavioral assessment was performed until the animals died or were put to death on day 7. Histologic analysis of the brain was carried out in all animals. Results: In the memantine group, 5 of 10 animals survived 7 days compared with 9 of 10 in the placebo group. The median behavioral score at day 7 was 3.5 in the memantine group and 7.5 in the placebo group (P >.2). Among the surviving animals, medians were 9.0 and 8.0 on day 7 (P >.2), respectively. The medians of recovered electroencephalographic bursts were equal in both groups. The median of total histopathologic score was 16 in the memantine group and 14 in the placebo group (P >.2). There was a negative correlation between glutamate levels and electroencephalographic burst recovery (τ = –0.377, P =.043). A positive correlation was found between the highest individual glutamate value and histopathologic score (τ = 0.336, P =.045). Conclusions: The present study demonstrates that memantine has no neuroprotective effect after hypothermic circulatory arrest in the pig. In addition, we have shown the accuracy of cerebral glutamate measurements to predict histopathologic injury after hypothermic ischemia. (J Thorac Cardiovasc Surg 2001;121:957-70

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

OBJECTIVESSince 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.METHODSSixteen 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.RESULTSFive 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.CONCLUSIONSAn extended FET graft with LBCA and SCP durations >65 min at 28°C results in a poor outcome.</p

Prolonged mild hypothermia after experimental hypothermic circulatory arrest in a chronic porcine model

AbstractObjectives: We sought to evaluate the potential efficacy of prolonged mild hypothermia after hypothermic circulatory arrest. Methods: Twenty pigs, after a 75-minute period of hypothermic circulatory arrest, were randomly assigned to be rewarmed to 37°C (normothermia group) or to 32°C and kept at that temperature for 14 hours from the start of rewarming (hypothermia group). Results: The 7-day survival was 30% in the hypothermia group and 70% in the normothermia group (P =.08). The hypothermia group had poorer postoperative behavioral scores than the normothermia group. Prolonged hypothermia was associated with lower oxygen extraction and consumption rates and higher mixed venous oxygen saturation levels during the first hours after hypothermic circulatory arrest. Decreased cardiac index, lower pH, and higher partial pressure of carbon dioxide were observed in the hypothermia group. There was a trend for beneficial effect of prolonged hypothermia in terms of lower brain lactate levels until the 4-hour interval and of intracranial pressure until the 10-hour interval. Postoperatively, total leukocyte and neutrophil counts were lower, and creatine kinase BB was significantly increased in the hypothermia group. At extubation, the hypothermia group had higher oxygen extraction rates and lower brain tissue oxygen tension. Conclusions: A 14-hour period of mild hypothermia after 75-minute hypothermic circulatory arrest seems to be associated with poor outcome. However, the results of this study suggest that mild hypothermia may preserve its efficacy when it is used for no longer than 4 hours, but the potentials of a shorter period of postoperative mild hypothermia still require further investigation.J Thorac Cardiovasc Surg 2002;123:724-3

Extracorporeal photopheresis in the treatment of acute graft-versus-host disease : a single-center experience

BACKGROUND: Steroid-refractory acute graft-versushost disease (aGVHD) is a serious complication after hematopoietic stem cell transplantation. The long-term outcome of the patients is poor. Various immunosuppressive agents have been proposed as the second-line therapy but none of them has turned out more effective than the others. Extracorporeal photopheresis (ECP) is a treatment option that does not predispose the patients to severe side effects of the immunosuppressive drugs. STUDY DESIGN AND METHODS: We analyzed the treatment results of ECP in 52 patients with steroidrefractory or steroid-dependent aGVHD. Eighty-one percent of the patients suffered from a severe, Grade III or IV, aGVHD. ECP was started alone as the second-line treatment in 23 patients and in combination with an immunosuppressive drug in 18 patients. Eleven patients received ECP as the third-line or later treatment. RESULTS: A total of 62% of the patients responded, with 48% achieving complete response. In the patients with complete or partial response, the probabilities of survival at 4 years were 54 and 17%, respectively. The outcome of nonresponders was poor. The 1-year overall survivals of the patients with ECP as the second-line treatment either alone or in combination with an immunosuppressive drug or as the third-line treatment were 51, 28, and 18%, respectively. In multivariate analysis, starting ECP no later than 10 days after the start of the first-line treatment correlated with a good response and a consequent survival benefit. CONCLUSION: Extracorporeal photopheresis is an effective and well-tolerated treatment that should be considered as a second-line treatment for aGVHD.Peer reviewe

Two novel direct SPIO labels and in vivo MRI detection of labeled cells after acute myocardial infarct

Background: Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide. Cellular decay due hypoxia requires rapid and validated methods for possible therapeutic cell transplantation. Purpose: To develop direct and rapid superparamagnetic iron oxide (SPIO) cell label for a large-animal model and to assess in vivo cell targeting by magnetic resonance imaging (MRI) in an experimental AMI model. Material and Methods: Bone marrow mononuclear cells (BMMNCs) were labeled with SPIO particles using two novel direct labeling methods (rotating incubation method and electroporation). Labeling, iron incorporation in cells and label distribution, cellular viability, and proliferation were validated in vitro. An AMI porcine model was used to evaluate the direct labeling method (rotating incubation method) by examining targeting of labeled BMMNCs using MRI and histology. Results: Labeling (1 h) did not alter either cellular differentiation potential or viability of cells in vitro. Cellular relaxation values at 9.4 T correlated with label concentration and MRI at 1.5 T showing 894% signal reduction compared with non-labeled cells in vitro. In vivo, a high spatial correlation between MRI and histology was observed. The extent of macroscopic pathological myocardial changes (hemorrhage) correlated with altered function detected on MRI. Conclusion: We demonstrated two novel direct SPIO labeling methods and demonstrated the feasibility of clinical MRI for monitoring targeting of the labeled cells in animal models of AMI.Peer reviewe

Exploring effects of remote ischemic preconditioning in a pig model of hypothermic circulatory arrest

Objectives. During aortic and cardiac surgery, risks for mortality and morbidity are inevitable. Surgical setups involving deep hypothermic circulatory arrest (DHCA) are effective to achieve organ protection against ischemic injury. The aim of this study was to identify humoural factors mediating additive protective effects of remote ischemic preconditioning (RIPC) in a porcine model of DHCA. Design. Twenty-two pigs were randomized into the RIPC group (n=11) and the control group (n=11). The RIPC group underwent four 5-minute hind limb ischemia-reperfusion cycles prior to cardiopulmonary bypass and DHCA. All animals underwent identical surgical procedures including 60min DHCA at 18 degrees C. Blood samples were collected from vena cava and sagittal sinus at several time points. After the 8-hour follow-up period, the brain, heart, and kidney tissue samples were collected for tissue analyses. Results. Serum levels of brain damage marker S100B recovered faster in the RIPC group, after 4hours of the arrest, (pPeer reviewe