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Hannu Tuominen

Publications and source records attributed to Hannu Tuominen.

12 recordsLinked to original sources

Hypertonic saline dextran improves outcome after hypothermic circulatory arrest: a study in a surviving porcine model.

BACKGROUND: Hypertonic saline dextran (HSD) has been shown to have neuroprotective properties. In the present study we have assessed its potential neuroprotective efficacy in the setting of hypothermic circulatory arrest in a surviving porcine model. METHODS: Twenty-four pigs were randomized to receive two 5-minute intravenous infusions (4 mL/kg) of either HSD (7.5 % saline, 6% dextran 70) or normal saline immediately after and 4 hours after a 75-minute period of hypothermic circulatory arrest at a brain temperature of 18 degrees C. RESULTS: The 7-day survival was 75% in the HSD group and 66% in the control group (p > 0.9). Brain total histopathologic score was lower in the HSD group (p = 0.01). Postoperative behavioral scores were higher in the HSD group on the second day after surgery (p = 0.03). Intracranial pressure was lower in the HSD group from 45 minutes to 8 hours after hypothermic circulatory arrest (p = 0.03). Cerebral perfusion pressure was higher in the HSD group from 45 minutes to 3 hours after hypothermic circulatory arrest (p = 0.06). Brain lactate concentration was lower in the HSD group when compared with controls (p = 0.05). Furthermore, brain glucose levels tended to be higher and brain lactate-pyruvate ratio and lactate-glucose ratio were lower in the HSD group. Brain tissue oxygen partial pressures were somewhat higher in the HSD group (p = 0.08). CONCLUSIONS: The use of HSD in experimental hypothermic circulatory arrest is associated with significantly better neurologic recovery, better histopathology, lower intracranial pressure, higher cerebral perfusion pressure, and better preservation of brain metabolism.

Animals↗

Aprotinin to improve cerebral outcome after hypothermic circulatory arrest: a study in a surviving porcine model.

BACKGROUND: Aprotinin is a serine protease inhibitor, which is usually used during cardiac surgery to reduce blood loss. There is evidence that aprotinin has neuroprotective effects during ischemia. We planned this study to evaluate its potential neuroprotective efficacy during hypothermic circulatory arrest (HCA). METHODS: Twenty piglets with a median weight of 25.7 kg (interquartile range, 23.9-26.6) were randomly assigned to receive aprotinin or placebo prior to a 75-minute period of HCA at 18 degrees C. Brain microdialysis parameters and neurological and histological scores were the primary outcome measures. RESULTS: Changes in brain metabolic parameters and histopathological findings were favorable in the aprotinin group. Brain lactate concentrations were significantly lower in the aprotinin group during the experiment (P = .02) along with blood lactate concentrations in the aprotinin group (P = .023). Brain glucose was significantly higher during the experiment (P = 0.02). Intracranial pressure tended to be higher in the control group. Two of 10 animals in the aprotinin group and 4 of 10 in the control group failed to reach full recovery on the seventh postoperative day. Four animals of 10 in the aprotinin group and 6 animals of 10 in the control group had brain infarction (P = .40). CONCLUSIONS: The present data suggest that aprotinin mitigates cerebral damage and improves neurological outcome following a period of HCA.

Animals↗

Propofol is associated with impaired brain metabolism during hypothermic circulatory arrest: an experimental microdialysis study.

BACKGROUND: Propofol is a widely used anesthetic in cardiac surgery. It has been shown to increase cerebrovascular resistance resulting in decreased cerebral blood flow. Efficient brain perfusion and tissue oxygenation during cardiopulmonary bypass (CPB) is essential in surgery requiring hypothermic circulatory arrest (HCA). The effects of propofol on brain metabolism are reported in a surviving porcine model of HCA. METHODS: Twenty female juvenile pigs undergoing 75 minutes of HCA at a brain temperature of 18 degrees C were assigned to either propofol- or isoflurane anesthesia combined with alpha-stat perfusion strategy during CPB cooling and rewarming. Brain microdialysis analysis was used for determination of brain metabolism, and tissue oxygen partial pressure and intracranial pressures were also followed-up until 8 hours postoperatively. RESULTS: Brain concentrations of glutamate and glycerol were significantly higher in the propofol group throughout the experiment (P < .01 and P < .01, respectively). The lactate/pyruvate ratio was significantly higher in the propofol group at 6-, 7-, and 8-hour intervals (P < .05, P < .01, and P < .05, respectively). The intracranial pressure was significantly higher at the 8-hour postoperative interval (P < .05) in the propofol group. A trend toward higher brain oxygen concentrations was observed in the isoflurane group. CONCLUSIONS: Anesthesia with propofol as compared with isoflurane is associated with impaired brain metabolism during experimental HCA.

Anesthetics, Intravenous↗

Fructose-1,6-bisphosphate supports cerebral energy metabolism in pigs after ischemic brain injury caused by experimental particle embolization.

BACKGROUND: Fructose-1,6-bisphosphate (FDP) is a high-energy intermediate that enhances glycolysis, preserves cellular adenosine triphosphate stores, and prevents the increase of intracellular calcium in ischemic tissue. Since it has been shown to provide metabolic support to the brain during ischemia, we planned this study to evaluate whether FDP is neuroprotective in the setting of combining hypothermic circulatory arrest (HCA) and irreversible embolic brain ischemic injury. METHODS: Twenty pigs were randomly assigned to receive 2 intravenous infusions of either FDP (500 mg/kg) or saline. The first infusion was given just before a 25-minute period of HCA and the second infusion immediately after HCA. Immediately before HCA, the descending aorta was clamped and 200 mg of albumin-coated polystyrene microspheres (250-750 mm in diameter) were injected into the isolated aortic arch in both study groups. RESULTS: There were no significant differences between the study groups in terms of neurological outcome. Brain lactate/pyruvate ratio was significantly lower (P = .015) and brain pyruvate levels (P = .013) were significantly higher in the FDP group compared with controls. Brain lactate levels were significantly higher 8 hours after HCA (P = .049). CONCLUSION: The administration of FDP before and immediately after HCA combined with embolic brain ischemic injury was associated with significantly lower brain lactate/pyruvate ratio and significantly higher levels of brain pyruvate, as well as lower lactate levels 8 hours after HCA. FDP seems to protect the brain by supporting energy metabolism. The neurological outcome was not improved, most likely resulting from the irreversible nature of the microsphere occlusion.

Animals↗

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Journal Article↗

Inflammation and prognosis in colorectal cancer.

AIM OF THE STUDY: Previous work has indicated that quantification of inflammatory cell reaction is of prognostic value in colorectal cancer. We evaluated the prognostic significance of inflammatory cell reaction patterns in colorectal cancer and developed a grading method which could be used in the routine assessment of tumours. METHODS: The intensity of overall inflammatory cell reaction, numbers of neutrophilic and eosinophilic granulocytes, lymphoid cells and macrophages in both the central region and the invasive margin were estimated in 386 colorectal cancer patients. Prognostic significance was analysed by uni- and multivariate analysis. RESULTS: Our method for classification of inflammatory reaction was reliable. High-grade inflammation at the invasive margin in Dukes' stage A and B cancers (pT1-2N0 and pT3N0, respectively) was associated with better 5-year-survival (87.6%) than low-grade inflammation (47.0%). CONCLUSIONS: Inflammatory cell response at the invasive border is a relevant prognostic indicator and could be easily incorporated into the routine evaluation of histopathological specimens.

Adolescent↗

Morphology and microsatellite instability in sporadic serrated and non-serrated colorectal cancer.

Colorectal serrated adenocarcinoma originates from serrated adenoma, but definite histological criteria have not yet been established. It presents with frequent DNA microsatellite instability (MSI), but the frequency of low-level (MSI-L) and high-level MSI (MSI-H) and the expression of mismatch-repair (MMR) enzymes in serrated adenocarcinoma are not known. To address these questions, morphological criteria for serrated cancers were established, their validity was tested, and MSI analysis was performed with NIH consensus markers and MMR enzyme immunohistochemistry for hMLH1, hMSH2, and hMSH6 in 35 serrated and 75 non-serrated colorectal carcinomas. Serrated carcinomas frequently showed a serrated, mucinous or trabecular growth pattern; abundant eosinophilic cytoplasm; chromatin condensation; preserved polarity; and the absence of necrosis. With these features, it was possible to distinguish them from non-serrated cancers, with the mean kappa score for five observers being 0.509. MSI analysis was successful in 31 serrated and 73 non-serrated carcinomas. 54.8% of serrated carcinomas were microsatellite-stable (MSS), 29.0% presented with MSI-L, and 16.1% presented with MSI-H, whereas 78.1% of non-serrated carcinomas were MSS, 13.7% were MSI-L, and 8.2% were MSI-H. MSI-L was more common in serrated cancers (p=0.035) and it was associated with patchy immunohistochemical staining (33.3%) of MLH1. MSI-H did not differ between serrated and non-serrated cancers (p=0.14). These results suggest that the biological background of serrated carcinomas differs from sporadic non-serrated colorectal cancer, but is not directly related to MSI.

Adaptor Proteins, Signal Transducing↗

pH-stat versus alpha-stat acid-base management strategy during hypothermic circulatory arrest combined with embolic brain injury.

BACKGROUND: There is some evidence of beneficial metabolic effects associated with the pH-stat than with alpha-stat perfusion strategy, but this is tempered by a likely increased risk of embolism to the brain, especially in adult patients. We investigated this possible adverse effect in an experimental model that combined hypothermic circulatory arrest (HCA) and embolic brain injury. METHODS: Twenty-four female juvenile pigs undergoing 25 minutes of HCA at a brain temperature of 18 degrees C were assigned to either alpha-stat (n = 12) or pH-stat (n = 12) strategy during cardiopulmonary bypass. Before the initiation of HCA, the descending aorta was clamped and 200 mg of albumin-coated polystyrene microspheres (250 to 750 microm in diameter) were injected into the isolated aortic arch in both groups. RESULTS: The 7-day survival rate was 75% in the pH-stat group and 50% in the alpha-stat group (p = 0.40). The pH-stat group had significantly better behavioral scores on postoperative days 5 (p = 0.03) and 6 (p = 0.04). The pH-stat strategy was associated with better postoperative intracranial pressures and histopathologic scores, but such differences did not reach statistical significance. The alpha-stat group had lower brain glucose concentrations postoperatively as well as higher brain lactate/glucose and lactate/pyruvate ratios CONCLUSIONS: These results suggest that pH-stat strategy does not cause any worse brain injury than the alpha-stat strategy. Indeed, the pH-stat strategy is associated with a slightly better outcome compared with the alpha-stat strategy, even in the setting of cerebral embolization. This observation suggests that the pH-stat strategy could also be used in adults during deep hypothermic cardiopulmonary bypass despite the increased risk of intraoperative cerebral embolization.

Animals↗

Collagen synthesis and degradation in polyneuropathy and myopathies.

To determine the mechanisms underlying the changes in collagen metabolism responsible for muscle fibrosis in patients with neuromuscular diseases, the synthesis and degradation of collagens was studied in muscles of patients with polyneuropathy and noninflammatory myopathies. The mRNA levels for type I, III, and IV collagens and immunohistochemical staining intensities for collagen propeptides and telopeptides were increased in polyneuropathy, suggesting enhanced synthesis of collagens. In myopathy, the mRNA levels were at the control level. Matrix metalloproteinase (MMP)-2 mRNA level was increased in polyneuropathy, although the quantity of proMMP-2 was not changed. An increase in type IV collagen concentration and proMMP-9 expression was observed in polyneuropathy but not in myopathies. Our results suggest that intramuscular accumulation of type IV collagen occurs in polyneuropathy, possibly leading to thickening of the capillary and muscle fiber basement membranes. This may complicate the transportation of nutrients and cellular excreta between blood and muscle cells.

Adolescent↗