Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypothermia improves resistance to subsequent ischemia in the cardioplegic-arrested heart (CAH). This adaptive process produces mRNA elevation for heat shock protein (HSP) 70-1 and mitochondrial proteins, adenine nucleotide translocator (ANT(1)), and beta-F(1)-ATPase. Glucose in cardioplegia also enhances myocardial protection. These processes might be linked to reduced ATP depletion. To assess for synergism between these protective processes, isolated rabbit hearts (n = 91) were perfused at 37 degrees C and exposed to ischemic cardioplegic arrest for 2 h. Hearts were in four groups: control (C), hypothermia adapted (H) perfused to 31 degrees C 20 min before ischemia, 22 mM glucose (G) in cardioplegia, and hypothermic adaptation and glucose (HG). Developed pressure (DP), dP/dt(max), and pressure-rate product (PRP) improved (P < 0.05) in G, H, and HG compared with C during reperfusion. DP and PRP were elevated in HG over H and G. ATP was higher in G, H, and HG, although no additional increase in HG over H was found. Lactate and CO(2) production were elevated in G only. The mRNA expression for HSP70-1, ANT(1), and beta-F(1)-ATPase was elevated severalfold in H and HG, but not G over C during reperfusion. In conclusion, glucose provides additional functional improvement in H. Additionally, neither ATP levels nor anaerobic metabolism are linked to mRNA expression for HSP70, ANT(1), or beta-F(1)-ATPase in CAH.
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PMID:Mitochondrial protein and HSP70 signaling after ischemia in hypothermic-adapted hearts augmented with glucose. 1040 52

This study examines the electrophysiological and metabolic changes that occur in rabbit hearts during hypothermic storage in vitro. Hearts were microperfused at 4 degrees C for 6 or 24 h with either normal Krebs-Henseleit buffer (KHB) or KHB containing 2,3-butanedione monoxime (BDM). After hypothermic storage, hearts were rewarmed to 37 degrees C with KHB. Cardiac function was then assessed in Langendorff perfusion mode. Electrophysiological changes were also assessed from the ventricular paced-evoked responses. After storage, mitochondria were isolated from the hearts and their respiratory control ratio, rate of ATP synthesis and outer membrane intactness were assessed. Compared with values from fresh non-stored hearts, hearts stored hypothermically for 24 h showed significant decreases in both left ventricular developed pressure and coronary flow when reperfused in Langendorff mode. On the other hand, the decrease in left ventricular developed pressure in hearts that were stored for only 6 h (with or without BDM) was not significant. Compared with values obtained from fresh non-stored hearts, hypothermic storage significantly decreased the R-wave amplitude, and both the R-E and ST-E intervals of paced-evoked responses. This was true for hearts microperfused for 6 h (with or without BDM) and for hearts microperfused with buffer containing BDM for 24 h. The ST-R intervals in hearts microperfused hypothermically for 6 h were prolonged, but this change was not statistically significant compared with those obtained from unstored hearts. In hearts microperfused with KHB containing BDM for 24 h, the ST-R interval was significantly prolonged. Hypothermic microperfusion for 24 h significantly decreased both the mitochondrial coupling ratio and the rate of ATP synthesis. In hearts microperfused with BDM for 6 h, mitochondrial coupling ratios and the rate of ATP synthesis were not significantly different from those in fresh hearts. In conclusion, the present study has shown that long-term hypothermic storage significantly impaired both paced-evoked responses and mitochondrial function. Inclusion of BDM in the perfusion buffer during storage significantly ameliorated some of these changes.
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PMID:Electrophysiological and biochemical changes in rabbit hearts stored at 4 degrees C for 6 or 24 h. 1156 74

This work investigates whether purine metabolism and release is related to cardioprotection with hyperkalemia and hypothermia. Langendorff guinea-pig hearts were used to either monitor metabolism during ischemia or to measure functional recovery, myocardial injury and release of purine during reperfusion. Hearts underwent 30 min ischemia using one of the following protocols: control (normothermic buffer), hyperkalaemia (high-potassium buffer), hypothermia (20 degrees C) and hyperkalemia + hypothermia. At the end of 30 min ischemia, hyperkalemia was associated with similar metabolic changes (rise in purine and lactate and fall in adenine nucleotides) to control group. Accumulation of purine was due to a rise in inosine, xanthine and hypoxanthine and was largely prevented by hypothermia and hyperkalemia + hypothermia. Upon reperfusion, there was a time-dependent release of all purine, lactate and AMP. A fast (peak in less than 20 sec) release of inosine, xanthine, hypoxanthine and lactate was highest in control followed by hyperkalemia then hypothermia and little release in hyperkalemia + hypothermia. Adenosine and AMP release was slow (peak at 3 min), only significant in control and was likely to be due to sarcolemmal disruption as the profile followed lactate dehydrogenase release. Recovery (left ventricular developed pressure) was 63% control, 82% hyperkalemia, 77% hypothermia and 98% for hyperkalemia + hypothermia. The loss of purine during reperfusion but not their production during ischemia is related to cardioprotection with hyperkalemia. The possibility that the consequences of hyperkalemia modulate a sodium-dependent purine efflux, is discussed. The reduced loss of purine in hypothermia or in hyperkalemia + hypothermia is likely to be due to a lower metabolic activity during ischemia.
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PMID:Purine metabolism and release during cardioprotection with hyperkalemia and hypothermia. 1223 79

Hypothermic perfusion of the heart decreases oxidative phosphorylation and increases NADH. Because O(2) and substrates remain available and respiration (electron transport system, ETS) may become impaired, we examined whether reactive oxygen species (ROS) exist in excess during hypothermic perfusion. A fiberoptic probe was placed on the left ventricular free wall of isolated guinea pig hearts to record intracellular ROS, principally superoxide (O(2)(-).), and an extracellular reactive nitrogen reactant, principally peroxynitrite (ONOO(-)), a product of nitric oxide (NO.) + O(2)(-). Hearts were loaded with dihydroethidium (DHE), which is oxidized by O(2)(-). to ethidium, or were perfused with l-tyrosine, which is oxidized by ONOO(-) to dityrosine (diTyr). Shifts in fluorescence were measured online; diTyr fluorescence was also measured in the coronary effluent. To validate our methods and to examine the source and identity of ROS during cold perfusion, we examined the effects of a superoxide dismutase mimetic Mn(III) tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP), the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME), and several agents that impair electron flux through the ETS: menadione, sodium azide (NaN(3)), and 2,3-butanedione monoxime (BDM). Drugs were given before or during cold perfusion. ROS measured by DHE was inversely proportional to the temperature between 37 degrees C and 3 degrees C. We found that perfusion at 17 degrees C increased DHE threefold versus perfusion at 37 degrees C; this was reversed by MnTBAP, but not by l-NAME or BDM, and was markedly augmented by menadione and NaN(3). Perfusion at 17 degrees C also increased myocardial and effluent diTyr (ONOO(-)) by twofold. l-NAME, MnTBAP, or BDM perfused at 37 degrees C before cooling or during 17 degrees C perfusion abrogated, whereas menadione and NaN(3) again enhanced the cold-induced increase in ROS. Our results suggest that hypothermia moderately enhances O(2)(-). generation by mitochondria, whereas O(2)(-). dismutation is markedly slowed. Also, the increase in O(2)(-). during hypothermia reacts with available NO. to produce ONOO(-), and drug-induced O(2)(-). dismutation eliminates the hypothermia-induced increase in O(2)(-).
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PMID:Hypothermia augments reactive oxygen species detected in the guinea pig isolated perfused heart. 1464 63

This study was undertaken to explore the myocardioprotective effects of the combination of ischemic preconditioning (IP) with hypothermia and St.II Thomas crystalloid cardioplegic solution (CCS) on immature hearts in the rabbit. Isolated immature rabbit hearts were perfused with Krebs-Henseleit bicarbonate buffer on Langendorff apparatus. In experiment 1, 24 hearts were divided into 4 groups (n=6 in each group): Con, IP1, IP2 and IP3 group. Hearts of the four groups underwent 0, 1, 2 or 3 cycles of IP respectively. Then all the hearts were subjected to a sustained ischemia period of 2 h at 20 degrees C and a postischemic reperfusion period of 30 min at 37 degrees C. In experiment 2, 48 hearts were divided into 6 groups (n=8 in each group): SCon1, SIP1, SCon2, SIP2, SCon3 and SIP3 group, according to hypothermia and the duration of sustained ischemia (30 min at 32 degrees C; 90 min at 25 degrees C, 2 h at 20 degrees C). The SIP1, SIP2 and SIP3 groups were preconditioned twice before the sustained hypothermic ischemia, while the SCon1, SCon2 and SCon3 groups were not preconditioned. CCS was applied during sustained ischemia, all the hearts were reperfused for 30 min at 37 degrees C. Heart rate (HR), left ventricular developed pressure (LVDP) and peak rate of increase or decrease of left ventricular pressure (+/-dp/dt(max)) were recorded. Tissue concentration of adenosine triphosphate (ATP), malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were measured. At the end of reperfusion, values of product of LVDP and HR, +/-dp/dt(max) in IP2 group were 96%+/-21%, 101%+/-19% and 84% +/-15% of the baseline values respectively, which were significantly higher than those of Con group and IP3 group (P<0.01, P<0.05); also, the ATP content of IP2 group was higher than that of the Con group (P<0.01). When CCS was applied during sustained period of hypothermic ischemia at 32 degrees C or 25 degrees C, recovery rates of RPP (rate product, =LVDPxHR) and +dp/dt(max) in SIP1 group were 87% +/-14% or 99% +/-26% of the baseline values respectively (P<0.05, vs SCon1 group), the values in SIP2 group changed to 87% +/-16% or 102% +/-20% respectively (P<0.05, vs SCon2 group). Contents of ATP in SIP1 and SIP2 groups were significantly higher than those of SCon1 or SCon2 groups respectively (P<0.05), but MDA content of the two groups were significantly lower than those of SCon1 or SCon2 groups (P<0.05) respectively. The study indicates that IP attenuates hypothermic ischemia/reperfusion injury to immature rabbit hearts under 20 degrees C ischemia, two cycles of IP showing better myocardioprotective effects than 1 or 3 cycles of IP. When IP was combined with CCS which were applied during hypothermic ischemia period, the beneficial effects of IP were weakened as the temperature during the hypothermic period was elevated.
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PMID:Myocardioprotective effects of the combination of ischemic preconditioning with hypothermia and crystalloid cardioplegia in immature rabbits. 1522 56

Aim of our study was to measure conduction velocity and pattern of excitation during hypothermia in hearts of ground squirrels Citellus undulatus, known to be most resilient hibernators. We imaged electrical conduction in intact isolated hearts of summer active and winter hibernating ground squirrels at temperatures varying from +37 degrees C to +3 degrees C. Electrical activity was mapped using CCD camera (500 frames/sec) and voltage-sensitive dye di-4-ANEPPS during normal sinus rhythm and ventricular pacing. No spontaneous tachyarrhythmia was observed in all hearts at any temperature. Hearts were able to maintain spontaneous sinus rhythm and normal pattern of epicardial excitation throughout the whole range of studied temperatures. Despite responsiveness to pacing in all hearts ventricular conduction velocity was significantly reduced (about 10-fold) at low temperatures +3 degrees C. Our data provides the first direct demonstration that isolated heart of the summer active and winter hibernating ground squirrel Citellus undulatus is able to maintain normal excitation pattern in a range of temperatures from +37 degrees C to +3 degrees C.
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PMID:[Pattern of excitation in isolated heart of hibernator ground squirrel Citellus undulatus]. 1594 Jan 84

We examined if sevoflurane given before cold ischemia of intact hearts (anesthetic preconditioning, APC) affords additional protection by further improving mitochondrial energy balance and if this is abolished by a mitochondrial KATP blocker. NADH and FAD fluorescence was measured within the left ventricular wall of 5 groups of isolated guinea pig hearts: (1) hypothermia alone; (2) hypothermia+ischemia; (3) APC (4.1% sevoflurane)+cold ischemia; (4) 5-HD+cold ischemia, and (5) APC+5-HD+cold ischemia. Hearts were exposed to sevoflurane for 15 minutes followed by 15 minutes of washout at 37 degrees C before cooling, 2 hours of 27 degrees C ischemia, and 2 hours of 37 degrees C reperfusion. The KATP channel inhibitor 5-HD was perfused before and after sevoflurane. Ischemia caused a rapid increase in NADH and a decrease in FAD that waned over 2 hours. Warm reperfusion led to a decrease in NADH and an increase in FAD. APC attenuated the changes in NADH and FAD and further improved postischemic function and reduced infarct size. 5-HD blocked the cardioprotective effects of APC but not APC-induced alterations of NADH and FAD. Thus, APC improves redox balance and has additive cardioprotective effects with mild hypothermic ischemia. 5-HD blocks APC-induced cardioprotective effects but not improvements in mitochondrial bioenergetics. This suggests that mediation of protection by KATP channel opening during cold ischemia and reperfusion is downstream from the APC-induced improvement in redox state or that these changes in redox state are not attenuated by KATP channel antagonism.
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PMID:Improved mitochondrial bioenergetics by anesthetic preconditioning during and after 2 hours of 27 degrees C ischemia in isolated hearts. 1611 32

Preserved ultrastructure is an important precondition for functional regeneration after heart transplantation. We investigated the effectiveness of a newly developed modified Langendorff system in extracorporeal heart perfusion. (Experiment I) Cardioplegia and cold ischaemia were performed in six pigs. Hearts were connected to a modified Langendorff system, and perfused with leucocyte depleted autologous blood. (Experiment II) The untreated hearts of three healthy pigs served as controls. Forty-seven myocardial biopsies at different timepoints (I: n = 29, II: n = 18) were investigated by transmission electronmicroscopy. Cardioplegia/hypothermia (I) induced mild-to-moderate mitochondrial swelling, mild myofibrillar degeneration in cardiomyocytes and moderate endothelial oedema. After 4 h reperfusion cardiomyocytes showed moderate myofibrillar and mild sarcolemmal damage. Moderate endothelial degeneration, mild interstitial oedema and haemorrhages appeared. Untreated hearts (II) showed severely damaged mitochondria and nuclei after 30 min while the myofibrillar structure remained unaffected until 4 h later. This is a promising model for extracorporeal heart perfusion. However, ultrastructural findings indicated that some necessary modifications to prevent cellular damages during reperfusion were needed.
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PMID:Ultrastructural findings in porcine hearts after extracorporeal long-term preservation with a modified Langendorff perfusion system. 1752 55

Continuous blood perfusion of donor hearts for transplantation has been the focus of an increasing amount of research, but the optimal preparation and perfusion techniques have not been clearly defined. Therefore, we investigated the effectiveness of different preservation strategies using continuous, normothermic heart perfusion after donor heart harvesting. Hearts of 12 pigs were randomly assigned to two groups receiving a constant pressure perfusion in a modified Langendorff system after different preparation techniques. In Group 1, six hearts were arrested with Bretschneider HTK cardioplegia (4 degrees C) and then reperfused with a circulating pressure of 80 to 90 mmHg using leukocyte depleted autologous blood. In Group 2, beating hearts of six pigs were explanted while being perfused, without cardioplegic arrest. Post-harvesting perfusion was similar to Group 1 except for a lower circulating pressure (40-50 mm Hg). At different time points (baseline and 1, 6, and 12 h after reperfusion), myocardial biopsies were taken, and contractility was assessed by measuring the maximum rate of left ventricular pressure rise (Deltap/Deltat (max)). Adenosine triphosphate (ATP) concentration was measured in all biopsies using a bioluminescence technique. Additionally, ultrastructural alterations were investigated using electron microscopy. Hypothermic cardioplegia and a higher reperfusion pressure (Group 1) were associated with an earlier and sharper decline in contractile function and intracellular ATP concentration. Ultrastructural alterations in Group 1 appeared earlier and were more distinctive than in Group 2. Endothelial ultrastructure, in particular, was better preserved in Group 2. Significant alterations were present in both groups after 12 h of perfusion but were more severe in Group 1. Blood perfusion provides protection against severe ischemic damage for a limited time. The use of a lower perfusion pressure, as well as avoiding cardioplegia and hypothermia, led to significantly better and longer preservation of perfused hearts.
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PMID:Functional, metabolic, and morphological aspects of continuous, normothermic heart preservation: effects of different preparation and perfusion techniques. 1950 81

Chloroform is still encountered occasionally in clinical and forensic toxicology, hence knowledge of the special problems presented in the detection and measurement of this compound in biological specimens may be required. The aim of this paper is to review the available documentation on this topic in the context of a chloroform-related death. Early one morning in February 1999 a 34-year-old female was found dead fully clothed on a path near to a neighbour's garden. Amfetamine intoxication combined with hypothermia was accepted as the cause of the death in the absence of any other identifiable cause. Further investigation 17 months later revealed a blood chloroform concentration of 31 mg/L and the cause of death was revised to chloroform poisoning. A murder trial ensued, the indictment specifying forced inhalation as the route of exposure. The liver chloroform concentration measured 38 months after collection was reported as 1064 mg/kg and opinions were offered at trial that the autopsy findings, which included a gastritis, but no evidence of injury to the inside of the mouth and oesophagus, excluded the possibility of ingestion of a toxic dose of chloroform. It was asserted that the explanation for the high liver concentration was that the liver had concentrated chloroform from blood after death against a concentration gradient. At appeal against conviction 7 years later the conviction was quashed. It was found that the liver concentration should have been reported at trial as 1 mg/kg. Moreover, chloroform found in the stomach contents (162 mg/kg) 86 months after collection was irrefutable evidence that some, if not all, of the chloroform had been ingested. Screening for volatile poisons should always be considered if a cause of death is not immediately obvious, especially in young people and in known substance abusers. If the presence of an unstable or volatile analyte is suspected then sample collection, transport, and storage must be performed with the analysis in mind. Quantitative analysis of all available specimens should proceed forthwith once the presence of an unstable analyte is established if the cause of death is in doubt or if prosecution may follow. In the case of chloroform especial precautions are needed: (i) headspace analysis should be performed at 35 degrees C to preclude the possibility of artefactual formation from trichloroacetic acid, (ii) precautions to prevent cross-contamination of biological samples in the laboratory must be taken, and (iii) interpretation of analytical results must take account of the widespread presence of chloroform in the environment on the one hand, and that the toxicity of chloroform varies greatly depending on the circumstances and intensity of exposure on the other.
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PMID:A chloroform-related death: analytical and forensic aspects. 2007 Nov 13


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