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Biomedical subjects

X Zhai

Publications and source records attributed to X Zhai.

At least 19 recordsLinked to original sources
PubMed2001

The telemedicine network of the People's Liberation Army.

In the early 1990s, the People's Liberation Army began to establish a telemedicine network for the non-emergency health-care of the personnel of military units and their families, as well as local civilian patients. All data were transferred over the ordinary telephone network. All the stations were uniformly equipped with PCs containing videoconferencing cards. The network comprised 13 management centres and 208 teleconsultation stations. To evaluate the telemedicine service, we conducted a survey with written questionnaires and telephone interviews. The questionnaire was sent to the person responsible for each telemedicine station. A total of 187 questionnaires were returned, a response rate of 85%. The survey showed that 1503 teleconsultation sessions had been conducted for military as well as civilian patients during the 18-month study period, and 1708 static images had been transferred across the network during these sessions.

China↗
PubMed2000

Mixed viral infection identified using heteroduplex mobility analysis (HMA).

It is now recognised that mixed viral infection, or infection of an individual with two or more distinct strains of a single viral species, often occurs particularly with RNA viruses. Current methods for detection of mixed infection normally involve genotyping or cloning and DNA sequencing. These methods are not always accurate or sensitive at detecting mixed infection and cannot be used for large numbers of samples. Furthermore subsequent sequence determination of the coinfecting viruses is labour intensive. This paper describes a simple, generic method based upon PCR and heteroduplex mobility analysis (HMA) that can be used to rapidly determine mixed infection with two strains of the same virus. The utility of this method is illustrated with hepatitis C virus (HCV) and TT virus (TTV) as examples. PCR-HMA detected mixed infection in 3 (8%) of 38 sera from intravenous drug users (IVDU) and 28 (30%) of 70 TTV-positive sera from Australia, China, and Vietnam. HMA can also be used to screen recombinant colonies to identify the sequences of the coinfecting viruses. The methods described here could be applied to analyse any PCR product containing two or more divergent sequences, whether derived from viruses, bacteria, or eukaryotic organisms.

Base Sequence↗
PubMed2000

Simplified hepatitis C virus genotyping by heteroduplex mobility analysis.

Heteroduplex mobility analysis (HMA) was used to genotype hepatitis C viruses (HCV) with PCR fragments derived from the 5' untranslated region (5'-UTR) or the NS5b region. HCV 5'-UTR fragments were amplified from 296 serum samples by use of a combined reverse transcription-PCR assay, and the genotypes of isolates were determined by sequencing. HCV genotype distributions in Australia were 39% for genotype 1a, 15% for 1b, 3% for 1a/b, <1% for 2a/c, 5% for 2b, 34% for 3a, <1% for 3b, and 1% for 4, and 1% of patients were infected with more than one genotype. Pairwise HMA of subtypes 1a, 1b, 2a/c, 2b, 3a, 3b, 4a, and 6a demonstrated that five distinct heteroduplex patterns were formed between the eight subtypes. A reference panel that contained a representative of each pattern (1a, 2b, 3a, 4a, and 6a) was used for genotyping. The pattern of heteroduplexes formed when a test isolate was mixed with the five reference isolates was correlated with the genotype, as determined by sequencing. Genotypes determined by HMA correlated exactly with sequencing results within the groups 1, 2, 3a, 3b/4, and 6. HMA was also used to simplify the identification of mixed infection with two HCV genotypes. In further studies, with amplicons from the NS5b region, HMA classified isolates into their respective subtypes, and the heteroduplex mobility ratio correlated closely with nucleotide sequence variation at the isolate, subtype, and genotype levels. HMA provides an adaptable, inexpensive, and rapid method of genotyping HCV that requires fewer resources than DNA sequencing.

5' Untranslated Regions↗
PubMed2000

[Modulating effect of vitamin D3 in vitro on EGFR mRNA expression of human breast cancer cell lines].

OBJECTIVE: To assess the modulating effects of vitamin D3, combined with or without tamoxifen, on cell proliferation and EGFR mRNA level of human breast cancer. METHODS: Two breast cancer cell lines (MCF-7 and ZR-75-1) were treated with various concentrations of vitamin D3, alone or in combination with tamoxifen, for 6 days. Cell proliferation was assessed by MIT uptake and EGFR mRNA level by Northern blot. RESULTS: 10(-10)-10(-7) mol/L vitamin D3 strongly inhibited proliferation of the 2 breast cancer lines, while 10(-9)-10(-7) mol/L tamoxifen stimulated proliferation of MCF-7 cell. The growth inhibitory effect on the 2 cell lines could be augmented and accompanied by a decrease in EGFR mRNA level after combined treatment with IC50 dose of tamoxifen and 10(-10)-10(-9) mol/L vitamin D3. CONCLUSION: Vitamin D3 can be considered as a useful anti-tumor drug in the treatment of breast cancer.

Antineoplastic Agents, Hormonal↗
PubMed2000

[Monitor visual function with flash visual evoked potential during orbital surgery].

OBJECTIVE: To evaluate the feasibility and reliability of monitoring visual function with flash visual evoked potential (FVEP) during orbital surgery. METHOD: The visual function of 82 cases was monitored during orbital surgery with FVEP. Of these cases, the intraoperative and postoperative visual functions (IOVF and POVF) were compared. RESULTS: Sixty-nine cases were successfully monitored. Sixty-seven cases obtained the accordance of IOVF and POVF, and there were false positive in 1 case and false negative in 1 case. CONCLUSION: Intraoperative monitoring of visual function with FVEP can show the surgical injury of the optic nerve and unsuitable procedures, and decrease the surgical blind rate.

Adolescent↗
PubMed1999

Partial glycosylation at asparagine-2181 of the second C-type domain of human factor V modulates assembly of the prothrombinase complex.

Thrombin-activated factor Va exists as two isoforms, factor Va(1) and factor Va(2), which differ in the size of their light chains and their affinity for biological membranes. The heterogeneity of the light chain remained following incubation of factor Va with N-glycanase. However, we found that the factor V C2 domain, which contains a single potential glycosylation site at Asn-2181, was partially glycosylated when expressed in COS cells. To confirm the structural basis for factor Va(1) and factor Va(2), we mutated Asn-2181 to glutamine (N2181Q) and expressed this mutant using a B domain deletion construct (rHFV des B) in COS cells. Thrombin activation of N2181Q released a light chain with mobility identical to that of factor Va(2) on SDS-PAGE. The functional properties of purified N2181Q were similar to those of factor Va(2) in prothrombinase assays carried out in the presence of limiting concentrations of phosphatidylserine. The binding of human factor Va(1) and factor Va(2) to 75:25 POPC/POPS vesicles was also investigated in equilibrium binding assays using proteins containing a fluorescein-labeled heavy chain. The affinity of human factor Va(2) binding to POPC/POPS vesicles was approximately 3-fold higher than that of factor Va(1). These results indicate that partial glycosylation of factor V at asparagine-2181 is the structural basis of the light chain doublet and that the presence of this oligosaccharide reduces the affinity of factor Va for biological membranes.

Animals↗
PubMed1998

Cisplatin-DNA adducts inhibit ribosomal RNA synthesis by hijacking the transcription factor human upstream binding factor.

Several eukaryotic cellular proteins recognize DNA modified by the anticancer drug cisplatin (cis-diamminedichloroplatinum(II) or cis-DDP); among these proteins is a class of DNA-binding molecules containing the HMG (high-mobility group) box DNA recognition motif. We have previously reported the extraordinarily high binding activity to cisplatin adducts by human upstream binding factor (hUBF), an HMG box containing transcription factor that stimulates ribosomal RNA synthesis (Treiber et al. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 5672-5676). In the present study, we discovered that (1) hUBF interacted selectively with DNA lesions formed by therapeutically effective platinum compounds [Pt(en)Cl2] and [Pt(dach)Cl2], in addition to the lesions formed by cis-DDP, suggesting a possible association with their anticancer effect; (2) multiple HMG boxes contributed additively to the hUBF-adduct interaction, providing a possible explanation for the unusually high affinity of hUBF for cis-DDP adducts as compared to the lower affinities of other HMG box proteins; and (3) ribosomal RNA transcription in a reconstituted system is specifically inhibited in the presence of cis-DDP adducts. In this third experiment, a ratio of adducts/promoter of approximately 4:1 completely abolished the transcription activated by hUBF. Taken together, these data lend support to the view that transcription factors involved in cellular growth regulation, such as ribosomal RNA transcription, may be hijacked by cis-DDP adducts resulting in functional inhibition.

Antineoplastic Agents↗
PubMed1997

Roles of factor Va heavy and light chains in protein and lipid rearrangements associated with the formation of a bovine factor Va-membrane complex.

Factor Va is an essential protein cofactor of the enzyme factor Xa, which activates prothrombin to thrombin during blood coagulation. Peptides with an apparent Mr of approximately 94,000 (heavy chain; HC) and approximately 74,000 or 72,000 (light chain; LC) interact in the presence of Ca2+ to form active Va. The two forms of Va-LC differ in their carboxyl-terminal C2 domain. Using Va reconstituted with either LC form, we examined the effects of the two LC species on membrane binding and on the activity of membrane-bound Va. We found that 1) Va composed of the 72,000 LC bound only slightly more tightly to membranes composed of a mixture of neutral and acidic lipids, the Kd being reduced by a factor of approximately 3 at 5 mM and by a factor of 6 at 2 mM Ca2+. 2) The two forms of Va seemed to undergo different conformational changes when bound to a membrane. 3) The activity of bovine Va varied somewhat with LC species, the difference being greatest at limiting Xa concentration. We have also addressed the role of the two Va peptides in membrane lipid rearrangements and binding: 1) Va binding increased lateral packing density in mixed neutral/acidic lipid membranes. In the solid phase, Va-HC had no effect, whereas Va-LC and whole Va had similar but small effects. In the fluid phase, Va-HC and whole Va both altered membrane packing, with Va-HC having the largest effect. 2) Va-HC bound reversibly and in a Ca2+-independent fashion to membranes composed of neutral phospholipid (Kd, approximately 0.3 microM; stoichiometry approximately 91). High ionic strength had little effect on binding. 3) The substantial effect of Va on packing within neutral phospholipid membranes was mimicked by Va-HC. 4) Based on measurements of membrane phase behavior, binding of Va or its peptide components did not induce thermodynamically discernible lateral membrane domains. These results suggest that the membrane association of factor Va is a complex process involving both chains of Va, changes in lipid packing, and changes in protein structure.

Animals↗
PubMed1997

Order in phospholipid Langmuir-Blodgett monolayers determined by total internal reflection fluorescence.

Orientational order parameters of two diphenylhexatriene (DPH)-based fluorescent probes, 2-(3-(diphenylhexatrienyl)propanoyl)-1-hexadecanoyl-sn-glycero-3-p hosphocholine (DPHpPC) and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH), in dipalmitoylphosphatidylcholine (DPPC) Langmuir-Blodgett monolayers on quartz have been determined by total internal reflection fluorescence (TIRF). From these order parameters orientation distributions were reconstructed by the maximum-entropy method. For monolayers transferred from the liquid-condensed phase, preferential tilt angles with respect to the substrate normal around 14 degrees in the tail region and 5 degrees near the glycerol-acyl chain linkage were found, as reflected by the DPHpPC and TMA-DPH probes, respectively. The degree of ordering near the headgroup region seems to be larger than that further away from the surface. A substantial fraction of the TMA-DPH probes have a flat orientation and are probably located between the phospholipid headgroups and the substrate surface. Monolayers transferred from the liquid-expanded phase show a more random ordering, and most of the probe molecules (DPHpPC) are more or less flat on the surface. The results are consistent with earlier atomic force microscopy measurements on identical monolayers and are in reasonable agreement with previously published data on other organized phospholipid systems.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1997

[Primary study on the sensitivity of cytokinesis blocked micronucleus assay in CHL cells].

Studies were performed to determine the cytochalasin B induced binucleated cell percentage influenced by clastogens and aneuploidgens and to compare the efficacy of cytokinesis blocked binucleated cells for scoring micronuclei with that of the conventional mononucleated method following the treatment with mitomycin C, methyl methanesulforate, colchicin and chloral hydrate. The results showed that mitomycin C decreased the binucleated cell percentage induced by cytochalasin B, whereas colchicin increased the frequencies of binucleated cells. The frequencies of micronuclei in binucleated cells were not significantly higher than those in the conventional mononucleated cells. The results suggest that cytokinesis blocked method is not more sensitive than the conventional method for scoring micronuclei. The factors that may influence the cytokinesis blocked micronucleus assay have been discussed.

Animals↗
PubMed1996

Late ischemic preconditioning is mediated in myocytes by enhanced endogenous antioxidant activity stimulated by oxygen-derived free radicals.

The primary objective of the study was to test the hypothesis that oxygen radical during initial anoxia stimulate endogenous antioxidant activity in late preconditioning in myocytes. Isolated rat myocytes were preconditioned in one group with two cycles of 5 minutes of anoxia and 5 minutes of reoxygenation and in another group with exogenous superoxide anion (.O2-) generated by reaction of xanthine oxidase with xanthine. Myocytes were kept for 24 hours, after which they were exposed to 60 minutes of anoxia and 60 minutes of reoxygenation. Preconditioned myocytes exhibited decreased LDH release, reduced malondialdehyde formation, increased cell viability, and well-preserved cell structure. .O2- production was increased in myocytes immediately after treatment with repetitive anoxia (1.65 +/- 0.08 nmol/mg protein) or exogenous .O2- (1.42 +/- 0.11 nmol/mg protein). Allopurinol, a xanthine oxidase inhibitor, abolished .O2- production during the initial preconditioning period. Twenty-four hours later, Mn SOD activity declined in anoxic control myocytes (0.38 +/- 0.06 U/mg protein), whereas it increased significantly in myocytes preconditioned with repetitive anoxia (3.25 +/- 0.15 nmol/mg protein) or with exogenous .O2- (2.27 +/- 0.10 nmol/mg protein). The increase in Mn SOD activity and myocardial protective effects observed in preconditioned myocytes were totally blocked by allopurinol. These results indicate that oxygen radicals generated during the initial preconditioning period activate endogenous antioxidant defense (increased Mn SOD activity) 24 hours later, which contributes to the late cardioprotection of preconditioning.

Animals↗
PubMed1996

Direct evidence that initial oxidative stress triggered by preconditioning contributes to second window of protection by endogenous antioxidant enzyme in myocytes.

BACKGROUND: We tested the hypothesis that late preconditioning is associated with increased antioxidant enzyme activity induced by initial oxidative stress. METHODS AND RESULTS: Isolated rat myocytes were preconditioned either with two cycles of 5 minutes of anoxia and 5 minutes of reoxygenation or with exogenous superoxide anion (O2-) generated by reaction of xanthine oxidase with xanthine. Myocytes were allowed to recover for 60 minutes or 24 hours, after which they were subjected to 60 minutes of anoxia and 60 minutes of reoxygenation. After 60 minutes or 24 hours, the protection was evidenced by decreased O2- production, increased Mn superoxide dismutase (Mn-SOD) activity, increased call viability, decreased LDH release, reduced malondialdehyde formation, high-energy phosphate preservation, and improved call morphology in preconditioned and O2(-)-treated myocytes. Immediately after treatment with O2- or repetitive, brief anoxia, O2- production was increased in myocytes. Longer anoxia resulted in loss of Mn-SOD activity in anoxic controls 24 hours later, whereas it was significantly increased in preconditioned and O2- -treated myocytes. O2- production was inhibited in preconditioned and O2(-)-myocytes. Myocytes treated with Mn-SOD during short, intermittent anoxia exhibited decreased activity of Mn-SOD and increased O2- production 24 hours later. Mn-SOD activity in late preconditioning was considerably higher than that in classic preconditioning. CONCLUSIONS: These results suggest that a burst of oxygen free radicals generated during the initial periods of brief, repetitive anoxia increases myocardial antioxidant activity 24 hours later and that it contributes to the late cardioprotective effect of preconditioning.

Adenosine Triphosphate↗
PubMed1996

Preconditioning of bovine endothelial cells. The protective effect is mediated by an adenosine A2 receptor through a protein kinase C signaling pathway.

We tested the hypothesis that anoxic preconditioning could protect coronary endothelial cells against anoxic and reoxygenation injury and that this preconditioning effect could be mediated by an adenosine A2 receptor via the protein kinase C (PKC) pathway. Cells were preconditioned with 10-minute anoxia and 10-minute reoxygenation and were then subjected to anoxia for 60 minutes, followed by 120 minutes of reoxygenation. In some groups, the preconditioning effect was prevented by 8-sulfophenyltheophylline (SPT [50 mumol/L], a nonselective adenosine receptor antagonist), or calphostin C (100 nmol/L, a PKC inhibitor). In other groups, 2-p-(2-carboxyethyl)phenethylamino-5'N-ethylcarboxyamido- adenosine (CGS-21680 [20 nmol/L], an adenosine A2 receptor agonist, R-(--)-N6-(2-phenylisopropyl)-adenosine (R-PIA [50 nmol/L], an adenosine A1 receptor agonist), or 4 beta-phorbol 12-myristate 13-acetate (PMA [100 nmol/L], a PKC activator) was given as a pretreatment to mimic the preconditioning effect. Endothelial cells were also pretreated with 100 nmol/L calphostin C to confirm whether inhibition of PKC can block the effects of adenosine A2 receptor activation by CGS-21680 on anoxia and reoxygenation injury. Preconditioning reduced LDH release, increased adenosine release, promoted translocation of PKC from cytosol to membrane, increased cell viability, and preserved ATP content and cell morphology. Pretreatment with either CGS-21680 or PMA resulted in protection similar to that seen with anoxic preconditioning. The protection was totally abolished by SPT or calphostin C. The results suggest that (1) preconditioning protects coronary endothelial cells against anoxia and reoxygenation injury, (2) the protection is probably mediated by activation of adenosine A2 receptors through the PKC pathway, and (3) the preservation of endothelial cells may be one of the mechanisms of myocardial preconditioning.

Adenosine↗
PubMed1995

Interaction of singlet oxygen with 5'-nucleotidase in rat hearts.

This study was aimed to determine whether singlet oxygen (1O2) attenuates 5'-nucleotidase activity in the ischemic myocardium. Isolated rat hearts were exposed to either exogenous 1O2 produced by irradiating rose bengal or 40-min ischemia and reperfusion. Ecto-5'-nucleotidase activity was inhibited by exogenous 1O2 (3.74 +/- 0.38 mumol/min/g dry weight), when compared with normal control (7.52 +/- 0.41 mumol/min/g dry weight; P < 0.05). The enzymatic activity was significantly preserved by histidine (25 mM)--a 1O2 scavenger (7.04 +/- 0.61 mumol/min/g dry weight; P < 0.05 v rose bengal group). After ischemia, the activity of ecto-5'-nucleotidase was greatly reduced (2.51 +/- 0.25 mumol/min/g dry weight), when compared with normal control. Histidine significantly enhanced ecto-5'-nucleotidase activity (6.55 +/- 0.52 mumol/min/g dry weight, P < 0.05 v ischemic control). Adenosine release was consistent with ecto-5'-nucleotidase activity. The time course studies of effects of 1O2 on coronary flow, cardiac function, and LDH release revealed that the damage by 1O2 to ecto-5'-nucleotidase activity and adenosine release primarily accounted for impaired coronary flow, cardiac dysfunction, and impaired cardiac metabolism. Lipid peroxidation induced by exogenous 1O2 or ischemia was in parallel with ecto-5'-nucleotidase deactivation by 1O2. It is concluded that 1O2 causes inactivation of ecto-5'-nucleotidase and attenuation of adenosine release which could possibly be one of the important mechanisms of oxygen radical-mediated myocardial injury.

5'-Nucleotidase↗
PubMed1995

The effect of load on atrophy, myosin isoform shifts and contractile function: studies in a novel rat heart transplant preparation.

A novel heterotopic rat heart transplant preparation was used with the objective of investigating the effect of load on cardiac contractile function, mass, myosin and high energy phosphates over a 7-day period. Donor hearts were excised, arrested with a hypothermic (4 degrees C) cardioplegic solution and transplanted (90-min operation time) into the abdomens of recipient rats. The transplanted hearts were reperfused in situ for 7 days. Two groups of hearts (n = 14/group) were studied. Group 1: a conventional unloaded transplanted preparation in which the aorta and pulmonary artery were anastomosed to the abdominal aorta and inferior vena cava, respectively. Group 2: a novel loaded preparation in which, additionally, the left atrium was anastomosed to the inferior vena cava which was then ligated proximally so as to divert distal venous flow to the left ventricle of the transplanted heart. Non-transplanted, fresh hearts served as controls. Seven days after transplantation the hearts were excised and perfused aerobically for 20 min. Systolic and diastolic functions had deteriorated severely in Group 1: left ventricular developed pressure (LVDP) had fallen to 96 +/- 11 v 162 +/- 6 mmHg in fresh controls (at 12 mmHg of end-diastolic pressure) and left ventricular volume to 80 +/- 12 v 268 +/- 20 microliters (P < 0.05 in both instances). In Group 2, LVDP (134 +/- 6 mmHg) and left ventricular volume (144 +/- 6 microliters) were significantly higher than in Group 1 but were still significantly lower than in fresh controls. Coronary flow in absolute terms was similar in all groups; however, when expressed as ml/min/g wet wt, coronary flow tended to be greater in unloaded hearts (19.8 +/- 0.6) than in fresh hearts (15.0 +/- 0.8; P < 0.05) and loaded hearts (17.6 +/- 1.3; N.S.). Unloaded hearts exhibited a significant loss of left ventricular weight (0.40 +/- 0.02 g) when compared with fresh aerobic controls (0.57 +/- 0.02 g; P < 0.05). However, there was no significant weight loss in the loaded hearts (0.53 +/- 0.03 g). The content of V1 isoform of myosin in left ventricular muscle was 77.8 +/- 5.0% in fresh hearts; this was reduced to 60.0 +/- 3.6% in the unloaded hearts (P < 0.05). The value in the loaded hearts (73.2 +/- 3.4%) did not differ significantly from that in fresh controls. The adenine nucleotide pool was similar in all groups. In conclusion, imposing a load on the heterotopically transplanted heart prevents the loss of cardiac mass and the shift of myosin isoforms, however, it does not totally prevent the development of systolic and diastolic dysfunction. The contractile abnormalities do not appear to be related to high energy phosphate content but might well arise as a consequence of the denervation associated with transplantation or the transplantation procedure itself.

Animals↗
PubMed1995

Protection against injury during ischemia and reperfusion by acadesine derivatives GP-1-468 and GP-1-668. Studies in the transplanted rat heart.

BACKGROUND: Acadesine (AICAr: 5-amino-4-imidazole carboxamide riboside) has been shown to afford sustained protection against injury during ischemia and reperfusion. The present studies used the heterotopically transplanted rat heart to assess the protective properties of two new acadesine analogs: GP-1-468 and GP-1-668. METHODS AND RESULTS: Hearts were excised, arrested with a 2-minute infusion of cardioplegic solution, and subjected to 4 hours of global ischemia (20 degrees C) with cardioplegic reinfusion for 2 minutes every 30 minutes. The hearts were then transplanted (1 hour of additional ischemia) into the abdomens of recipient rats and reperfused in situ for 30 minutes or 24 hours. The hearts were then excised, perfused aerobically for 20 minutes, and contractile function was assessed. GP-1-468 or GP-1-668 was administered to donor rats (20 mg/kg intravenously, 30 minutes before excision). They were also added to the cardioplegic solution (10 mumol/L for GP-1-468, 5 mumol/L for GP-1-343, the active metabolite of GP-1-668) and were also given to recipient rats (20 mg/kg intravenously, 30 minutes before transplantation, so that the drugs were present during reperfusion). Nine groups of hearts were studied. Three groups of studies were carried out (n = 24 transplants for each group). The first group of hearts was reperfused for 30 minutes, the second group was reperfused for 24 hours, and the third group was transplanted but not reperfused; instead, they were frozen at the end of 5 hours of ischemia and taken for metabolite analysis. Within each group were three subgroups (n = 8 per group) receiving GP-1-468, GP-1-668, or saline solution. In the 30-minute reperfusion group the recoveries of left ventricular developed pressure were 88 +/- 4, 87 +/- 7, and 50 +/- 9 mm Hg, respectively (p < 0.05 versus saline-treated controls); left ventricular volumes (recorded at 12 mm Hg) were 112 +/- 20, 132 +/- 28, and 41 +/- 9 microliters, respectively (p < 0.05 versus saline-treated controls), and coronary flows were 13.1 +/- 0.7, 13.4 +/- 1.0, and 9.9 +/- 0.5 ml/min, respectively (p < 0.05 versus saline-treated controls). In addition to improving functional recovery, the two analogs increased the tissue content of adenosine at the end of the ischemic period (5.4 +/- 0.6 and 7.3 +/- 0.5 mumol/gm dry weight, respectively, versus 2.7 +/- 0.4 mumol/gm dry weight in the saline-treated controls; p < 0.05); however, they did not influence adenosine triphosphate or its catabolites. In the 24-hour reperfusion group the corresponding values were 77 +/- 6 and 88 +/- 6 versus 35 +/- 4 mm Hg for left ventricular developed pressure (p < 0.05), 111 +/- 9 and 121 +/- 11 versus 41 +/- 8 microliters for left ventricular volume (p < 0.05), and 13.7 +/- 0.7 and 13.0 +/- 0.6 versus 11.7 +/- 0.7 ml/min for coronary flow (no significant difference). Thus both analogs afforded an early and comparable degree of protection of contractile function that was sustained even after 24 hours of reperfusion. CONCLUSIONS: Both GP-1-468 and GP-1-668 increase the rate and extent of early postischemic recovery, and this protection is sustained for at least 24 hours. These beneficial actions were associated with an increase of the tissue content of adenosine during ischemia, but they appeared to be independent of the status of the high-energy metabolism.

Adenosine↗
PubMed1995

Direct detection and quantification of singlet oxygen during ischemia and reperfusion in rat hearts.

To detect singlet oxygen (1O2) in postischemic reperfused hearts, 5,8-endoperoxide, an oxidation product of beta-carotene, was used as a marker for 1O2 generation and was quantified using high-performance liquid chromatography (HPLC). Isolated rat hearts were subjected to ischemia for 5, 10, 20, 30, and 60 min followed by 10 min of reperfusion with buffer containing 25 microM beta-carotene. The coronary effluent was collected, extracted, and injected into the HPLC unit. The production of 5,8-endoperoxide was maximum during the first 2 min of reperfusion. Maximal accumulated amount of 1O2 was observed in hearts subjected to 60-min ischemia (36.2 +/- 1.7 nmol.10 min-1.g-1) as compared with 10-min ischemia (6.2 +/- 1.0 nmol.10 min-1.g-1). There was a good correlation between the amount of 1O2 production and cardiac function. Treatment with 25 mM histidine significantly decreased 5,8-endoperoxide from 7.02 +/- 0.47 to 0.98 +/- 0.11 nmol.min-1.g-1 (P < 0.01) and improved cardiac function in the group with 60-min ischemia. This study demonstrates that 1) the present method is useful and reliable for the measurement of 1O2 in the heart, 2) 1O2 production during reperfusion is dependent on the duration of initial ischemia, and 3) 1O2 is one of the major factors in postischemic reperfusion injury.

Animals↗