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G S Liu

Publications and source records attributed to G S Liu.

At least 37 records · Page 2Linked to original sources
PubMed1996

An irreversible A1-selective adenosine agonist preconditions rabbit heart.

This study tested whether an irreversible agonist of the A1 adenosine receptor, m-DITC ADAC, can mimic the protective effect of ischemic preconditioning in the rabbit heart. Isolated Krebs buffer-perfused rabbit hearts experienced 30 mins of regional ischemia and 120 mins of reperfusion. Infarct size was measured with tetrazolium staining. In untreated hearts 32 +/- 2% of the risk zone infarcted while only 9 +/- 2% infarction was seen in hearts that were preconditioned with 5 mins of global ischemia followed by 10 mins of reperfusion (P < 0.05 versus control). Exposure to 200 nM of the A1-selective agonist 2-chloro-N6-cyclopentyladenosine (CCPA) for 5 mins followed by 10 mins of washout protected the hearts as well as preconditioning with 13 +/- 7% infarction (P < 0.05 versus control). Protection from CCPA was completely blocked by 200 nM DPCPX (8-cyclopentyl-1,3-dipropylxanthine) with 34 +/- 7% infarction (P < 0.05 versus CCPA) confirming that protection was via the A1 adenosine receptor. m-DITC ADAC, which irreversibly stimulates the A1 adenosine receptor, also protected the hearts with only 15 +/- 4% infarction (P < 0.05 versus control). It was concluded that m-DITC ADAC does mimic ischemic preconditioning and that an irreversible agonist might be a novel way to provide an extended window of protection to the heart from a single intracoronary injection.

Animals↗
PubMed1995

Potassium channels and preconditioning of isolated rabbit cardiomyocytes: effects of glyburide and pinacidil.

Calcium tolerant rabbit cardiomyocytes, isolated by collagenase perfusion, were preincubated for varying periods of time followed by resuspension in fresh media and centrifugation into an ischaemic pellet with restricted extracellular fluid. Pellets were incubated for 240 min under oil at 37 degrees C to mimic severe ischaemia. Time to onset of ischaemic contracture (rod to square transformation) and trypan blue permeability following resuspension in 85 mOSM media were monitored at sequential times. The protocol of Series 1 was a 5-10 min pre-incubation, immediately followed by ischaemic pelleting. Preincubation with pinacidil (50 microM) protected cells from ischaemic insult, but pinacidil added only into the ischaemic pellet did not protect. Protection was abolished by the protein kinase (PKC) inhibitors chelerythrine (10 microM) added with pinacidil and calphostin C (200nM) added only into the ischaemic pellet. Neither PKC inhibitor had an effect on injury of untreated ischaemic myocytes (data not shown). Series 2-5 were preconditioning protocols with a 10 min intervention period, followed by a 30 min oxygenated drug-free period, prior to ischaemic pelleting. In series 2 pinacidil protected cells from ischaemic insult and this protection was abolished when glyburide (10 microM) was present during preincubation, or during post-incubation and ischaemia. Glyburide only partially inhibited the protection when glyburide was added only into the ischaemic pellet. In Series 3, 8-sulfophenyltheophyline (SPT)(100 microM) or adenosine deaminase during preincubation, or SPT only added into the ischaemic pellet abolished pinacidil's protection. In Series 4, cardiomyocytes were ischaemically preconditioned by pelleting for 10 min followed by 30 min reoxygenation. Glyburide during initial ischaemic blocked protection, but when added during post incubation and into the final pellet protection was not reduced. In Series 5 8-cyclopentyl-1,3,dipropylxanthine (DPCPX) (10 microM) added into the final pellet abolished protection by pinacidil, but not protection following ischaemic preconditioning. In contrast to pinacidil, ischaemically preconditioned cells maintain protection in the presence of glyburide, indicating that: (1) pinacidil does not exactly mimic preconditioning and (2) ischaemically preconditioned cells do not require opened K+ATP channels for protection, although they appear to be important during initiation of the preconditioned state. It is hypothesized that pinacidil opening of K+ channels may facilitate induction of preconditioning.

Analysis of Variance↗
PubMed1994

Evidence that the adenosine A3 receptor may mediate the protection afforded by preconditioning in the isolated rabbit heart.

OBJECTIVE: Agonists selective for the A1 adenosine receptor mimic the protective effect of ischaemic preconditioning against infarction in the rabbit heart. Unselective adenosine antagonists block this protection but, paradoxically, the A1 adenosine receptor selective antagonist 8-cyclopentyl- 1,3-dipropylxanthine (DPCPX) does not. The aim of this study was to test the hypothesis that the newly described A3 adenosine receptor, which has an agonist profile similar to the A1 receptor but is insensitive to DPCPX, might mediate preconditioning. METHODS: Isolated rabbit hearts perfused with Krebs buffer experienced 30 min of regional ischaemia followed by 120 min of reperfusion. Infarct size was measured by tetrazolium staining. RESULTS: In control hearts infarction was 32.2(SEM 1.5)% of the risk zone. Preconditioning by 5 min ischaemia and 10 min reperfusion reduced infarct size to 8.8(2.3)%. Replacing the regional ischaemia with 5 min perfusion with 10 microM adenosine or 65 nM N6-[2-(4-aminophenyl)ethyl]adenosine (APNEA), an adenosine A3 receptor agonist, was equally protective. The unselective antagonist 8-p-sulphophenyl theophylline at 100 microM abolished protection by preconditioning, adenosine, and APNEA, but 200 nM DPCPX did not block protection by any of the interventions. Likewise the potent but unselective A3 receptor antagonist 8-(4-carboxyethenylphenyl)-1,3-dipropylxanthine (BW A1433) completely blocked protection from ischaemic preconditioning. CONCLUSIONS: Because protection against infarction afforded by ischaemic preconditioning, adenosine, or the A3 receptor agonist APNEA could not be blocked by DPCPX and because the potent A3 receptor antagonist BW A1433 blocked protection from ischaemic preconditioning, these data indicate that the protection of preconditioning is not exclusively mediated by the adenosine A1 receptor in rabbit heart and could involve the A3 receptor.

Adenosine↗
PubMed1994

Rat and rabbit heart infarction: effects of anesthesia, perfusate, risk zone, and method of infarct sizing.

Rabbits and rats are becoming popular models for in vitro as well as in situ studies of myocardial infarction. In the present analysis we evaluated the results of several of our completed investigations and tested whether blood-free perfusate, anesthesia, or risk zone size affects infarction in these species. In addition, the influence of the method used for determining infarct size (histology or histochemistry) was examined in rabbits. All hearts experienced 30 min of regional ischemia followed by either 2-3 h of reperfusion in animals in which infarct size was assessed by staining with triphenyltetrazolium chloride or 72 h in those in which histological methods were used to measure infarct size. Eighteen rabbit and seven rat hearts perfused with Krebs buffer, seventeen open-chest rabbits, eight rats anesthetized with pentobarbital, and ten conscious rabbits were studied. Risk zone size measured with fluorescent particles was plotted against infarct size. Infarct size was linearly correlated with risk zone size and did not differ among models for each species. In rat hearts the regression line passed through the origin so that zero infarction occurred with zero risk zone size. However, in the rabbit heart there was no apparent infarction for risk zone sizes < 0.3 cm3. Although the relationship between risk zone and infarction was found to be remarkably independent of the model chosen, the nonzero intercept for the rabbit heart can be an important, previously unrecognized source of experimental variability when infarct size is expressed as a percentage of the risk zone.

Anesthesia↗
PubMed1994

alpha 1-adrenergic agonists precondition rabbit ischemic myocardium independent of adenosine by direct activation of protein kinase C.

Ischemic preconditioning in the rabbit is initiated by adenosine A1-receptor stimulation, which activates protein kinase C (PKC). Additionally, alpha 1-adrenergic agonists can similarly protect ischemic myocardium, but there has been confusion about the role adenosine receptors play in this protection. To characterize the interaction between adrenergic and adenosine receptors and to study the possible role of PKC in this protection, we used isolated rabbit hearts perfused with oxygenated Krebs' buffer. All hearts were subjected to 30 minutes of regional myocardial ischemia and 2 hours of reperfusion. Infarct size was determined by triphenyltetrazolium staining. Pharmacologic preconditioning in hearts with a 5-minute phenylephrine (PE) infusion 10 minutes before the prolonged regional ischemia resulted in significantly smaller infarcts (9.7 +/- 1.3% of risk area) than in control hearts (31.0 +/- 2.6%, P < .05). This protection could be effectively blocked by administration of the alpha-adrenergic blocker phenoxybenzamine. Methoxamine, an alpha 1a-selective agonist, failed to protect, whereas the alpha 1b-selective antagonist chloroethylclonidine aborted the protective effect of PE. Polymyxin B, an inhibitor of PKC, also blocked the protective effect of PE, implying that PKC has an important role in preconditioning. The adenosine receptor blocker 8-(p-sulfophenyl)theophylline (SPT) given at the same time as the PE infusion did not affect the protection, implying that an alpha 1-agonist could initiate protection independent of adenosine, presumably by direct coupling to PKC. However, the protective effect of PE could be blocked if SPT were administered during the 30-minute regional ischemia. This observation suggested that adenosine receptor occupancy is necessary during long ischemia to reactivate PKC and mediate the protection. However, the addition of a second PE infusion beginning 5 minutes before and continuing throughout the long ischemic period restored the protective effect of PE despite the presence of SPT. Thus, as long as at least one of the receptors (alpha 1-adrenegic or adenosine A1) is activated during long ischemia, protection will be realized. These data indicate that alpha 1 receptors do not precondition through an adenosine intermediate but that alpha 1-adrenergic and adenosine receptors activate parallel pathways within the myocyte that can trigger and mediate protection.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1994

Depot drug delivery system for 5-fluorouracil after filtration surgery in the rabbit.

We investigated the potential value of 50:50 poly (DL glycolic acid-lactic acid) (PGLA) copolymer as a degradable depot delivery system for 5-fluorouracil (5-FU) after filtration surgery. Analysis of retrieved discs after implantation in 22 eyes of 22 pigmented rabbits showed a dual drug release profile and polymer mass loss characteristics. In a second group of pigmented rabbits implantation of PGLA discs impregnated with 5-FU (22 eyes) significantly lengthened the survival time of filtration fistulae compared with discs without 5-FU (18 eyes) or no disc (10 eyes) (p < 0.0001). Use of PGLA copolymer impregnated with 5-FU could prove valuable for patients undergoing glaucoma filtering surgery.

Animals↗
PubMed1994

Ocular timolol levels after drug withdrawal: an experimental model.

Carbon 14-labelled timolol maleate was instilled into both eyes of 12 pigmented rabbits daily for 42 days. Drug levels in the aqueous humour and ocular tissues were measured up to 42 days after drug withdrawal. The results indicate that timolol concentrates mainly in melanotic tissues, with slow release. Even 42 days after withdrawal the drug was still present in pigmented ocular tissues. Timolol was detected in the aqueous up to 5 days after withdrawal. These findings explain the long-term depressant effect of topically administered timolol on aqueous production. We conclude that lower or less frequent doses of timolol should be considered in patients with glaucoma.

Animals↗
PubMed1994

Fifty:fifty poly (DL glycolic acid-lactic acid) copolymer as a drug delivery system for 5-fluorouracil: a histopathological evaluation.

Fifty:fifty poly (DL glycolic acid-lactic acid) copolymer (PGLA) is a potentially useful depot drug delivery system for 5-fluorouracil (5-FU). The purpose of this study was to evaluate the fibroinflammatory reaction induced by this polymer. Polymer discs without 5-FU were inserted subconjunctivally in one eye of each of two guinea pigs and four pigmented rabbits (control group), and discs containing 20% 5-FU were inserted subconjunctivally in both eyes of nine pigmented rabbits (study group). The tissue reaction to the copolymer did not differ between rabbits and guinea pigs, with a mild mixed inflammatory reaction 1 week after implantation. At 2 weeks a thin fibrous capsule surrounded the discs, with no change in the amount of inflammation. At 4 weeks the disc had disintegrated, but residual polymer was seen within multinucleated giant cells in the episcleral tissue. Granulation tissue and inflammatory responses were mild. Less inflammation and fibrosis occurred in the study eyes, although the pattern of response was similar in the two groups. The inflammatory response to PGLA was markedly less than that to implanted collagen shields, and our findings suggest that PGLA implant is a promising ocular drug delivery system for 5-FU after filtration surgery.

Animals↗
PubMed1994

[Observations of changes in ultrastructure and calcium ion distribution in rabbit heart after various periods of ischemia].

The ultrastructural degenerative changes and calcium ion distribution observed in the rabbit myocardium after various periods of ischemia and 30 minutes after postischemia reperfusion after 30 minutes reperfusion following 15 minutes of ischemia, near complete recovery of substructures is seen, anyhow the number of calcium ion deposits along the sarcolemma are still lower than normal. After 30 and 45 minutes of ischemia, severe degenerative changes in various cellular substructures took place. The sarcolemma of most myocytes became devoid of precipitate. After reperfusion, large calcium ion deposits accumulated in the form of clusters in the mitochondria. It was recognized that the herein described cytochemical calcium ion shifts may be indicative of structural damage bordering irreversibility. After 60 to 75 minutes of ischemia and then postischemia reperfusion, cell damage is observed as disrupted sarcolemma completely devoid of calcium ion deposit, large swollen mitochondria without signs of calcium ions and presence of flocculent precipitates, all signs of terminal impairment of metabolism.

Animals↗
PubMed1993

Pretreatment with pertussis toxin blocks the protective effects of preconditioning: evidence for a G-protein mechanism.

We tested whether a pertussis toxin-sensitive G-protein mediates the protective effects of preconditioning. Thirty-one small (1 kg) rabbits were used. All rabbits experienced 30 min regional myocardial ischaemia followed by 3 h reperfusion. Infarct size was determined by tetrazolium. The percentage of the risk zone which infarcted in controls was 37.4 +/- 4.6%. Preconditioning with a 5 min occlusion followed by 10 min reperfusion prior to the 30 min ischaemic insult protected against infarction (5.2 +/- 2.1% infarction). 25 micrograms/kg pertussis toxin, administered 48 h prior to surgery, blocked G-protein signal transduction as tested by challenge with iv acetylcholine which normally slows the heart. Pertussis toxin treatment had no effect on infarct size in non-preconditioned rabbits (37.6 +/- 4.7% infarction) but blocked protection in preconditioned rabbits (27.3 +/- 4.3% infarction). To test the involvement of G-proteins further in preconditioning, we tested the ability of the M2 agonist carbachol to substitute for ischaemic preconditioning and protect the heart from infarction. Rabbits hearts were excised and perfused with Kreb's buffer. Control animals subjected to 30 min of regional ischaemia and 2 h reperfusion yielded 29.4 +/- 2.9% infarction. Preconditioning with 5 min global ischaemia and 10 min reperfusion prior to the 30 min regional ischaemia significantly protected the isolated heart from infarction (8.41 +/- 3.26% infarction). Carbachol, infused for 5 min at 1 microM concentration, protected the hearts as well as preconditioning, yielding 8.90 +/- 2.08% infarction. We conclude that preconditioning involves a pertussis toxin-sensitive G-protein and that the same G-protein couples to muscarinic M2 receptors.

Animals↗
PubMed1993

Acadesine lowers temporal threshold for the myocardial infarct size limiting effect of preconditioning.

OBJECTIVE: The aim was to test the hypothesis that adenosine A1 receptor activation triggers the cardioprotective effects of ischaemic preconditioning, by determining whether pretreatment with acadesine (5-amino-4-imidazolecarboxamide riboside), an agent which increases cardiac adenosine level during ischaemia, could alter the threshold for preconditioning. METHODS: A branch of the left coronary artery of rabbit hearts was occluded for 30 min and reperfused for 3 h. Infarct size and risk zone size were determined with tetrazolium and fluorescent particles, respectively. Four groups were studied: untreated controls, a group which was pretreated with acadesine (2.5 mg.kg-1.min-1 for 5 min followed by 0.5 mg.kg-1.min-1 for 30 min ending 10 min prior to ischaemia), a group which was preconditioned with 2 min coronary branch occlusion + 10 min reperfusion, and a group which received pretreatment with acadesine prior to 2 min ischaemic preconditioning. RESULTS: Percent infarction, normalised as a percentage of the ischaemic zone, in the 2 min preconditioning group was 43.2(SEM 5.1)% which was not different from control [40.2(3.5)%]. Two minutes of preconditioning was not long enough to confer the cardioprotective effect of preconditioning. Acadesine alone had no protective effect on infarct size [38.5(4.5)%], but acadesine + 2 min preconditioning significantly limited infarction [18.1(2.7)%; p < 0.01]. CONCLUSIONS: Acadesine lowered the threshold for preconditioning in the rabbit to below 2 min of ischaemia. This observation supports the theory that endogenous adenosine which accumulates during the preconditioning ischaemia mediates the protective effects, and that this response can be augmented by acadesine.

Adenosine↗
PubMed1993

Pretreatment with the adenosine A1 selective agonist, 2-chloro-N6-cyclopentyladenosine (CCPA), causes a sustained limitation of infarct size in rabbits.

OBJECTIVE: The highly selective adenosine A1 receptor agonist, 2-chloro-N6-cyclopentyl-adenosine (CCPA), has been shown to be as cardioprotective as ischaemic preconditioning when evaluated with an early staining method using tetrazolium. However, tetrazolium-positive tissue measured 3 h after reperfusion may still overestimate the long term salvage. To test for this possible artefact, a 72 h reperfusion rabbit model of myocardial infarction was used, and infarct size was assessed by histology. METHODS: Myocardial infarction was induced by a 30 min coronary occlusion. Rabbits were assigned to a control group receiving no treatment, pretreatment with 0.125 mg.kg-1 CCPA, or 0.25 mg.kg-1 pretreatment with CCPA (0.25 mg.kg-1) followed by an A1 selective antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) 30 min after reperfusion to reverse the haemodynamic side effects. RESULTS: In the 0.125 mg.kg-1 CCPA group, 30.8(SEM 4.2)% of the ischaemic zone was infarcted, which was significantly less than that seen in the control group [46.5(3.0)%; p < 0.01]. Reversing the side effects of CCPA by giving DPCPX soon after reperfusion did not block the protective effects [26.2(1.9)% infarction; p < 0.01 v control]. CONCLUSIONS: This finding confirms a genuine anti-infarct effect of adenosine A1 receptor stimulation when given prior to the onset of ischaemia. Furthermore blocking the A1 receptors soon after reperfusion reverses the side effects but does not block protection.

Adenosine↗
PubMed1993

[Free radical scavenging and antifatigue activities of Saussurea involucrata polysaccharides].

The polysaccharides of Saussurea involucrata Kar et Kir was first isolated and identified by us. The polysaccharides scavenged superoxide anions by nitroblue tetraazolium colorimetric method with a median scavenging concentration of 22 micrograms.ml-1 and 95% confidence limit was 19.9-24.1 micrograms.ml-1. The polysaccharides inhibited the formation of thiobarbituric acid reaction substance in mouse liver homogenate and its IC50 was 2.3 mg/g fresh liver and 95% confidence limit was 2.05-2.55 mg/g fresh liver. By ip 25 mg.kg-1.d-1 x d in mice, the polysaccharides decreased oxygen consumption by 34.4% and ip same dosage x 6 d, the polysaccharide prolonged swimming time by 1.69-fold.

Animals↗
PubMed1992

Protection of human, rat, and guinea-pig atrial muscle by mioflazine, lidoflazine, and verapamil against the destructive effects of high concentrations of Ca2+.

In right atrial trabeculae from humans and in left atria from rat and guinea-pig hearts, the protective effects of mioflazine, lidoflazine, and verapamil against the accumulation of cellular calcium were investigated. Two consecutive, cumulative increases in the extracellular calcium concentration, [Ca2+]o (1-25 mmol/l), were induced, in between which the muscles were exposed for at least 30 minutes to solvent or drug. When using solvent in the 30-minute interval, the force of contraction was much lower during the second Ca2+ challenge, while the aftercontractions and the increase in passive tension at high [Ca2+]o tended to be larger. These signs of functional impairment were prevented by exposure to mioflazine or lidoflazine (3 mumol/l each) but not to verapamil (3 mumol/l). Muscles were fixed with glutaraldehyde at the end of the second Ca2+ challenge for morphological and cytochemical examination. After solvent treatment, more than half of the cells were severely damaged, showing cellular edema, contraction-band necrosis, mitochondrial swelling, and nuclear pyknosis; the sarcolemma was devoid of calcium deposits, damaged mitochondria contained either large deposits of calcium or flocculent densities, and in some cells, the cytoplasm was filled with calcium deposits. Following exposure to mioflazine and lidoflazine, but not to verapamil, the number of intact cells after the second Ca2+ challenge was not different from time-matched controls (80-90%). Furthermore, the shifts in cellular calcium distribution were prevented with mioflazine and lidoflazine, whereas verapamil was less effective. There were no species differences with respect to either morphological or contractile changes. In conclusion, exposure of atria to high [Ca2+]o induced similar ultrastructural and cytochemical changes as seen after ischemia-reperfusion induced damage. Indeed, under the mentioned conditions the sarcolemma lost its capacity to exclude Ca2+ after a challenge with high [Ca2+]o and allowed excessive Ca2+ entry. The pathway for this extra Ca2+ remains to be elucidated. L-type calcium channels are probably not involved, since verapamil cannot prevent the Ca2+ overload.

Animals↗
PubMed1992

Ischaemic preconditioning is not dependent on neutrophils or glycolytic substrate at reperfusion in rabbit heart.

OBJECTIVE: The aim was to determine whether reperfusion with either neutrophil free reperfusate or perfusate containing only pyruvate as the metabolic substrate would alter the protection against infarction afforded by preconditioning. METHODS: Rabbit hearts (n = 4-14 per group) underwent 30 minutes of regional ischaemia followed by 120 minutes of reperfusion. Blood reperfused groups experienced both ischaemia and reperfusion in situ while Krebs reperfused groups experienced regional ischaemia in situ but were reperfused with Krebs buffer in vitro. In another group, glucose in Krebs buffer was replaced by pyruvate. RESULTS: Preconditioning with 5 minutes regional ischaemia caused smaller infarct size in the blood reperfused hearts: 43.0(SEM 5.4)% v 8.8(4.2)%. In Krebs reperfused hearts, preconditioning caused a similar reduction of infarct size [49.9(2.5)% v 22.9(4.3)%] which was not different from that seen in the blood reperfused hearts. Replacing the glucose in the Krebs buffer by pyruvate also had no effect on infarct size in either the control or the preconditioned hearts [40.9(6.1)% v 11.8(5.2)%]. Histology of the ischaemic zones revealed 59.6(15.0) neutrophils per 10 high power fields in hearts reperfused in situ but only 2.6(0.6) in Krebs reperfused hearts, equal to the numbers in nonischemic blood perfused myocardium [2.8(0.9)]. CONCLUSIONS: The mechanism of preconditioning is not due to attenuation of neutrophil function during reperfusion. Furthermore, substituting pyruvate for glucose in the reperfusate did not prevent the protection against infarction afforded by ischaemic preconditioning.

Animals↗
PubMed1992

Intravenous pretreatment with A1-selective adenosine analogues protects the heart against infarction.

BACKGROUND: Recent data from this laboratory indicate that pretreatment with adenosine can protect the heart against infarction via A1-receptors, but because of systemic hypotension, adenosine had to be given into the coronary circulation. METHODS AND RESULTS: In this study, we tested whether the protection could be achieved by intravenous administration of the A1-selective adenosine agonists N6-(phenyl-2R-isopropyl)-adenosine (PIA) and 2-chloro-N6-cyclopentyladenosine (CCPA). Nine groups of open-chest anesthetized rabbits were subjected to 30 minutes of regional coronary ischemia and 3 hours of reperfusion. Infarct size was determined by tetrazolium staining. Control hearts receiving no treatment had 38 +/- 4% of the risk zone infarcted. Preconditioning with 5 minutes of ischemia and 10 minutes of reperfusion before ischemia limited the infarct to 8 +/- 4%. Intravenous PIA 15 minutes before 30-minute ischemia also limited infarct size to 6 +/- 2% at the highest dose. CCPA offered similar protection. When the PIA was given at reperfusion, infarct size was 46 +/- 6%, indicating that receptor activation must precede ischemia to protect. Pretreatment with CGS 21680, a selective A2-receptor agonist, caused identical hypotension but failed to limit infarct size (43 +/- 3%), indicating again that the A1-receptor is involved. When rabbits pretreated with PIA were paced at 220 beats per minutes, PIA still limited infarct size (16 +/- 4%), indicating that protection was not the result of bradycardia. CONCLUSIONS: These results indicate that stimulation of adenosine A1-receptors causes the heart to become resistant to ischemia and that this protection can be achieved with intravenous administration of A1-selective agents.

Adenosine↗
PubMed1992

Cyclooxygenase products are not involved in the protection against myocardial infarction afforded by preconditioning in rabbit. Cyclooxygenase pathway's involvement in preconditioning.

The mechanism whereby preconditioning with a transient period of ischemia renders the heart resistant to infarction from a subsequent ischemic insult is unknown. The purpose of this study was to determine whether cyclooxygenase pathways are involved in preconditioning's protection. Two inhibitors of that pathway, meclofenamate (MEC) and aspirin (ASP), were test in an in situ and a blood perfused isolated heart model, respectively. Preconditioning was achieved with 5 minute ischemia and 10 minutes reperfusion. All in situ hearts underwent 30 minute ischemia followed by 180 minute reperfusion, while the isolated hearts experienced 45 minute ischemia plus 120 minute reperfusion. Infarct size was measured with TTC stain. In the in situ model, 39.9% +/- 4.2% of the ischemic zone was infarcted in control hearts but only 8.8% +/- 2.2% in preconditioning hearts. Pretreatment with MEC (5 mg/Kg) caused no alteration of infarct size in either non preconditioned (34.3% +/- 8.3%) or preconditioned hearts (6.7% +/- 3.3%). In isolated hearts, 45 minute ischemia caused 31.0% +/- 5.9% of the ischemic zone to be infarcted in control hearts and only 5.4% +/- 2.2% in preconditioned hearts. Pretreatment with ASP (1 mg/Kg) failed to affect infarct size in either non preconditioned (35.7% +/- 3.7%) or preconditioned hearts (10.2% +/- 1.9%). The data indicate that cyclooxygenase pathways are not involved in the preconditioning's protection.

Analysis of Variance↗