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PubMed1988

Rate of reperfusion blood flow modulates reperfusion injury in skeletal muscle.

The mechanisms of ischemia-reperfusion (I-R) injury in skeletal muscle remain controversial. We investigated the effect of the rate of reperfusion blood flow on I-R injury in an isolated in vivo canine gracilis muscle model in six anesthetized dogs. In all animals, both gracilis muscles were subjected to 6 hr of ischemia followed by 1 hr of reperfusion. During reperfusion, one gracilis artery was partially occluded to limit the rate of reperfusion blood flow to its preischemic rate (limited reperfusion, LR), while the contralateral artery was allowed to perfuse freely at a normal rate (normal reperfusion, NR). Muscle injury was quantified by histochemical staining (triphenyltetrazolium chloride, TTC) with computerized planimetry of the infarct size, and by spectrophotometric determination of technetium-99m pyrophosphate uptake. Endothelial permeability was quantified by measurement of gracilis muscle weight gain and 125I-albumin radioactivity after intravenous injection. Results are presented as the means +/- SEM, and differences are considered to be statistically significant if P less than 0.05 by Student's t test for paired data. LR resulted in significantly less blood flow (9.7 +/- 1.7 cc/min/100 g) when compared to NR (55.7 +/- 11.6 cc/min/100 g). I-R injury was significantly reduced by LR as evidenced by a decrease in TTC infarct size from 41 +/- 7% to 11 +/- 5%, and a decrease in technetium-99m pyrophosphate uptake from 512 +/- 20 to 163 +/- 44 X 10(3) counts/min/g. LR also significantly decreased the postreperfusion edema formation as evidenced by a reduction in the muscle weight gain from 27 +/- 6 to 9 +/- 1 g, and a reduction in the 125I-albumin radioactivity from 45 +/- 14 to 32 +/- 8 counts/min/g. These data suggest that the hyperemic rate of reperfusion blood flow is a significant factor in the pathophysiology of postreperfusion edema and that clinical control of reperfusion injury in skeletal muscle may be achieved by limiting the rate of reperfusion blood flow.

Animals↗

PubMed1987

Myocardial thallium-201 kinetics and regional flow alterations with 3 hours of coronary occlusion and either rapid reperfusion through a totally patent vessel or slow reperfusion through a critical stenosis.

Myocardial thallium-201 kinetics and regional blood flow alterations were examined in a canine model using 3 hours of coronary occlusion and different methods of reperfusion. Group I comprised 10 dogs undergoing a 3 hour left anterior descending artery occlusion and no reperfusion. Group II comprised seven dogs undergoing 3 hours of left anterior descending artery occlusion and rapid reperfusion through a totally patent vessel. Group III comprised 10 dogs undergoing 3 hours of left anterior descending artery occlusion and slow reperfusion through a residual stenosis. All dogs received 1.5 mCi of thallium-201 after 40 minutes of coronary occlusion. During occlusion and 2 hours of reperfusion, serial hemodynamic, blood flow and myocardial thallium-201 activity measurements were made. The relative thallium-201 gradient (normal zone minus ischemic zone activity when initial normal activity is expressed as 100%) during left anterior descending coronary occlusion was similar in all groups. Group I, 87 +/- 3%; Group II, 78 +/- 6%; Group III, 83 +/- 6% (p = NS). After 2 hours of either method of reperfusion, the final relative gradient had decreased to a similar level (Group II, 51 +/- 9%; Group III, 42 +/- 6%). These values were not significantly different from the final relative thallium-201 gradient seen in dogs undergoing a sustained 3 hour occlusion (Group I, 55 +/- 5%). After 2 hours of reperfusion, both methods of reflow were associated with similar degrees of "no reflow." Transmural flows in the central ischemic zone were 89 +/- 10% of normal in Group II and 71 +/- 6% of normal in Group III after reperfusion, with both flows substantially higher than the relative thallium-201 activities in these dogs. Infarct size (percent of left ventricle) determined with triphenyltetrazolium chloride was similar in all groups (Group I, 24 +/- 4%; Group II, 29 +/- 4%; Group III, 25 +/- 4%). Thus, in this experimental canine model, 3 hours of coronary occlusion followed by either rapid reperfusion through a totally patent vessel or slow reperfusion through a critical stenosis resulted in little delayed thallium-201 redistribution or myocardial salvage as assessed histologically, despite significant recovery of regional flow.

Animals↗

PubMed1988

Measurement of superoxide-derived free radicals in the reperfused heart. Evidence for a free radical mechanism of reperfusion injury.

There has been considerable controversy regarding the role of oxygen free radicals as important mediators of cell damage in reperfused myocardium. This controversy regards whether superoxide and hydroxyl free radicals are generated on reperfusion and if these radicals actually cause impaired contractile function. In this study, EPR studies using the spin trap 5,5-dimethyl-1-pyroline-n-oxide (DMPO) demonstrate the formation of .OH and R. free radicals in the reperfused heart. EPR signals of DMPO-OH, aN = aH = 14.9 G, and DMPO-R aN = 15.8 G aH = 22.8 G are observed, with peak concentrations during the first minute of reperfusion. It is demonstrated that these radicals are derived from .O2- since reperfusion in the presence of enzymatically active recombinant human superoxide dismutase markedly reduced the formation of these signals while inactive recombinant human superoxide dismutase had no effect. On reperfusion with perfusate pretreated to remove adventitial iron, the concentration of the DMPO-OH signal was increased 2-fold and a 4-fold decrease in the DMPO-R signal was observed demonstrating that iron-mediated Fenton chemistry occurs. Hearts reperfused with recombinant human superoxide dismutase exhibited improved contractile function in parallel with the marked reduction in measured free radicals. In order to determine if the reperfusion free radical burst results in impaired contractile function, simultaneous measurements of free radical generation and contractile function were performed. A direct relationship between free radical generation and subsequent impaired contractile function was observed. These studies suggest that superoxide derived .OH and R. free radicals are generated in the reperfused heart via Fenton chemistry. These radicals appear to be key mediators of myocardial reperfusion injury.

Animals↗

PubMed1986

Reperfusion conditions: critical importance of total ventricular decompression during regional reperfusion.

This study tests the hypothesis that failure to minimize left ventricular oxygen demands by venting during reperfusion diminishes recovery after controlled blood cardioplegic reperfusion. Of 25 dogs undergoing 2 hours of left anterior descending coronary occlusion, nine were reperfused with normal blood without bypass and five were reperfused with normal blood during total vented bypass. Eleven other dogs were reperfused with aspartate-glutamate-enriched, diltiazem-supplemented blood cardioplegic solution for 20 minutes during cardiopulmonary bypass; the left ventricle was decompressed by venting in only five of them. Regional systolic shortening was measured by ultrasonic crystals and myocardial damage estimated from triphenyltetrazolium chloride staining. All segments developed systolic bulging during ischemia (-23% systolic shortening, p less than 0.05), with no segmental recovery after reperfusion with normal blood without bypass (-27% systolic shortening, p less than 0.05) and negligible recovery following reperfusion with normal blood during total vented bypass (6 +/- 2%, p less than 0.05). In contrast, there was immediate recovery of regional contractility (+ 53% systolic shortening, p less than 0.05) in bypassed hearts reperfused with aspartate-glutamate-enriched, diltiazem-supplemented blood cardioplegic solution when venting was used and triphenyltetrazolium chloride nonstaining fell from 43% to 12% (p less than 0.05). Conversely, there was no postischemic recovery (-8% systolic shortening, p less than 0.05) when the same blood cardioplegic reperfusate was given over a comparable time without venting; triphenyltetrazolium chloride damage increased to 25% (p less than 0.05). Minimizing O2 demands by left ventricular decompression with venting during blood cardioplegic reperfusion is essential to ensure immediate functional recovery and limit histochemical damage.

Animals↗

PubMed2005

Microvascular oxygenation and oxidative stress during postischemic reperfusion. PO2, ROS, and NO during reperfusion.

Increased formation of ROS on reperfusion after ischemia underlies ischemia reperfusion (I/R) damage. We measured, in real time, both oxygen tension in microvessels and tissue and oxidant stress during postischemic reperfusion in hamster cheek pouch microcirculation. We measured PO2 by using phosphorescence quenching microscopy and oxygen radical species (ROS) production in the systemic blood. We evaluated the effects of a NOS inhibitor (L-NMMA) and superoxide dismutase (SOD) on the oxidative stress during reperfusion. Microvascular injury was assessed by measuring diameter change, the perfused capillary length (PCL), and leukocyte adhesion. Our findings demonstrate that early reperfusion is characterized by low concentration of oxygen linked to increased production of ROS. After this initial transience in arterioles, the oxygen tension and production of ROS return to normal after reperfusion, while the blood flow and capillary perfusion decrease. The early increased ROS production, in turn, may impair oxygen consumption by endothelial cells, thus further promoting activation of oxygen to ROS. This event is substantiated by the finding that treatment with SOD maintains ROS at normal levels, which, in turn, should be effective to increase the production of endothelial NO. Conversely, a decrease in NO levels led to decreased ROS production during early reperfusion, which increased later during reperfusion, ultimately causing vasoconstriction and greatly increasing venular leukocyte adhesion on postcapillary venules during hypoxic conditions. Therefore, low-flow hypoxia is primarily responsible for vascular endothelial damage during reperfusion through changes in ROS and NO production.

Animals↗

PubMed2006

Nitroglycerin reperfusion reduces ischemia-reperfusion injury in non-heart-beating donor lungs.

BACKGROUND: Lung transplantation is severely limited by an inadequate supply of lungs from brain-dead donors. A potential solution is use of lungs from non-heart-beating donors (NHBDs) with retrieval at intervals after circulatory arrest and death. A warm ischemic period with concomitant reperfusion injury is a major limiting factor in the transplantation of lungs retrieved from NHBDs. We hypothesized that the administration of the nitric oxide-donor nitroglycerin to lungs from NHBDs would reduce ischemia-reperfusion injury by activation of guanylate cyclase to form guanosine 3',5'-cyclic monophosphate (cGMP). METHODS: An in situ isolated perfused rat lung model was used. Lungs were retrieved from rats at varying intervals after circulatory arrest and death. Lungs were either ventilated with O(2) in situ or not ventilated. Lungs were reperfused at intervals after death with Earle's solution with or without nitroglycerin (0.1 mg/ml). Lung ischemia-reperfusion injury was assessed by capillary filtration coefficient, wet-to-dry lung weight ratio, and pulmonary hemodynamics. Tissue levels of adenine nucleotides and cGMP concentrations were measured by high-performance liquid chromatography and enzyme immunoassay, respectively. RESULTS: Reperfusion with nitroglycerin decreased capillary filtration coefficient compared with reperfusion without nitroglycerin at all post-mortem ischemic times, irrespective of pre-harvest ventilation. cGMP levels increased significantly with nitroglycerin-reperfusion and attenuated decreases in high-energy adenine nucleotides. CONCLUSIONS: Reperfusion of lungs with nitroglycerin may facilitate safe lung transplantation from NHBDs by reducing capillary leak after reperfusion.

Animals↗

PubMed1989

Reperfusion of infarcting myocardium: benefit of surgical reperfusion in a chronic model.

Surgical reperfusion of experimental infarction leads to improved recovery of regional function compared with medical reperfusion, but sustained myocardial salvage has not been demonstrated. Twenty-two dogs were subjected to two hours of anterior descending occlusion and divided into three groups: group P (n = 7), no reperfusion; group M (n = 8), medical reperfusion; and group S (n = 7), controlled surgical reperfusion. Ischemia caused systolic bulging (-36% of control systolic shortening, p less than 0.01) and decreased regional work (9% of control pressure-length loop area, p less than 0.05). Thirty minutes after reperfusion group M had persistent systolic bulging (-9% of control systolic shortening) and decreased regional work (9% of control pressure-length loop area), whereas group S had +17% of control systolic shortening and 33% of control pressure-length loop area. After 1 week, regional function improved in all three groups (percent of control systolic shortening: group P, 26%; group M, 19%; group S, 52%), but systolic shortening was significantly better in group S (p less than 0.05 versus group M). Surgical reperfusion also resulted in one half of the eventual myocardial necrosis found in the other groups (group P, 45% of area at risk; group M, 38%; group S, 19%; p less than 0.05, group S versus group P or M). In this model, medical reperfusion offered no demonstrable benefit, whereas controlled surgical reperfusion led to a sustained (1 week) improvement in regional function and significant myocardial salvage.

Animals↗

PubMed2001

Usefulness of reperfusion ventricular arrhythmias in non-invasive prediction of early reperfusion and sustained coronary artery patency in acute myocardial infarction.

BACKGROUND: Established tenets of occurrence of reperfusion ventricular arrhythmias in acute myocardial infarction (AMI) do not provide insight into the timing of achieving reperfusion or whether coronary artery patency is sustained. We assessed the significance of ventricular arrhythmias in the non-invasive prediction of timely reperfusion and sustained restoration of coronary patency after thrombolysis in patients with AMI. METHODS: 24-hour Holter monitors were placed in 163 patients with an AMI before administration of thrombolytic therapy. Patients were classified into 3 groups of early (within 2 hours) or late reperfusion, or no-reperfusion, according with clinical and continuous ST-segment electrocardiographic criteria. Ventricular fibrillation, ventricular tachycardia (VT) and accelerated idioventricular rhythm (AIVR) were also categorized as having occurred early (within the first 2 hours) or late (after the first 2-hour period). Angiographic confirmation of coronary patency was determined 2 to 6 days after AMI. RESULTS: Early reperfusion was predicted by early sustained AIVR in 86% of patients and early non-sustained AIVR in 62.5% of patients, with sensitivity 38% and 77%, and specificity 96% and 69%, respectively; p<0.0001. Late non-sustained AIVR was commonly seen in early and late reperfused patients (92-97%) as well as in non-reperfused patients (74%). Sustained coronary patency was predicted by early sustained AIVR in 93% of patients, as well as by early non-sustained AIVR in 86% of patients and late non-sustained AIVR in 79% of patients, with sensitivity 22%, 55% and 94%, and specificity 95%, 71% and 18%, respectively; p<0.05. CONCLUSION: Only the occurrence of sustained AIVR, and probably early non-sustained AIVR convey useful information about both early reperfusion and sustained coronary artery patency. The absence of AIVR does not preclude successful thrombolysis.

Adult↗

PubMed2006

Beneficial effects of supplemental nitric oxide donor given during reperfusion period in reperfusion-induced lung injury.

BACKGROUND: Reperfusion injury is a perplexing cause of early graft failure after lung transplantation and today we know that reperfusion may be more harmful to tissues than the preceding ischemia. We hypothesized that administration of the nitric oxide donor nitroglycerin (NTG) during flush perfusion and reperfusion periods would ameliorate reperfusion-induced lung injury. METHODS: Using an IN SITU normothermic ischemic lung rabbit model, three groups were studied (n = 7/group): (1) NTG given during flush perfusion (ischemia group); (2) NTG given in the flush perfusion and the reperfusion period (reperfusion group); and (3) no NTG (control group). All groups were flushed with low potassium dextran glucose solution. Blood gas analysis, tissue nitrite (nitric oxide metabolite) level analysis, bronchoalveolar lavage (BAL) fluid examination and morphological examinations were performed. RESULTS: Compared with the ischemia group, the reperfusion group had significantly improved arterial oxygenation (318 +/- 31.4 mmHg vs. 180 +/- 14.7 mmHg, P < 0.05), decreased BAL fluid neutrophil percentage (21 +/- 1.9 % vs. 30 +/- 5.6 %, P < 0.05), increased tissue nitrite level (32.55 +/- 4.12 nmol/g vs. 27.81 +/- 1.05 nmol/g, P < 0.05), and decreased tissue histopathological lesion scores (0.42 +/- 0.53 vs. 1.14 +/- 0.37, P < 0.05). CONCLUSIONS: This study suggests that nitric oxide donors supplemented during flush perfusion and reperfusion have more beneficial effects on lung functions against reperfusion injury than any other treatment modalities during IN SITU normothermic ischemic lung model.

Analysis of Variance↗

PubMed2000

Calcium antagonist protects the myocardium from reperfusion injury by interfering with mechanisms directly related to reperfusion: an experimental study with the ultrashort-acting calcium antagonist clevidipine.

To test the hypothesis that calcium antagonists protect the myocardium from reperfusion-induced damage by local myocardial mechanisms just at the time of reperfusion, the myocardioprotective effects of the dihydropyridine clevidipine were investigated, taking advantage of its ultrashort-acting effect. Pigs were subjected to 45 min of myocardial ischemia by occlusion of the left anterior descending coronary artery followed by 4 h of reperfusion. Either clevidipine (0.3 nmol/kg/min, n = 6) or the corresponding amount of vehicle (n = 6) was administered to the ischemic myocardium by retrograde coronary venous infusion over a 30-min period starting 10 min before reperfusion. Hemodynamic variables (heart rate, left ventricular systolic and end-diastolic pressure, max dP/dt, and mean arterial blood pressure) as well as coronary blood flow were measured throughout the experiment. At the end of reperfusion, the area at risk (percentage of left ventricle) was determined by infusion of Evans blue into the left atrium, and the infarct size, by triphenyl tetrazolium chloride (TTC) staining. The plasma level of endothelin-like immunoreactivity (ET-LI) was analyzed in blood from the aorta and the anterior coronary vein before ischemia and at different times during reperfusion. The area at risk was similar in the vehicle and the clevidipine groups. The infarct size, expressed as a percentage of the area at risk, was 80 +/- 9.2 in the vehicle group, whereas it was significantly reduced to 51 +/- 9.2% in the clevidipine group (p < 0.01). Clevidipine did not influence any of the hemodynamic variables measured throughout the study. A nonsignificant trend toward decreased total ET-LI overflow during 4-h reperfusion was observed in the clevidipine-treated pigs compared with vehicle-treated ones (5.3 +/- 1.4 vs. 7.1 +/- 3.4 pmol). These results demonstrate that, in this model of ischemia/reperfusion-induced myocardial infarction, clevidipine reduced the damage to the myocardium when given in association with reperfusion. The local administration of the compound together with its short blood half-life shows that clevidipine reduces reperfusion-induced damage by local mechanisms within the ischemic tissue rather than by peripheral mechanisms.

Animals↗

PubMed1989

Reperfused-viable and reperfused-infarcted myocardium: differentiation with in vivo P-31 MR spectroscopy.

The ability of in vivo phosphorus-31 magnetic resonance (MR) spectroscopy to permit accurate distinction between reperfused-viable and reperfused-infarcted myocardium was examined in a canine model of acute coronary occlusion. In vivo myocardial pH and phosphocreatine, adenosine triphosphate, and inorganic phosphate levels were measured at baseline and for the first 90 minutes after reperfusion of a total coronary artery occlusion producing either predominantly viable (nine animals) or infarcted (nine animals) myocardium in the region of metabolic study. Myocardial viability was assessed in each animal by means of postmortem triphenyltetrazolium chloride staining. Tissue was characterized from the in vivo P-31 MR data by means of logistic regression analysis. The accuracy of using the P-31 MR data for distinguishing reperfused-viable from reperfused-infarcted myocardium was 100% (69 of 69 data points, 18 of 18 animals). Results of the logistic regression procedure indicated that phosphocreatine was the metabolic variable enabling most effective separation of reperfused-viable and reperfused-infarcted myocardium. Thus, metabolic data obtained with P-31 MR spectroscopy permit effective separation of reperfused-viable from reperfused-infarcted myocardium.

Adenosine Triphosphate↗

PubMedDate not supplied

Cardioprotective effect of edaravone against ischaemia-reperfusion injury in the rabbit heart before, during and after reperfusion treatment.

The free radical scavenger edaravone is able to stimulate prostacyclin release and inhibit the lipoxygenase pathway in the arachidonic acid cascade. The effect of edaravone administration on myocardial damage in rabbit hearts subjected to ischaemia-reperfusion was examined at different times relative to reperfusion. All rabbits underwent sustained coronary artery occlusion for 30 min followed by 3 h of reperfusion. Rabbits were divided into the following groups: control; early (3 mg/kg edaravone IV 10 min before reperfusion); immediate (3 mg/kg edaravone IV immediately after the start of reperfusion); and late (3, 6 or 10 mg/kg edaravone IV 5 min after the start of reperfusion). Single bolus administration of edaravone 10 min before reperfusion or immediately upon initiation of reperfusion appears to be associated with reductions in infarction size and the percentage of apoptotic cells, but treatment with edaravone 5 min after initiation of reperfusion does not appear to have this protective effect.

Animals↗

PubMed1992

Release of endothelin during reperfusion of ischemic myocardium. ET-1 release from reperfused heart.

Endothelin, the most potent endothelium-derived vasoconstrictor, was found to be released from the isolated ischemic rat heart after a prolonged period of reperfusion. No endothelin release was observed up to 1 hour of reperfusion following 30 minutes of global ischemic arrest. Although most of the endothelin release occurred as a burst after 1 hour of reperfusion, the endothelin release increased progressively at a slower rate up to 2 hours of reperfusion. The calcium slow channel blocker, nifedipine, and the phospholipase inhibitor, mepacrine, but not the free radical scavengers, superoxide dismutase (SOD) and catalase, prevented the endothelin release from the heart. Unlike endothelin release that did not occur until after 1 hour of reperfusion, lipid peroxidation assessed by thiobarbituric acid reactive product formation, and cellular injury as monitored by creatine kinase (CK) release, occurred upon reperfusion, and increased progressively with the duration of reperfusion. All the interventions including nifedipine, mepacrine, and SOD plus catalase, prevented the lipid peroxidation and CK release significantly. Coronary flow was reduced significantly after 1 hour of reperfusion, when endothelin release occurred, an event that also coincided with myocardial endothelial injury as assessed by transmission electron microscopy. These results indicate that endothelin is released only after a prolonged period of reperfusion, and the release process seems to be controlled by calcium and phospholipase, but not by free radicals.

Analysis of Variance↗

PubMed1991

[Collins blood diluting reperfusion--an effective measure of controlled reperfusion for the heart hypothermically preserved for 24 hours in modified Collins solution].

Controlled reperfusion is assumed to provide an appropriate environment surrounding the ischemic cardiac tissue at the initial reperfusion phase. Hence, this procedure might play a key role in resuscitating the long term preserved hearts. This study was designed to assess the efficacy of the newly devised reperfusion method; namely Collins Blood Diluting Reperfusion (CBDR), for those hearts subjected to 24-hours cold (4 degrees C) storage in modified Collins (MC) solution. Coronary reperfusion is commenced with the MC solution, and the oxygenated blood is successively added to dilute this perfusate with gradual rewarming under controlled perfusion pressure. Initial reperfusate, therefore, is supposed to be a blood cardioplegia with low Ca2+ and high Mg2+ content. During this procedure, any difference in the ionic composition between the storage solution and the reperfusate is completely abolished and myocardium is free from hastiness of temperature elevation. Using an isolated isovolum contracting heart prepared with an ex vivo apparatus incorporating a support dog, each heart was reperfused by unmodified blood (Group I: n = 7) or CBDR method (Group II: n = 10) under equally controlled low perfusion pressure. There was no difference in the myocardial creatine phosphate level between the 2 groups. However, the adenosine triphosphate content, which had been depleted to 30% of the preischemic level during the 24-hour preservation period, was restored to 52.0% after CBDR procedure (p less than 0.01) and consequently to 57.9% of the control at 60 minutes after reperfusion. Group I showed a significantly lower repletion effect at this phase (41.2% control; p less than 0.05 versus group II).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1994

Nucleoside trapping during reperfusion prevents ventricular dysfunction, "stunning," in absence of adenosine. Possible separation between ischemic and reperfusion injury.

A previous study has shown that endogenous adenosine trapping during ischemia (by blocking adenine nucleoside transport and inhibiting adenosine breakdown) prevents myocardial stunning. In this study, we tested the hypothesis that delay of administration of inhibitors until reperfusion would similarly prevent myocardial stunning in the absence of entrapped adenosine. In both studies, a selective nucleoside transport blocker, p-nitrobenzyl-thioinosine, was used in combination with a potent adenosine deaminase inhibitor, erythro-9-(2-hydroxy-3-nonyl)adenine, to entrap adenosine (preischemic treatment) or inosine (postischemic treatment) in an in vivo canine model of reversible global ischemia. Twenty-five anesthetized adult dogs were instrumented (by sonomicrometry) to monitor left ventricular performance from the relationship between stroke work and end-diastolic length as a sensitive and load-independent index of contractility. Hearts of animals supported by cardiopulmonary bypass were subjected to 30 minutes of normothermic global ischemia and 60 minutes of reperfusion. Saline solution containing the pharmacologic agents were infused into the bypass circuit before ischemia (group 1) or during reperfusion (group 2). Control group (group 3) received saline before and after ischemia. Myocardial biopsy specimens were obtained before, during, and after ischemia, and levels of adenine nucleotides, nucleosides, oxypurines, and the oxidized form of nicotinamide-adenine dinucleotide were determined. Left ventricular contractility fully recovered within 30 minutes of reperfusion in the groups treated with erythro-9-(2-hydroxy-3-nonyl)adenine and p-nitrobenzyl-thioinosine (p < 0.05 versus control group). Myocardial adenosine triphosphate was depleted by 50% in all groups at the end of ischemia. Adenosine triphosphate recovered during reperfusion only in the group that was treated with inhibitors before ischemia (group 1). At the end of ischemia, adenosine levels were low (< 10% of total nucleosides) in the control group (group 3) and in the group treated only after ischemia (group 2). A high level of adenosine (> 90% of total nucleosides) was present in group 1. We infer that selective pharmacologic blockade of nucleoside transport, only after ischemic injury, accelerated functional recovery during reperfusion, even without trapping of endogenous adenosine during ischemia and without adenosine triphosphate recovery during reperfusion. Recovery of myocardial adenosine triphosphate required preischemic treatment and adenosine entrapment during ischemia and reperfusion. Therefore, nucleoside trapping may be used to prevent reperfusion-mediated injury after reversible ischemic injury.

Adenine↗

PubMed1993

[Serial changes in QT interval during acute myocardial infarction: comparison of QT interval changes of reperfused cases and non-reperfused cases].

The serial changes in QT intervals during the course of acute myocardial infarction are of interest from the standpoint of the electrocardiogram itself, the development of ventricular tachyarrhythmias, residual cardiac function, and the prognosis of the patients. However, only sparse literature has dealt with this issue because it is difficult to obtain ECGs for analysis, and multiple factors influence the QT interval including the degree of reperfusion, electrolyte imbalance, hemodynamic changes and drugs which alter the QT interval. The ECGs of patients with acute myocardial infarction who underwent reperfusion therapy were analyzed: Sixteen consecutive patients were enrolled in this study, 9 with TIMI grade II and III (TIMI: the thrombolysis in myocardial infarction study group criteria) and 7 with TIMI grade 0, myocardial infarction with (9) and without (7) reperfusion. Patients with collaterals, TIMI grade I, hypertrophic cardiomyopathy, electrolyte imbalance, Ia antiarrhythmic drugs, beta adrenoreceptor blockades, atrial fibrillation, and intraventricular conduction disturbances were excluded from the study. Serial ECG recordings were performed at 3, 6, 9, 12, 24, 48, and 72 hours after the onset of myocardial infarction. One week after and one month after the onset, the ECGs were recorded. Patients who exhibited reocclusion on their arteriograms in the chronic phase were also excluded from the study. Measurements of the QT intervals were performed at the ischemic lead (II in the standard limb lead in inferior infarction and V2 in anteroseptal infarction), and values were averaged from 5 consecutive QRS complexes according to Lepeschkin's method and corrected using Bazett's method. The left ventricular ejection fraction (LVEF) and percent fractional shortening (FS) in segments 2, 3, 4 or 5 were calculated from the ventriculogram in the chronic phase. The QT interval revealed a lengthening with its peak within 12 hours after the onset and it became shorter thereafter in reperfused patients. In patients without reperfusion, the QT interval became progressively prolonged without showing a peak point, up to one month. LVEF and FS were significantly higher values in patients with reperfusion than in those without reperfusion. In conclusion, in patients with reperfusion, the QT interval was transiently prolonged and later shortened with improved LVEF and FS than in patients without reperfusion.

Adult↗

PubMed1997

Na(+)-H+ exchange inhibition at reperfusion is cardioprotective during myocardial ischemia-reperfusion; 31P NMR studies.

To help resolve the controversy as to whether or not Na(+)-H+ exchange is functioning during reperfusion of the ischemic myocardium we assessed the effects of dimethylamiloride (DMA, an amiloride analogue possessing selectivity for inhibition of the Na(+)-H+ exchanger) on cardiac function and intracellular pH during ischemia-reperfusion. Studies were performed in the presence of bicarbonate (modified Krebs-Henseleit buffer) or in the nominal absence of bicarbonate (HEPES buffer) in order to determine if similar cardioprotection and effects on intracellular pH were observed in the presence and absence of bicarbonate dependent transport processes. Isovolumic rat hearts were perfused in the Langendorff mode at a constant pressure of 80 mm Hg and subjected to 28 min total global ischemia at 37 degrees C. Intracellular pH was determined from the pH dependent shift of the inorganic phosphate peak in 31P nuclear magnetic resonance spectra. DMA (20 microM) was infused for either 2.5 min before ischemia, for the initial 5 min of reperfusion, or at both time intervals. DMA had no effect on the intracellular pH during ischemia. Intracellular pH returned to pre-ischemic levels within 2.5 min of reperfusion in bicarbonate buffer. This normalization of pH was slower in HEPES perfusate. In both bicarbonate and HEPES perfused hearts all drug dosing regimens caused a significant increase in the recovery of mechanical function after reperfusion and slowed the recovery of intracellular pH during reperfusion. These results suggest that the Na(+)-H+ exchanger is activated during reperfusion of the ischemic myocardium, that this activation of the exchanger contributes to ischemia-reperfusion induced cardiac dysfunction and that administration of an inhibitor of Na(+)-H+ exchange at reperfusion significantly attenuates the deleterious effects of exchanger activation.

Amiloride↗

PubMed1996

Synergic effects of NO and oxygen free radicals in the injury of ischemia-reperfused myocardium--ESR studies on NO free radicals generated from ischemia-reperfused myocardium.

The ESR signal of NO bound to hemoglobin was detected during the ischemia-reperfusion of myocardium with low temperature ESR technique, and the synergic effects of NO and oxygen free radicals in the injury of the process were studied with this technique. Oxygen free radicals and NO bound to beta-subunit of hemoglobin (beta-NO complex) could be detected simultaneously in the ischemia-reperfused myocardium. Those signals could not be detected from the normal myocardium even in the presence of L-arginine. However, those signals could be detected and were dose-dependent with L-arginine in the ischemia-reperfused myocardiums and the signal could be suppressed with the inhibitor of NO synthetase, NG-nitro-L-arginine methylester (NAME). Measurement of the activities of lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary artery effluent of ischemia-reperfused heart showed that L-arginine at lower concentration (< 1 mmol/L) could protect the heart form the ischemia-reperfusion injury but at higher concentration aggravate the injury. Addition of NAME to the reperfusion solution could also protect the myocardium. Addition of xanthine (X)/xanthine oxidase (XO) or Fe2+/H2O2 to the reperfusion solution increased the production of NO and oxygen free radicals and the ischemia-reperfused injury simultaneously. Addition of superoxide dismutase (SOD) and catalase decreased the production of NO and oxygen free radicals and the ischemia-reperfusion injury.

Animals↗