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Results for “Reperfusion”

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PubMed1989

Marked reduction of free radical generation and contractile dysfunction by antioxidant therapy begun at the time of reperfusion. Evidence that myocardial "stunning" is a manifestation of reperfusion injury.

Recent evidence suggests that postischemic myocardial dysfunction ("stunning") may be mediated by oxygen free radicals, but the exact time window during which the critical radical-mediated damage develops remains unknown. Furthermore, the evidence for the oxyradical hypothesis is indirect and, therefore, inconclusive. Thus, the potent and cell-permeable antioxidant N-(2-mercaptopropionyl)-glycine (MPG) was administered as an intra-coronary infusion (8 mg/kg/hr) to three groups of open-chest dogs undergoing a 15-minute coronary occlusion followed by 4 hours of reperfusion. In group I (n = 8), the infusion of MPG was started 15 minutes before occlusion and ended 2 hours after reperfusion; in group II (n = 9), MPG was started 1 minute before reperfusion and ended 2 hours thereafter; in group III (n = 10), MPG was started 1 minute after reperfusion and ended 2 hours and 15 minutes thereafter. Control dogs (group IV) (n = 10) received vehicle. Recovery of contractile function (assessed as systolic wall thickening) was equivalent in groups I and II, and in both groups it was substantially greater than in controls (p less than 0.005 at 4 hours). In contrast, in group III recovery of function was indistinguishable from controls. To determine whether the protection afforded by MPG was due to inhibition of free radical reactions, myocardial production of free radicals was directly assessed by intracoronary infusion of the spin trap alpha-phenyl N-tert-butyl nitrone (PBN). In control dogs (group VII, n = 6), radical adducts of PBN were released in the coronary venous blood after reperfusion, with a burst occurring in the first 5 minutes. MPG given as in group II (group V, n = 5) markedly suppressed myocardial production of PBN adducts (delta = -98% over 3 hours, p less than 0.01 vs. controls); this effect was evident immediately after reperfusion. MPG given as in group III (group VI, n = 5) also suppressed PBN adduct production (delta = -83% over 3 hours, p less than 0.025 vs. controls), but this effect was delayed. Hence, the radicals important in myocardial stunning appear to be those generated immediately after reperfusion. In vitro studies demonstrated that MPG is an exceptionally powerful scavenger of .OH (rate constant = 8.1 x 10(9) M-1 sec-1 by pulse radiolysis) but has no significant effect on .O2- (rate constant less than 10(3) M-1 sec-1), H2O2 (rate constant = 1.6 M-1 sec-1), or non-.OH-initiated lipid peroxidation, suggesting that removal of .OH is the major mechanism of the beneficial effects of MPG.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMedDate not supplied

Ischemia and reperfusion injury in isolated rat heart: effect of reperfusion duration on xanthine oxidase, lipid peroxidation, and enzyme antioxidant systems in myocardium.

The aim of this work was to assess the catalytic activity of xanthine oxidase, the level of lipid peroxides and enzymic antioxidant systems in isolated rat heart muscle subjected to a globally partial ischemia followed by varying durations of reperfusion. After 40 min of globally partial ischemia (residual perfusion flow rate: 0.1 ml/min), four different durations of reperfusion were investigated (0, 20, 40, and 60 min). After each experimental ischemia/reperfusion sequence, the heart was frozen in liquid nitrogen. Lipid peroxides were assayed in the cardiac homogenate and the catalytic activity of xanthine oxidase and enzymic antioxidant systems (glutathione peroxidase, superoxide dismutase and catalase) were determined in the centrifuged supernatant. In the different experimental protocols studied in this work, there was no significant increase in the activity of cardiac xanthine oxidase or in the level of lipid peroxides when compared to the non reperfused or to the continuously perfused hearts. Indeed, enzymic antioxidant systems were also not significantly modified in the different periods of reperfusion when compared to control hearts (continuously perfused hearts). These results suggest that xanthine oxidase is apparently not a major source of free radicals in the course of an ischemia-reperfusion sequence in heart muscle, in particular, if we consider the early phases of reperfusion. The process of lipid peroxidation, assessed by assaying thiobarbituric acid reactants, is not a predominant phenomenon of reperfusion-induced injury, at least in the experimental model used here. However, enzymic antioxidant systems investigated in this study do not seem modified. This could mean that the small quantity of oxygen free radicals produced does not overwhelm the enzymic antioxidant systems of myocardium which is in agreement with peroxidatized lipid results.

Animals↗

PubMed2006

Assessment of non-reperfused and reperfused myocardial infarction using diffusible or deposited radiolabelled perfusion imaging agents.

PURPOSE: Incomplete microvascular reperfusion is often observed in patients undergoing thrombolytic therapy or angioplasty for acute myocardial infarction and has important prognostic implications. We compared the myocardial uptake of diffusible ((201)Tl) and deposited ((99m)TcN-NOET) perfusion imaging agents in the setting of experimental infarction. METHODS: Rats were subjected to permanent coronary occlusion (OCC, n=10) or to 45-min occlusion and reperfusion (REP, n=17). Seven days later, the tracers were co-injected and the animals were euthanised 15 min (all ten rats in the OCC group and 12 rats in the REP group) or 120 min (five rats from the REP group, euthanised at this time point to evaluate any redistribution of the tracers: REP-RED group) afterwards. Infarct size determination and (99m)TcN-NOET/(201)Tl ex vivo imaging were performed. Regional flow and tissue oedema were quantified using radioactive microspheres and (99m)Tc-DTPA, respectively. RESULTS: (99m)TcN-NOET and (201)Tl defect magnitudes were similar in OCC animals (0.11+/-0.01 vs 0.13+/-0.01). In REP animals, (201)Tl defect magnitude (0.25+/-0.02) was significantly lower than the magnitude of (99m)TcN-NOET and flow defects (0.14+/-0.03 and 0.17+/-0.01, respectively; p<0.05), despite the lack of (201)Tl redistribution (REP-RED animals). (99m)Tc-DTPA indicated the presence of oedema in the reperfused area. Blood distribution studies showed that, unlike (99m)TcN-NOET, (201)Tl plasma activity was mostly unbound to plasma proteins. CONCLUSION: (99m)TcN-NOET and (201)Tl delineated the non-viable area in chronic non-reperfused and reperfused myocardial infarction. The significantly decreased (201)Tl defect in reperfused infarction was likely due to partial diffusion of the tracer from the plasma into the oedema present in the infarcted area. Deposited perfusion tracers might be better suited than diffusible agents for the assessment of regional flow following reperfusion of myocardial infarction.

Animals↗

PubMed1999

Hypothermic neuroprotection of peripheral nerve of rats from ischemia-reperfusion injury: intraischemic vs. reperfusion hypothermia.

The pathophysiology of ischemic fiber degeneration (IFD) is not known, but mechanisms involved during nerve ischemia differ from those during reperfusion. We have previously demonstrated hypothermic neuroprotection of peripheral nerve from IFD. We now evaluate the efficacy of hypothermia in the intraischemic vs. the reperfusion period, using our established model of ischemia-reperfusion injury. Intraischemic hypothermia resulted in significant recovery of all indices (behavior score, electrophysiology and histology, P<0.01 or 0.05) while hypothermia during reperfusion period showed less improvement, significant only for the histological score compared to normothermia group (IFD index, P<0.05). Once hypothermia was applied in the ischemic period, the resultant neuroprotection continued into the reperfusion period, even if nerve temperature was then raised during the reperfusion period. These results indicate that hypothermic neuroprotection is more efficacious during the intraischemic period than during reperfusion, when a lesser degree of neuroprotection ensued.

Action Potentials↗

PubMed2001

Enhanced protection from renal ischemia-reperfusion [correction of ischemia:reperfusion] injury with A(2A)-adenosine receptor activation and PDE 4 inhibition.

BACKGROUND: We previously demonstrated in rats and mice that agonists of A(2A)-adenosine receptors (A(2A)-ARs) reduce renal injury following ischemia-reperfusion. We now extend these studies and examine the effects of ATL-146e (formerly DWH-146e), an A(2A)-AR agonist, and rolipram, a type IV phosphodiesterase (PDE 4) inhibitor, on murine renal injury following ischemia-reperfusion. METHODS: C57BL/6 mice were treated with rolipram, ATL-146e, or both compounds combined and were subjected to renal ischemia for 32 minutes and reperfusion for 24 to 48 hours. In vitro studies were performed on suspended and adhering human neutrophils. RESULTS: Continuous delivery of rolipram or ATL-146e during reperfusion reduced renal injury in a dose-dependent manner. Maximal protection was observed when ATL-146e was infused for six hours during reperfusion. Elevated plasma creatinine and myeloperoxidase activity produced by ischemia-reperfusion were reduced by rolipram (0.1 ng/kg/min) and ATL-146e (10 ng/kg/min) by up to approximately 60% and 70%, respectively. Co-infusion of both compounds produced a maximum reduction of plasma creatinine of approximately 90% and myeloperoxidase activity. In vitro studies on suspended and adhering human neutrophils demonstrated that selective stimulation of A(2A)-ARs by ATL-146e increased cAMP accumulation, reduced oxidative activity of activated neutrophils, and decreased activated neutrophil adherence. These responses were potentiated by rolipram. CONCLUSIONS: We conclude that the combined infusion of ATL-146e and rolipram leads to enhanced renal tissue protection from ischemia-reperfusion by mechanisms that may include reduced neutrophil adherence/recruitment and release of reactive oxygen species.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2001

Early peak creatine kinase activity is not always a marker of successful reperfusion with myocardial salvage in patients with reperfused anterior acute myocardial infarction.

BACKGROUND: Although early peak creatine kinase activity (peak CK) is considered a reliable marker of coronary reperfusion in patients with acute myocardial infarction (AMI), whether early peak CK indicates good myocardial salvage is unclear. Moreover, some patients have late peak CK despite successful reperfusion, and its clinical implication remains to be elucidated. METHODS AND RESULTS: We examined the association of the time to peak CK with predischarge left ventricular function in 124 patients with a first AMI who had successful reperfusion within 6 hours from symptom onset. Patients were classified according to the time from reperfusion to peak CK: group A, 61 patients with peak CK < 6 hours; group B, 42 with peak CK from 6 to 12 hours; and group C, 21 with peak CK > 12 hours. There were no differences among the 3 groups in age, sex, method of reperfusion, time from symptom onset to reperfusion, collateral circulation, or the extent of risk area estimated by number of leads with ST-segment elevation. Left ventricular ejection fraction measured by predischarge left ventriculography was lowest in group A, followed by group B, and highest in group C (median values, 43%, 52%, and 60%, P < .01). Left ventricular dysfunction (left ventricular ejection fraction < or = 40%) occurred in 26 (43%) patients in group A, 8 (19%) in group B, and none in group C (P < .01). CONCLUSIONS: We conclude that compared with early peak CK, late peak CK consistently reflects good myocardial salvage in patients with anterior AMI who had successful reperfusion within 6 hours from symptom onset.

Adult↗

PubMed1997

Reperfusion injury: demonstration of brain damage produced by reperfusion after transient focal ischemia in rats.

During reperfusion after ischemia, deleterious biochemical processes can be triggered that may antagonize the beneficial effects of reperfusion. Research into the understanding and treatment of reperfusion injury (RI) is an important objective in the new era of reperfusion therapy for stroke. To investigate RI, permanent and reversible unilateral middle cerebral artery/common carotid artery (MCA/CCA) occlusion (monitored by laser Doppler) of variable duration in Long-Evans (LE) and spontaneously hypertensive (SH) rats and unilateral MCA and bilateral CCA occlusion in selected LE rats was induced. In LE rats, infarct volume after 24 hours of permanent unilateral MCA/CCA occlusion was 31.1 +/- 34.6 mm3 and was only 28% of the infarct volume after 120 to 300 minutes of reversible occlusion plus 24 hours of reperfusion, indicating that 72% of the damage of ischemia/reperfusion is produced by RI. When reversible ischemia was prolonged to 480 and 1080 minutes, infarct volume was 39.6 mm3 and 16.6 mm3, respectively, being indistinguishable from the damage produced by permanent ischemia and significantly smaller than damage after 120 to 300 minutes of ischemia. Reperfusion injury was not seen in SH rats or with bilateral CCA occlusion in LE rats, in which perfusion is reduced more profoundly. Reperfusion injury was ameliorated by the protein synthesis inhibitor cycloheximide or spin-trap agent N-tert-butyl-alpha-phenylnitrone pretreatment.

Animals↗

PubMed2005

Ischemic postconditioning during reperfusion activates Akt and ERK without protecting against lethal myocardial ischemia-reperfusion injury in pigs.

Transient episodes of ischemic preconditioning (PC) render myocardium protected against subsequent lethal injury after ischemia and reperfusion. Recent studies indicate that application of short, repetitive ischemia only during the onset of reperfusion after the lethal ischemic event may obtain equivalent protection. We assessed whether such ischemic postconditioning (Postcon) is cardioprotective in pigs by limiting lethal injury. Pentobarbital sodium-anesthetized, open-chest pigs underwent 30 min of complete occlusion of the left anterior descending coronary artery and 3-h reflow. PC was elicited by two cycles of 5-min occlusion plus 10-min reperfusion before the 30-min occlusion period. Postcon was elicited by three cycles of 30-s reperfusion, followed by 30-s reocclusion, after the 30-min occlusion period and before the 3-h reflow. Infarct size (%area-at-risk using triphenyltetrazolium chloride macrochemistry; means +/- SE) after 30 min of ischemia was 26.5 +/- 5.2% (n = 7 hearts/treatment group). PC markedly limited myocardial infarct size (2.8 +/- 1.2%, n = 7 hearts/treatment group, P < 0.05 vs. controls). However, Postcon had no effect on infarct size (37.8 +/- 5.1%, n = 7 hearts/treatment group). Within the subendocardium, Postcon increased phosphorylation of Akt (74 +/- 12%) and ERK1/2 (56 +/- 10%) compared with control hearts subjected only to 30-min occlusion and 15-min reperfusion (P < or = 0.05), and these changes were not different from the response triggered by PC (n = 5 hearts/treatment group). Phosphorylation of downstream p70S6K was also equivalent in PC and Postcon groups. These data do not support the hypothesis that application of 30-s cycles of repetitive ischemia during reperfusion exerts a protective effect on pig hearts subjected to lethal ischemia, but this is not due to a failure to phosphorylate ERK and Akt during early reperfusion.

Animals↗

PubMed2000

Antiarrhythmic efficacy of dipyridamole in treatment of reperfusion arrhythmias : evidence for cAMP-mediated triggered activity as a mechanism responsible for reperfusion arrhythmias.

BACKGROUND: Intracellular calcium overload is believed to play an important role in development of reperfusion arrhythmias. Dipyridamole, an inhibitor of cellular uptake of adenosine, may prevent or terminate reperfusion arrhythmias by reducing intracellular calcium overload. METHODS AND RESULTS: First, we tested for a preventive effect of dipyridamole. Sixty-one patients who underwent primary PTCA for treatment of acute anterior wall myocardial infarction were enrolled in this prospective study. Patients were divided into dipyridamole (DP) and nondipyridamole (non-DP) groups. The 2 groups had similar baseline characteristics. In the DP group, dipyridamole 0.5 mg/kg was infused intravenously for 3 minutes immediately before reperfusion during primary PTCA. Arrhythmias after reperfusion were analyzed from continuous ECG recordings. None of the patients in the DP group (n=23) had accelerated idioventricular rhythms (AIVR) or ventricular tachycardia (VT). In contrast, 7 (18.4%) had AIVR and 3 (7.9%) had VT in the non-DP group (n=38; P<0.01). Second, we tested for a termination effect of dipyridamole. Dipyridamole 0.5 mg/kg was infused intravenously while continuous ECG recordings were obtained in 9 patients who had either sustained AIVR (n=7) or sustained VT (n=2) after reperfusion of occluded coronary artery. Arrhythmias were terminated in all patients. CONCLUSIONS: These results indicate that administration of dipyridamole can prevent and terminate reperfusion arrhythmias such as AIVR and VT. cAMP-mediated triggered activity may, at least in part, be responsible for reperfusion-induced AIVR and VT.

Adenosine↗

PubMed1993

Illusion of reperfusion. Does anyone achieve optimal reperfusion during acute myocardial infarction?

Thrombolytic therapy significantly improves the natural history of acute myocardial infarction, but recent data suggest that current reperfusion strategies have yet to realize the maximum potential for reduction of mortality and salvage of ventricular function. Coronary patency rates as high as 85% assessed by angiography 90 minutes after initiation of treatment greatly overestimate the efficacy of thrombolytic regimens, as this conventional angiographic "snapshot" view does not satisfactorily reflect the dynamic processes of coronary artery recanalization and reocclusion or the adequacy of myocardial perfusion. In fact, only the unusual patient appears to achieve optimal reperfusion for acute myocardial infarction, with a substantial deterioration of benefit in many patients due to insufficiently early or rapid recanalization, incomplete patency with TIMI grade 2 flow or critical residual coronary stenoses, absence of myocardial tissue reflow despite epicardial artery patency, intermittent coronary patency, subsequent reocclusion, or reperfusion injury. Recently developed techniques to critically assess the quality of reperfusion, coupled with the introduction of novel pharmacological agents and an improved understanding of the roles and mechanisms of existing thrombolytic and adjunctive drugs, have provided the opportunity to overcome many of the present limitations of reperfusion therapy. Emerging strategies to achieve optimal reperfusion are directed at enhancement of the velocity and quality of thrombolysis, amelioration of the adverse effects of reperfusion, and use of alternative pathways to myocardial salvage.

Coronary Vessels↗

PubMed2000

Postischemic reperfusion of the spinal cord: prolonged reperfusion alleviates the metabolic alterations induced by 25 min ischemia in the cervical and thoracolumbal segments.

In recent years, increasing amount of information has indicated that in some tissues the main damage due to oxidative stress does not occur during reperfusion but during the ischemic episode of the ischemia/reperfusion event. In this respect, serious doubts were also expressed about the origin of the increased amounts of free radicals which were believed to form and reported to appear in the perfusate during the first minutes of reperfusion. Moreover, speculative explanations were only available for a second increase in lipid peroxidation which was reported to occur after postischemic reperfusions exceeding 60 min. For this reasons, the present paper reports the results of investigation of ischemia/reperfusion injury to the cervical (CE) and thoracolumbal (ThL) segments of the spinal cord (SP) after an acute 25 min occlusion of the abdominal aorta, followed by 60-120 min reperfusion of the ischemic areas in rabbits. In CE and ThL segments of the SP, the ischemia induced: 1) a decrease in activities of superoxide dismutase (SOD), from 57.35+/-6.36 to 45.27+/-5.45 U x mg(-1) x min(-1) (S.E.M., 20.92%), p < 0.01, and from 58.36+/-5.45 to 33.00+/-4.55 U x mg(-1) x min(-1) (S.E.M., 43.46%), p < 0.001; 2) a significant decrease in gamma-glutamyl transpeptidase (gamma-GTP), from 114.66+/-1.45 to 99.88+/-4.4 micromol p-nitroaniline x mg(-1) x h(-1) (S.E.M. 12.89 %), p < 0.05 and from 112.24+/-1.20 to 95.09+/-2.40 micromol p-nitroaniline x mg(-1) x h(-1) (S.E.M., 16.26%), p < 0.05; 3) a considerable depression in Na,K-ATPase activity, from 7.14+/-0.58 to 5.08+/-0.32 micromol Pi x mg(-1) x h(-1) (S.E.M., 28.86%), p < 0.01, and from 7.23+/-0.11 to 5.09+/-0.31 micromol Pi x mg(-1) x h(-1) (S.E.M., 30.00%), p < 0.01. The Na,K-ATPase activity became decreased by ischemia and remained depressed significantly (all p < 0.01) throughout the experiment. After 60 min of reperfusion, SOD activity in the CE segment and that of gamma-GTP in the CE as well as ThL segments recovered, even slightly surpassing the control values, wheras SOD activity in the ThL segment became stabilized again close to its post-ischemic value. Prolonged, reperfusion for 120 min resulted in a further increase in gamma-GTP activity in the CE and ThL segments (to 132.79 and 132.30%, p < 0.01), and this was accompanied by a slight (p > 0.05) elevation in the content of conjugated dienes as well as by a new wave of depression of the SOD activity (p < 0.05) in both the CE and the ThL segment. From our results it could be concluded that all considerable damage to the spinal cord occurred during the ischemic period. In the period of reperfusion reparative changes started to predominate. This is in accordance with the recent discoveries indicating that, when coupled with an increase in tissue gamma-GTP activity, the post-ischemic reparative changes comprise a replenishment of the cell glutathione pool. This process is accompanied with a gradual increase in H2O2 production that results in repeatead inhibition of the SOD activity and a tendency to conjugated dienes formation.

Animals↗

PubMedDate not supplied

Liver glutathione level influences myocardial reperfusion injury following liver ischemia-reperfusion.

BACKGROUND: N-acetyl-L-cysteine (NAC) both replenishes reduced glutathione (GSH) and mitigates reperfusion injury. We hypothesized that liver content of GSH could affect remote myocardial reperfusion injury following liver ischemia-reperfusion. MATERIAL AND METHODS: Following stabilization (30 min), isolated rat livers (6/group) were perfused with Krebs-Henseleit solution (two control groups) or made globally ischemic (two ischemia groups) for 120 min. Paired livers + paced hearts (Langendorff preparation) were then reperfused for 15 min after which the hearts were recirculated alone for 50 min. NAC was added to Krebs (2 mM) that perfused livers during stabilization and reperfusion phases in one control and one ischemia group. RESULTS: GSH levels in the two control liver groups were identical (30.1 +/- 5.7 [SD] nmol/mg protein), and similar to that of the ischemia + NAC livers (28.6 +/- 2.8) but 2-fold that of the ischemia + 0 livers (15.8 +/- 2.4 nmol/mg protein, p<0.05). While hearts paired with control livers maintained unchanged their myocardial velocity of contraction, the contraction in the ischemia + NAC-paired hearts reduced, but was better than in the ischemia + 0-paired hearts (71 +/- 8% vs. 41 +/- 6% off baseline, p<0.05). Coronary flow also decreased dissimilarly in the two ischemia-associated groups of heart: 72 +/- 9% (ischemia + NAC) vs. 46 +/- 7% (ischemia + 0, p<0.05). Xanthine oxidase in the ischemia + 0 livers was 7.5-folds higher than in the ischemia-treated livers. CONCLUSIONS: NAC treatment of ischemia-reperfused livers, associated with GSH replenishment, prevents remote myocardial reperfusion injury. The role of NAC and GSH in reducing liver-associated oxidative burst propagation is discussed.

Acetylcysteine↗

PubMed1992

[Clinical value of PMN elastase activity before reperfusion therapy in acute myocardial infarction: comparison with clinical characteristics, reperfusion events and myocardial damage].

Many recent studies demonstrate that neutrophils may be involved in the genesis and propagation of myocardial ischemia and reperfusion injury. Clinical value of PMN elastase activity before reperfusion which is released from activated polymorphonuclear leucocyte were evaluated in 30 patients with acute myocardial infarction. 19 patients with normal or moderately elevated PMN elastase activity (G1: less than 200 micrograms/l) revealed similar clinical characteristics before reperfusion therapy, compared to 11 patients with extremely high PMN elastase activity (Group 1: greater than or equal to 200 micrograms/l). But Group 1 represented fewer incidence of reperfusion events (Group 1 2/19, Group 2 7/11, p less than 0.01) such as arrhythmia, BP down, re-elevation of ST segments, and increased chest pain just after reperfusion, and higher incidence of salvaged myocardium in the risk area (Group 1 5/11, Group 2 4/19 p less than 0.1) evaluated by Tc-99m PYP, T1-201 dual SPECT, than Group 2. Wall motion analysis also showed that both global and regional wall motion were severely depressed in Group 2 compared with Group 1 (Group 1: Global EF 66.6 +/- 13.5, Extent 26.5 +/- 17.4, Severity 63.1 +/- 48.5, Group 2: Global EF 51.2 +/- 10.6, Extent 40.1 +/- 16.3, Severity 112.8 +/- 55.5, p less than 0.01 for Global EF, Extent, and p less than 0.05 for Severity). These data suggest that leucocyte activation before reperfusion may play important role in the genesis of reperfusion injury.

Aged↗

PubMedDate not supplied

[The role of Ca2+, entering the cell during reperfusion, in the mechanism of initiation and maintenance of reperfusion arrhythmias].

The role of calcium ions entering cells upon reperfusion of ischemic myocardium for reperfusion arrhythmias has been investigated on the model of isolated rat right ventricle perfused through coronary artery. Manipulation by concentration of calcium ions in the reperfusion solution demonstrates that calcium ions entering cells upon reperfusion do not play a major role in the initiation of reperfusion extrasystoles and tachycardias, but have a significant influence on the maintenance of tachycardias. Multielectrode mapping revealed a focal source as the mechanism underlying reperfusion arrhythmias at low concentration or in the absence of calcium ions in the reperfusion solution.

Animals↗

PubMed1998

[From the study of biochemical changes in ischemic and reperfused skeletal muscle to the controlled reperfusion of limbs in patients with acute severe ischemia].

The reperfusion of a limb which has been submitted to a severe and prolonged period of ischemia may be followed by dramatic local and systemic complications. The results of several experimental studies have given insights on the biochemical and physiopathological alterations occurring in the ischemic and reperfused skeletal muscle. Therefore the technique of the controlled limb reperfusion has been developed. we present the results obtained in two patients with this technique. Two patients were admitted for a limb-threatening ischemia consecutive to embolism. After removal of the thrombi with a Fogarty's catheter and before reperfusion with the normal blood, a controlled limb reperfusion was performed by mixing the systemic blood with a crystalloid solution in order to obtain a hyperosmolar, hypocalcemic, alcalotic and substrate-enriched (aspartate and glutamate) reperfusate. This reperfusate was infused during 30 min with a roller pump into the deep and superficial femoral arteries. The delivery conditions (temperature, flow and reinjection pressure) were closely monitored. In both cases, no post-operative complication was observed and the pedal pulses were restored after the operation. Complete recovery of the motor and sensitive functions were observed and the patient were discharged at the 10th post-operative day.

Acute Disease↗

PubMedDate not supplied

Intracoronary superoxide dismutase for the treatment of "reperfusion injury", A blind randomized placebo-controlled trial in ischemic, reperfused porcine hearts.

The effect of recombinant human superoxide dismutase (rh-SOD) on infarct size was investigated in porcine hearts. The left anterior descending coronary artery was occluded in each of 24 anesthetized pigs for 45 min and reperfused for 24 h. The animals were randomly assigned to either rh-SOD (n = 12) or placebo treatment (n = 12). 2 min before reperfusion, an intracoronary (i.c.) infusion of rh-SOD (total dose: 2000 U/kg) or placebo was started which lasted for up to 45 min reperfusion. At the end of the experiment, the infarcted myocardium was assessed using a tetrazolium stain (NBT) and related to the risk region which was determined with a fluorescent dye. Two pigs of the SOD group and one of the control group died before the end of the experiments. Except for a lower calculated myocardial oxygen consumption and a lower dp/dtmax in the SOD group during ischemia, hemodynamic parameters of the two groups did not differ significantly. rh-SOD i.c. treatment during reperfusion did not reduce infarct size significantly. Infarct size amounted to 74 +/- 13% in the control group and to 66 +/- 19% in the treated group. The incidence of reperfusion arrhythmias was not affected by rh-SOD treatment. It is concluded that i.c. rh-SOD treatment at the beginning of reperfusion neither significantly reduces infarct size nor diminishes the incidence of reperfusion arrhythmias in this preparation.

Animals↗

PubMed1986

Optimal calcium concentration in the initial reperfusate for post-ischemic myocardial performance (calcium concentration during reperfusion).

The dose-response curves of calcium concentration in the initial reperfusate to mechanical recovery of ischemic myocardium was investigated with an isolated working rat heart preparation. After 20 mins of normothermic ischemic arrest, the recovery of aortic flow by reperfusion with Krebs-Henseleit buffer was 54.0 +/- 2.4% (mean +/- S.E.M.). Reduction of calcium concentration during 10 mins of initial reperfusion after 20 mins of normothermic ischemic arrest increased or decreased the recovery of aortic flow with a bell-shaped dose-response curves obtained. The maximal percent recovery of aortic flow was 75.2 +/- 1.7 at 0.5 mM calcium with normal potassium-normal magnesium solution, 74.9 +/- 3.1 at 0.1 mM with high potassium (20 mM)-normal magnesium solution, 65.4 +/- 1.5 at 1.2 mM with high potassium-high magnesium (20 mM K, 16 mM Mg) solution, and 73.4 +/- 2.7 at 1.3 mM with normal potassium-high magnesium (16 mM) solution. All of them were significantly better than that of the control group (P less than 0.01). A high concentration of potassium and magnesium affected the dose-response of calcium in the initial reperfusate. These results suggest that the control of calcium concentration in the reperfusate is important during the early stages of reperfusion, and reperfusion injury may be considerably reduced.

Animals↗

PubMed1986

Reperfusate composition: supplemental role of intravenous and intracoronary coenzyme Q10 in avoiding reperfusion damage.

This study tests the hypothesis that the oxygen radical scavenger coenzyme Q10 can be given both intravenously and in the cardioplegic solution and can improve muscle salvage following surgical revascularization. Pilot studies were carried out in dogs undergoing 40 minutes of coronary artery ligation with reperfusion with normal blood, with the heart in the beating, working state. Intravenous infusions of coenzyme Q10 (10 mg/kg) 5 minutes before reperfusion resulted in improved recovery of creatine phosphate, adenosine triphosphate, total adenine nucleotide, and myocardial function reverse estimated by postextrasystolic potentiation, in comparison with the degree of recovery in untreated dogs. Experimental studies were done on 27 dogs undergoing 2 hours of left anterior descending coronary artery occlusion and subsequent reperfusion with and without total vented bypass. Thirteen dogs received intravenous coenzyme Q10 10 minutes before extracorporeal circulation, six received substrate-enriched blood cardioplegic solution with added coenzyme Q10, and six received normal blood reperfusate. Six others had cardioplegic reperfusion without coenzyme Q10. The systolic bulging that occurred during ischemia (ultrasonic crystals) persisted after reperfusion with normal blood (-25% systolic shortening, p less than 0.05), and 44% transmural triphenyltetrazolium chloride nonstaining occurred in the area at risk. Conversely, hearts receiving substrate-enriched blood cardioplegic solution recovered 37% contractility (p less than 0.05), with the least, and only, subendocardial triphenyltetrazolium chloride nonstaining (25% of area at risk) occurring with intravenous coenzyme Q10 before bypass and coenzyme Q10 supplementation of the cardioplegic solution. Intravenous coenzyme Q10, given just before reperfusion (possibly in transit to the operating room), enhances the role of substrate-enriched blood cardioplegic solution (especially when added to the cardioplegic solution) in salvaging ischemic myocardium and allowing immediate functional recovery.

Adenosine Triphosphate↗