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At least 19 recordsLinked to original sources
PubMed2000

Myocardial ischemic preconditioning and mitochondrial F1F0-ATPase activity.

A short period of ischemia followed by reperfusion (ischemic preconditioning) is known to trigger mechanisms that contribute to the prevention of ATP depletion. In ischemic conditions, most of the ATP hydrolysis can be attributed to mitochondrial F1F0-ATPase (ATP synthase). The purpose of the present study was to examine the effect of myocardial ischemic preconditioning on the kinetics of ATP hydrolysis by F1F0-ATPase. Preconditioning was accomplished by three 3-min periods of global ischemia separated by 3 min of reperfusion. Steady state ATP hydrolysis rates in both control and preconditioned mitochondria were not significantly different. This suggests that a large influence of the enzyme on the preconditioning mechanism may be excluded. However, the time required by the reaction to reach the steady state rate was increased in the preconditioned group before sustained ischemia, and it was even more enhanced in the first 5 min of reperfusion (101 +/- 3.0 sec in preconditioned vs. 83.4 +/- 4.4 sec in controls, p < 0.05). These results suggest that this transient increase in activation time may contribute to the cardioprotection by slowing the ATP depletion in the very critical early phase of post-ischemic reperfusion.

Adenosine Triphosphate↗
PubMed2006

[The role of oxygen free radicals in the mechanisms of local and distant ischemic myocardial preconditioning].

The phenomenon of ischemic preconditioning consists in increase in myocardial tolerance to ischemia after short periods of ischemia and reperfusion of the myocardium (local preconditioning) or a distant organ (distant preconditioning). This study is dedicated to the role of oxygen free radicals (OFR) in the mechanisms of preconditioning; pharmacological inhibition of OFR with N-2-mercaptopropionylglycin, a synthetic anti-oxidant, was used. Mouse experiments demonstrated a reduction in the infarction-limiting effect of local preconditioning as a result of OFR inhibiting. This confirms the hypothesis according to which OFR play an important role in the mechanisms of launching and mediating the protective effect of local preconditioning. On the contrary, application of the same dose of N2-mercaptopropionylglycin does not lead to a significant weakening of the infarction-limiting effect of distant preconditioning caused by 20 min of ischemia and 15 min of reperfusion of the small intestine. Thus, it is unlikely that OFR participate in the realization of the effect of distant preconditioning caused by small intestinal ischemia. The authors discuss hypothetic molecular mechanisms of distant myocardial preconditioning.

Animals↗
PubMed2003

Intermittent warm blood cardioplegia induces the expression of heat shock protein-72 by ischemic myocardial preconditioning.

OBJECTIVE: Recent studies have demonstrated that the induction of heat shock protein-72 (HSP72) by different stimuli preserves the heart function after cardioplegic arrest. Based on these findings, we investigated whether intermittent warm blood cardioplegia would induce changes in the myocardial expression of HSP72. METHODS: Forty patients scheduled for aortocoronary bypass were randomly assigned to receive either cold or warm intermittent blood cardioplegia. In all patients HSP72 and HSP72 mRNA were assayed in biopsies from the right atrium at baseline, and during the reperfusion period. Plasma CK-MB and troponin-T, and myocardial oxygen extraction and lactate release were also measured. RESULTS: In both groups, myocardial expression of HSP72 increased throughout the reperfusion period, but the values of HSP72 band lengths were significantly higher in the warm group. Correspondingly, HSP72 mRNA levels increased progressively in both groups, with significant difference between groups observed in biopsies at the reperfusion. Warm blood cardioplegia was associated with lower levels of CK-MB and troponin-T. Myocardial oxygen extraction and lactate release were higher during intermittent warm cardioplegia, indicating a more profound ischemic anaerobic metabolism in the warm group. CONCLUSIONS: Intermittent warm blood cardioplegia induces an increased expression of HSP72 and it is associated with a better myocardial protection, by a mechanism involving a variant of the classical ischemic preconditioning model.

Coronary Artery Bypass↗
PubMed1996

Naloxone blockade of myocardial ischemic preconditioning is stereoselective.

This study tested the hypothesis that endogenous opioids are involved in the infarct limitation of myocardial ischemic preconditioning (IP). Blockade of IP-induced infarct limitation by (-)naloxone hydrochloride (-NAL) or its receptor-inactive stereoisomer (+)naloxone (+NAL) was evaluated. Fifty-two pentobarbitone-anesthetized, open-chest rabbits underwent 30 min coronary artery occlusion and 180 min reperfusion. Treatment groups were: control (n = 9), i.p. (n = 8), -NAL (n = 9) and -NAL/i.p. (n = 12), or +NAL (n = 6) and +NAL/i.p. (n = 8). i.p. was elicited with 5 min regional ischemia, beginning 15 min before the 30 min coronary occlusion. -NAL or +NAL, 3 mg/kg i.v. bolus, was given 25 min before the 30 min coronary occlusion. Infarct size was assessed with tetrazolium and expressed as a percentage of area-at-risk. There were no significant intergroup differences of area-at-risk. IP resulted in marked infarct limitation compared to control (control, 32.9 +/- 7.6% v i.p., 5.8 +/- 4.5%; P = 0.04). Neither -NAL nor +NAL alone altered infarct size compared to control, but -NAL did block the infarct limitation of i.p. (-NAL, 31.4 +/- 6.7% v -NAL/i.p., 24.3 +/- 6.2%) whereas +NAL did not (+NAL, 40.5 +/- 5.0% v +NAL/i.p., 13.7 +/- 3.6%; P = 0.02). In conclusion, naloxone blockade of i.p.-induced cardioprotection is stereospecific and therefore likely to be opioid receptor-mediated.

Animals↗
PubMedDate not supplied

Sarcolemmal and mitochondrial K(ATP) channels and myocardial ischemic preconditioning.

Ischemic preconditioning (IPC) is the phenomenon whereby brief periods of ischemia have been shown to protect the myocardium against a sustained ischemic insult. The result of IPC may be manifest as a marked reduction in infarct size, myocardial stunning, or incidence of arrhythmias. While many substances and pathways have been proposed to play a role in the signal transduction mediating the cardioprotective effect of IPC, overwhelming evidence indicates an intimate involvement of the ATP-sensitive potassium channel (K(ATP) channel) in this process. Initial hypotheses suggested that the surface or sarcolemmal K(ATP) (sarcK(ATP)) channel mediated the cardioprotective effects of IPC. However, much research has subsequently supported a major role for the mitochondrial K(ATP) channel (mitoK(ATP)) as the one involved in IPC-mediated cardioprotection. This review presents evidence to support a role for the sarcK(ATP) or the mitoK(ATP) channel as either triggers and/or downstream mediators in the phenomenon of IPC.

Adenosine Triphosphate↗
PubMed2005

Role of beta-adrenergic signal transduction pathway on myocardial ischemic preconditioning of rats.

To study the changes in every part of the beta-adrenergic signal transduction pathway and their effects on ischemic preconditioning of rat myocardium in vivo. SD rats were divided into three groups: IP group, I/R group and CON group. The IP group was further divided into PC1-, 2-, 3-, and PC1+, 2+, 3+ groups according to preconditioning procedure. The rats received surgical procedure and underwent left coronary artery occlusion and reperfusion. We analyzed the infarct size by TTC staining, measured serum myocardial enzymes, studied the beta-AR Bmax and Kd by radioligand binding assay of receptors, checked the activity of AC and PKA by the method of biochemistry and examined the content of cAMP by radioimmunoassay. The infarct area was much smaller in the IP group than in the I/R group (P < 0.001), while the enzymes were significantly higher in I/R (P < 0.001). The Bmax of beta-AR in IP was much higher than that in I/R (P < 0. 001), but no difference in Kd could be seen between IP and I/R groups. In IP, the activity of AC and PKA and the content of cAMP were higher than those in I/R (P < 0.05, 0.002 and 0.001, respectively). In the procedure of preconditioning, the content of cAMP and the activity of PKA showed the characteristic of cyclic fluctuation. Ischemic preconditioning can protect the heart from necrosis and reduce endo-enzyme leakage. The system of beta-adrenergic signal transduction pathway probably takes part in the protection effect of the IP, which might be elicited by the PKA.

Animals↗
PubMed2000

[Nitric oxide and myocardial ischemic preconditioning].

Preconditioning is an endogenous mechanism of cardioprotection that develops secondary to a brief ischemia and a dramatic reduction in infarct size is observed when the myocardium undergoes a subsequent and long period of ischemia after the induction of preconditioning. Since its initial discovery, it appears that the kinetic of preconditioning is biphasic. Early preconditioning is effective within 1 to 3 hours after the initial brief ischemia. A second windows of preconditioning has been also described within the following 24-48 h. Although late preconditioning against myocardial stunning is well established, its protection against infarction still remains debated. Whereas nitric oxide is not involved in the early preconditioning, its role during the late phase of preconditioning has been recently well described. Indeed, nitric oxide triggers the delayed cardioprotection through the formation of oxiradicals. This leads to the translocation of protein kinase C. Secondary, the activation of the tyrosine kinases pathway and the transcriptional factor NF kappa B induces iNOS. Therefore, nitric oxide also plays a key role in the late preconditioning phenomenon as a mediator of this cardioprotection, although its final effector still remains unknown. The knowledge of the mechanisms responsible for preconditioning is necessary in order to develop new pharmacological concepts in order to protect the heart against ischemia. It is interesting to underline that nitric oxide donors are able to mimic late preconditioning.

Animals↗
PubMed1998

Non-ischemic myocardial preconditioning.

The reduction of infarct size produced by brief ischemic episodes prior to a sustained occlusion of a coronary artery, called ischemic preconditioning, is a well known phenomenon that occurs in several species, but its mechanism is still under investigation. Recent reports support the idea that this protection can also be obtained by non-ischemic maneuvers like distention of the left ventricle and metabolic stimulation of myocardial cells. The features of non-ischemic preconditioning (temporal limitation, second window, tolerance development, remote preconditioning and efficiency of the protection), as opposed to those of ischemic preconditioning, are still to be determined. Neither is it known if non-ischemic preconditioning occurs in humans. From a physiological point of view the protective effect of an increase in metabolic rate of the heart means a constant feed-back mechanism in the myocardial cell that counteracts the presumptive damage consequent to the increase in metabolism. Therefore, in the presence of a sudden coronary occlusion the metabolic rate of the heart immediately before the occlusion would have a dual role of increasing the degree of ischemia and of protecting against it.

Animals↗
PubMed2000

[The roles of alpha B-crystallin during early phase of myocardial ischemic preconditioning in rats].

OBJECTIVE: This study designed to observe intracellular translocation of alpha B-crystallin, a small heat shock protein, and its possible implication during the early phase of myocardial ischemic preconditioning in isolated Langendorff rat hearts. Eighteen male Wistar rats(180-250 g) were randomly divided into three groups: 1. Control group(Ctrl) was perfused with K-H solution throughout the experiment; 2. ischemia-reperfusion group (I-R) experienced 30 min of global ischemia and 120 min of reperfusion and 3. preconditioning and ischemia-reperfusion group(PC + I-R) was preconditioned with three cycles of short myocardial ischemia(5 min each, separated by 5 min of reperfusion) prior to 30 min of ischemia and 120 min of reperfusion. It was showed that cytosolic soluble alpha B-crystallin rapidly translocated to insoluble intracellular structure after ischemic preconditioning, then gradually returned to soluble cytosol pool and almost completely recovered at about 60 min after preconditioning. In the meanwhile, ischemic preconditioning markedly alleviated subsequent myocardial ischemia-reperfusion injury, as indicated by the improvement of LVP, + dp/dt max, coronary flow, heart rate, CPK release and malondialdehyde(MDA) production. The results suggest that the intracellular translocation of alpha B-crystallin might be important for myocardial protection during the early phase of ischemic preconditioning.

Animals↗
PubMed2003

Myocardial ischemic preconditioning during minimally invasive direct coronary artery bypass grafting attenuates ischemia-induced electrophysiological changes in human ventricle.

OBJECTIVE: Ischemic preconditioning (IPC) has been found to protect the myocardium in animal studies. However, clinical studies have been limited and the clinical effects of IPC are still uncertain. The purpose of this study was to assess whether IPC has any protective effect on the human myocardium during minimally invasive CABG (MIDCAB), by means of epicardial electrophysiological testing. METHOD: Forty-five patients with left anterior descending artery disease who underwent a MIDCAB procedure were evaluated. In the present study, the electrical potentials which were not affected by cardio-pulmonary bypass or cardioplegia were measured. The ratio of longitudinal to transverse conduction velocity (phiL /phiT), and QT, JT dispersions were measured using plaque electrodes in the preischemic state, during a 5-minute coronary occlusion, during the subsequent 5-minute reperfusion, during 5- and 10-minute anastomosis periods, and after anastomosis. RESULT: The phiL/phiT was 2.2 +/- 0.2 at baseline. Anisotropy was exaggerated during the 5-minute coronary occlusion (2.6 +/- 0.3). During anastomosis, conduction velocities were decreased, but showed no further deterioration (2.4 +/- 0.3, and 2.4 +/- 0.3, respectively). QT and JT dispersions were improved by reperfusion. CONCLUSION: The effectiveness of IPC during the MIDCAB procedure was confirmed electrophysiologically. Anisotropy and dispersions were minimized after IPC, therefore IPC demonstrated antiarrhythmic protective effects on the human myocardium.

Aged↗
PubMed2001

[Myocardial ischemic preconditioning: pathophysiological mechanisms and prospects of clinical application (a literature review)].

Ischemic preconditioning (IPC, i.e. increase in the organ resistance to a prolonged ischemia which occurs after a brief ischemic challenge) seems to be one of the most powerful endogenous cardioprotective mechanisms known to date. Current data regarding molecular mechanisms of early (classic) IPC as well as the second window of protection are reviewed in the context of the concept of sequential three-staged development of protective effect. Based on original and published data, possible mechanisms of remote IPC are considered. The review comprises current ideas of existence of the IPC clinical correlates and its use in clinic.

Angina Pectoris↗
PubMed2006

[Sarcolemmal sodium-calcium exchanger mediated the beneficial effects of myocardial ischemic preconditioning and pharmacological preconditioning].

OBJECTIVE: To investigate the role of sodium-calcium exchanger (NCX) on ischemic preconditioning and pharmacological preconditioning. METHODS: Cultured rat neonatal cardiomyocytes were randomly divided into 6 groups: (1) ischemia/reperfusion group (9 h ischemia followed by 1 h reperfusion, I/R), (2) ischemic preconditioning group (1.5 h ischemia/1 h reperfusion + I/R), (3) pharmacologic preconditioning group, adenosine (10 micromol/L) pretreated for 1 h + I/R, (4) calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-93 (0.5 micromol/L for 0.5 h) + ischemic preconditioning group, (5) KN-93 + pharmacologic preconditioning group, (6) control group. The leakage of intracellular lactate dehydrogenase (LDH) in various groups was determined by biochemical autoanalyzer. Semi-quantitative RT-PCR was employed to measure the mRNA levels of sodium-calcium exchanger. Activity of sodium-calcium exchanger (Na(+)-dependent (45)Ca(2+) uptake) was measured by liquid scintillation counting. RESULTS: (1) Compared to the I/R group, the LDH leakages in both ischemic preconditioning group and pharmacologic preconditioning group were significantly reduced (P < 0.05) while significantly increased in the KN-93 + pharmacologic preconditioning group and the KN-93 + ischemic preconditioning group (P < 0.05). (2) The Na(+)-dependent (45)Ca(2+) uptake was significantly increased in the I/R group (P < 0.05) compared to control group and this increase could be significantly attenuated in ischemic preconditioning group and adenosine pretreatment group (P < 0.05). (3) The expression of NCX mRNA in I/R group was also significantly increased (P < 0.05) in the I/R group (P < 0.05) compared to control group and this increase could be significantly attenuated in ischemic preconditioning group and adenosine pretreatment group (P < 0.05), CaMKII inhibitor KN-93 significantly abolished these effects in preconditioning group (P < 0.05) and in adenosine pretreated group (P < 0.05). CONCLUSION: NCX mediated the cardioprotective effects of ischemic preconditioning and pharmacological preconditioning in the neonatal cardiomyocytes I/R model.

Animals↗
PubMed2000

Ischemic preconditioning, myocardial stunning and anesthesia.

Brief periods of ischemia have been shown to protect the heart against a subsequent prolonged ischemic insult, a phenomenon known as ischemic preconditioning. The protective effects of preconditioning markedly reduce myocardial ischemic injury in vivo. Volatile anesthetics have been shown to protect myocardium against infarction by a mechanism similar to that of ischemic preconditioning. Contractile dysfunction occurs after a brief period of myocardial ischemia, despite restoration of coronary blood flow in the absence of tissue necrosis. This process is known as myocardial stunning and has important clinical ramifications. Evidence indicates that adenosine triphosphate-regulated potassium channel function plays a central role in ischemic preconditioning, stunned myocardium, and in anesthetic-induced protection against ischemic injury.

Journal Article↗
PubMed2001

Myocardial ischemic preconditioning in rodents is dependent on poly (ADP-ribose) synthetase.

BACKGROUND: Activation of the nuclear enzyme poly (ADP-ribose) synthetase (PARS) in response to oxidant-mediated DNA injury has been shown to play an important role in the pathogenesis of reperfusion injury. Here we investigated the role of PARS in myocardial ischemic preconditioning (IPC). MATERIALS AND METHODS: Mice with or without genetic disruption of PARS and rats in the absence or presence of the PARS inhibitor 3-aminobenzamide underwent coronary occlusion and reperfusion with or without IPC. RESULTS: Both poly(ADP-ribose) synthetase (PARS) deficiency and ischemic preconditioning (IPC) induced protection from reperfusion injury, attenuated inflammatory mediator production, and reduced neutrophil infiltration when compared to the response in wild-type mice. Surprisingly, the protective effect of IPC not only disappeared in PARS-/- mice, but the degree of myocardial injury and inflammatory response was similar to the one seen in wild-type animals. Similarly, in the rat model of IPC, 3-aminobenzamide pretreatment blocked the beneficial effect of IPC. Myocardial NAD+ levels were maintained in the PARS-deficient mice during reperfusion, while depleted in the wild-type mice. The protection against reperfusion injury by IPC was also associated with partially preserved myocardial NAD+ levels, indicating that PARS activation is attenuated by IPC. This conclusion was further strengthened by poly(ADP-ribose) immunohistochemical measurements, demonstrating that IPC markedly inhibits PARS activation during reperfusion. CONCLUSIONS: The mode of IPC's action is related, at least in part, to an inhibition of PARS. This process may occur either by self-auto-ribosylation of PARS during IPC, and/or via the release of endogenous purines during IPC that inhibit PARS activation during reperfusion.

Animals↗
PubMed2005

Pretreatment with an adenosine A1 receptor agonist and lidocaine: a possible alternative to myocardial ischemic preconditioning.

OBJECTIVE: The heart possesses an extraordinary ability to remember short episodes of sublethal ischemia and reperfusion (angina), which protects the myocardium and coronary vasculature from a subsequent lethal insult, a phenomenon known as ischemic preconditioning. A therapeutic goal for more than 2 decades has been to develop a pharmacologic mimetic comparable with ischemic preconditioning. Our aim was to investigate the preconditioning effect of a new combinatorial therapy targeting adenosine A1 receptors and voltage-dependent sodium fast channels in the in vivo rat model of regional ischemia. METHODS: Ischemia-reperfusion was achieved by placing a reversible tie around the left coronary artery in anesthetized and ventilated Sprague-Dawley rats (n = 37). Rats were randomly assigned to 1 of 5 groups: (1) saline control (n = 13); (2) ischemic preconditioning (n = 6); (3) lidocaine only (608 microg . kg -1 . min -1 , n = 5); (4) adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA; 5 microg/kg, n = 7); and (5) CCPA plus lidocaine (n = 6). Ischemic preconditioning was achieved by using 3 cycles of ischemia and reperfusion lasting 3 minutes each. Lidocaine was infused continuously 5 minutes before and throughout 30 minutes of ischemia and ceased at reperfusion. A bolus of CCPA was infused 5 minutes before ligation along with a constant infusion of lidocaine (as above). All animals were reperfused for 120 minutes for infarct size measurement. RESULTS: Fifty-four percent of saline control rats, 17% of ischemic preconditioning-treated rats, and 29% of CCPA-treated rats died during ischemia from ventricular fibrillation. Infarct size of saline control animals was 61% +/- 5%. Pretreating with CCPA and lidocaine infusion resulted in no deaths, no severe arrhythmias, and significant infarct size reduction compared with that seen in saline control animals (P < .05). Remarkably, infarct size reduction in CCPA plus lidocaine-treated rats (12% +/- 4%) was equivalent to that achieved with ischemic preconditioning (11% +/- 3%), whereas infarct size in rats undergoing CCPA-only and lidocaine-only treatments was 42% +/- 7% and 60% +/- 6%, respectively. Although CCPA plus lidocaine treatment reduced heart rate, mean arterial pressure, and systolic pressure during ischemia, no correlation was found between these variables and infarct size reduction. CONCLUSION: We conclude that activating adenosine A1 receptor subtype with CCPA and concomitantly modulating sodium fast channels with lidocaine was comparable with ischemic preconditioning and might offer a new therapeutic window to minimize myocardial damage during surgical ischemia and reperfusion.

Adenosine↗
PubMed2003

Mechanisms of myocardial ischemic preconditioning are age related: PKC-epsilon does not play a requisite role in old rabbits.

Data obtained from adult cohorts have implicated activation/translocation of protein kinase C (PKC)-epsilon as an important cellular mediator of myocardial infarct size reduction with ischemic preconditioning (PC). Age-related alterations in cellular signaling may, however, confound the extrapolation of mechanistic insight derived from adults to the aging population, the specific subset in which cardioprotection is undoubtedly most relevant. Accordingly, our aim was to investigate the role of PKC-epsilon as a mediator of infarct size reduction with PC in old vs. adult rabbits. In protocol 1, we assessed the effect of PKC-epsilon translocation inhibitor peptide (PKC-epsilon-TIP) and the pan-PKC inhibitor chelerythrine on infarct size reduction with PC in adult and approximately 4-yr-old rabbits, a population previously shown to exhibit definitive hallmarks of cardiovascular aging. Rabbits received 5 min of PC ischemia or a matched control period followed by 30 min of coronary artery occlusion and 3 h of reperfusion, with infarct size (delineated by tetrazolium staining) serving as the primary endpoint. In protocol 2, we obtained insight (by Western immunoblotting) into the subcellular redistribution of PKC-epsilon in response to the 5-min PC stimulus in adult and old rabbits. In adults, infarct size reduction with PC was abrogated by both PKC-epsilon-TIP and chelerythrine. However, in old rabbits, 1). PC-induced cardioprotection was maintained despite inhibitor treatment and 2). brief PC ischemia was not associated with activation/translocation of PKC-epsilon. Thus the mechanisms responsible for PC are age related in the rabbit heart, with no apparent, requisite role of PKC-epsilon in aging animals.

Aging↗