Electrocardiography as a tool for validating myocardial ischemia-reperfusion procedures in mice

This paper evaluates the modifications induced by ischemia and ischemia-reperfusion in mice after permanent or transient, respectively, ligation of the left coronary artery and establishes a correlation among the extent of ischemia, electrocardiograph features, and infarct size. The left coronary artery was ligated 1 mm distal from the tip of the left auricle. Histologic analysis revealed that 30-min ischemia (n = 9) led to infarction involving 9.7% ± 0.5% of the left ventricle, whereas 1-h ischemia (n = 9) resulted in transmural infarction of 16.1% ± 4.6% of the left ventricle. In contrast, 24-h ischemia (n = 8) and permanent ischemia (n = 8) induced similarly sized infarcts (33% ± 2% and 31.8% ± 0.7%, respectively), suggesting ineffective reperfusion after 24-h ischemia. Electrocardiography revealed that ligation of the left coronary artery led to ST height elevation (204 compared with 14 μV) and QTc prolongation (136 compared with 76 ms). Both parameters rapidly normalized on reperfusion, demonstrating that electrocardiography was important for validating correct ligation and reperfusion. In addition, electrocardiography predicted the severity of the myocardial damage induced by ischemia. Our results show that electrocardiographic changes present after 30-min ischemia were reversed on reperfusion; however, prolonged ischemia induced pathologic electrocardiographic patterns that remained even after reperfusion. The mouse model of myocardial ischemia-reperfusion can be improved by using electrocardiography to validate ligation and reperfusion during surgery and to predict the severity of infarction.     

beta1-Adrenoreceptor activation contributes to ischemia-reperfusion damage as well as playing a role in ischemic preconditioning

Protein kinase A (PKA) activation has been implicated in early-phase ischemic preconditioning. We recently found that during ischemia PKA activation causes inactivation of cytochrome-c oxidase (CcO) and contributes to myocardial damage due to ischemia-reperfusion. It may be that beta-adrenergic stimulation during ischemia via endogenous catecholamine release activates PKA. Thus beta-adrenergic stimulation may mediate both myocardial protection and damage during ischemia. The present studies were designed to determine the role of the beta(1)-adrenergic receptor (beta(1)-AR) in myocardial ischemic damage and ischemic preconditioning. Langendorff-perfused rabbit hearts underwent 30-min ischemia by anterior coronary artery ligation followed by 2-h reperfusion. Occlusion-reperfusion damage was evaluated by delineating the nonperfused volume of myocardium at risk and volume of myocardial necrosis after 2-h reperfusion. In some hearts ischemic preconditioning was accomplished by two 5-min episodes of global low-flow ischemia separated by 10 min before coronary occlusion-reperfusion. Orthogonal electrocardiograms were recorded, and coronary flow was monitored by a drip count. Three hearts from each experimental group were used to determine mitochondrial CcO and aconitase activities. Two-hour reperfusion after occlusion caused an additional decrease in CcO activity vs. that after 30-min occlusion alone. Blocking the beta(1)-AR during occlusion-reperfusion reversed CcO activity depression and preserved myocardium at risk for necrosis. Similarly, mitochondrial aconitase activity exhibited a parallel response after occlusion-reperfusion as well as for the other interventions. Furthermore, classic ischemic preconditioning had no effect on CcO depression. However, blocking the beta(1)-AR during preconditioning eliminated the cardioprotection. If the beta(1)-AR was blocked after preconditioning, the myocardium was preserved. Interestingly, in both of the latter cases the depression in CcO activity was reversed. Thus the beta(1)-AR plays a dual role in myocardial ischemic damage. Our findings may lead to therapeutic strategies for preserving myocardium at risk for infarction, especially in coronary reperfusion intervention.     

Noradrenaline dynamics in prolonged ischemia after ischemic preconditioning

AIM OF THE STUDY: To determine the effects of two-staged ischemic preconditioning on myocardial noradrenaline in prolonged ischemia and reperfusion. METHODS: Thirty-two male Wistar rats anesthetised with urethane randomly divided into 2 groups: group 1 (ischemic preconditioning group, n = 16), and group 2 (control, n = 16). Myocardial interstitial noradrenaline levels were measured using a microdialysis technique. Ischemic preconditioning was elicited by two episodes: 5 min of ischemia and 10 min of reperfusion. The intermittent occlusions were followed by prolonged occlusion (60 min) and reperfusion (60 min). RESULTS: An increase in interstitial noradrenaline was observed in 10 min of prolonged ischemia in group 2, and in 20 min in group 1. After 20 min of myocardial ischemia there was a significant difference between groups (p < 0.05) in interstitial noradrenaline levels. In control group, it was 60% higher. In reperfusion, noradrenaline levels decreased markedly in group 1. CONCLUSION: We suggest that ischemic preconditioning by two episodes: 5-min ischemia and 10-min reperfusion prevents excessive noradrenaline interstitial accumulation, perhaps, through protection of physiological uptake I carrier.     

Prevention of reperfusion-induced ventricular arrhythmias in isolated rat heart with magnesium

The effects of magnesium (from 1.2 to 7.2 mM) were investigated in isolated perfused rat heart subjected to coronary artery ligation and reperfusion. Increasing magnesium concentrations, of the medium containing 3.00 mM of calcium, induced a significant bradycardia and a protective effect towards reperfusion arrhythmias. A significant correlation was found between the heart rate and the antiarrhythmic activity of increasing magnesium concentrations. The effects of high magnesium concentration (4.8 mM) were also investigated after labelling of internal stores of noradrenaline with [3H]noradrenaline. Without any marked change in the pattern of release of radioactivity, a significant reduction of the sudden release of radioactivity was observed during the reperfusion. However, magnesium did not change the uptake of noradrenaline by the heart. Our results suggest that the antiarrhythmic effect of magnesium might be of importance in the clinical treatment of myocardial ischemia.     

Sites of action of adenosine in interorgan preconditioning of the heart

The mechanism underlying interorgan preconditioning of the heart remains elusive, although a role for adenosine and activation of a neurogenic pathway has been postulated. We tested in rats the hypothesis that adenosine released by the remote ischemic organ stimulates local afferent nerves, which leads to activation of myocardial adenosine receptors. Preconditioning with a 15-min mesenteric artery occlusion (MAO15) reduced infarct size produced by a 60-min coronary artery occlusion (60-min CAO) from 68 +/- 2% to 48 +/- 4% (P < 0.05). Pretreatment with the ganglion blocker hexamethonium or 8-(p-sulfophenyl)theophylline (8-SPT) abolished the protection by MAO15. Intramesenteric artery (but not intraportal vein) infusion of adenosine (10 microg/min) was as cardioprotective as MAO15, which was also abolished by hexamethonium. Whereas administration of hexamethonium at 5 min of reperfusion following MAO15 had no effect, 8-SPT at 5 min of reperfusion abolished the protection. Permanent reocclusion of the mesenteric artery before the 60-min CAO enhanced the cardioprotection by MAO15 (30 +/- 5%), but all protection was abolished when 8-SPT was administered after reocclusion of the mesenteric artery. Together, these findings demonstrate the involvement of myocardial adenosine receptors. We therefore conclude that locally released adenosine during small intestinal ischemia stimulates afferent nerves in the mesenteric bed during early reperfusion, initiating a neurogenic pathway that leads to activation of myocardial adenosine receptors.     

Effect of graduated embolization of the coronary vessels using microspheres on the pumping function and contractility of the left ventricle in rats

Left ventricle (LV) function and systemic hemodynamic changes after coronary artery embolization by 15 microns radioactive microspheres were studied in anesthetized rats. Selective coronary embolization was produced by microsphere injection during ascending aorta occlusion in closed chest animal by using "L"-shaped wire. Maximal pressure (Pmax) developed was evaluated during ascending aorta occlusion. Coronary embolization evoked dose-dependent reduction in Pmax and dP/dtmax and then decrease in basal LV systolic pressure. dP/dt/P, with parallel increase in end diastolic LV pressure. Changes of cardiac output were bidirectional: after administration of relatively small amount of microspheres cardiac output increased. This method can be used for producing quantitative myocardial ischemia and we suggest that it may be a suitable model of the chronic heart failure.     

Cardioprotective effect induced by brief exposure to nitric oxide before myocardial ischemia-reperfusion in vivo.

Administration of nitric oxide (NO) donors during ischemia and reperfusion protects from myocardial injury. However, whether administration of an NO donor during a brief period prior to ischemia protects the myocardium and the endothelium against ischemia-reperfusion injury in vivo is unknown. To study this possibility anesthetized pigs were subjected to 45-min ligation of the left anterior descending coronary artery (LAD) followed by 4h of reperfusion. In initial dose-finding experiments, vehicle or three different doses of the NO donor S-nitroso-N-acetyl-D,L-penicillamin (SNAP; 0.1; 0.5; 2.5 micromol) were infused into the LAD for 3 min starting 13 min during ischemia. Only the 0.5 micromol dose of SNAP reduced infarct size (from 85+/-3% of the area at risk in the vehicle group to 63+/-3% in the SNAP-treated group; p<0.01). There were no significant differences in hemodynamics in the vehicle and SNAP groups during ischemia-reperfusion. Endothelium-dependent dilatation of coronary microvasculature induced by substance P was larger in the SNAP group than in the vehicle group. Myeloperoxidase activity was lower in the ischemic/reperfused myocardial area of pigs given SNAP (4.97+/-0.61 U/g) than in vehicle-treated pigs (8.45+/-0.25 U/g; p<0.05). It is concluded that intracoronary administration of the NO donor SNAP for a brief period before ischemia reduces infarct size, attenuates neutrophil accumulation, and improves endothelial function. These results suggest that NO exerts a classic preconditioning-like protection against ischemia-reperfusion injury in vivo in a narrow concentration range.     

Endothelial NOS activity and myocardial oxygen metabolism define the salvageable ischemic time window for ischemic postconditioning

Ischemic postconditioning (IPOC) could be ineffective or even detrimental if the index ischemic duration is either too short or too long. The present study is to demonstrate that oxygen supply and metabolism defines a salvageable ischemic time window of IPOC in mice. C57BL/6 mice underwent coronary artery occlusion followed by reperfusion (I/R), with or without IPOC by three cycles of 10 s/10 s R/I. In vivo myocardial tissue oxygenation was monitored with electron paramagnetic resonance oximetry. Regional blood flow (RBF) was measured with a laser Doppler monitor. At the end of 60 min reperfusion, tissue from the risk area was collected, and mitochondrial enzyme activities were assayed. Tissue oximetry demonstrated that I/R induced a reperfusion hyperoxygenation state in the 30- and 45-min but not 15- and 60-min ischemia groups. IPOC attenuated the hyperoxygenation with 45 but not 30 min ischemia. RBF, eNOS phosphorylation, and mitochondrial enzyme activities were suppressed after I/R with different ischemic time, and IPOC afforded protection with 30 and 45 but not 60 min ischemia. Infarct size measurement indicated that IPOC reduced infarction with 30 and 45 min but not 60 min ischemia. Clearly, IPOC protected mouse heart with a defined ischemic time window between 30 and 45 min. This salvageable time window was accompanied by the improvement of RBF due to increased phosphorylated eNOS and the preservation of mitochondrial oxygen consumption due to conserved mitochondrial enzyme activities. Interestingly, this salvageable ischemic time window was mirrored by tissue hyperoxygenation status in the postischemic heart.     

Membrane alterations in acute myocardial ischemia

The molecular consequences of acute myocardial ischemia induced in rabbit hearts by ligation of the left circumflex branch of the coronary artery were assessed in terms of the biochemical properties of subcellular organelles. Mitochondrial alteration, as reflected in progressive decrease in the activity of azide-sensitive ATPase, was apparent as early as 5 min postligation, but the activity of another mitochondrial enzyme, cytochrome c oxidase, was unchanged, even following 60 min of coronary ligation. Sarcolemmal Na+K+-ATPase exhibited a time course of inactivation similar to that of the mitochondrial ATPase, but differed from the latter in that the impairment was not reversed on reperfusion. Cellular levels of ATP, which decreased in parallel with the loss of ATPase activities, also remained depressed following reperfusion. Decreases in lysosomal enzyme latency were noted, but these occurred somewhat later than the sarcolemmal and mitochondrial alterations. Attempts to demonstrate the production of a population of labile lysosomal structures during ischemia were unsuccessful. Similarly, no alterations in the gel electrophoretic profiles of proteins or in the P phosphatidylcholine/P phosphatidylethanolamine ratio of isolated mitochondrial or sarcolemmal membranes from hearts subjected to ischemia and (or) subsequent reperfusion could be found. It is suggested that sarcolemmal Na+,K+-ATPase may serve as a sensitive and readily quantifiable index of irreversible cellular necrosis and, therefore, be of value in assessing the possible beneficial effects of pharmacological interventions.     

Relation between energy metabolism,glycolysis, noradrenaline release and duration of ischemia

We studied the effect of 12–36 min of global ischemia followed by 36 min of reperfusion in Langendorff perfused rabbit hearts (n = 26). Metabolism was determined in terms of peak and total release of purines (adenosine, inosine, hypoxanthine), lactate and noradrenaline during reperfusion; and myocardial content of nucleotides (ATP, ADP, AMP), glycogen and noradrenaline at the end of reperfusion. An inverse relationship (r = –0.79) existed between duration of ischemia and developed pressure post-ischemia. Early during reperfusion, after 12 min of ischemia, the purine concentration (peak release) increased 100x (p < 0.01), that of lactate and noradrenaline lOx (p < 0.05) . Total purine release rose with progression of the ischemic period (30x after 36 min of ischemia; p < 0.01), concomitant with a reduction in nucleotide content. Lactate release was independent from the duration of ischemia, although glycogen had declined by 30% (p < 0.01) after 36 min of ischemia. The acid insoluble glycogen fraction, which presumably contains proglycogen, increased substantially during short-term ischemia. Peak noradrenaline increased 100x and 200x (p < 0.05) after 24 and 36 min of ischemia, respectively. Total noradrenaline release due to various periods of ischemia mirrored its peak release. Function recovery was inversely related to total purine and noradrenaline efflux (both r =–0.81); it correlated with tissue nucleotide content (r = 0.84). In conclusion, larger amounts of noradrenaline are released only after a substantial drop in myocardial ATP. During severe ischemia ATP consumption more than limited ATP production by anaerobic glycolysis, is a key factor affecting recovery on subsequent reperfusion. In contrast to lactate efflux, purine and noradrenaline release are useful markers of ischemic and reperfusion damage.     

Effect of ethanol on myocardial infarct size in a canine model of coronary artery occlusion-reperfusion

This study was conducted to determine if elevated blood alcohol prior to acute coronary artery occlusion affects myocardial infarct size in an in vivo canine model. Seven pentobarbital anesthetized open-chest dogs received 10 min Iv infusion of ethanol (0.08 g/kg/min). Ten min after ethanol, the left anterior descending coronary artery (LAD) was occluded distal to its first major branch for 60 min. The LAD was then reperfused for 5 h. Following electrically induced ventricular fibrillation, the area at risk of infarction was delineated with dye. The area of infarction was identified by staining with triphenyl tetrazolium chloride. Eleven untreated control experiments were also conducted. Mean blood ethanol concentration was 155 ± 26 mg/dl just prior to LAD occlusion and 47 ± 3 mg/dl after 4 h reperfusion. Ethanol infusion had no effect on systemic hemodynamic variables during ischemia. In ethanol treated animals, the area at risk was 19.7 ± 3.0% of the left ventricle, and the infarct size was 20.9 ± 4.8% of the area at risk. In control experiments, the area at risk was 23.0 ± 4.1% of the left ventricle (p > 0.05), and the infarct size was 21.6 ± 3.8% of the area at risk (p > 0.05). Collateral blood flow to ischemic region did not differ between the two groups, and the relationships between infarct size and collateral flow were similar for control and untreated hearts. Acute ethanol exposure prior to coronary artery occlusion and subsequent reperfusion does not affect myocardial infarct size in the heart of the anesthetized dog.     

Na(+)/H(+) exchange subtype 1 inhibition reduces endothelial dysfunction in vessels from stunned myocardium

Myocardial ischemia and reperfusion cause myocyte and vascular dysfunction, frequently termed "stunning." We hypothesized that inhibiting the Na(+)/H(+) exchanger subtype 1 isoform (NHE(1)) during ischemia and reperfusion limits myocardial and coronary microvascular stunning. Anesthetized rats completed 2 x 10-min coronary artery occlusions separated by 5-min of reperfusion, followed by 15 or 60 min of reperfusion. Vehicle (saline) or the NHE(1) inhibitor cariporide (HOE-642) was administered 15 min before ischemia and was continued throughout each protocol. After reperfusion, hearts were excised, and the reactivity of resistance arteries (internal diameter, approximately 120 microm) was assessed. The first derivative of left ventricular (LV) pressure, LV developed pressure, and LV systolic wall thickening were depressed (P < 0.05) similarly in vehicle- and cariporide-treated rats during ischemia and after 15 or 60 min of reperfusion compared with sham-operated animals that were not exposed to ischemia (i.e., controls). In vessels obtained after 15 min of reperfusion, the maximal response to acetylcholine-induced relaxation (10(-8)-10(-4) M) was blunted (P < 0.05) in vessels from vehicle- (approximately 35%) and cariporide-treated rats (approximately 55%) compared with controls (approximately 85%). However, the percent relaxation to acetylcholine was greater (P < 0.05) in cariporide-treated rats compared with vehicle-treated rats. Maximal contractile responses to endothelin-1 (10(-11)-10(-7) M) were increased (P < 0.05) similarly in vehicle- and cariporide-treated rats compared with controls. Relaxation to sodium nitroprusside (10(-4) M) was not different among groups. Results were similar in vessels obtained from animals after 60 min of reperfusion. These findings suggest that NHE(1) inhibition before coronary occlusion lessens ischemia-induced microvascular dysfunction for 15-60 min after reperfusion but does not alter myocardial contractile function in the area at risk.     

Microdialysis study in vivo of the release of adenine nucleotide degradation products into intercellular space of canine myocardium during regional ischemia and reperfusion

Intercellular concentrations of adenine nucleotide degradation products (ANDP)--adenosine inosine and hypoxanthine--in ischemic and control regions of the canine myocardium were measured by microdialysis technique during 20- and 40-min coronary artery occlusion and reperfusion. In hearts that fibrillated on reperfusion during the ischemic 40-min period catabolism of adenine nucleotides was more intensive, which could be the min cause of the reperfusion ventricular fibrillation. Reperfusion ventricular fibrillation was accompanied by an increase in the intercellular ANDP level in the control region, that indicated the development of the total myocardial ischemia. During the initial period of reperfusion after 20-min, a sharp increase in the interstitial ANDP level was observed in the ischemic region as compared with the end of the ischemia which could be explained as a result of demasking of reperfusion damage in such a case. The 40-min reperfusion induced slow reduction of the intercellular ANDP level in the ischemic region, while the regional blood flow already 5 min after the reperfusion did not differ from the blood flow in the control region. It is supposed that a slow washout of ANDP could be caused by the "no-reflow" phenomenon.     

The anti-thromboxane A2 synthetase activity of myocardial tissue and its variation during ischemia and reperfusion in isolated rabbit heart.

In this investigation, an anti-thromboxane A2 (TXA2) synthetase activity in the myocardial tissue, which can be modulated by ischemia and reperfusion, was observed. Regional ischemia was induced by 60 min occlusion of the left anterior descending coronary artery in isolated Langendorff rabbit hearts. Biosynthesis of TXA2 was carried out by using arachidonic acid (AA) as substrate, horse platelet microsomes (HPM) as the source of TXA2 synthetase and left ventricle microsomes (LVM) from ischemic and non-ischemic areas as effectors TXB2, the stable metabolite of TXA2, was determined by radioimmunoassay. Experiments carried out under the adopted conditions showed that LVM from control hearts were able to inhibit by up to 50% the biosynthesis of TXA2 from HPM. This anti-TXA2 synthetase activity was more pronounced when LVM from the non-ischemic area were used, rather then LVM from the ischemic one. A 60 min reperfusion decreased the anti-TXA2 activity. A superfused rabbit aorta strip was also used as a cascade bioassay to study the effect of LVM on the TX2-synthetase activity of HPM, and this confirmed our findings. These results suggest that the left ventricle possesses a self-defense mechanism against acute myocardial ischemia, independently from the circulation. The postulated mechanism may be initiated in the non-ischemic area.     

高氧液预处理对兔心肌缺血再灌注损伤的影响

目的:研究高氧液预处理对兔心肌缺血再灌注损伤的影响。方法:雄性新西兰白兔32只,随机分为4组(n=8),结扎-开放冠状动脉左前降支(LAD)建立心肌缺血再灌注模型。假手术组(Sham组)只穿线环绕LAD不结扎;吸氧组(OX组)结扎前30 min经鼻吸纯氧2L/min;在结扎LAD前30 min分别静脉注射HO 10 ml/kg(HO1组)、20 ml/kg(HO2组)。于结扎LAD前即刻(T0,基础值)、开放LAD前即刻(T1)、再灌注60 min(T2)及再灌注120 min(T3)时记录HR和MAP,于T3时抽取动脉血样3 ml,测定血清肌酸激酶(CK)、肌钙蛋白I(cTNI)的活性和IL-6和TNF-α的浓度,并测定心肌梗死范围。结果:I/S组与T0时比较,T 1-3时各组HR、MAP进行性下降(P<0.05);三组间HR、MAP比较差异无统计学意义(P>0.05)。与Sham组比较,I/S组血清CK、cTNI、IL-6和TNF-α含量明显升高(P 0.01);与OX组比较,HO2组上述酶及炎症因子浓度显著下降(P<0.01),心肌梗死范围减小(P<0.05)。结论:高氧液预处理可减轻兔心肌缺血再灌注损伤,机制可能与其抑制炎性反应有关。     

Microdialysis separately monitors myocardial interstitial myoglobin during ischemia and reperfusion

Direct monitoring of myoglobin efflux during ischemia and reperfusion has been limited because of inherent sample collection problems in the ischemic region. Recently, the cardiac dialysis technique has offered a powerful method for monitoring myocardial interstitial levels of low-molecular-weight compounds in the cardiac ischemic region. In the present study, we extended the molecular target to high-molecular-weight compounds by use of microdialysis probes with a high-molecular-mass cutoff and monitored myocardial interstitial myoglobin levels. A dialysis probe was implanted in the left ventricular free wall in anesthetized rabbits. The main coronary artery was occluded for 60 or 120 min. We examined the effects of myocardial ischemia and reperfusion on myocardial interstitial myoglobin levels. Interstitial myoglobin increased within 15 min of ischemia and continued to increase during 120 min of ischemia, whereas blood myoglobin increased at 45 min of ischemia. Lactate and myoglobin in the interstitial space increased during the same period. At 60 min of ischemia, reperfusion markedly accelerated interstitial myoglobin release. The interstitial myoglobin level was fivefold higher at 0-15 min of reperfusion than at 60-75 min of coronary occlusion. The dialysis technique permits earlier detection of myoglobin release and separately monitors myoglobin release during ischemia and reperfusion. Myocardial interstitial myoglobin levels can serve as an index of myocardial injury evoked by ischemia or reperfusion.     

Left ventricular catecholamines during acute myocardial infarction in the dog

To determine whether changes in left ventricular catecholamine content occur during the first 30 to 90 min of acute myocardial infarction, myocardial catecholamine (radioenzymatic assay) over the interval was studied in the dog. In nine pentobarbital-anesthetized opened-chest dogs without coronary ligation, myocardial catecholamine at 2.5 h after pentobarbital (i) consisted mainly of norepinephrine (87% total catecholamine), (ii) showed a base to apex gradient in norepinephrine (1.44 +/- 0.10 vs. 1.03 +/- 0.10 micrograms/g, p less than 0.05) and dopamine (0.20 +/- 0.03 vs. 0.12 +/- 0.02 micrograms/g, p less than 0.05) but not epinephrine (0.017 vs. 0.016 micrograms/g), and (iii) showed no difference in norepinephrine, dopamine, or epinephrine across basal, mid, and apical left ventricular transverse planes spanning the vascular territories of the two coronary arteries. In 18 pentobarbital-anesthetized dogs with coronary ligation, (i) norepinephrine, measured in 14 regions across the mid left ventricle after 90 min ischemia in four dogs, was less in the ischemic center of the occluded bed than normal myocardium (1.01 +/- 0.04 vs. 1.29 +/- 0.04 micrograms/g, p less than 0.05), and (ii) norepinephrine was unchanged in normal myocardium of 14 dogs at 30, 60, 90 min, and 48 h but decreased in ischemic myocardium by 31% at 60 min (0.89 +/- 0.10 vs. 1.29 +/- 0.08 micrograms/g, p less than 0.025) and 79% at 48 h (0.27 +/- 0.04 vs. 1.26 +/- 0.08 micrograms/g, p less than 0.001). Thus, norepinephrine depletion from ischemic but not normal myocardium is detectable by 60 min during acute myocardial infarction.     

Impulse activity of the nodose ganglion neurons in myocardial ischemia

Standard microelectrode techniques were used to study the impulse activity of different types of nodosal ganglion neurons in the course of the development of myocardial ischemia. The cardiopulmonary late inspiratory and inspiratory-expiratory neuronal responses were estimated upon ligation of the coronary artery during the first respiratory cycle after blood flow stoppage. Spontaneous activity of cardiopulmonary neurons was not dependent on coronary circulation disturbances at the moment of coronary artery ligation. Later on, however, during the development of myocardial ischemia, there occurred substantial changes in all the types of nodosal ganglion neuronal activity, excluding real inspiratory neurons.     

Emoxipin in reperfusion of ischemic myocardium in dogs: effects on infarct size and plasma creatine kinase activity

The effects of synthetic antioxidant emoxypine on infarct size and plasma creatine kinase (CK) activity was studied on open-chest anesthetized dogs with 180-min myocardial ischemia followed by reperfusion. Emoxypine (10 and 40 mg/kg) was injected intravenously, beginning since 120th min of coronary artery occlusion. Emoxypine (10 mg/kg) resulted in infarct size limitation and reduction in plasma CK activity. An increase in dose of emoxypine to 40 mg/kg largely attenuated its protective effect on infarct size. CK activity during post-ischemic reperfusion was even higher in emoxypine (40 mg/kg) group compared with control. Augmented CK leakage from irreversibly injured myocardium to plasma under these experimental conditions may be owing to preservation of microvascular integrity and improving of drainage of infarcted tissue exerted by emoxypine.     

Left ventricular interstitial 8-hydroxy-deoxyguanosine concentration following myocardial ischemia and reperfusion in anesthetized rats

Summary

The effect of myocardial ischemia and reperfusion on left ventricular interstitial 8-hydroxydeoxyguanosine (8-OH-dG), a possible biomarker for in vivo oxidative deoxyribonucleic acid damage, in anesthetized rats was investigated. A microdialysis probe was implanted. Levels of 8-OH-dG in microdialysates were analyzed via an on-line high performance liquid chromatography system equipped with an electrochemical detector. Myocardial ischemia for 10 or 20 min, induced by clamping of the left anterior descending coronary artery, did not affect 8-OH-dG levels. However, reperfusion following either 10-min or 20-min ischemia significantly increased 8-OH-dG levels in collected microdialysates. Reperfusion-induced increases in 8-OH-dG levels were more prominent in the 20 min ischemia group (as high as 3.5 fold relative to basal levels) than in the 10 min ischemia group as high as 2.0 fold relative to basal levels). In conclusion, we observed that left ventricular interstitial 8-OH-dG concentration increased following myocardial ischemia and reperfusion in anesthetized rats. These results suggest that 8-OH-dG might be a useful biomarker for oxidative damage following myocardial ischemia and reperfusion.