Effect Of Brief Ischemia Research Articles

Effects of brief ischemia on oxygen consumption, tissue oxygenation, and blood flow during recovery from ischemia in rat skeletal muscle (674.13)

The effects of brief ischemia (5, 15, 30, and 60 s duration; Isch) on interstitial PO2 (PISFO2), arteriolar PO2 (PaO2), blood flow (Q) and O2 consumption (VO2) during the recovery period was observed in exteriorized spinotrapezius muscles of 29 male Sprague‐Dawley rats (284 ± 20 g) for intravital microscopy. Phosphorescence quenching microscopy was used to obtain PISFO2, PaO2 and VO2. Arteriolar blood flow was calculated from arteriolar diameter and centerline RBC velocity obtained from an Optical Doppler Velocimeter. Ischemia was initiated by rapidly pressurizing an airbag attached to the microscope objective for a selected ischemic duration. The average baseline value of arteriolar blood flow was 5.8±0.8 µl/min; as expected, reactive hyperemia was observed during the recovery from Isch. Flow recovery (dQ/dt) was fastest [3.88±0.64 (µl·min‐1)/s] after 60 seconds of Isch. Average baseline PISFO2 was 62±4 mmHg; PISFO2 decreased to 75%, 34%, 10% and 2% of baseline following 5, 15, 30 and 60 s of Isch, respectively. Up to 30 s of ischemia, the rate of recovery of PISFO2 steadily increased as the ischemic duration increased; however, it dropped off following 60 s of ischemia. The drop in the rate of recovery of PISFO2 despite an increase in flow recovery following 60 s of ischemia is suggestive of a period of imbalance during which the rate at which the tissue was consuming oxygen temporarily exceed the rate at which it could be supplied. The rate of recovery of PISFO2 was fastest (4.2±0.7 mmHg/s) following 30 s of Isch. Average baseline VO2 was 120±19 nl O2/cm3·s and it increased above baseline during the early part of the recovery period. The time course of recovery of PISFO2 represented a balance between O2 delivery, proportional to local arteriolar blood flow, and local VO2.Grant Funding Source: NHLBI grant HL18292

The effects of brief ischemia and reperfusion on interstitial PO2 in the rat spinotrapezius muscle

The involvement of oxygen in reactive hyperemia following brief periods of local flow arrest was investigated by measuring PO2 under conditions of different ischemic durations of 5, 15, 30, 60, and 300 sec. Spinotrapezius muscles of anesthetized male Sprague‐Dawley rats were used; the muscle was covered with a gas barrier film to isolate it from atmospheric oxygen. Well perfused sites were chosen with one or more arterioles and a capillary network. Phosphorescence quenching microscopy was used to measure interstitial PO2 with a topically applied phosphorescent probe. Localized ischemia was produced by rapidly inflating an airbag over the muscle; reperfusion was initiated by deflating the bag. Baseline PO2 varied between 52 and 60 mmHg. During ischemia, PO2 dropped to 45 mmHg for 5 s ischemia down to 3 mmHg for >;30 s ischemia. Maximum PO2 during the reperfusion phase ranged from 52 to 71 mmHg. The time required for PO2 recovery to baseline ranged from 9 (5 s ischemia) to 122 sec (300 s ischemia). These data exhibited a positive correlation between ischemic duration and the time for PO2 recovery, as well as to the maximum PO2 reached during reperfusion. The data will be used to establish a relationship between ischemic duration and tissue oxygen consumption (VO2) during reperfusion.Support: NHLBI grant HL18292

Mitochondrial superoxide production and respiratory activity: Biphasic response to ischemic duration

Long bouts of ischemia are associated with electron transport chain deficits and increases in free radical production. In contrast, little is known regarding the effect of brief ischemia on mitochondrial function and free radical production. This study was undertaken to examine the relationship between the duration of ischemia, effects upon electron transport chain activities, and the mitochondrial production of free radicals. Rat hearts were subjected to increasing ischemic durations, mitochondria were isolated, and superoxide production and electron transport chain activities were measured. Results indicate that even brief ischemic durations induced a significant increase in superoxide production. This rate was maintained with ischemic durations less than 15 min, and then increased further with longer ischemic times. Mechanistically, brief ischemia was accompanied by an increase in NADH oxidase activity, reflected by a specific increase in complex IV activity. In contrast, longer ischemic durations were accompanied by a decrease in NADH oxidase activity, reflected by deficits in complexes I and IV activities.

Brief Episode of Myocardial Ischemia Before Prolonged Ischemia Attenuates Cardiac Sympathetic Nerve Injury

The aim of this study was to investigate the effects of brief ischemia before prolonged ischemia on cardiac sympathetic neural function. Brief ischemia inhibits the sympathetic neural release of norepinephrine (NE) during subsequent sustained ischemia. However, whether it can attenuate the neural function after sustained ischemia remains unknown. Sympathetic neural function was assessed using 123I-metaiodobenzylguanidine (MIBG) in patients who with (Group I) or without angina (Group II) within 3 days prior to acute myocardial infarction. In the rat experiment, cardiac interstitial NE (iNE) with or without pretreatment of 5-min coronary ligation was determined during a 30-min occlusion. Differences between MIBG and Thallium-201 for the total defect score were significantly greater in Group II than in Group I (6.1 +/- 4.0 vs 0.4 +/- 4.4). Levels of iNE were less in rats with a 5-min pretreatment (7.3 +/- 2.3 vs 18.6 +/- 5.9 x 10(3) pg/ml, p < 0.01) and MIBG uptake of ischemic region was greater (0.061 +/- 0.029 vs 0.031 +/- 0.011 %kg dose/g, p < 0.05) compared with rats without the pretreatment. A brief episode of ischemia attenuates the sympathetic neural injury caused by subsequent prolonged ischemia and this protective effect is associated with attenuation of NE release during the prolonged ischemia.

Effects of brief ischemia and reperfusion on the myocardium and the role of nitric oxide.

Brief myocardial ischemia/reperfusion has complex effects on the myocardium. In the short term the myocardium may be stunned with temporarily reduced contractile function, though this may also be accompanied by the modification and de novo synthesis of proteins that protect the heart against subsequent early or delayed insults. Repeated episodes of non-lethal ischemia, which are common in the clinical setting, combine all of these phenomena and may ultimately result in chronic contractile dysfunction. Nitric oxide is intimately linked to many of these alterations in cellular function and defense. This article examines data predominantly from in vivo large animal studies that relate to these ischemia-induced changes, the evidence for the proposed mechanisms behind both myocardial stunning and preconditioning while concentrating on the role of nitric oxide in these conditions.

Renal protection by brief liver ischemia in rats.

In this study, we evaluated the beneficial effect of brief ischemia and reperfusion, which was shown to have local effects on liver previously, on kidney as a remote organ in rats. Male Wistar rats were divided into three groups: group I, sham; group II, renal ischemia for 45 min; and group III, 10 min of brief hepatic ischemia and 10 min of reperfusion after 45 min of renal ischemia. Biochemical determination, tumor necrosis factor (TNF)-alpha and tissue thiobarbituric acid-reactive substances (TBARS) levels, and histopathologic findings were evaluated at 45 min and 24 hr of reperfusion. Although blood urea nitrogen and creatinine levels were similar at 45 min in groups II and III, these levels were lower in group III at 24 hr. Creatine clearance values were higher and fraction excretion of sodium values were lower in group II than in group III at 24 hr. Lactate dehydrogenase levels of groups III and II were similarly elevated at 45 min, whereas group III values decreased more rapidly than those of group II at 24 hr. At 45 min of reperfusion, TNF-alpha and tissue TBARS levels were found lower in group III than in group II. Histopathologic parameters including congestion and tubular vacuolization, tubular cell detachment, and necrosis were significantly reduced in group III as compared with results of group II 45 min after ischemia. All histopathologic parameters were defined as statistically better in group II at 24 hr. The beneficial effect of brief ischemia of liver on renal ischemia as a remote organ was confirmed by biochemical, histopathologic, and ultrastructural findings.

Preconditioning Skeletal Muscle Before Exercise: The Effects of Brief Ischemia and Reperfusion on MVC

Preconditioning Skeletal Muscle Before Exercise: The Effects of Brief Ischemia and Reperfusion on MVC

Undiminished mitochondrial function during stunning in rabbit heart at 28 degrees C.

To investigate effect of brief ischemia on mitochondrial function in intact myocardium, rather than in isolated mitochondria. The mitochondrial response was characterized by the mean response time (tmito) of cardiac mitochondrial O2 consumption to steps in heart rate. Isolated isovolumic rabbit hearts were perfused at 28 degrees C with a constant flow of Tyrode solution containing 11 mM glucose. O2 consumption and tmito were determined before ischemia and after 25 min of no-flow global ischemia during which hearts were either paced (I + P, n = 8) or unpaced (I - P, n = 8). A non-ischemic control group (N = 8) was also examined. At 20 min reperfusion, developed left ventricular pressure (DLVP) after I + P was decreased to 47 +/- 3% (mean +/- s.e.m.; P < 0.05) of control DLVP without significant changes in venous creatine kinase efflux, indicating contractile stunning. In contrast complete contractile recovery was observed after I - P. Before ischemia, tmito was 11.2 +/- 0.6 and 14.9 +/- 0.7 s for heart rate steps from 60 to 70 and from 60 to 120 beats/min, respectively. The tmito was lower (P < 0.05) for the corresponding downward steps (10.5 +/- 0.6 and 12.4 +/- 0.6 s, respectively). An increase (P < 0.05) in tmito was observed in the course of the experiment for upward (1.2 +/- 0.3 s) and downward steps (1.4 +/- 0.3 s), but the change was similar after ischemia to that in time-matched controls (P > 0.05, both for I - P and I + P vs. control). Oxygen consumption, compared at fixed levels of the rate x pressure product, was unchanged after ischemia (P > 0.05, for both I - P and I + P vs. controls), suggesting undiminished efficiency of mitochondrial ATP production. Twenty-five minutes ischemia does not affect mitochondrial function in rabbit hearts at 28 degrees C, even when contractile stunning resulted.

Electrophysiologic recovery in postischemic, stunned myocardium despite persistent systolic dysfunction

Previous investigators have hypothesized that myocardial “stunning” may result either from a primary impairment in excitation or from electromechanical dissociation. Thrombolytic therapy and angioplasty have increased the importance of understanding the electrophysiologic effects of brief ischemia followed by reperfusion. We investigated the electrophysiologic properties of mechanically dysfunctional stunned myocardium in 18 dogs anesthetized with pentobarbital (30 mg/kg, intravenously administered). After thoracotomy, the proximal anterior descending coronary artery was occluded for 15 minutes, which was followed by 20 minutes of reperfusion. At baseline, peak ischemia, and 20 minutes of reperfusion, local electrogram durations, activation times, and refractory periods were measured from 12 standardized sites within the ischemic and border zones. Echocardiographic percentage of systolic wall thickening confirmed normal preischemic and markedly reduced postischemic function in the investigated region. Depspite the marked electrophysiologic abnormalities observed in the ischemic zone during ischemia, mean electrogram duration, calculated conduction velocity, and mean effective refractory period after 20 minutes of reperfusion had returned almost to baseline values 39.2 ± 11.5 msec versus 37.2 ± 12.1 msec, 0.65 ± 0.15 m/sec versus 0.68 ± 0.15 m/sec, and 134 ± 14 msec versus 131 ± 8 msec, respectively. Corresponding mean values within the ischemic border zone were similarly close to baseline values after reperfusion. There was no significant difference in local heterogeneity (coefficient of variation) within the ischemic or border zone after reperfusion versus baseline values. Although the postischemic electrophysiologic status returned to normal, systolic thinning and dyskinesis persisted in the region of measurement. The contractile dysfunction that results from reperfusion-induced injury can thus occur in the setting of apparent excitation-contraction uncoupling.