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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several studies have suggested that L-carnitine may limit the cellular alterations induced by myocardial hypoxia or ischemia. In the present study, rats were subjected to chronic treatment with L-carnitine (0, 25, 50 or 200 mg/kg/day i.p.) for 9 days prior to being submitted to permanent regional myocardial ischemia by left coronary artery ligation in situ. Following 48 hours of coronary occlusion, infarct size was measured using planimetry of transverse sections of the hearts, which had been stained with nitro-blue tetrazolium. Various functional and metabolic parameters have also been measured in isolated perfused hearts. Treatment with L-carnitine at 200 mg/kg/day i.p. for 9 days led to a significant reduction in infarct size and a better preservation of residual cardiac function. However, none of the metabolic parameters measured were modified. In conclusion, we suggest that the preservation of cardiac contractile function observed with L-carnitine pretreatment is secondary to carnitine-induced infarct size limitation.
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PMID:Cardioprotective effect of L-carnitine in rats submitted to permanent left coronary artery ligation. 751 37

The aim of this study was to determine whether pharmacologic preconditioning, without a short episode of myocardial hypoxia or ischemia, could improve myocardial function after a prolonged period of ischemia. Isolated rat hearts were perfused with .01, .1 or 1 mg/L of phenylephrine for 5 min followed by a 10-min washout period (preconditioning) before the induction of 30 min of normothermic global ischemia and 30 min of reperfusion. Hearts preconditioned with increasing concentrations of phenylephrine (an alpha-1 adrenergic receptor agonist) produced a reduction in the incidence of reperfusion-induced ventricular fibrillation (VF) and ventricular tachycardia (VT). Preconditioning of the hearts with the highest dose of phenylephrine (1.0 mg/L), after 30 min of ischemia, reduced the incidence of reperfusion-induced VF and VT from their nonpreconditioned control values of 87% and 100% to 33% (P < .05) and 50% (P < .05), respectively. After 30 min of ischemia, the recovery of myocardial function was significantly improved in phenylephrine-preconditioned groups. Thus, .1 and 1.0 mg/L of phenylephrine increased aortic flow from its nonpreconditioned control value of 10.8 +/- .9 ml/min to 22.4 +/- 2.4 ml/min (P < .05) and 26.5 +/- 1.5 ml/min (P < .05), respectively. Phenylephrine (1.0 mg/L) preconditioning significantly reduced ischemia/reperfusion-induced tissue Na+ and Ca2+ gains and prevented K+ and Mg2+ loss measured by an atomic absorption spectro-photometer. Our results show that alpha-1 adrenergic stimulation (preconditioning) can prevent postischemic abnormalities in intracellular ions, reperfusion arrhythmias, and contractile function without the inhibition of O2 delivery.
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PMID:Alpha-1 adrenergic receptor agonist-induced preconditioning in isolated working rat hearts. 775 71

The major enzyme responsible for adenosine production during myocardial hypoxia or ischemia is 5'-nucleotidase. We purified an AMP-specific 5'-nucleotidase to homogeneity from the 150,000-g supernatant of dog heart homogenate using phosphocellulose, DEAE-cellulose, and ADP-agarose affinity chromatography. Sodium dodecyl sulfate-poly-acrylamide gel electrophoresis of the purified enzyme yielded a single protein band of 43 kDa. The molecular mass of the holoenzyme, determined by gel filtration and sucrose density-gradient centrifugation, was approximately 166 kDa, suggesting a tetrameric structure. Dog heart cytosolic 5'-nucleotidase was active at physiological pH (6.8-7.8) and demonstrated a preference for AMP over IMP as substrate. The enzyme exhibited sigmoidal saturation kinetics, with half-maximal activity at 2.6 mM AMP in the absence of ADP. ADP (0-250 microM) activated cytosolic 5'-nucleotidase by increasing maximal velocity and affinity for AMP. The enzyme was inhibited by 4 mM ATP, but 5'-nucleotidase activity increased as [ATP] was reduced. Mg2+ was required for activity, with maximal activation at approximately 3.5 mM free Mg2+. These data suggest that the regulation of AMP-specific cytosolic 5'-nucleotidase by adenine nucleotides and free Mg2+ may be important in the production of adenosine during conditions promoting ATP hydrolysis, such as myocardial hypoxia or ischemia.
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PMID:Purification and regulation of an AMP-specific cytosolic 5'-nucleotidase from dog heart. 849 66

Misonidazole and related compounds are metabolically trapped in viable cells as a function of reduced cellular pO2. [18F]fluoromisonidazole has been used to detect hypoxia in the heart and in tumors noninvasively with positron emission tomography. The purpose of this study was to characterize the uptake of the iodinated misonidazole congener iodovinylmisonidazole (IVM) in ischemic myocardium. In six open chest dogs (Group 1), the left anterior descending (LAD) coronary artery was partially occluded and in four dogs (Group 2), demand ischemia was produced by the combination of atrial pacing and catecholamine infusion in the presence of a LAD stenosis. [131I]IVM (5-15 microCi/kg, i.v.) was given following the onset of ischemia. Tracer deposition was measured by postmortem tissue sampling 4 hr postinjection and compared to microsphere myocardial blood flow (MBF) measurements made at baseline and at 2 hr postinjection. In Group 1, regional IVM deposition in heart samples within the ischemic area was inversely related to MBF with maximum tissue:blood ratios of 3.2. For a given level of reduced blood flow, IVM uptake was higher in the subendocardium indicating a greater vulnerability of the subendocardium to reductions in oxygen delivery. In Group 2, enhanced IVM deposition was detected as a result of demand ischemia, even in some regions where absolute flow was normal or increased from baseline, indicating that flow per se is not the principal determinant of tracer uptake. We conclude that IVM is a promising marker for myocardial hypoxia with potential clinical application using gamma camera imaging.
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PMID:Characterization of iodovinylmisonidazole as a marker for myocardial hypoxia. 850 59

It is almost twenty-five years since stress myocardial perfusion imaging was first described for the detection of ischemia. Since that time, significant refinements have occurred in the technology of making the measurements, and in the range of clinical indications to perform these measurements. In parallel with the growth of radionuclide techniques, other imaging technologies have developed substantial tools to examine the heart. Although radionuclide imaging remains unique in its ability to visualize the regional distribution of perfusion, the value of perfusion imaging is being called into question by practitioners of the competing technologies. To address these comments, every facet of the examination should be reviewed, and the examination tailored to answer the specific clinical question raised by the patients condition. Particular attention should be paid to data interpretation and the specific choice of words used to describe the images in the report. In addition, the information provided by the examination can be enriched by adding measurements of ejection fraction, regional wall motion and regional wall thickening to the procedure. This combination of additional data and a clear, clinically focussed report make the information more valuable to the referring clinician. Several new techniques are on the horizon, including 99mTc glucarate imaging, to identify acute myocardial necrosis, and direct identification of myocardial hypoxia with 99mTc labeled nitroimidazoles. Initial studies in humans with glucarate suggest that acute necrosis can be identified with one hour of onset of chest pain. Experimental studies with the nitroimidazoles suggest that they will be valuable to identify myocardial ischemia as a zone of increased uptake. Both techniques may be useful in the evaluation of patients presenting with chest pain syndromes in the emergency room. Other areas of potential promise include the possibility of detecting residual clots following thrombolytic therapy and identifying macrophages in unstable plaque.
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PMID:Myocardial perfusion imaging: perspectives from a turbulent twenty-five years. 868 Oct 9

Impairment of myocardial contraction ("myocardial stunning") occurs during reperfusion after short ischemic periods. Substance P (SP) is widely distributed in heart and can be released by various stimuli including myocardial hypoxia. Our previous study shows SP has a negative inotropic effect in guinea pig heart. The objective of this study was to investigate whether SP contributes to the myocardial stunning after brief global ischemia. Guinea pig hearts in a Langendorff preparation were subjected to 15 min of global ischemia followed by 60 min reperfusion. Experiments were performed without and with pretreatment with neurokinin-1 (NK1) receptor antagonists, spantide (10(-6)M) or CP-99,994-01 (10(-6)M) in order to study the role of SP. Experiments were also performed in hearts which were perfused with atropine, phentolamine, and nadolol (10(-6)M each) to examine the role of neurotransmitters and autonomic receptors. A group of hearts obtained from capsaicin-pretreated guinea pigs was also investigated. Left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), heart rate, and perfusion pressure were monitored. At the end of reperfusion, the LVDP of control hearts recovered to only 55 +/- 6% (+/- SEM) of preischemic baseline and the LVEDP increased significantly (P > 0.05). With pretreatment with spantide or CP-99,994-01, LVDP recovered to 88 +/- 2% or 78 +/- 2% of the preischemic baseline, respectively. The LVEDP of these hearts was not different from preischemic baseline and much smaller than in control hearts. There were no differences in heart rate and perfusion pressure compared to baseline among all groups. Similar results were obtained in hearts perfused with autonomic blockers. However, recoveries of LVDP and LVEDP were faster in hearts perfused with autonomic blockers during the first 10 min of reperfusion. Pretreatment with capsaicin also significantly improved recovery of LVDP and LVEDP. In conclusion, substance P is involved in postischemic myocardial dysfunction and neurokinin-1 receptors mediate this action. The NK1 receptor antagonists may be useful in prevention of "myocardial stunning".
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PMID:The role of substance P in myocardial dysfunction during ischemia and reperfusion. 893 6

Increased tolerance to ischemia exhibited in chronically hypoxia immature rabbit hearts is associated with increased activation of ATP-sensitive potassium (KATP) channels. We determined whether exposure to hypoxia from birth alters the electrophysiological characteristics of Purkinje fibers obtained from rabbits (n = 12/group) which were raised in a normoxic (F O2 = 0.21) or hypoxic (F1O2 = 0.12) environment from birth to 9 days of age and the involvement of the KATP channel. The endocardial surface was exposed and impaled with microelectrodes to record action potential characteristics from Purkinje fibers under control conditions and following exposure to glibenclamide (3 microM). Action potential durations (APD)90 in Purkinje fibers were significantly shorter in hypoxic hearts compared with normoxic controls (110 +/- 5 ms v 121 +/- 4 ms). Glibenclamide increased APD90 in hypoxic hearts (120 +/- 4 ms) to values similar to those observed in normoxic controls (121 +/- 4 ms). Glibenclamide had no effect on APD90 in normoxic hearts. Maximum diastolic potential was more negative in hypoxic hearts and this effect was attenuated by glibenclamide. We conclude that chronic myocardial hypoxia results in a shorter APD as compared with normoxic controls by enhanced activation of KATP channels.
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PMID:KATP channel activation in a rabbit model of chronic myocardial hypoxia. 914 Aug 41

To avoid damage of myocardial ischemia, myocardial hypoxia and reperfusion injury, we designed mitral valve replacement in beating heart under extracorporeal circulation with low dose temperature of 31 degrees C to 35 degrees C in 137 cases of rheumatic heart disease, congenital heart disease mitral stenosis and mitral insufficiency, or concurrent aortic insufficiency. The patients were rept in unblocking aorta, unfilling cardiac arrest perfusion, idle pulse and dradycardia of 40-50 times/min, nose temperature of 32 +/- 1 degrees C. Patients with concurrent aortic insufficiency should first undergo replacement of aorta under cold cardiac arrest and then replacement mitral valve under beating heart to reduce the time of cold heart ischemia. Plastic surgery for tricuspid valve was done under beating heart. Good postoperative prognosis was nated: an average arterial pressure of 9.5-10.5 kPa (70 to 80 mmHg), dose of dopamine was obviously reduced. No low cardiac output syndrome, acute renal failure and severe arrythmia were observed in 137 cases, except 4 deaths due to infection and blood coagulation (2.9%). A left cardiac chamber no-level air removal device and aorta perfusioner leading flow device were designed for exsufflation of left pneumatocardia.
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PMID:[Mitral valve replacement under beating heart in 137 cases]. 959 Jul 59

Bassett and Howley contend that the 1996 J. B. Wolffe lecture is erroneous because: 1) A. V. Hill did establish the existence of the "plateau phenomenon," 2) the maximum oxygen consumption (VO2max) is limited by the development of anaerobiosis in the active muscle, and 3) endurance performance is also determined by skeletal muscle anaerobiosis because the VO2max is the best predictor of athletic ability. As a result, 4) cardiovascular and not skeletal muscle factors determine endurance performance. They further contend that Hill's "scientific hunches were correct," requiring "only relatively minor refinements" in the past 70 yr. But the evidence presented in this rebuttal shows that Hill neither sought nor believed in either the "plateau phenomenon" or the concept of the individual maximum oxygen consumption. These twin concepts were created by Taylor et al. (97) in 1955 and erroneously attributed to Hill. Rather Hill believed that there was a universal human VO2max of 4 L x min(-1). His error resulted from his incorrect belief that the real VO2 unmeasurable because it includes a large "anaerobic component," rose exponentially at running speeds greater than 13.2 km x h(-1). But Hill and his colleagues were indeed the first to realize the danger that a plateau in cardiac output (CO) and hence in VO2 would pose for the heart itself. For unlike skeletal muscle, the pumping capacity of the heart is both dependent on, but also the determinant of, its own blood supply. Thus, if the CO reaches a peak causing the "plateau phenomenon," the immediate cause of that peak will have been a plateau in myocardial oxygen delivery, causing a developing myocardial ischemia. The ischemia must worsen as exercise continues beyond the supposed VO2 "plateau." To accommodate this dilemma, Hill and his colleagues proposed a governor "either in the heart muscle or in the nervous system" necessary to prevent myocardial ischemia developing during maximal exercise. This governor would cause maximal exercise to terminate before the development of a plateau in either coronary flow, CO, or VO2, or the onset of skeletal muscle anaerobiosis. Accordingly, a new physiological model is proposed in which skeletal muscle recruitment is regulated by a central "governor" specifically to prevent the development of a progressive myocardial ischemia that would precede the development of skeletal muscle anaerobiosis during maximum exercise. As a result cardiovascular function "limits" maximum exercise capacity, probably as a result of a limiting myocardial oxygen delivery. The model is compatible with all the published findings of cardiovascular function during exercise in hypobaric hypoxia, in which there is a greater likelihood that myocardial hypoxia will develop.
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PMID:Maximal oxygen uptake: "classical" versus "contemporary" viewpoints: a rebuttal. 1064 33

Direct "hot spot" imaging of myocardial tissue hypoxia is potentially of great clinical importance because available noninvasive approaches for the detection of myocardial ischemia have generally been based on the detection of flow heterogeneity or identification of regional alterations of myocardial metabolism. These existing approaches provide only an indirect assessment of regional myocardial ischemia, and may be affected by either sympathetic activation or substrate availability. The assessment of tissue oxygenation with hypoxic compounds may be the best indicator of the balance of flow and oxygen consumption. These compounds may provide a means of identifying dysfunctional chronically ischemic but viable "hibernating" myocardium and find a critical place in the assessment of angiogenesis. Nitroimidazole compounds hold promise for positive imaging of hypoxia in the heart. However, refinement of these compounds is needed to improve target specificity. The potential of technetium-99m (Tc99m) complexes derived from removal of the nitroimidazole moiety from a nitroimidazole-containing ligand is interesting and warrants further investigation. Experimental studies support the possibility of identifying myocardial hypoxia with the positron-emitting compound F18-fluoromisonidazole noninvasively. The potential of a Tc99m labeled nitroimidazole for positive imaging of myocardial ischemia is tremendous because single-photon imaging is more widely available. The true clinical potential of these nitroimidazole compounds can only be defined with future experimental and clinical studies. Ideally, these studies should include comparisons of tracer uptake with independent measures of regional ischemia or measures of oxygen tension, potentially using magnetic resonance imaging.
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PMID:The potential for myocardial imaging with hypoxia markers. 1053 35


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