Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of cardiac markers to identify high-risk patients in the observation unit is undeniable. As the literature reviewed here reveals, the history and ECG miss a significant portion of patients with acute cardiac ischemia. It appears that acute MI and some high-risk "unstable angina" observation unit patients can be identified within 6 hours of hospital presentation using a combination of cardiac markers. Testing these patients soon after symptom onset or on arrival in the ED for myoglobin, CK-MB subforms, or CK-MB delta appears to provide the best diagnostic usefulness. For testing later in the clinical course, CK-MB troponin I, or troponin T are of clear diagnostic and prognostic value. The markers currently used are unable to identify the significant subset of patients with "non-AMI" coronary syndromes, however. These patients require further testing with appropriate noninvasive or invasive diagnostic studies.
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PMID:Cardiac markers protocols in a chest pain observation unit. 1121 4

Recently, it has been demonstrated in multiple clinical research studies that non-Q-wave myocardial infarction shares many of the features of unstable angina pectoris and that both diseases initially are managed similarly. Important new antiplatelet drugs (glycoprotein IIb-IIIa inhibitors) and antithrombin agents (low-molecular-weight heparin) are currently recommended for patients with unstable angina pectoris/non-ST-segment elevation MI who are at high or intermediate risk on the basis of symptoms, electrocardiographic findings, and the presence or absence of serum markers (eg, troponin I, troponin T, and creatine kinase-MB). This review provides important information concerning the results of clinical studies of glycoprotein IIb-IIIa inhibitors (tirofiban hydrochloride and eptifibatide) when used with unfractionated heparin in patients with this syndrome or with low-molecular weight heparin (enoxaparin sodium) in similar patients. The Thrombolysis in Myocardial Infarction IIIB, Veterans Affairs Non-Q-Wave Infarction Studies in Hospital, and Fast Revascularization During Instability in Coronary Artery Disease II studies evaluating a conservative, ischemia-guided approach vs an early aggressive approach to such patients are presented, with a practical algorithm for treating such patients.
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PMID:New approaches to diagnosis and management of unstable angina and non-ST-segment elevation myocardial infarction. 1186 90

Myocardial stunning is a form of ischemic injury, which occurs with transient ischemia followed by re-establishment of flow, and which results in reversible cardiac dysfunction. There is evidence that the molecular defect in stunning is at the level of the contractile apparatus. Selective proteolysis of the myofilament protein, troponin I, appears to underlie the phenotype of stunning in some models, but other myofilament protein modifications may also have a role.
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PMID:The role of troponin abnormalities as a cause for stunned myocardium. 1149 Nov 98

p38 Mitogen-activated protein kinase (MAPK) is one of the most ancient signaling molecules and is involved in multiple cellular processes, including cell proliferation, cell growth, and cell death. In the heart, enhanced activation of p38 MAPK is associated with ischemia/reperfusion injury and the onset of heart failure. In the present study, we investigated the function of p38 MAPK in regulating cardiac contractility and its underlying mechanisms. In cultured adult rat cardiomyocytes, activation of p38 MAPK by adenoviral gene transfer of an activated mutant of its upstream kinase, MKK3bE, led to a significant reduction in baseline contractility, compared with uninfected cells or those infected with a control adenoviral vector (Adv-beta-galactosidase). The inhibitory effect of MKK3bE on contractility was largely prevented by coexpressing a dominant-negative mutant of p38 MAPK or treating cells with a p38 MAPK inhibitor, SB203580. Conversely, inhibition of endogenous p38 MAPK activity by SB203580 rapidly and reversibly enhanced cell contractility in a dose-dependent manner, without altering L-type Ca(2+) currents or Ca(2+)(i) transients. MKK3bE-induced p38 activation had no significant effect on pH(i), whereas SB203580 had a minor effect to elevate pH(i). Furthermore, activation of p38 MAPK was unable to increase troponin I phosphorylation. Thus, we conclude that the negative inotropic effect of p38 MAPK is mediated by decreasing myofilament response to Ca(2+), rather than by altering Ca(2+)(i) homeostasis and that the reduced myofilament Ca(2+) sensitivity is unlikely attributable to troponin I phosphorylation or alterations in pH(i). These findings reveal a novel function of p38 MAPK and shed a new light on our understanding of the coincidence of p38 MAPK activation and the onset of heart failure.
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PMID:p38 Mitogen-activated protein kinase mediates a negative inotropic effect in cardiac myocytes. 1183 12

Effects of ischemia time and treatment interventions upon troponin I (TnI) proteolysis and function of reperfused myocardium were examined in isolated, perfused rabbit hearts. Hearts were randomized to 90 min aerobic perfusion, 15 min low-flow (1 ml/min) ischemia (I) and 60 min reperfusion (R) or 60 min low-flow I and 60 min R. Hearts subject to 60 min I and 60 min R received either no treatment, l -arginine treatment, or treatment with oxygen free radical (OFR) scavengers (mercapto-proponyl-glycine, catalase and superoxide dismutase). Hearts from cholesterol-fed rabbits were also studied after 60 min I and R. Isovolumic LV pressure and heart rate were recorded throughout and Western analysis of ventricular myocardium, using 3 specific antibodies, detected intact TnI (29 kDa) and TnI fragment (25 kDa). Hearts subject to 15 min I had minimal irreversible injury (TTC negative region=0.6+/-0.4% LV) but hearts subject to 60 min I had more extensive injury (TTC negative=40.7+/-5.8% LV). Recovery of rate-pressure product after 15 min I and 60 min R (56+/-9% of baseline) was better than after 60 min I and 60 min R (23+/-9%, P<0.01). Both l -arginine and OFR scavengers were associated with better recovery of function after 60 min I, (66+/-7% and 72+/-3% of baseline respectively, P<0.01 v no treatment) but cholesterol hearts had poor recovery after 60 min I (37+/-8%). The 25 kDa TnI (% total TnI immunoreactivity) was 8.7+/-0.9% in controls, 10.0+/-1.6% after 15 min I and 60 min R, and 17.4+/-2.4% after 60 min I and 60 min R (P<0.01 v controls and 15 min I). The proportion of 25 kDa TnI was increased in all hearts after 60 min I and did not change with treatment (l -arginine 16.8+/-1.8%, OFR scavengers 16.0+/-3.2%, cholesterol 14.0+/-1.9%). There was no relation between proportion of 25 kDa TnI and recovery of function. Samples from freshly excised rabbit hearts and human right atria also had 25 kDa TnI (relative intensities 8.5+/-2.3% and 5.1+/-2.6% respectively). Although TnI fragmentation increases after prolonged ischemia and reperfusion, the functional recovery of stunned myocardium is independent of degree of TnI fragmentation.
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PMID:Effect of treatment on ventricular function and troponin I proteolysis in reperfused myocardium. 1199 27

To investigate the mechanism underlying postischemic contractile dysfunction (myocardial stunning) we examined myocardial sulflhydryl group content, myofibrillar Ca2+-dependent Mg2+-ATPase activity and protein profile after global ischemia and reperfusion. The Langerdorff-perfused rabbit hearts were subjected to 15 min normothermic ischemia followed by 10 min reperfusion and myofibrils were isolated from homogenates of left ventricular tissues. Depressed contractile function during reperfusion was accompanied by a decrease in total sulfhydryl group content. However, myofibrillar protein profile was unchanged and Western immunoblotting analysis showed no significant differences in troponin I immunoreactive bands between control and stunned hearts. Likewise, myofibrillar Mg2+-ATPase activity was unaltered after ischemia and reperfusion. We conclude that myocardial stunning is not caused by altered myofibrillar function and protein degradation but may be partly due to the oxidative modification of as yet undefined proteins.
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PMID:Effect of myocardial stunning on thiol status, myofibrillar ATPase and troponin I proteolysis. 1208 69

The present study investigated whether genistein, a broad-spectrum tyrosine kinase inhibitor, could increase the myofilament Ca(2+) sensitivity and partially reverse postischemic depressed myocardial function. Left ventricular papillary muscles were isolated from adult Wistar rats and loaded with the Ca2+ indicator, aequorin. The use of fluorocarbon immersion with hypoxia simulated a model of ischemia. Myofilament responsiveness to Ca2+ was evaluated from force-[Ca2+]i relationship recorded during tetani in papillary muscles. Protein levels of troponin I (TnI) were measured in postischemic papillary muscles with the Western blot technique. Isometric contraction was depressed during the period of ischemia and remained low after 60 min of reoxygenation without a corresponding significant change of peak [Ca2+]i in the control group (n = 7). In contrast, the depression of isometric contraction was ameliorated during ischemia in muscle preparations in the presence of genistein (2 micro M; n = 8), and postischemic depressed myocardial contractility partially recovered after a 60-min reperfusion. The myofilament Ca2+ responsiveness was significantly increased in papillary muscles in the presence of genistein. Protein levels of TnI were reduced in postischemic papillary muscles, whereas genistein partially restored decreased protein levels of TnI. Our results reveal that genistein produces an effective attenuation of postischemic depressed myocardial function and improves myofibrillar Ca2+ responsiveness in rat myocardium.
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PMID:Genistein attenuates postischemic depressed myocardial function by increasing myofilament Ca2+ sensitivity in rat myocardium. 1219 6

Early exercise testing (first 24 hours) was evaluated in the stratification of patients seen in the emergency room for chest pain. One hundred and forty-two consecutive patients without ischemia in the ECG or troponin I elevation were included. Ninety-two patients were discharged after the exercise testing (group I, 82 negative and 10 inconclusive test results) and 50 patients were hospitalized (group II, 29 positive and 21 inconclusive test results). In group I, cardiac events (unstable angina and non-fatal infarction) occurred in the next 30 days of follow-up in 2 patients with inconclusive test results; no cardiac events occurred in patients with negative test results. In group II, unstable angina was diagnosed in 30 patients and 3 presented recurrent angina. There were no complications during exercise testing. In conclusion, early exercise testing is safe and useful in the stratification of patients seen in the emergency room for chest pain. Only patients with negative test results should be discharged early.
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PMID:[Value of early exercise stress testing in a chest pain unit protocol]. 1238 83

Degradation of troponin I (TnI) by calpain occurs with myocardial stunning in ischemia-reperfusion injury. Glucocorticoids attenuate myocardial ischemia-reperfusion injury, but their effect on TnI degradation is unknown. A piglet model was used to test the hypotheses that cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) are associated with TnI degradation and that TnI alterations could be prevented by glucocorticoid treatment. Piglets were cooled to 18 degrees C, subjected to 2 h of circulatory arrest, rewarmed to 37 degrees C, and allowed to recover for 2 h. Methylprednisolone was administered 6 h before surgery (3 0 mg/kg) and at initiation of CPB (30 mg/kg). The untreated group received saline. Left ventricular tissue was collected after recovery and analyzed by Western blot for TnI, calpain, and calpastatin (the natural inhibitor of calpain). CPB/DHCA animals had 27.4 +/- 0.2% of total detected TnI present in degraded form. Glucocorticoid treatment significantly decreased the percentage of degraded TnI (12.0 +/- 0.1%, p < 0.05). Calpain I and calpain II increased after CPB/DHCA compared with non-CPB/DHCA controls (p < 0.05), with or without glucocorticoid treatment. Calpastatin significantly decreased in untreated CPB/DHCA animals compared with non-CPB/DHCA controls (p < 0.05), but levels were preserved by glucocorticoids. Glucocorticoids were associated with preservation of maximum rate of increase of left ventricular pressure at 95 +/- 10% of baseline, whereas maximum rate of increase of left ventricular pressure decreased to 62 +/- 12% of baseline without steroids. TnI degradation occurs after CPB/DHCA in neonatal pigs. Reduction in reperfusion injury by glucocorticoids may depend partly on preservation of calpastatin activity and intact TnI.
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PMID:Glucocorticoids preserve calpastatin and troponin I during cardiopulmonary bypass in immature pigs. 1264 18

Myocardial stunning is defined as the prolonged contractile dysfunction following an ischemic episode that does not result in necrosis, which also occurs in patients with coronary artery disease. There is also evidence to consider myocardial stunning as a fundamental component of hibernating myocardium. Various experimental approaches (from a brief episode to prolonged partial ischemia) and animal models (from rodents to large mammals) have been developed to investigate the pathogenesis of myocardial stunning. Three hypotheses to explain the mechanism, i.e. oxygen radical, Troponin I degradation, and Ca(2+), have been proposed. The first was tested primarily using large mammalian models, whereas the others were tested primarily using rodent models. Recently, the Ca(2+) handling hyothesis has been tested in a large mammalian swine model of myocardial stunning, in which both Ca(2+) and transients and L-type Ca(2+) current density were decreased. Relaxation function and phospholamban phosphorylation are also radically different in large mammalian and rodent models. In addition, troponin I degradation, which was identified as the mechanism of stunning in rodent models, was not found in stunned swine myocardium. Interestingly, the large mammalian model demonstrates that stunning elicits broad changes in gene and protein regulation, some of which have not been observed in the heart previously. The overall genomic adaptation upregulates the expression of survival genes that prevent irreversible damage. Pursuing these new concepts derived from large mammalian models of ischemia/reperfusion will provide more comprehensive mechanistic information underlying myocardial stunning and will serve to devise new therapeutic modalities for patients.
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PMID:Novel mechanisms mediating stunned myocardium. 1276 93


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