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

In a prospective trial, the diagnostic performance of the second version of the troponin T rapid assay (Trop T; cutoff 0.2 microg/L) was compared with the quantitative cardiac-specific troponin T assay (cTnT ELISA; cutoff 0.1 microg/L) and other established cardiac markers such as CK, CK-MB activity, CK-MB mass and myoglobin. Additionally, a 30-day follow-up was performed to determine the suitability of the Trop T assay and the reference markers for short-term risk stratification. Two-hundred-and-eighty-six consecutive patients with chest pain and suspected acute myocardial infarction (AMI) were enrolled in two CCU departments. Serial blood specimens were taken at admission and at 3, 6, 12, 24, 48, 72 and 96 h after admission. According to the biochemical criterion CK-MB mass, the patients were classified as having AMI in 154 patients (54%), unstable angina (UAP) in 72 patients (27%) and no evidence for acute cardiac ischemia in 55 patients (19%). Analytical method comparison of Trop T with cTnT ELISA (cutoff 0.1 microg/L) showed a good agreement, Trop T yielded only 4% false-negative and 3% false-positive results. The diagnostic performance of Trop T for the detection of AMI was only slightly inferior compared to cTnT ELISA. Beyond 12 h after admission, Trop T and cTnT ELISA maintained a sensitivity close to 100%, whereas the sensitivity of the other cardiac markers decreased sharply. The diagnostic sensitivity of Trop T for the detection of minor myocardial damage in UAP patients was the same as for cTnT ELISA. Death within 30 days' follow-up occurred only in AMI patients with a positive Trop T test result within the first 6 h after admission. The admission Trop T and cTnT ELISA were the only significant biochemical predictors of major cardiac events. In conclusion, these data show that Trop T has similar diagnostic sensitivity as cTnT ELISA and is a useful tool to confirm acute or subacute myocardial infarction. Trop T is an excellent marker in detecting minor myocardial damage in UAP patients and is suitable for short-term risk stratification.
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PMID:Time-dependent diagnostic performance of a rapid troponin T version 2 bedside test in patients with acute coronary syndromes. 1121 49

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

Diagnosis and risk stratification of patients with acute coronary syndromes remain extremely important in order to avoid unnecessary hospitalizations on the one hand, and to improve prognosis of these patients on the other. For diagnosis of acute coronary syndromes, an ECG should be obtained at rest, troponin T and I should be measured on admission and again 6 to 12 h later, and myoglobin or CK-MB should be determined in patients with recent syndromes and those with recurring ischemia. Risk should be assessed upon admission and repeatedly during the hospital stay. Early risk indicators are: age, male sex, previous manifestation of coronary artery disease, history of left ventricular dysfunction or congestive heart failure and ongoing chest pain, as well as ST depression, transient ST segment elevation, and elevated levels of troponin T or I. Longer term risk assessment in unstable coronary artery disease includes rest and stress echocardiography, exercise ECG, thallium scintigraphy, as well as coronary angiography and left ventriculography. Markers of high long-term risk are old age, prior history of myocardial infarction, diabetes, elevated levels of C-reactive protein, and the extent of coronary artery disease and left ventricular dysfunction.
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PMID:Diagnosis and risk stratification in patients with acute coronary syndromes according to ESC guidelines. 1156 70

We examined the effect of fibroblast growth factor (FGF)-2 on myocardial resistance to injury when administered after the onset of ischemia, in vivo and ex vivo, and the role of FGF-2 receptors and protein kinase C (PKC). FGF-2 was injected into the left ventricle of rats undergoing permanent surgical coronary occlusion leading to myocardial infarction (MI). After 24 h, FGF-2-treated hearts displayed significantly reduced injury, determined by histological staining and troponin T release, and improved developed pressure compared with untreated controls. An FGF-2 mutant with diminished affinity for the tyrosine kinase FGF-2 receptor 1 (FGFR1) was not cardioprotective. FGF-2-treated hearts retained improved function and decreased damage at 6 wk after MI. In the ex vivo heart, FGF-2 administration during reperfusion after 30-min ischemia improved functional recovery and increased relative levels of PKC subtypes alpha, epsilon, and zeta in the particulate fraction, in a chelerythrine-preventable mode; it also decreased loss of energy metabolites. We conclude that intramyocardial FGF-2 administration shortly after the onset of ischemia confers protection from acute and chronic cardiac dysfunction and damage; FGF-2 delivered during reperfusion protects from ischemia-reperfusion injury; and protection by FGF-2 requires intact binding to FGFR1 and is likely mediated by PKC.
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PMID:Acute protection of ischemic heart by FGF-2: involvement of FGF-2 receptors and protein kinase C. 1183 6

The aim of this study was to compare ischemic preconditioning (IPC) with two established methods of myocardial protection, namely cold crystalloid cardioplegia and intermittent cross-clamp fibrillation (ICCF), in coronary artery bypass graft (CABG) surgery. This was a prospective randomised study. Thirty CABG patients were randomised to receive: (a) St Thomas' cardioplegia solution no. 2; (b) ICCF; or (c) IPC (two 3-min periods of ischemia with 2-min of reperfusion). Surgery was performed under standardised conditions by one surgeon (WBP). The primary endpoint was cardiac troponin T release during the first 72 h after surgery. Mean troponin T at 72 h was significantly lower in the IPC group (0.5 microg/l; p=0.05, ANOVA) compared with the cardioplegia and ICCF groups (2.1 and 1.3 microg/l respectively). This suggests that ischemic preconditioning is superior at limiting myocardial necrosis during CABG, but there is no difference between cold crystalloid cardioplegia and intermittent cross-clamp fibrillation.
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PMID:A comparison between ischemic preconditioning, intermittent cross-clamp fibrillation and cold crystalloid cardioplegia for myocardial protection during coronary artery bypass graft surgery. 1204 34

In the heart, the contractile apparatus is adapted to the specific demands of the organ for continuous rhythmic contraction. The specialized contractile properties of heart muscle are attributable to the expression of cardiac-specific isoforms of contractile proteins. This review describes the isoforms of the thin filament proteins actin and tropomyosin and the three troponin subunits found in human heart muscle, how the isoform profiles of these proteins change during development and disease, and the possible functional consequences of these changes. During development of the heart, there is a distinctive switch of isoform expression at or shortly after birth; however, during adult life, thin filament protein isoform composition seems to be stable despite protein turnover rates of 3 to 10 days. The pattern of isoforms of actin, tropomyosin, troponin I, troponin C, and troponin T is not affected by aging or heart disease (ischemia and dilated cardiomyopathy). The evidence for proteolysis of thin filament proteins in situ during ischemia and stunning is evaluated, and it is concluded that C-terminal cleavage of troponin I is a feature of irreversibly injured myocardium but may not play a role in reversible stunning.
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PMID:Modulation of thin filament activation by breakdown or isoform switching of thin filament proteins: physiological and pathological implications. 1467 Aug 32

The purpose of this article is to describe mechanisms of cell death in patients with acute myocardial infarction, particularly the activation of the complement system. Various pro-inflammatory cytokines, released by the inflamed tissue, play a role in the activation of the complement system. Several complement inhibitors have been developed to reduce tissue damage following ischemia. According to animal studies the deleterious effects of activators of the complement system can be diminished by complement inhibition. Several clinical studies have been conducted for the potential treatment of cell injury during acute myocardial infarction. C1 inhibitor dose-dependently inhibited complement activation and appeared to reduce myocardial injury after reperfusion therapy in patients with acute myocardial infarction. C1 inhibitor dose-dependently reduced plasma levels of C4 activation fragments. In addition, cardiac enzymes (troponin T and creatine kinase-MB) returned to baseline levels more rapidly among patients treated with C1 inhibitor, compared with controls. Furthermore, preliminary results from a placebo-controlled trial indicate that treatment with intravenous pexelizumab (anti-C5 antibody) was well tolerated in a large number of patients undergoing coronary artery bypass graft surgery. Further, more randomized trials are necessary to clarify the clinical significance of this new and innovative treatment with complement inhibition.
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PMID:Prevention of cardiac cell injury during acute myocardial infarction: possible role for complement inhibition. 1472 77

We have previously shown that atherosclerotic apolipoprotein E-deficient (apoE(-/-)) x LDL receptor-deficient (LDLR(-/-)) mice develop myocardial infarction when exposed to hypoxic stress. This study was performed to assess the role of thrombin and thrombosis in this process. ApoE(-/-) x LDLR(-/-) mice were fed a cholesterol-rich diet for 8 mo and were then subjected to hypoxic stress while receiving isoflurane anesthesia. One group received a bolus dose (5.6 micromol/kg) of the thrombin inhibitor melagatran, and control animals received PBS 10 min before the hypoxic stress. The mice were exposed to 10 min of hypoxia followed by normoxia. Ten minutes after the stress, Alzet pumps delivering melagatran (20 nmol x kg x (-1)min(-1)) or PBS were implanted, and the mice were allowed to recover for 48 h. The cardiac response was analyzed by histology, immunohistochemistry, and serum troponin T assay. All animals showed reversible ECG changes as a sign of ischemia during hypoxic stress, and 50% developed infarctions afterward as judged by troponin T levels. The group that received thrombin inhibitor had significantly lower troponin T and smaller myocardial infarctions than the PBS-treated group. These data show that thrombin generation is an important pathogenetic factor and suggest that coronary thrombosis is involved in myocardial infarction in atherosclerotic mice. Exposure of atherosclerotic mice to hypoxia leads to myocardial infarction through a two-phase pathway in which acute transient ischemia is followed by thrombin-dependent, irreversible, myocardial ischemia and myocardial cell death.
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PMID:Thrombin inhibitor reduces myocardial infarction in apoE-/- x LDLR-/- mice. 1503 Nov 24

We have proposed that pharmacological preconditioning, leading to PKC-epsilon activation, in hearts improves postischemic functional recovery through a decrease in actomyosin ATPase activity and subsequent ATP conservation. The purpose of the present study was to determine whether moderate PKC-independent decreases in actomyosin ATPase are sufficient to improve myocardial postischemic function. Rats were given propylthiouracil (PTU) for 8 days to induce a 25% increase in beta-myosin heavy chain with a 28% reduction in actomyosin ATPase activity. Recovery of postischemic left ventricular developed pressure (LVDP) was significantly higher in PTU-treated rat hearts subjected to 30 min of global ischemia than in control hearts: 57.9 +/- 6.2 vs. 32.6 +/- 5.1% of preischemic values. In addition, PTU-treated hearts exhibited a delayed onset of rigor contracture during ischemia and a higher global ATP content after ischemia. In the second part of our study, we demonstrated a lower maximal actomyosin ATPase and a higher global ATP content after ischemia in human troponin T (TnT) transgenic mouse hearts. In mouse hearts with and without a point mutation at F110I of human TnT, recovery of postischemic LVDP was 55.4 +/- 5.5 and 62.5 +/- 14.5% compared with 20.0 +/- 2.9% in nontransgenic mouse hearts after 35 min of global ischemia. These results are consistent with the hypothesis that moderate decreases in actomyosin ATPase activity result in net ATP conservation that is sufficient to improve postischemic contractile function.
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PMID:Modest actomyosin energy conservation increases myocardial postischemic function. 1549 25


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