Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MRI myocardial tagging is now a well-developed method for evaluation of regional myocardial contraction. A series of progressively more refined imaging strategies, combined with advances in analytic strategies have provided a strong armamentarium of methods. Important insights into normal human physiology of left ventricular systolic and diastolic function have been developed using one-dimensional, two-dimensional and three-dimensional analyses of myocardial deformation. In disease states, improved understanding and detection of early alterations in myocardial function in hypertensive heart disease has been possible. In addition, improved understanding of effects of ischemia and infarction on regional function has been possible. Further, after acute myocardial infarction, clearer definition of the natural history of contractile dysfunction in the infarct region and the zone adjacent to the infarct have been possible. Similarly, effects on regional function of a number of important pharmacologic agents used for treatment, such as angiotensin converting enzyme inhibitors, beta blockers and angiotensin receptor blockers have been characterized. In the cardiomyopathies, myocardial tagging has permitted more reliable assessment of heterogeneity of segmental function, especially in hypertrophic cardiomyopathy. Finally, initial applications of myocardial tagging to assessment of right ventricular regional function in hypertrophied hearts with and without major congenital abnormalities have generated advances in understanding of effects of hypertrophy on right ventricular function.J. Magn. Reson. Imaging 1999;10:609-616.
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PMID:MRI myocardial tagging. 1054 69

The effect of an endothelin (ET) A/ETB receptor antagonist, TAK-044, and/or an angiotensin converting enzyme (ACE) inhibitor, temocaprilat, on myocardial metabolism and contraction during ischemia and reperfusion was examined by phosphorus 31-nuclear magnetic resonance (31P-NMR) in Langendorff rabbit hearts. After normothermic 15 min global ischemia, 60min of postischemic reperfusion was carried out. TAK-044 and/or temocaprilat was administered from 40 min prior to the global ischemia. Adenosine triphosphate (ATP), creatine phosphate, inorganic phosphate, pH, left ventricular systolic developed pressure (LVDev.P), left ventricular end-diastolic pressure (LVEDP) and coronary flow were measured. Twenty-eight hearts were divided into 4 experimental groups consisted of seven hearts each: Group I consisted of controls, Group II was perfused with TAK-044 (10(-6) mol/L), Group III was perfused with temocaprilat (10(-6) mol/L), and Group IV was perfused with TAK-044 (10(-6) mol/L) in combination with temocaprilat (10(-6) mol/L). Group II showed a more early recovery of ATP during postischemic reperfusion (82+/-3%) compared with Group I (71+/-3%). Group III showed a significant inhibition of the decrease in ATP during global ischemia (54+/-3%) compared with Group I (45+/-3%). Group IV also showed a significant marked inhibition of the decrease in ATP during global ischemia (59+/-5%) and a more significant improvement on recovery of ATP during postischemic reperfusion (86+/-3%) compared with the other 3 groups. There were no differences in LVDev.P, LVEDP and coronary flow among these groups. In conclusion, TAK-044 in combination with temocaprilat had a significant potentiation on myocardial metabolism during both ischemia and reperfusion.
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PMID:Effect of an endothelin receptor antagonist and an angiotensin converting enzyme inhibitor on metabolism and contraction in the ischemic and reperfused rabbit heart. 1055 19

Hospital mortality from acute myocardial infarction has decreased in the last two decades. Left ventricular dysfunction therefore have been mainly due to ischemia. After extensive myocardial infarction, there are processes of adaptation (remodeling) which result in altered geometry of the left ventricle. The effects of this on neurohormonal systems (organ regulation), on the changed ratio of myocyte mass and collagen content owing to reactive and reparative fibrosis (organ texture) and on the molecular and cellular mechanisms (organ structure) are of crucial importance. Depending on the structural changes, the myocardial contractility decreases. This is associated with an activation of the circulating renin-angiotensin-aldosterone system (RAAS). The fundamental knowledge available has led to the therapeutic use of ACE inhibitors in the post-infarct period. This treatment enabled a sustained reduction of mortality in several large-scale randomized studies. The effect of early administration in patients with clinical signs of heart failure and/or left ventricular dysfunction was very much greater compared to unselected controls. Only 17 and 13 patients had to be treated after selection in order to save one life in the AIRE and TREACE Study respectively (NNT: number needed to treat), whereas e.g. in the ISIS-4 study 200 unselected patients had to be treated. In clinical practice, however, this life-saving therapy is only used in every second patient requiring treatment. With consideration of an individual form of treatment (anterior infarction, large infarct area, reinfarction, clinical signs of heart failure as well as arterial hypertension and diabetes mellitus), a greater acceptance of evidence-based guidelines is thus desirable. Treatment with a high dose may be expected to be of additional benefit.
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PMID:[Left ventricular remodeling: pathophysiological mechanisms and therapeutic recommendations]. 1065 89

Primary diastolic failure is typically seen in patients with hypertensive or valvular heart disease as well as in hypertrophic or restrictive cardiomyopathy but can also occur in a variety of clinical disorders, especially tachycardia and ischemia. Diastolic dysfunction has a particularly high prevalence in elderly patients and is generally associated, with low mortality but high morbidity. The pathophysiology of diastolic dysfunction includes delayed relaxation, impaired LV filling and/or increased stiffness. These conditions result typically in an upward displacement of the diastolic pressure-volume relationship with increased end-diastolic, left atrial and pulmo-capillary wedge pressure leading to symptoms of pulmonary congestion. Diagnosis of diastolic heart failure requires three conditions: (1) presence of signs or symptoms of heart failure; (2) presence of normal or slightly reduced LV ejection fraction (EF > 50%) and (3) presence of increased diastolic filling pressure. Assessment of diastolic function can be performed with several non-invasive (2D- and Doppler-echocardiography, color Doppler M-mode, Doppler tissue imaging, MR-myocardial tagging, radionuclide ventriculography) and invasive techniques (micromanometry, angiography, conductance method). Doppler-echocardiography is the most useful tool to routinely measure diastolic function. Different techniques can be used alone or in combination to assess LV diastolic function, but most of them are dependent on heart rate, pre- and afterload. The transmitral flow pattern remains the starting point, since it is easy to acquire and rapidly categorizes patients into normal (E > A), delayed relaxation (E < A), and restrictive (E >> A) filling patterns. Invasive assessment of diastolic function allows determination of the time constant of relaxation from the exponential pressure decay during isovolumic relaxation, and the evaluation of the passive elastic properties from the slope of the diastolic pressure-volume (= constant of chamber stiffness) and stress-strain relationship (= constant of myocardial stiffness). The prognosis of diastolic heart failure is usually better than for systolic dysfunction. Diastolic heart failure is associated with a lower annual mortality rate of approximately 8% as compared to annual mortality of 19% in heart failure with systolic dysfunction, however, morbidity rate can be substantial. Thus, diastolic heart failure is an important clinical disorder mainly seen in the elderly patients with hypertensive heart disease. Early recognition and appropriate therapy of diastolic dysfunction is advisable to prevent further progression to diastolic heart failure and death. There is no specific therapy to improve LV diastolic function directly. Medical therapy of diastolic dysfunction is often empirical and lacks clear-cut pathophysiologic concepts. Nevertheless, there is growing evidence that calcium channel blockers, beta-blockers, ACE-inhibitors and AT2-blockers as well as nitric oxide donors can be beneficial. Treatment of the underlying disease is currently the most important therapeutic approach.
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PMID:Diastolic heart failure. 1072 7

The effect of angiotensin converting enzyme (ACE) inhibitor, temocaprilat and/or angiotensin II type 1 (AT1) receptor antagonist, CV-11974 on myocardial metabolism and contraction during ischemia and reperfusion was examined by phosphorus 31-nuclear magnetic resonance (31P-NMR) in Langendorff rabbit hearts. After normothermic 15 min global ischemia, postischemic reperfusion of 60min was carried out. Temocaprilat and/or CV-11974 were administered from 40 min prior to the global ischemia. Adenosine triphosphate (ATP), creatine phosphate (PCr), inorganic phosphate (Pi), intracellular pH (pHi), left ventricular developed pressure (LVDevP), left ventricular end-diastolic pressure (LVEDP) and coronary flow were measured. Twenty-eight hearts were divided into 4 experimental groups consisting of 7 hearts each: group I consisted of controls, group II was perfused with temocaprilat (10(-6)mol/L), group III was perfused with CV-11974 (10(-6)mol/L), and group IV was perfused with temocaprilat (10(-6)mol/L) in combination with CV-11974 (10(-6) mol/L). Groups II and III showed a significant (p<0.05) inhibition of an overshoot phenomenon of PCr during postischemic reperfusion compared with group I. Group IV also showed a more pronounced significant (p<0.01) inhibition of the overshoot of PCr during reperfusion compared with group I. Groups II, III and IV showed a significant (p<0.05) inhibition of the decrease in ATP during global ischemia (59+/-2, 54+/-3 and 54+/-7%, respectively) compared with group I (45+/-3%). Groups II and IV showed a significant (p<0.05) early recovery of ATP during reperfusion (81+/-2, 80+/-6%) compared with group I (71+/-3%) and group II (73+/-2%). Group IV showed no more significant recovery in ATP than group III. There were no differences in LVDevP, LVEDP and coronary flow among these groups. In conclusion, temocaprilat in combination with CV-11974 has significant potential for improving myocardial energy metabolism during both myocardial ischemia and reperfusion.
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PMID:Effect of angiotensin converting enzyme inhibitor and angiotensin II type 1 receptor antagonist on metabolism and contraction in ischemia-reperfused rabbit heart. 1078 50

Pyruvate dehydrogenase is one of the mitochondrial enzymes considered important in the regulation of oxidative metabolism. To further understand the relationship between its activity and ischemic brain damage we conducted three experiments. We studied the effects of (1) duration of cerebral ischemia, (2) the Ca2+ channel blocker, nicardipine, and (3) the immunosuppressant, FK506, on PDH activity and energy metabolites during ischemia and reperfusion. In the first study we also measured regional cerebral blood flow (rCBF). (1) Increasing the duration of the ischemic insult delayed the deactivation of PDH, slowed the resynthesis of high energy phosphates and the clearance of lactate, and impaired recovery of rCBF. Additionally, (2) nicardipine normalized PDH activities and improved the impaired metabolism after reperfusion, and (3) FK506 did not effect PDH activity, but significantly improved the impaired metabolism during the early phase of reperfusion. From these studies we conclude that PDH plays a role in the recovery of metabolism during reperfusion, and both nicardipine and FK506 improve metabolism during the early phase of reperfusion.
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PMID:[Studies on brain pyruvate dehydrogenase (PDH) activity and energy metabolites during ischemia and reperfusion]. 1079 Nov 3

It is of primary importance for the clinical cardiologist to keep in mind the parameters allowing an adequate prognostic stratification in post-infarct patients in view of making the best diagnostic and therapeutic choices. A diagnostic strategy, based on a pathophysiologic approach, should evaluate four aspects: spontaneous and stress-induced ischemia, myocardial viability, and ventricular arrhythmias. Spontaneous ischemia has an undefined prognostic value, especially in the thrombolytic era; therefore it seems reasonable to perform invasive procedures in patients who are not stabilized by an adequate medical therapy or with large jeopardized areas. In asymptomatic patients, a provocative stress test allows a more articulated decisional iter. It is preferably to perform the test by the most physiological exercise EKG, together with the echocardiographic imaging, after the acute phase. It has a high negative predictive value, but a low positive predictive value. The detection of myocardial viability is frequently performed, mainly in patients with large post-ischemic myocardial dysfunction. Among all the proposed methods, the echo-dobutamine test mainly allows to estimate patients in whom revascularization may result in more benefit. The role of ventricular arrhythmias as an independent prognostic factor is debated and has to be always considered in relationship to other parameters, particularly left ventricular function. Regarding the therapeutic strategy, the indications from recent trials, related to antithrombotic drugs, beta-blockers, ACE-inhibitors, nitrates, Ca-blockers and antiarrhythmic drugs, are emphasized.
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PMID:[Diagnostic and therapeutic strategies in post-infarct]. 1082 80

The clinical relevance of diastolic dysfunction in heart failure has recently been emphasized. In fact, the presence of signs of heart failure does not imply a depressed left ventricular systolic function; moreover, the severity of heart failure and effort tolerance are more closely related to diastolic than to systolic indexes. However, the principal trials about the treatment of heart failure were mainly addressed to patients with significant left ventricular systolic dysfunction, whereas the optimal therapy for diastolic dysfunction is not well known. The aim of this review was to assess the rationale and the therapeutic options in heart failure due to diastolic dysfunction. A diastolic dysfunction can be exclusive or associated with systolic dysfunction, as in dilated cardiomyopathy. It has to be noted that in this disease an improvement of diastolic function was demonstrated for most of the drugs currently employed in the treatment of heart failure, such as vasodilators, ACE inhibitors, beta-blockers, digitalis, and other inotropic drugs. Moreover, the favorable effect of the treatment on diastolic parameters (reduction of left ventricular filling pressure, regression of restrictive filling pattern) is associated with a positive prognostic impact. The main objective of the treatment of heart failure with preserved left ventricular systolic function is to control the symptoms by means of lowering high left ventricular filling pressure without significantly lowering cardiac output. According to the therapeutic guidelines of the American College of Cardiology/American Heart Association Task Force, the drugs indicated to treat symptomatic patients with heart failure and preserved left ventricular systolic function are diuretics and nitrates. Potentially useful, but with insufficiently proven efficacy are beta-blockers, calcium antagonists and ACE inhibitors, whereas direct vasodilators and inotropic drugs were considered inadvisable. It is important to remember that the treatment might possibly be oriented to the cause and also to the possible precipitating factors of the heart failure syndrome (i.e. ischemia, tachycardia, arrhythmias, hypertension). In conclusion, considering the relatively common incidence of heart failure due to prevalent diastolic dysfunction, and the few available data about the therapeutic options in these patients, large multicenter trials devoted to the treatment of this syndrome are needed.
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PMID:[Heart failure due to diastolic dysfunction: the treatment principles]. 1083 33

Cardiovascular disease is the leading cause of death in patients receiving dialysis. This is attributed in part to the shared risk factors of cardiovascular disease and end-stage renal disease. The risk factors for coronary artery disease include the classic cardiac risk factors of diabetes mellitus, hypertension, dyslipidemia, and smoking. Also in this population, hyperparathyroidism, hypoalbuminemia, hyperhomocysteinemia, elevated levels of apolipoprotein (a), and the type of dialysis membrane may play a role. Management begins with risk factor modification and medical therapy including aspirin, beta blockers, angiotensin converting enzyme (ACE) inhibitors, and lipid-lowering agents. Revascularization is often important, and coronary artery bypass grafting appears to be preferable to percutaneous transluminal coronary angioplasty. This is especially true for those with multivessel disease, impaired left ventricular function, severe symptoms, or ischemia. Congestive heart failure is another common problem in dialysis patients. The management includes correction of underlying abnormalities, optimal dialysis, and medical therapy. Data obtained from the general population indicate obvious benefits from ACE inhibitors and beta blockers, and these agents would be considered the therapies of choice. Erythropoetin is also an essential component of therapy, but the ideal hemoglobin concentration has yet to be determined. Peritoneal dialysis may be helpful in severe cases of heart failure. Pericarditis is seen in less than 10% of dialysis patients and is best diagnosed by clinical examination and echocardiography. Intensive dialysis is often the best initial therapy. Pericardiocentesis is reserved for the setting of pericardial tamponade, but a pericardial window is more definitive.
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PMID:Cardiac complications of end-stage renal disease. 1092 9

Multiple indirect lines of evidence point at a cardioprotective role for enhanced bradykinin formation. In particular, the inhibition of angiotensin-converting enzyme, also known as kininase II, can protect against cardiac ischemia, putatively via accumulation of bradykinin. To address whether an increase in kinin formation is sufficient to protect against cardiac ischemia, we studied transgenic rats harboring the human tissue kallikrein gene TGR(hKLK1) under the control of the metallothionein promoter, which drives expression of the transgene in various organs including the heart. We subjected the isolated hearts from transgenic rats and their transgene negative littermates to ex vivo regional cardiac ischemia and reperfusion. During the experiment, the hearts were treated with either vehicle or the specific bradykinin type 2 receptor antagonist HOE 140 (10-9 M). In the transgenic rats, overflow of nucleotide breakdown products upon reperfusion was significantly less (455 +-54 nmol/min/g in transgene negative rats vs. 270+-57 nmol/min/g in the transgenic rats, P.
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PMID:Increased kallikrein expression protects against cardiac ischemia. 1102 68


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