Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of calcium antagonists for postinfarct cardioprotection remains controversial. Several major trials have failed to show benefit, despite positive expectations based on promising experimental data. A clue to the problem with the calcium antagonists was provided by the diltiazem trial, in which an adverse effect in the presence of congestive heart failure masked a benefit in those without heart failure. Accordingly, the most recent trial, DAVIT-II, was carried out in patients in whom preexisting left ventricular failure had been excluded. One of the interesting byproducts of that study was the possibility that verapamil prevented postinfarct sudden death, which implies a potential antiarrhythmic mechanism. It is proposed that cytosolic calcium overload could play a role in ischemic ventricular fibrillation. Experimentally, calcium antagonists are most effective antifibrillatory agents when catecholamine stimulation is combined with acute ischemia, as would be the situation in the acute phase of myocardial infarction. This potential benefit of calcium antagonists may be offset in the presence of congestive heart failure because left ventricular dilation is directly arrhythmogenic. The ideal calcium antagonist, aimed at preventing postinfarct ischemic arrhythmias, but without a significant negative inotropic effect, could be based on 1 of 2 principles. First, the agent could be highly selective for the ischemic but not the nonischemic zone of the myocardium (ischemic-selective agent). Second, the agent could be highly vascular selective, so that left ventricular dilation would be avoided. A comparative study of these two types of calcium antagonists should be undertaken in postinfarct patients.
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PMID:Should calcium antagonists be used after myocardial infarction? Ischemia selectivity versus vascular selectivity. 836 8

The effects of MCI-154, a cardiotonic agent with Ca++ sensitizing actions, on the ischemic contractile failure and myocardial acidosis were studied in the dog heart, in which the left anterior descending coronary artery (LAD) was partially occluded for 90 min, and compared with those of dobutamine, milrinone, pimobendan and isosorbide dinitrate (ISDN). Partial occlusion of LAD decreased segment shortening (measured by sonomicrometry) and myocardial pH (assessed by a micro glass pH electrode) in the ischemic myocardium. MCI-154, when administered i.v. 30 min after ischemia, improved the segment shortening in the ischemic zone, whereas dobutamine, milrinone and pimobendan failed to improve it when the drugs increased peak positive left ventricular dP/dt. Among the cardiotonic agents tested only MCI-154 attenuated myocardial acidosis during ischemia. The degree of the attenuation of acidosis by MCI-154 was equivalent with that by ISDN. However, the improvement of the ischemic zone segment shortening by MCI-154 was more pronounced than that by ISDN. These results suggest that in addition to the attenuation of myocardial acidosis the positive inotropic action of MCI-154, presumably increasing the responses of myofilaments to Ca++, may be possibly responsible for the improvement of regional contractile function in the ischemic myocardium. Thus, MCI-154 may be useful in the management of ischemic heart failure.
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PMID:Beneficial effect of MCI-154, a cardiotonic agent, on ischemic contractile failure and myocardial acidosis of dog hearts: comparison with dobutamine, milrinone and pimobendan. 160 75

Ischemic hepatitis is not an uncommon complication of reversible severe hypotension or cardiac failure. The prognosis usually is determined by the cause of the initial hypotension or cardiac failure, rather than the subsequent hepatic dysfunction. We report a retrospective analysis of nine patients with ischemic hepatitis in which previously unreported clinical and biochemical abnormalities are noted. The clinical and biochemical course of the patients were reviewed until recovery or death from ischemic hepatitis. All the patients had a rapid striking elevation of aspartate aminotransferase, and lactic dehydrogenase, with an equally rapid resolution of these parameters. Abnormal serum glucose levels occurred in six patients (none of whom had a prior carbohydrate intolerance). Insulin therapy was given to three patients for a limited period. Renal impairment was manifest in all nine patients, and it resolved spontaneously within 10 days. Altered mental status was detected in six patients; the changes reverted to normal within 7 days of their onset. A preexisting anemia (hemoglobin less than 11.0 g/dl) was noted on admission in four patients, and it did not appear to potentiate the manifestations of the hepatic ischemia. We conclude that ischemic hepatitis should be anticipated in all patients with a recent history of systemic hypotension. It should be considered in the differential diagnosis of patients with unexplained hepatitis; the early massive rise in lactic dehydrogenase, the rapid fall in transaminases, and the early mild/moderate renal failure strongly suggest ischemic hepatitis. Patients with ischemic hepatitis can manifest reversible renal failure, mental confusion, and hyperglycemia which may require insulin for its control.
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PMID:Ischemic hepatitis: widening horizons. 848 Jul 56

The clinical usefulness of cardiac imaging modalities that rely upon the detection of perfusion defects and wall motion disturbances requires conditions that provoke a heterogeneity of coronary flow and a myocardial oxygen imbalance, respectively. Traditionally, this has been achieved by exercise stress testing. Many patients cannot perform dynamic exercise sufficiently for various reasons. Pharmacologic stress has been proven to be an attractive alternative for physical exercise. Currently, several stressing agents are used in conjunction with thallium-201 scintigraphy, 2-D echocardiography and, recently, MRI. The most employed agents include vasodilators, such as dipyridamole and adenosine, and catecholamines, such as dobutamine (Table VI). The predominant rationale of thallium-201 perfusion scintigraphy is based on the creation of a flow maldistribution between territories supplied by normal arteries and those supplied by stenotic arteries that does not necessarily require ischemia. Dipyridamole and adenosine, as rather selective coronary vasodilators, are well suited to provoke such a condition and may be classified as the ideal markers of myocardial perfusion. 2-D echocardiography and MRI have the potential to provide noninvasively derived information of cardiac dynamics and regional myocardial function. To assess the functional significance of coronary artery disease, detection of wall motion abnormalities and alterations in ejection fraction require the presence of myocardial ischemia. Dobutamine, as a widely applied inotropic agent in the management of severely depressed left ventricular contractile function, seems to be an appropriate pharmacologic stressor when heart failure is absent. By increasing contractility, heart rate, and systolic arterial pressure, it is capable of inducing an imbalance between myocardial oxygen demand and supply, leading to ischemia in patients with coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New developments in pharmacologic stress imaging. 163 90

Prior studies of vascular rejection in transplanted human hearts have stressed the importance of accelerated coronary arteriosclerosis (chronic vascular rejection). We, however, have had four patients with sudden onset of acute heart failure within 90 days of transplantation who have died without significant myocardial interstitial rejection or the concentric intimal thickening with dense collagen that is typical of chronic vascular rejection. In contrast, the coronary arteries in our patients had a prominent lymphocytic infiltrate, a loosely organized intimal thickening composed of smooth muscle cells, and extensive endothelial injury. We believe that these changes define acute vascular rejection of the coronary artery. In 14 transplanted hearts obtained consecutively, at autopsy or at a second transplant procedure, graft failure was caused by acute coronary vascular rejection in six cases and by chronic coronary vascular rejection in one case. The remaining seven patients showed no evidence of vascular rejection and died primarily of sepsis. Cytomegalovirus (CMV) disease was present in 6 of 7 patients with vascular rejection, of which 43% were CMV-negative recipients of hearts from CMV-positive donors. The adoption of a triple-drug protocol, in which azathioprine was added to cyclosporine and prednisone, reduced the incidence of acute vascular rejection from 27% to 8%. We conclude that acute coronary vascular rejection may be initially seen as global cardiac ischemia in the absence of significant interstitial myocardial rejection. Further, acute vascular rejection should be pathologically distinguished from chronic vascular rejection, although both are probably stages in the natural history of immune-mediated vascular injury.
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PMID:Acute vascular rejection of the coronary arteries in human heart transplantation: pathology and correlations with immunosuppression and cytomegalovirus infection. 165 3

Although current knowledge concerning drug responsiveness in the human heart is still deficient at both extremes of age, i.e. in the fetus and the elderly, new information is beginning to emerge. Pharmacodynamic studies have provided a fairly comprehensive picture of the appearance and maturation of the automatic receptors, and also of the emergence and development of sympathetic-adrenergic and parasympathetic-cholinergic mechanisms in the prenatal human heart. A timetable can now be drawn up for the earliest detection of intrinsic responsiveness to numerous adrenergic and cholinergic agonists and antagonists, and to inotropic and antiarrhythmic drugs in the human embryonic and fetal heart. Information on the antenatal cardiac pharmacodynamics of antiarrhythmics and inotropic drugs is mostly confined to some of the classical remedies, so that a systematic study of the effects of the various newer drugs is warranted. As legal abortions yield prenatal hearts only in very limited numbers, human embryonic and fetal cardiac tissue and cell cultures could also be used for such research under both physiological and pathological conditions, such as hypoxia or simulated ischemia. Since the sporadic data available on the transplacental efficacy of maternally administered cardioactive agents are encouraging, extensive clinical investigation into the pharmacological control of intrauterine cardiac arrhythmias and heart failure, based on new, high-resolution fetal echocardiographic techniques to monitor the success of drug therapy at the various stages of prenatal development, is also a stimulating challenge. In the elderly human heart, pharmacodynamically-based alterations in responsiveness to drugs have so far been conclusively proven for adrenergic agents.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiac responses to drugs at the extremes of age. 168 23

Patients with left ventricular hypertrophy (LVH) often exhibit manifestations of myocardial ischemia. In 17 hypertensive patients (group 1, mean age of 56 +/- 4 years, 10 females, 7 males) with ST-segment depression during the exercise electrocardiogram (ECG) and effort angina and normal coronary arteriograms, the left ventricular function at rest and during exercise was studied by heart catheterization. The results were compared with 17 hypertensive patients (group 2, mean age of 56 +/- 6 years, 6 females, 11 males) with coronary artery disease (CAD). The normal pulmonary wedge pressure at rest (group 1, 8.9 +/- 3 mm Hg; group 2, 8.9 +/- 3 mm Hg) was pathologically increased (p less than 0.001) in both groups (group 1, 27.1 +/- 5 mm Hg; group 2, 28.8 +/- 7 mm Hg) even at a work load of 50 W with a further increase at 75 W to 31 +/- 4 and 29.7 +/- 4 mm Hg, respectively. Cardiac output was normal. There was no significant correlation between ST-segment depression, pulmonary wedge pressure, LVH, and Holter ECG. Hypertensive patients without CAD may reveal a disturbed pump function due to ischemia even at low work loads, which does not differ significantly from patients with CAD. This may provoke subendocardial fibrosis and thereby contribute to the development of heart failure.
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PMID:Impaired left ventricular function during exercise in hypertensive patients with normal coronary arteriograms. 171 61

Intracellular overloading by calcium ions may play an important role in the development of ischemic ventricular fibrillation, as shown by experimental data. Mechanisms are those that develop secondary to the rise in cytosolic calcium thought to occur in ischemia. After-depolarizations are stressed as a possible cause of automaticity and triggered arrhythmias in ventricular tissue. The ideal calcium antagonist should be able to inhibit such afterdepolarizations in ischemic tissue without having a negative inotropic effect on nonischemic tissue. Hence, it might be possible to extend the beneficial results of verapamil found in a recent postinfarct trial to show even better postinfarct protection by a calcium antagonist with these specific properties. On the other hand, a highly vascular-selective calcium antagonist, by avoiding any effect on the myocardium, could also be desirable in postinfarct patients with heart failure. Future trials should compare these two types of calcium antagonists. If the adverse effect of calcium antagonists on heart failure could be avoided, then the calcium antagonists would stand along-side the beta-blockers as agents able to prevent postinfarct sudden death. Furthermore, the combination of calcium antagonists and beta-blockade could then become attractive as potentially powerful postinfarct protection.
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PMID:Calcium antagonists, ventricular arrhythmias, and sudden cardiac death: a major challenge for the future. 172 11

The initiating cause of the first ectopic beat and its precipitation of sustained lethal arrhythmia in acute myocardial ischemia is not clear. Comparable uncertainties surround sudden death in myocardial failure. Progress in control of ventricular fibrillation has been slow, perhaps because diagnosis and treatment have been based on the premise that ischemic biochemical changes solely cause the alterations in electrophysiological behavior. Alternative approaches need exploration. Evidence that mechanical changes can initiate electrophysiological changes by a process sometimes referred to as "mechanoelectric feedback" is accumulating. It operates when any primary mechanical change in ventricular muscle, e.g., contraction produces a change in its electrical properties. Mechanical changes are prevalent in ischemia and cardiac failure. If mechanoelectric feedback operates here, it is not surprising that arrhythmias in some of these pathologies parallel the degree of mechanical myocardial dysfunction rather than electrophysiological changes, independent of etiology. This mechanoelectric feedback system may exist as an intrinsic property of normal myocardium, providing a feedback control of activation processes at both the cellular and gross levels. Its disruption during pathological events produces instability in the system and thus ventricular arrhythmia. This concept provides a new potential avenue for arrhythmia therapy.
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PMID:Myocardial mechanics and arrhythmia. 172 49

We prospectively compared the differences in perioperative cardiac ischemic events in 140 patients undergoing major abdominal (n = 53) versus infrainguinal (n = 87) vascular operations. Preoperative dipyridamole thallium cardiac scintigraphy was performed in a subset of 38 of these patients, with treating physicians blinded to the test results. Myocardial ischemia was measured during operation with use of continuous 12-lead electrocardiography (ECG) and transesophageal echocardiography. Continuous two-lead ambulatory ECG (Holter monitoring) was performed before, during, and after operation for 4 days. Outcome events were cardiac death, nonfatal myocardial infarction, unstable angina, ventricular tachycardia, and congestive heart failure. Results of the study indicated that most demographic variables, such as age, hypertension, cigarette smoking, serum cholesterol, were comparable between patients having aortic or infrainguinal arterial operations. However, in the infrainguinal group more patients had diabetes, second vascular operations, angina pectoris, heart failure, dysrhythmias, and used digitalis. Abnormalities in preoperative Holter monitoring, ECGs, and thallium scan abnormalities were equivalent between groups. During operation, whereas Holter and ECG abnormalities were comparable, more patients undergoing aortic procedures suffered ischemia as determined by transesophageal echocardiography (26% vs 10%, p = 0.019). After operation there were 21 (24%) outcome events in patients having infrainguinal bypasses compared with 15 (28%) patients having aortic procedures (p = NS). Ischemia by Holter monitoring (n = 133) occurred after operation in 46 (57%) patients having infrainguinal operations compared with 16 (31%) patients having aortic reconstructions (p = 0.005). Because preoperative cardiac disease and adverse cardiac outcomes occurred with similar or even greater frequency in both groups of patients, we conclude that the risk for postoperative cardiac ischemic events in lower extremity vascular operations is at least as great as for aortic operations.
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PMID:Comparison of cardiac morbidity between aortic and infrainguinal operations. Study of Perioperative Ischemia (SPI) Research Group. 173 96


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